Functional assays for BRCA1 and BRCA2 variant analysis: new tools and their applications

Genetic variants perturbing BRCA1 and BRCA2 function are linked to hereditary breast and ovarian cancers. As BRCA1 and BRCA2 are critical for homologous recombination-mediated DNA repair, interpretation of variants of uncertain significance is essential. Here, we review established and emerging assays used to functionally characterize BRCA1 and BRCA2 variants and highlight the strengths and limitations of each approach, as well as their general relevance to variant classification and clinical applications.