Public Example SOC
This document is not intended to support clinical reporting and must be strictly limited to academic research use only.
Cancer type:
Serous Ovarian Cancer
Putative functionally relevant variants: 4
| Gene | Gene Info | Alteration | Functional relevance evidence | Reported biomarker(s) |
|---|---|---|---|---|
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - missense, exon 18/27 p.Cys2689Phe |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
stop gained
p.Lys2008Ter
exon 11/27
more
chr13:32914514 A/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Lys2008Ter HGVSc: ENST00000380152.3:c.6022A>T Location: exon 11/27 Consequence: stop gained Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Lys2008Ter HGVSc: ENST00000544455.1:c.6022A>T Location: exon 11/28 Consequence: stop gained |
Evidence A (curated):
>Pathogenic, ClinVar
BRCA2 p.Lys2008Ter https://www.ncbi.nlm.nih.gov/clinvar/variation/216029 Effect: Pathogenic Allele origin: BRCA2 Review status: reviewed by expert panel >Pathogenic, BRCA Exch.
|
Others - Prognostic, 2 assertions
Alterations reported to be prognostic biomarkers
Please check the original assertions provided by each knowledgebase listed below https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Better Outcome Drug: - Disease: epithelial ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 22274685 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Better Outcome Drug: - Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26740259 Tier 1-Ready for use, 7 assertions
Tier 1 includes variants described as drug/prognostic biomarkers with ready-for-use clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Bevacizumab; Niraparib; Olaparib; Rucaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 28882436 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib,Bevacizumab Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 28882436 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 30345884 Tier 2-Investig. (basket match), 1 assertions
Tier 2 includes variants described as drug/prognostic biomarkers according to investigational clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Olaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 19553641 Tier 2-Investigational, 7 assertions
Tier 2 includes variants described as drug/prognostic biomarkers according to investigational clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Cediranib; Olaparib; Platinum Compound; Rucaparib; Talazoparib https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23346317 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21862407 https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Talazoparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 28242752 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cediranib,Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 25218906 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 27908594 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 Tier 3-Cancer repurposing, 35 assertions
Tier 3 includes variants described as drug/prognostic biomarkers for other cancer types (cancer type repurposing)
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Abiraterone; Abiraterone Acetate; Bevacizumab; Carboplatin; Cisplatin; Enzalutamide; Gemcitabine; Iniparib; Niraparib; Olaparib; Platinum Compound; Prednisone; Rucaparib; Talazoparib; Veliparib https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib,Abiraterone,Prednisone Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Talazoparib,Enzalutamide Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib,Bevacizumab Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib,Bevacizumab Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Olaparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: her2-receptor negative breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 34081848 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Olaparib Disease: prostate cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 26510020 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Talazoparib Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Niraparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: triple-receptor negative breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 34081848 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cisplatin,Gemcitabine,Veliparib Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 29338080 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 25072261 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 25366685 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cisplatin,Carboplatin Disease: triple-receptor negative breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 25847936 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28792849 https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: her2-receptor negative breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 28578601 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib,Abiraterone Acetate,Prednisone Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Unknown Clinical significance: Sensitivity/Response Drug: Olaparib Disease: castration-resistant prostate carcinoma Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 32343890 https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Talazoparib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28242752 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: pancreatic adenocarcinoma Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31157963 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Iniparib Disease: pancreatic cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 21508395 |
|
AKT1
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu17Lys
exon 4/15
more
chr14:105246551 C/T (GRCh37/hg19)
Transcript: ENST00000349310 HGVSp: ENSP00000270202.4:p.Glu17Lys HGVSc: ENST00000349310.3:c.49G>A Location: exon 4/15 Consequence: missense variant,splice region variant Representative Transcript ──────────────────────── Transcript: ENST00000402615 HGVSp: ENSP00000385326.2:p.Glu17Lys HGVSc: ENST00000402615.2:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000407796 HGVSp: ENSP00000384293.2:p.Glu17Lys HGVSc: ENST00000407796.2:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000544168 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000554581 HGVSp: ENSP00000451828.1:p.Glu17Lys HGVSc: ENST00000554581.1:c.49G>A Location: exon 2/13 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000554826 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000554848 HGVSp: ENSP00000451166.1:p.Glu17Lys HGVSc: ENST00000554848.1:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000555380 HGVSp: - HGVSc: ENST00000555380.1:c.-138G>A Location: exon 2/5 Consequence: splice region variant,5 prime UTR variant ──────────────────────── Transcript: ENST00000555528 HGVSp: ENSP00000450688.1:p.Glu17Lys HGVSc: ENST00000555528.1:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000555926 HGVSp: ENSP00000451824.1:p.Glu17Lys HGVSc: ENST00000555926.1:c.49G>A Location: exon 4/5 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000556836 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000557552 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic, ClinVar
AKT1 p.Glu17Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13983 Effect: Pathogenic Allele origin: AKT1 Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
AKT1 p.Glu17Lys https://oncokb.org/#/gene/AKT1/alteration/E17K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Sensitivity/Response, CIViC
AKT1 p.Glu17Lys https://civicdb.org/links/variants/4 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/4 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: breast cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 26351323
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
AKT1 p.Glu17Lys This variant is observed across population databases with max AF< 1% (8.872e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.872e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - |
Tier 2-Investig. (basket match), 1 assertions
Tier 2 includes variants described as drug/prognostic biomarkers according to investigational clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Capivasertib https://civicdb.org/links/variants/4 Biomarker: AKT1 E17K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 Tier 2-Investigational, 1 assertions
Tier 2 includes variants described as drug/prognostic biomarkers according to investigational clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Capivasertib https://oncokb.org/#/gene/AKT1/alteration/E17K Biomarker: AKT1 E17K Effect: drug Responsive Evidence level: LEVEL_3A Drug: Capivasertib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. Tier 3-Cancer repurposing, 4 assertions
Tier 3 includes variants described as drug/prognostic biomarkers for other cancer types (cancer type repurposing)
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Capivasertib; Fulvestrant https://oncokb.org/#/gene/AKT1/alteration/E17K Biomarker: AKT1 E17K Effect: drug Responsive Evidence level: LEVEL_3A Drug: Capivasertib Disease: Endometrial Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/AKT1/alteration/E17K Biomarker: AKT1 E17K Effect: drug Responsive Evidence level: LEVEL_1 Drug: Capivasertib,Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/AKT1/alteration/Oncogenic Mutations (excluding E17K) Biomarker: AKT1 Oncogenic Mutations (excluding E17K) Effect: drug Responsive Evidence level: LEVEL_2 Drug: Capivasertib,Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/4 Biomarker: AKT1 E17K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: breast cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 26351323 |
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CDKN2A
|
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
stop gained
p.Arg58Ter
exon 2/3
more
chr9:21971186 G/A (GRCh37/hg19)
Transcript: ENST00000304494 HGVSp: ENSP00000307101.5:p.Arg58Ter HGVSc: ENST00000304494.5:c.172C>T Location: exon 2/3 Consequence: stop gained Representative Transcript ──────────────────────── Transcript: ENST00000361570 HGVSp: ENSP00000355153.3:p.Pro113Leu HGVSc: ENST00000361570.3:c.338C>T Location: exon 2/3 Consequence: missense variant ──────────────────────── Transcript: ENST00000380150 HGVSp: - HGVSc: ENST00000380150.2:n.146C>T Location: exon 1/2 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000380151 HGVSp: - HGVSc: ENST00000380151.3:c.*95C>T Location: exon 2/3 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000404796 HGVSp: - HGVSc: ENST00000404796.2:c.348-58246G>A Location: intron 4/5 Consequence: intron variant,NMD transcript variant ──────────────────────── Transcript: ENST00000441769 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000446177 HGVSp: ENSP00000394932.1:p.Arg58Ter HGVSc: ENST00000446177.1:c.172C>T Location: exon 2/3 Consequence: stop gained ──────────────────────── Transcript: ENST00000479692 HGVSp: ENSP00000466887.1:p.Arg7Ter HGVSc: ENST00000479692.2:c.19C>T Location: exon 2/3 Consequence: stop gained ──────────────────────── Transcript: ENST00000494262 HGVSp: ENSP00000464952.1:p.Arg7Ter HGVSc: ENST00000494262.1:c.19C>T Location: exon 3/4 Consequence: stop gained ──────────────────────── Transcript: ENST00000497750 HGVSp: ENSP00000468510.1:p.Arg7Ter HGVSc: ENST00000497750.1:c.19C>T Location: exon 2/2 Consequence: stop gained ──────────────────────── Transcript: ENST00000498124 HGVSp: ENSP00000418915.1:p.Arg58Ter HGVSc: ENST00000498124.1:c.172C>T Location: exon 2/4 Consequence: stop gained ──────────────────────── Transcript: ENST00000498628 HGVSp: ENSP00000467857.1:p.Arg7Ter HGVSc: ENST00000498628.2:c.19C>T Location: exon 2/3 Consequence: stop gained ──────────────────────── Transcript: ENST00000530628 HGVSp: ENSP00000432664.2:p.Pro72Leu HGVSc: ENST00000530628.2:c.215C>T Location: exon 2/3 Consequence: missense variant ──────────────────────── Transcript: ENST00000577854 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000578845 HGVSp: ENSP00000467390.1:p.Arg7Ter HGVSc: ENST00000578845.2:c.19C>T Location: exon 1/2 Consequence: stop gained ──────────────────────── Transcript: ENST00000579122 HGVSp: ENSP00000464202.1:p.Arg58Ter HGVSc: ENST00000579122.1:c.172C>T Location: exon 2/3 Consequence: stop gained ──────────────────────── Transcript: ENST00000579755 HGVSp: ENSP00000462950.1:p.Pro72Leu HGVSc: ENST00000579755.1:c.215C>T Location: exon 2/3 Consequence: missense variant |
Evidence A (curated):
>Pathogenic, ClinVar
CDKN2A p.Arg58Ter https://www.ncbi.nlm.nih.gov/clinvar/variation/376310 Effect: Pathogenic Allele origin: CDKN2A Review status: criteria provided, multiple submitters, no conflicts |
Tier 4-Hypothet. (basket match), 3 assertions
Tier 4 includes variants described as drug/prognostic biomarkers according to preclinical data
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Abemaciclib; Palbociclib; Ribociclib https://oncokb.org/#/gene/CDKN2A/alteration/Oncogenic Mutations Biomarker: CDKN2A Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: Ribociclib Disease: SOLID The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/CDKN2A/alteration/Oncogenic Mutations Biomarker: CDKN2A Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: Palbociclib Disease: SOLID The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/CDKN2A/alteration/Oncogenic Mutations Biomarker: CDKN2A Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: Abemaciclib Disease: SOLID The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - stop gained, exon 11/27 p.Lys2008Ter |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
missense
p.Cys2689Phe
exon 18/27
more
chr13:32937405 G/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Cys2689Phe HGVSc: ENST00000380152.3:c.8066G>T Location: exon 18/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Cys2689Phe HGVSc: ENST00000544455.1:c.8066G>T Location: exon 18/28 Consequence: missense variant |
Evidence C (predicted):
Note that the evidence of type C is only based on bioinformatic calculations and thus it should be considered as the supporting evidence with lower strength. See our paper in Nature Cancer for more details about the rationale and benchmarking of the methods employed here.
>Tumor supp. - missense of very high predicted deleteriousness score, see more
BRCA2 p.Cys2689Phe This missense mutation shows a very high deleteriousness score (Phred CADD = 32.0), which is predicted to lead to the loss of BRCA2 tumor suppressor function (very high deleteriousness score is defined as CADD>30, which discriminates reported loss-of-function vs. neutral missense mutations in tumor suppressors with a true positive rate of ~90% according to our in-house benchmarking) |
Others - Prognostic, 2 assertions
Alterations reported to be prognostic biomarkers
Please check the original assertions provided by each knowledgebase listed below https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Better Outcome Drug: - Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26740259 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Better Outcome Drug: - Disease: epithelial ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 22274685 Tier 1-Ready for use, 7 assertions
Tier 1 includes variants described as drug/prognostic biomarkers with ready-for-use clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Bevacizumab; Niraparib; Olaparib; Rucaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 30345884 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 28882436 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 28882436 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib,Bevacizumab Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. Tier 2-Investig. (basket match), 1 assertions
Tier 2 includes variants described as drug/prognostic biomarkers according to investigational clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Olaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 19553641 Tier 2-Investigational, 7 assertions
Tier 2 includes variants described as drug/prognostic biomarkers according to investigational clinical data for this cancer type
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Cediranib; Olaparib; Platinum Compound; Rucaparib; Talazoparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21862407 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Talazoparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 28242752 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 27908594 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cediranib,Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 25218906 https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23346317 Tier 3-Cancer repurposing, 35 assertions
Tier 3 includes variants described as drug/prognostic biomarkers for other cancer types (cancer type repurposing)
Please check the original assertions provided by each knowledgebase listed below >Reported sensitivity/response: Abiraterone; Abiraterone Acetate; Bevacizumab; Carboplatin; Cisplatin; Enzalutamide; Gemcitabine; Iniparib; Niraparib; Olaparib; Platinum Compound; Prednisone; Rucaparib; Talazoparib; Veliparib https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib,Abiraterone,Prednisone Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Talazoparib,Enzalutamide Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib,Bevacizumab Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib,Bevacizumab Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Talazoparib Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Niraparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Olaparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cisplatin,Carboplatin Disease: triple-receptor negative breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 25847936 https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Talazoparib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28242752 https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: her2-receptor negative breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 28578601 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28792849 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 25366685 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 25072261 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cisplatin,Gemcitabine,Veliparib Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 29338080 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Iniparib Disease: pancreatic cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 21508395 https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Unknown Clinical significance: Sensitivity/Response Drug: Olaparib Disease: castration-resistant prostate carcinoma Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 32343890 https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: pancreatic adenocarcinoma Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31157963 https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: her2-receptor negative breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 34081848 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib,Abiraterone Acetate,Prednisone Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Olaparib Disease: prostate cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 26510020 https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: triple-receptor negative breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 34081848 |
Variants of unknown/contradictory functional significance: 1
| Gene | Gene Info | Alteration | Functional relevance evidence | Reported biomarker(s) |
|---|---|---|---|---|
|
KIT
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Gln922Leu
exon 20/21
more
chr4:55603409 A/T (GRCh37/hg19)
Transcript: ENST00000288135 HGVSp: ENSP00000288135.5:p.Gln922Leu HGVSc: ENST00000288135.5:c.2765A>T Location: exon 20/21 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000412167 HGVSp: ENSP00000390987.2:p.Gln918Leu HGVSc: ENST00000412167.2:c.2753A>T Location: exon 20/21 Consequence: missense variant ──────────────────────── Transcript: ENST00000512959 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant |
Inconclusive curation:
>No conclusive criteria, more
KIT p.Gln922Leu No conclusive effect for this variant is reported by the knowledgebases employed here. No biological bona fide assumption or bioinformatic prediction (see PMID: 35221333) applies and/or is conclusive to classify the variant. |
Not contemplated
Potential match with cancer biomarkers is only contemplated for variants that are classified as functionally relevant.
|
Putative functionally neutral variants: 1
| Gene | Gene Info | Alteration | Functional relevance evidence | Reported biomarker(s) |
|---|---|---|---|---|
|
APC
|
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
missense
p.Arg1171Cys
exon 16/16
more
chr5:112174802 C/T (GRCh37/hg19)
Transcript: ENST00000257430 HGVSp: ENSP00000257430.4:p.Arg1171Cys HGVSc: ENST00000257430.4:c.3511C>T Location: exon 16/16 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000457016 HGVSp: ENSP00000413133.1:p.Arg1171Cys HGVSc: ENST00000457016.1:c.3511C>T Location: exon 16/16 Consequence: missense variant ──────────────────────── Transcript: ENST00000502371 HGVSp: - HGVSc: ENST00000502371.1:n.1864C>T Location: exon 3/3 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000504915 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000507379 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000508376 HGVSp: ENSP00000427089.2:p.Arg1171Cys HGVSc: ENST00000508376.2:c.3511C>T Location: exon 17/17 Consequence: missense variant ──────────────────────── Transcript: ENST00000508624 HGVSp: - HGVSc: ENST00000508624.1:c.*2833C>T Location: exon 17/17 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000512211 HGVSp: ENSP00000423828.2:p.Arg1171Cys HGVSc: ENST00000512211.2:c.3511C>T Location: exon 16/16 Consequence: missense variant ──────────────────────── Transcript: ENST00000514164 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000520401 HGVSp: - HGVSc: ENST00000520401.1:c.230+10133C>T Location: intron 3/7 Consequence: intron variant,NMD transcript variant |
Evidence A (curated):
>Benign/Likely benign, ClinVar
APC p.Arg1171Cys https://www.ncbi.nlm.nih.gov/clinvar/variation/133518 Effect: Benign/Likely benign Allele origin: APC Review status: criteria provided, multiple submitters, no conflicts
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
APC p.Arg1171Cys This variant is observed across population databases with max AF< 1% (0.001215), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 0.0003436 gnomAD African/African American: 6.33e-05 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 0.000309 gnomAD South Asian: 0 gnomAD Other: 0.001152 1000G European: 0.001 1000G African: 0 1000G American: 0 1000G East Asian: 0 1000G South Asian: 0 |
Not contemplated
Potential match with cancer biomarkers is only contemplated for variants that are classified as functionally relevant.
|
Tier 1 - Ready for use biomarkers: 2
| Gene | Gene Info | Alteration | Functional relevance evidence | Biomarker |
|---|---|---|---|---|
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - missense, exon 18/27 p.Cys2689Phe |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
stop gained
p.Lys2008Ter
exon 11/27
more
chr13:32914514 A/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Lys2008Ter HGVSc: ENST00000380152.3:c.6022A>T Location: exon 11/27 Consequence: stop gained Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Lys2008Ter HGVSc: ENST00000544455.1:c.6022A>T Location: exon 11/28 Consequence: stop gained |
Evidence A (curated):
>Pathogenic, ClinVar
BRCA2 p.Lys2008Ter https://www.ncbi.nlm.nih.gov/clinvar/variation/216029 Effect: Pathogenic Allele origin: BRCA2 Review status: reviewed by expert panel >Pathogenic, BRCA Exch.
|
Sensitivity/Response
> Niraparib (OncoKB
BRCA2 p.Lys2008Ter Drug: Niraparib https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Olaparib (OncoKB; CIViC
BRCA2 p.Lys2008Ter Drug: Olaparib 2 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 30345884 > Olaparib; Bevacizumab (OncoKB
BRCA2 p.Lys2008Ter Drug: Olaparib; Bevacizumab https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib;Bevacizumab Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Rucaparib (CIViC; OncoKB
BRCA2 p.Lys2008Ter Drug: Rucaparib 3 assertions found: https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 28882436 ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 28882436 |
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - stop gained, exon 11/27 p.Lys2008Ter |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
missense
p.Cys2689Phe
exon 18/27
more
chr13:32937405 G/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Cys2689Phe HGVSc: ENST00000380152.3:c.8066G>T Location: exon 18/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Cys2689Phe HGVSc: ENST00000544455.1:c.8066G>T Location: exon 18/28 Consequence: missense variant |
Evidence C (predicted):
Note that the evidence of type C is only based on bioinformatic calculations and thus it should be considered as the supporting evidence with lower strength. See our paper in Nature Cancer for more details about the rationale and benchmarking of the methods employed here.
>Tumor supp. - missense of very high predicted deleteriousness score, see more
BRCA2 p.Cys2689Phe This missense mutation shows a very high deleteriousness score (Phred CADD = 32.0), which is predicted to lead to the loss of BRCA2 tumor suppressor function (very high deleteriousness score is defined as CADD>30, which discriminates reported loss-of-function vs. neutral missense mutations in tumor suppressors with a true positive rate of ~90% according to our in-house benchmarking) |
Sensitivity/Response
> Niraparib (OncoKB
BRCA2 p.Cys2689Phe Drug: Niraparib https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Olaparib (CIViC; OncoKB
BRCA2 p.Cys2689Phe Drug: Olaparib 2 assertions found: https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 30345884 ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Olaparib; Bevacizumab (OncoKB
BRCA2 p.Cys2689Phe Drug: Olaparib; Bevacizumab https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib;Bevacizumab Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Rucaparib (CIViC; OncoKB
BRCA2 p.Cys2689Phe Drug: Rucaparib 3 assertions found: https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 28882436 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 28882436 ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
Special - Other biomarkers of clinical interest: 2
| Gene | Gene Info | Alteration | Functional relevance evidence | Biomarker |
|---|---|---|---|---|
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - missense, exon 18/27 p.Cys2689Phe |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
stop gained
p.Lys2008Ter
exon 11/27
more
chr13:32914514 A/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Lys2008Ter HGVSc: ENST00000380152.3:c.6022A>T Location: exon 11/27 Consequence: stop gained Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Lys2008Ter HGVSc: ENST00000544455.1:c.6022A>T Location: exon 11/28 Consequence: stop gained |
Evidence A (curated):
>Pathogenic, ClinVar
BRCA2 p.Lys2008Ter https://www.ncbi.nlm.nih.gov/clinvar/variation/216029 Effect: Pathogenic Allele origin: BRCA2 Review status: reviewed by expert panel >Pathogenic, BRCA Exch.
|
Prognostic
> Epithelial Ovarian Cancer (CIViC
BRCA2 p.Lys2008Ter Disease: Epithelial Ovarian Cancer https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Better Outcome Drug: - Disease: epithelial ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 22274685 > Ovarian Cancer (CIViC
BRCA2 p.Lys2008Ter Disease: Ovarian Cancer https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Better Outcome Drug: - Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26740259 |
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - stop gained, exon 11/27 p.Lys2008Ter |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
missense
p.Cys2689Phe
exon 18/27
more
chr13:32937405 G/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Cys2689Phe HGVSc: ENST00000380152.3:c.8066G>T Location: exon 18/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Cys2689Phe HGVSc: ENST00000544455.1:c.8066G>T Location: exon 18/28 Consequence: missense variant |
Evidence C (predicted):
Note that the evidence of type C is only based on bioinformatic calculations and thus it should be considered as the supporting evidence with lower strength. See our paper in Nature Cancer for more details about the rationale and benchmarking of the methods employed here.
>Tumor supp. - missense of very high predicted deleteriousness score, see more
BRCA2 p.Cys2689Phe This missense mutation shows a very high deleteriousness score (Phred CADD = 32.0), which is predicted to lead to the loss of BRCA2 tumor suppressor function (very high deleteriousness score is defined as CADD>30, which discriminates reported loss-of-function vs. neutral missense mutations in tumor suppressors with a true positive rate of ~90% according to our in-house benchmarking) |
Prognostic
> Epithelial Ovarian Cancer (CIViC
BRCA2 p.Cys2689Phe Disease: Epithelial Ovarian Cancer https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Better Outcome Drug: - Disease: epithelial ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 22274685 > Ovarian Cancer (CIViC
BRCA2 p.Cys2689Phe Disease: Ovarian Cancer https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Prognostic Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Better Outcome Drug: - Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 26740259 |
Tier 2 - Investigational biomarkers: 6
| Gene | Gene Info | Alteration | Functional relevance evidence | Biomarker |
|---|---|---|---|---|
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - missense, exon 18/27 p.Cys2689Phe |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
stop gained
p.Lys2008Ter
exon 11/27
more
chr13:32914514 A/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Lys2008Ter HGVSc: ENST00000380152.3:c.6022A>T Location: exon 11/27 Consequence: stop gained Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Lys2008Ter HGVSc: ENST00000544455.1:c.6022A>T Location: exon 11/28 Consequence: stop gained |
Evidence A (curated):
>Pathogenic, ClinVar
BRCA2 p.Lys2008Ter https://www.ncbi.nlm.nih.gov/clinvar/variation/216029 Effect: Pathogenic Allele origin: BRCA2 Review status: reviewed by expert panel >Pathogenic, BRCA Exch.
|
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Olaparib (CIViC
BRCA2 p.Lys2008Ter Drug: Olaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 19553641 Sensitivity/Response
> Cediranib;Olaparib (CIViC
BRCA2 p.Lys2008Ter Drug: Cediranib;Olaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cediranib,Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 25218906 > Olaparib (CIViC
BRCA2 p.Lys2008Ter Drug: Olaparib 2 assertions found: https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23346317 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21862407 > Platinum Compound (CIViC
BRCA2 p.Lys2008Ter Drug: Platinum Compound 2 assertions found: https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 > Rucaparib (CIViC
BRCA2 p.Lys2008Ter Drug: Rucaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 27908594 > Talazoparib (CIViC
BRCA2 p.Lys2008Ter Drug: Talazoparib https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Talazoparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 28242752 |
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - stop gained, exon 11/27 p.Lys2008Ter |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
missense
p.Cys2689Phe
exon 18/27
more
chr13:32937405 G/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Cys2689Phe HGVSc: ENST00000380152.3:c.8066G>T Location: exon 18/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Cys2689Phe HGVSc: ENST00000544455.1:c.8066G>T Location: exon 18/28 Consequence: missense variant |
Evidence C (predicted):
Note that the evidence of type C is only based on bioinformatic calculations and thus it should be considered as the supporting evidence with lower strength. See our paper in Nature Cancer for more details about the rationale and benchmarking of the methods employed here.
>Tumor supp. - missense of very high predicted deleteriousness score, see more
BRCA2 p.Cys2689Phe This missense mutation shows a very high deleteriousness score (Phred CADD = 32.0), which is predicted to lead to the loss of BRCA2 tumor suppressor function (very high deleteriousness score is defined as CADD>30, which discriminates reported loss-of-function vs. neutral missense mutations in tumor suppressors with a true positive rate of ~90% according to our in-house benchmarking) |
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Olaparib (CIViC
BRCA2 p.Cys2689Phe Drug: Olaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 19553641 Sensitivity/Response
> Cediranib;Olaparib (CIViC
BRCA2 p.Cys2689Phe Drug: Cediranib;Olaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cediranib,Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 25218906 > Olaparib (CIViC
BRCA2 p.Cys2689Phe Drug: Olaparib 2 assertions found: https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21862407 ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23346317 > Platinum Compound (CIViC
BRCA2 p.Cys2689Phe Drug: Platinum Compound 2 assertions found: https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 > Rucaparib (CIViC
BRCA2 p.Cys2689Phe Drug: Rucaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 27908594 > Talazoparib (CIViC
BRCA2 p.Cys2689Phe Drug: Talazoparib https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Talazoparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 28242752 |
|
AKT1
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu17Lys
exon 4/15
more
chr14:105246551 C/T (GRCh37/hg19)
Transcript: ENST00000349310 HGVSp: ENSP00000270202.4:p.Glu17Lys HGVSc: ENST00000349310.3:c.49G>A Location: exon 4/15 Consequence: missense variant,splice region variant Representative Transcript ──────────────────────── Transcript: ENST00000402615 HGVSp: ENSP00000385326.2:p.Glu17Lys HGVSc: ENST00000402615.2:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000407796 HGVSp: ENSP00000384293.2:p.Glu17Lys HGVSc: ENST00000407796.2:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000544168 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000554581 HGVSp: ENSP00000451828.1:p.Glu17Lys HGVSc: ENST00000554581.1:c.49G>A Location: exon 2/13 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000554826 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000554848 HGVSp: ENSP00000451166.1:p.Glu17Lys HGVSc: ENST00000554848.1:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000555380 HGVSp: - HGVSc: ENST00000555380.1:c.-138G>A Location: exon 2/5 Consequence: splice region variant,5 prime UTR variant ──────────────────────── Transcript: ENST00000555528 HGVSp: ENSP00000450688.1:p.Glu17Lys HGVSc: ENST00000555528.1:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000555926 HGVSp: ENSP00000451824.1:p.Glu17Lys HGVSc: ENST00000555926.1:c.49G>A Location: exon 4/5 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000556836 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000557552 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic, ClinVar
AKT1 p.Glu17Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13983 Effect: Pathogenic Allele origin: AKT1 Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
AKT1 p.Glu17Lys https://oncokb.org/#/gene/AKT1/alteration/E17K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Sensitivity/Response, CIViC
AKT1 p.Glu17Lys https://civicdb.org/links/variants/4 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/4 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: breast cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 26351323
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
AKT1 p.Glu17Lys This variant is observed across population databases with max AF< 1% (8.872e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.872e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - |
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Capivasertib (CIViC
AKT1 p.Glu17Lys Drug: Capivasertib https://civicdb.org/links/variants/4 Biomarker: AKT1 E17K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 Sensitivity/Response
> Capivasertib (OncoKB
AKT1 p.Glu17Lys Drug: Capivasertib https://oncokb.org/#/gene/AKT1/alteration/E17K Biomarker: AKT1 E17K Effect: drug Responsive Evidence level: LEVEL_3A Drug: Capivasertib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - missense, exon 18/27 p.Cys2689Phe |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
stop gained
p.Lys2008Ter
exon 11/27
more
chr13:32914514 A/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Lys2008Ter HGVSc: ENST00000380152.3:c.6022A>T Location: exon 11/27 Consequence: stop gained Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Lys2008Ter HGVSc: ENST00000544455.1:c.6022A>T Location: exon 11/28 Consequence: stop gained |
Evidence A (curated):
>Pathogenic, ClinVar
BRCA2 p.Lys2008Ter https://www.ncbi.nlm.nih.gov/clinvar/variation/216029 Effect: Pathogenic Allele origin: BRCA2 Review status: reviewed by expert panel >Pathogenic, BRCA Exch.
|
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Olaparib (CIViC
BRCA2 p.Lys2008Ter Drug: Olaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 19553641 Sensitivity/Response
> Cediranib;Olaparib (CIViC
BRCA2 p.Lys2008Ter Drug: Cediranib;Olaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cediranib,Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 25218906 > Olaparib (CIViC
BRCA2 p.Lys2008Ter Drug: Olaparib 2 assertions found: https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23346317 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21862407 > Platinum Compound (CIViC
BRCA2 p.Lys2008Ter Drug: Platinum Compound 2 assertions found: https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 > Rucaparib (CIViC
BRCA2 p.Lys2008Ter Drug: Rucaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 27908594 > Talazoparib (CIViC
BRCA2 p.Lys2008Ter Drug: Talazoparib https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Talazoparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 28242752 |
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - stop gained, exon 11/27 p.Lys2008Ter |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
missense
p.Cys2689Phe
exon 18/27
more
chr13:32937405 G/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Cys2689Phe HGVSc: ENST00000380152.3:c.8066G>T Location: exon 18/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Cys2689Phe HGVSc: ENST00000544455.1:c.8066G>T Location: exon 18/28 Consequence: missense variant |
Evidence C (predicted):
Note that the evidence of type C is only based on bioinformatic calculations and thus it should be considered as the supporting evidence with lower strength. See our paper in Nature Cancer for more details about the rationale and benchmarking of the methods employed here.
>Tumor supp. - missense of very high predicted deleteriousness score, see more
BRCA2 p.Cys2689Phe This missense mutation shows a very high deleteriousness score (Phred CADD = 32.0), which is predicted to lead to the loss of BRCA2 tumor suppressor function (very high deleteriousness score is defined as CADD>30, which discriminates reported loss-of-function vs. neutral missense mutations in tumor suppressors with a true positive rate of ~90% according to our in-house benchmarking) |
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Olaparib (CIViC
BRCA2 p.Cys2689Phe Drug: Olaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 19553641 Sensitivity/Response
> Cediranib;Olaparib (CIViC
BRCA2 p.Cys2689Phe Drug: Cediranib;Olaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cediranib,Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 25218906 > Olaparib (CIViC
BRCA2 p.Cys2689Phe Drug: Olaparib 2 assertions found: https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 21862407 ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 23346317 > Platinum Compound (CIViC
BRCA2 p.Cys2689Phe Drug: Platinum Compound 2 assertions found: https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: ovarian carcinoma Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 24240112 > Rucaparib (CIViC
BRCA2 p.Cys2689Phe Drug: Rucaparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Rucaparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 27908594 > Talazoparib (CIViC
BRCA2 p.Cys2689Phe Drug: Talazoparib https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Talazoparib Disease: ovarian cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 28242752 |
|
AKT1
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu17Lys
exon 4/15
more
chr14:105246551 C/T (GRCh37/hg19)
Transcript: ENST00000349310 HGVSp: ENSP00000270202.4:p.Glu17Lys HGVSc: ENST00000349310.3:c.49G>A Location: exon 4/15 Consequence: missense variant,splice region variant Representative Transcript ──────────────────────── Transcript: ENST00000402615 HGVSp: ENSP00000385326.2:p.Glu17Lys HGVSc: ENST00000402615.2:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000407796 HGVSp: ENSP00000384293.2:p.Glu17Lys HGVSc: ENST00000407796.2:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000544168 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000554581 HGVSp: ENSP00000451828.1:p.Glu17Lys HGVSc: ENST00000554581.1:c.49G>A Location: exon 2/13 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000554826 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000554848 HGVSp: ENSP00000451166.1:p.Glu17Lys HGVSc: ENST00000554848.1:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000555380 HGVSp: - HGVSc: ENST00000555380.1:c.-138G>A Location: exon 2/5 Consequence: splice region variant,5 prime UTR variant ──────────────────────── Transcript: ENST00000555528 HGVSp: ENSP00000450688.1:p.Glu17Lys HGVSc: ENST00000555528.1:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000555926 HGVSp: ENSP00000451824.1:p.Glu17Lys HGVSc: ENST00000555926.1:c.49G>A Location: exon 4/5 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000556836 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000557552 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic, ClinVar
AKT1 p.Glu17Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13983 Effect: Pathogenic Allele origin: AKT1 Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
AKT1 p.Glu17Lys https://oncokb.org/#/gene/AKT1/alteration/E17K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Sensitivity/Response, CIViC
AKT1 p.Glu17Lys https://civicdb.org/links/variants/4 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/4 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: breast cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 26351323
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
AKT1 p.Glu17Lys This variant is observed across population databases with max AF< 1% (8.872e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.872e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - |
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Capivasertib (CIViC
AKT1 p.Glu17Lys Drug: Capivasertib https://civicdb.org/links/variants/4 Biomarker: AKT1 E17K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 Sensitivity/Response
> Capivasertib (OncoKB
AKT1 p.Glu17Lys Drug: Capivasertib https://oncokb.org/#/gene/AKT1/alteration/E17K Biomarker: AKT1 E17K Effect: drug Responsive Evidence level: LEVEL_3A Drug: Capivasertib Disease: Ovarian Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
Tier 3 - Potential cancer-repurposing opportunities: 3
| Gene | Gene Info | Alteration | Functional relevance evidence | Biomarker |
|---|---|---|---|---|
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - missense, exon 18/27 p.Cys2689Phe |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
stop gained
p.Lys2008Ter
exon 11/27
more
chr13:32914514 A/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Lys2008Ter HGVSc: ENST00000380152.3:c.6022A>T Location: exon 11/27 Consequence: stop gained Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Lys2008Ter HGVSc: ENST00000544455.1:c.6022A>T Location: exon 11/28 Consequence: stop gained |
Evidence A (curated):
>Pathogenic, ClinVar
BRCA2 p.Lys2008Ter https://www.ncbi.nlm.nih.gov/clinvar/variation/216029 Effect: Pathogenic Allele origin: BRCA2 Review status: reviewed by expert panel >Pathogenic, BRCA Exch.
|
Sensitivity/Response
> Cisplatin;Carboplatin (CIViC
BRCA2 p.Lys2008Ter Drug: Cisplatin;Carboplatin https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cisplatin,Carboplatin Disease: triple-receptor negative breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 25847936 > Cisplatin;Gemcitabine;Veliparib (CIViC
BRCA2 p.Lys2008Ter Drug: Cisplatin;Gemcitabine;Veliparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cisplatin,Gemcitabine,Veliparib Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 29338080 > Iniparib (CIViC
BRCA2 p.Lys2008Ter Drug: Iniparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Iniparib Disease: pancreatic cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 21508395 > Niraparib (OncoKB
BRCA2 p.Lys2008Ter Drug: Niraparib 3 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Niraparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Niraparib; Abiraterone Acetate; Prednisone (OncoKB
BRCA2 p.Lys2008Ter Drug: Niraparib; Abiraterone Acetate; Prednisone https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib;Abiraterone Acetate;Prednisone Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Olaparib (OncoKB; CIViC
BRCA2 p.Lys2008Ter Drug: Olaparib 15 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Olaparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: her2-receptor negative breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 34081848 ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Olaparib Disease: prostate cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 26510020 ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: triple-receptor negative breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 34081848 ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 25366685 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28792849 ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: her2-receptor negative breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 28578601 ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Unknown Clinical significance: Sensitivity/Response Drug: Olaparib Disease: castration-resistant prostate carcinoma Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 32343890 ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: pancreatic adenocarcinoma Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31157963 > Olaparib; Abiraterone; Prednisone (OncoKB
BRCA2 p.Lys2008Ter Drug: Olaparib; Abiraterone; Prednisone https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib;Abiraterone;Prednisone Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Olaparib; Bevacizumab (OncoKB
BRCA2 p.Lys2008Ter Drug: Olaparib; Bevacizumab 2 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib;Bevacizumab Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib;Bevacizumab Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Platinum Compound (CIViC
BRCA2 p.Lys2008Ter Drug: Platinum Compound https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 25072261 > Rucaparib (OncoKB
BRCA2 p.Lys2008Ter Drug: Rucaparib 6 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Talazoparib (OncoKB; CIViC
BRCA2 p.Lys2008Ter Drug: Talazoparib 2 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Talazoparib Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Talazoparib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28242752 > Talazoparib; Enzalutamide (OncoKB
BRCA2 p.Lys2008Ter Drug: Talazoparib; Enzalutamide https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Talazoparib;Enzalutamide Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
|
BRCA2
!!
BRCA2 bears additional molecular findings:
Putative functional Mutation - stop gained, exon 11/27 p.Lys2008Ter |
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
missense
p.Cys2689Phe
exon 18/27
more
chr13:32937405 G/T (GRCh37/hg19)
Transcript: ENST00000380152 HGVSp: ENSP00000369497.3:p.Cys2689Phe HGVSc: ENST00000380152.3:c.8066G>T Location: exon 18/27 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000544455 HGVSp: ENSP00000439902.1:p.Cys2689Phe HGVSc: ENST00000544455.1:c.8066G>T Location: exon 18/28 Consequence: missense variant |
Evidence C (predicted):
Note that the evidence of type C is only based on bioinformatic calculations and thus it should be considered as the supporting evidence with lower strength. See our paper in Nature Cancer for more details about the rationale and benchmarking of the methods employed here.
>Tumor supp. - missense of very high predicted deleteriousness score, see more
BRCA2 p.Cys2689Phe This missense mutation shows a very high deleteriousness score (Phred CADD = 32.0), which is predicted to lead to the loss of BRCA2 tumor suppressor function (very high deleteriousness score is defined as CADD>30, which discriminates reported loss-of-function vs. neutral missense mutations in tumor suppressors with a true positive rate of ~90% according to our in-house benchmarking) |
Sensitivity/Response
> Cisplatin;Carboplatin (CIViC
BRCA2 p.Cys2689Phe Drug: Cisplatin;Carboplatin https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cisplatin,Carboplatin Disease: triple-receptor negative breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 25847936 > Cisplatin;Gemcitabine;Veliparib (CIViC
BRCA2 p.Cys2689Phe Drug: Cisplatin;Gemcitabine;Veliparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Cisplatin,Gemcitabine,Veliparib Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 29338080 > Iniparib (CIViC
BRCA2 p.Cys2689Phe Drug: Iniparib https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Iniparib Disease: pancreatic cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 21508395 > Niraparib (OncoKB
BRCA2 p.Cys2689Phe Drug: Niraparib 3 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Niraparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Niraparib; Abiraterone Acetate; Prednisone (OncoKB
BRCA2 p.Cys2689Phe Drug: Niraparib; Abiraterone Acetate; Prednisone https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Niraparib;Abiraterone Acetate;Prednisone Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Olaparib (OncoKB; CIViC
BRCA2 p.Cys2689Phe Drug: Olaparib 15 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Olaparib Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Olaparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: her2-receptor negative breast cancer Evidence level: B - Clinical Trust rating: 3/5 Source PMID: 28578601 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28792849 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 25366685 ──────────────────────── https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Unknown Clinical significance: Sensitivity/Response Drug: Olaparib Disease: castration-resistant prostate carcinoma Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 32343890 ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: pancreatic adenocarcinoma Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 31157963 ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: her2-receptor negative breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 34081848 ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Olaparib Disease: prostate cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 26510020 ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Olaparib Disease: triple-receptor negative breast cancer Evidence level: A - Guideline Trust rating: 5/5 Source PMID: 34081848 > Olaparib; Abiraterone; Prednisone (OncoKB
BRCA2 p.Cys2689Phe Drug: Olaparib; Abiraterone; Prednisone https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib;Abiraterone;Prednisone Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Olaparib; Bevacizumab (OncoKB
BRCA2 p.Cys2689Phe Drug: Olaparib; Bevacizumab 2 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib;Bevacizumab Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Olaparib;Bevacizumab Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Platinum Compound (CIViC
BRCA2 p.Cys2689Phe Drug: Platinum Compound https://civicdb.org/links/variants/186 Biomarker: BRCA2 Mutation Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Platinum Compound Disease: pancreatic cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 25072261 > Rucaparib (OncoKB
BRCA2 p.Cys2689Phe Drug: Rucaparib 6 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Peritoneal Cancer, NOS The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Ovarian/Fallopian Tube Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Rucaparib Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Uterine Sarcoma The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_2 Drug: Rucaparib Disease: Pancreatic Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Talazoparib (OncoKB; CIViC
BRCA2 p.Cys2689Phe Drug: Talazoparib 2 assertions found: https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_3A Drug: Talazoparib Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/132 Biomarker: BRCA2 Loss-of-function Evidence type: Predictive Evidence direction: Supports Variant origin: Rare Germline Clinical significance: Sensitivity/Response Drug: Talazoparib Disease: breast cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28242752 > Talazoparib; Enzalutamide (OncoKB
BRCA2 p.Cys2689Phe Drug: Talazoparib; Enzalutamide https://oncokb.org/#/gene/BRCA2/alteration/Oncogenic Mutations Biomarker: BRCA2 Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_1 Drug: Talazoparib;Enzalutamide Disease: Prostate Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
|
AKT1
|
OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Glu17Lys
exon 4/15
more
chr14:105246551 C/T (GRCh37/hg19)
Transcript: ENST00000349310 HGVSp: ENSP00000270202.4:p.Glu17Lys HGVSc: ENST00000349310.3:c.49G>A Location: exon 4/15 Consequence: missense variant,splice region variant Representative Transcript ──────────────────────── Transcript: ENST00000402615 HGVSp: ENSP00000385326.2:p.Glu17Lys HGVSc: ENST00000402615.2:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000407796 HGVSp: ENSP00000384293.2:p.Glu17Lys HGVSc: ENST00000407796.2:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000544168 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000554581 HGVSp: ENSP00000451828.1:p.Glu17Lys HGVSc: ENST00000554581.1:c.49G>A Location: exon 2/13 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000554826 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000554848 HGVSp: ENSP00000451166.1:p.Glu17Lys HGVSc: ENST00000554848.1:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000555380 HGVSp: - HGVSc: ENST00000555380.1:c.-138G>A Location: exon 2/5 Consequence: splice region variant,5 prime UTR variant ──────────────────────── Transcript: ENST00000555528 HGVSp: ENSP00000450688.1:p.Glu17Lys HGVSc: ENST00000555528.1:c.49G>A Location: exon 3/14 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000555926 HGVSp: ENSP00000451824.1:p.Glu17Lys HGVSc: ENST00000555926.1:c.49G>A Location: exon 4/5 Consequence: missense variant,splice region variant ──────────────────────── Transcript: ENST00000556836 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000557552 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant |
Evidence A (curated):
>Pathogenic, ClinVar
AKT1 p.Glu17Lys https://www.ncbi.nlm.nih.gov/clinvar/variation/13983 Effect: Pathogenic Allele origin: AKT1 Review status: criteria provided, multiple submitters, no conflicts >Oncogenic, Biomarker, OncoKB
AKT1 p.Glu17Lys https://oncokb.org/#/gene/AKT1/alteration/E17K Effect: Oncogenic, Biomarker The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. >Sensitivity/Response, CIViC
AKT1 p.Glu17Lys https://civicdb.org/links/variants/4 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: cancer Evidence level: B - Clinical Trust rating: 4/5 Source PMID: 28489509 https://civicdb.org/links/variants/4 Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: breast cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 26351323
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
AKT1 p.Glu17Lys This variant is observed across population databases with max AF< 1% (8.872e-06), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 4e-06 gnomAD African/African American: 0 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 8.872e-06 gnomAD South Asian: 0 gnomAD Other: 0 1000G European: - 1000G African: - 1000G American: - 1000G East Asian: - 1000G South Asian: - |
Sensitivity/Response
> Capivasertib (OncoKB; CIViC
AKT1 p.Glu17Lys Drug: Capivasertib 2 assertions found: https://oncokb.org/#/gene/AKT1/alteration/E17K Biomarker: AKT1 E17K Effect: drug Responsive Evidence level: LEVEL_3A Drug: Capivasertib Disease: Endometrial Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://civicdb.org/links/variants/4 Biomarker: AKT1 E17K Evidence type: Predictive Evidence direction: Supports Variant origin: Somatic Clinical significance: Sensitivity/Response Drug: Capivasertib Disease: breast cancer Evidence level: C - Case study Trust rating: 3/5 Source PMID: 26351323 > Capivasertib; Fulvestrant (OncoKB
AKT1 p.Glu17Lys Drug: Capivasertib; Fulvestrant 2 assertions found: https://oncokb.org/#/gene/AKT1/alteration/E17K Biomarker: AKT1 E17K Effect: drug Responsive Evidence level: LEVEL_1 Drug: Capivasertib;Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. ──────────────────────── https://oncokb.org/#/gene/AKT1/alteration/Oncogenic Mutations (excluding E17K) Biomarker: AKT1 Oncogenic Mutations (excluding E17K) Effect: drug Responsive Evidence level: LEVEL_2 Drug: Capivasertib;Fulvestrant Disease: Breast Cancer The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
Tier 4 - Hypothetical preclinical biomarkers: 1
| Gene | Gene Info | Alteration | Functional relevance evidence | Biomarker |
|---|---|---|---|---|
|
CDKN2A
|
TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
stop gained
p.Arg58Ter
exon 2/3
more
chr9:21971186 G/A (GRCh37/hg19)
Transcript: ENST00000304494 HGVSp: ENSP00000307101.5:p.Arg58Ter HGVSc: ENST00000304494.5:c.172C>T Location: exon 2/3 Consequence: stop gained Representative Transcript ──────────────────────── Transcript: ENST00000361570 HGVSp: ENSP00000355153.3:p.Pro113Leu HGVSc: ENST00000361570.3:c.338C>T Location: exon 2/3 Consequence: missense variant ──────────────────────── Transcript: ENST00000380150 HGVSp: - HGVSc: ENST00000380150.2:n.146C>T Location: exon 1/2 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000380151 HGVSp: - HGVSc: ENST00000380151.3:c.*95C>T Location: exon 2/3 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000404796 HGVSp: - HGVSc: ENST00000404796.2:c.348-58246G>A Location: intron 4/5 Consequence: intron variant,NMD transcript variant ──────────────────────── Transcript: ENST00000441769 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000446177 HGVSp: ENSP00000394932.1:p.Arg58Ter HGVSc: ENST00000446177.1:c.172C>T Location: exon 2/3 Consequence: stop gained ──────────────────────── Transcript: ENST00000479692 HGVSp: ENSP00000466887.1:p.Arg7Ter HGVSc: ENST00000479692.2:c.19C>T Location: exon 2/3 Consequence: stop gained ──────────────────────── Transcript: ENST00000494262 HGVSp: ENSP00000464952.1:p.Arg7Ter HGVSc: ENST00000494262.1:c.19C>T Location: exon 3/4 Consequence: stop gained ──────────────────────── Transcript: ENST00000497750 HGVSp: ENSP00000468510.1:p.Arg7Ter HGVSc: ENST00000497750.1:c.19C>T Location: exon 2/2 Consequence: stop gained ──────────────────────── Transcript: ENST00000498124 HGVSp: ENSP00000418915.1:p.Arg58Ter HGVSc: ENST00000498124.1:c.172C>T Location: exon 2/4 Consequence: stop gained ──────────────────────── Transcript: ENST00000498628 HGVSp: ENSP00000467857.1:p.Arg7Ter HGVSc: ENST00000498628.2:c.19C>T Location: exon 2/3 Consequence: stop gained ──────────────────────── Transcript: ENST00000530628 HGVSp: ENSP00000432664.2:p.Pro72Leu HGVSc: ENST00000530628.2:c.215C>T Location: exon 2/3 Consequence: missense variant ──────────────────────── Transcript: ENST00000577854 HGVSp: - HGVSc: - Location: - Consequence: upstream gene variant ──────────────────────── Transcript: ENST00000578845 HGVSp: ENSP00000467390.1:p.Arg7Ter HGVSc: ENST00000578845.2:c.19C>T Location: exon 1/2 Consequence: stop gained ──────────────────────── Transcript: ENST00000579122 HGVSp: ENSP00000464202.1:p.Arg58Ter HGVSc: ENST00000579122.1:c.172C>T Location: exon 2/3 Consequence: stop gained ──────────────────────── Transcript: ENST00000579755 HGVSp: ENSP00000462950.1:p.Pro72Leu HGVSc: ENST00000579755.1:c.215C>T Location: exon 2/3 Consequence: missense variant |
Evidence A (curated):
>Pathogenic, ClinVar
CDKN2A p.Arg58Ter https://www.ncbi.nlm.nih.gov/clinvar/variation/376310 Effect: Pathogenic Allele origin: CDKN2A Review status: criteria provided, multiple submitters, no conflicts |
Sensitivity/Response (basket match)
This biomarker is reported to be pan-cancer, and thus it is matched regardless of the tumor type of the sample under analysis.
> Abemaciclib (OncoKB
CDKN2A p.Arg58Ter Drug: Abemaciclib https://oncokb.org/#/gene/CDKN2A/alteration/Oncogenic Mutations Biomarker: CDKN2A Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: Abemaciclib Disease: SOLID The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Palbociclib (OncoKB
CDKN2A p.Arg58Ter Drug: Palbociclib https://oncokb.org/#/gene/CDKN2A/alteration/Oncogenic Mutations Biomarker: CDKN2A Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: Palbociclib Disease: SOLID The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. > Ribociclib (OncoKB
CDKN2A p.Arg58Ter Drug: Ribociclib https://oncokb.org/#/gene/CDKN2A/alteration/Oncogenic Mutations Biomarker: CDKN2A Oncogenic Mutations Effect: drug Responsive Evidence level: LEVEL_4 Drug: Ribociclib Disease: SOLID The use of a valid OncoKB token is needed to show more OncoKB annotation details here; please see MTBP FAQs for more information. |
Alterations not classified as functional: 2
| Gene | Gene Info | Alteration | Functional classification | Functional relevance evidence | Biomarker |
|---|---|---|---|---|---|
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APC
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TS
Tumor Suppressor
This gene acts (predominantly) as a tumor suppressor, and thus loss-of-function (or dominant-negative) alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. Secondary Findings
Pathogenic variants of germline origin in This gene are recommended to be reported as secondary findings by the Cancer Core Europe consensus when appropriate. |
Mutation
missense
p.Arg1171Cys
exon 16/16
more
chr5:112174802 C/T (GRCh37/hg19)
Transcript: ENST00000257430 HGVSp: ENSP00000257430.4:p.Arg1171Cys HGVSc: ENST00000257430.4:c.3511C>T Location: exon 16/16 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000457016 HGVSp: ENSP00000413133.1:p.Arg1171Cys HGVSc: ENST00000457016.1:c.3511C>T Location: exon 16/16 Consequence: missense variant ──────────────────────── Transcript: ENST00000502371 HGVSp: - HGVSc: ENST00000502371.1:n.1864C>T Location: exon 3/3 Consequence: non coding transcript exon variant ──────────────────────── Transcript: ENST00000504915 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000507379 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000508376 HGVSp: ENSP00000427089.2:p.Arg1171Cys HGVSc: ENST00000508376.2:c.3511C>T Location: exon 17/17 Consequence: missense variant ──────────────────────── Transcript: ENST00000508624 HGVSp: - HGVSc: ENST00000508624.1:c.*2833C>T Location: exon 17/17 Consequence: 3 prime UTR variant,NMD transcript variant ──────────────────────── Transcript: ENST00000512211 HGVSp: ENSP00000423828.2:p.Arg1171Cys HGVSc: ENST00000512211.2:c.3511C>T Location: exon 16/16 Consequence: missense variant ──────────────────────── Transcript: ENST00000514164 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant ──────────────────────── Transcript: ENST00000520401 HGVSp: - HGVSc: ENST00000520401.1:c.230+10133C>T Location: intron 3/7 Consequence: intron variant,NMD transcript variant |
Putative neutral |
Evidence A (curated):
>Benign/Likely benign, ClinVar
APC p.Arg1171Cys https://www.ncbi.nlm.nih.gov/clinvar/variation/133518 Effect: Benign/Likely benign Allele origin: APC Review status: criteria provided, multiple submitters, no conflicts
Inconclusive curation:
>Population AF<1%, gnomAD/1000G
APC p.Arg1171Cys This variant is observed across population databases with max AF< 1% (0.001215), which is the threshold used to assume that the variant should be neutral gnomAD combined population: 0.0003436 gnomAD African/African American: 6.33e-05 gnomAD Ashkenazi Jewish: 0 gnomAD East Asian: 0 gnomAD European (Finnish): 0 gnomAD European (non-Finnish): 0.000309 gnomAD South Asian: 0 gnomAD Other: 0.001152 1000G European: 0.001 1000G African: 0 1000G American: 0 1000G East Asian: 0 1000G South Asian: 0 |
Not contemplated
Potential match with cancer biomarkers is only contemplated for variants that are classified as functionally relevant.
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KIT
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OG
Oncogene
This gene acts (predominantly) as an oncogene, and thus activating alterations are the main drivers. Gene mechanism of action has been determined based on the Cancer Gene Census, the 20/20 rule and manual curation. |
Mutation
missense
p.Gln922Leu
exon 20/21
more
chr4:55603409 A/T (GRCh37/hg19)
Transcript: ENST00000288135 HGVSp: ENSP00000288135.5:p.Gln922Leu HGVSc: ENST00000288135.5:c.2765A>T Location: exon 20/21 Consequence: missense variant Representative Transcript ──────────────────────── Transcript: ENST00000412167 HGVSp: ENSP00000390987.2:p.Gln918Leu HGVSc: ENST00000412167.2:c.2753A>T Location: exon 20/21 Consequence: missense variant ──────────────────────── Transcript: ENST00000512959 HGVSp: - HGVSc: - Location: - Consequence: downstream gene variant |
Unknown significance |
Inconclusive curation:
>No conclusive criteria, more
KIT p.Gln922Leu No conclusive effect for this variant is reported by the knowledgebases employed here. No biological bona fide assumption or bioinformatic prediction (see PMID: 35221333) applies and/or is conclusive to classify the variant. |
Not contemplated
Potential match with cancer biomarkers is only contemplated for variants that are classified as functionally relevant.
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