Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance.

ABSTRACT: Variants of Uncertain Significance (VUS) are genetic variants whose association with a disease phenotype has not been established. They are a common finding in sequencing-based genetic tests and pose a significant clinical challenge. The objective of this study was to assess the use of functional data to classify variants according to pathogenicity. We conduct functional analysis of a large set of BRCA1 VUS combining a validated functional assay with VarCall, a Bayesian hierarchical model to estimate the likelihood of pathogenicity given the functional data. The results from the functional assays were incorporated into a joint analysis of 214 BRCA1 VUS to predict their likelihood of pathogenicity (breast cancer). We show that applying the VarCall model (1.0 sensitivity; lower

SUBMITTER: Woods NT 

PROVIDER: S-EPMC5539989 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature