부산대학교 도서관

ABSTRACT:: Missense variants in the BRCA2 gene are routinely detected during clinical screening for pathogenic mutations in patients with a family history of breast and ovarian cancer. These subtle changes frequently remain of unknown clinical significance because of the lack of genetic information that may help establish a direct correlation with cancer predisposition. Therefore, alternative ways of predicting the pathogenicity of these variants are urgently needed. Since BRCA2 is a protein involved in important cellular mechanisms such as DNA repair, replication, and cell cycle control, functional assays have been developed that exploit these cellular activities to explore the impact of the variants on protein function. In this review, we summarize assays developed and currently utilized for studying missense variants in BRCA2. We specifically depict details of each assay, including variants of uncertain significance analyzed, and describe a validation set of (genetically) proven pathogenic and neutral missense variants to serve as a golden standard for the validation of each assay. Guidelines are proposed to enable implementation of laboratory-based methods to assess the impact of the variant on cancer risk. : Many variants of uncertain clinical significance are identified in the BRCA2 gene, complicating the clinical management of carriers and their families. This review describes the functional assays that are currently used to establish the impact of a variant on BRCA2 protein function. In the absence of sufficient clinical and genetic data, functional assays will be a valuable and indispensable tool for the assessment of the clinical relevance of these variants.(Figure is included in full-text article.)