An integrative model for the comprehensive classification of BRCA1 and BRCA2 variants of uncertain clinical significance.

ABSTRACT: Loss-of-function variants in the BRCA1 and BRCA2 susceptibility genes predispose carriers to breast and/or ovarian cancer. The use of germline testing panels containing these genes has grown dramatically, but the interpretation of the results has been complicated by the identification of many sequence variants of undefined cancer relevance, termed "Variants of Uncertain Significance (VUS)." We have developed functional assays and a statistical model called VarCall for classifying BRCA1 and BRCA2 VUS. Here we describe a multifactorial extension of VarCall, called VarCall XT, that allows for co-analysis of multiple forms of genetic evidence. We evaluated the accuracy of models defined by the combinations of functional, in silico protein predictors, and family data for VUS classification. Var

SUBMITTER: Iversen ES 

PROVIDER: S-EPMC9166814 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature