Functional evaluation and clinical classification of BRCA2 variants out on Nature This study focuses on the functional characterization and clinical classification of BRCA2 variants, specifically those within exons 15 to 26, which encode a DNA-binding domain commonly associated with pathogenic missense variants. By using CRISPR–Cas9-based saturation genome editing in human haploid HAP1 cells, the researchers evaluated 6,959 single-nucleotide variants to determine their pathogenicity. The assay, calibrated with known pathogenic and benign standards, was integrated with models from ClinGen and other authoritative groups for clinical classification. Ultimately, 91% of the variants were classified as pathogenic or benign, offering enhanced guidance for clinical management of individuals carrying BRCA2 variants and addressing the challenge posed by variants of uncertain significance. buff.ly/3PwIOBA @FergusCouch @rohavavidg @AmbryGenetics @paulocilasjr @AccidentalGenet @SidYadavMD @KLNathanson @ChrisHaiman @GENES_PK