Functional evaluation and clinical classification of BRCA2 variants.

ABSTRACT: Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers^1-5. However, variants of uncertain significance limit the clinical utility of test results. Thus, there is a need for functional characterization and clinical classification of all BRCA2 variants to facilitate the clinical management of individuals with these variants. Here we analysed all possible single-nucleotide variants from exons 15 to 26 that encode the BRCA2 DNA-binding domain hotspot for pathogenic missense variants. To enable this, we used saturation genome editing CRISPR-Cas9-based knock-in endogenous targeting of human haploid HAP1 cells⁶. The assay was calibrated relative to nonsense and silent variants and was validated using

SUBMITTER: Huang H 

PROVIDER: S-EPMC11821525 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature