A new bioinformatics tool to help assess the significance of BRCA1 variants

Human Genomics
Isabelle CusinPascale Gaudet

Abstract

Germline pathogenic variants in the breast cancer type 1 susceptibility gene BRCA1 are associated with a 60% lifetime risk for breast and ovarian cancer. This overall risk estimate is for all BRCA1 variants; obviously, not all variants confer the same risk of developing a disease. In cancer patients, loss of BRCA1 function in tumor tissue has been associated with an increased sensitivity to platinum agents and to poly-(ADP-ribose) polymerase (PARP) inhibitors. For clinical management of both at-risk individuals and cancer patients, it would be important that each identified genetic variant be associated with clinical significance. Unfortunately for the vast majority of variants, the clinical impact is unknown. The availability of results from studies assessing the impact of variants on protein function may provide insight of crucial importance. We have collected, curated, and structured the molecular and cellular phenotypic impact of 3654 distinct BRCA1 variants. The data was modeled in triple format, using the variant as a subject, the studied function as the object, and a predicate describing the relation between the two. Each annotation is supported by a fully traceable evidence. The data was captured using standard ontologi...Continue Reading

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Citations

Nov 15, 2019·Nucleic Acids Research·Monique Zahn-ZabalLydie Lane

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Software Mentioned

neXtProt Cancer variant portal
ClinVar
ARUP
PolyPhen
BRCA Circos
COSMIC
SIFT
neXtProt
neXtProt Cancer portal
neXtProt Cancer

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