RESUMO
Pathogenic variants in the coding regions of the BRCA1/2 lead dysfunctional or nonfunctional BRCA proteins however the contribution of non-coding BRCA1/2 variants to BRCA-related disease risk has not been fully elucidated. Thus, we characterized the functional impact of both coding and non-coding BRCA1/2 variants identified in individuals with personal and/or family history of BRCA-related cancers. The data were produced by resequencing the exons and exon-intron junctions of the BRCA1/2 in 125 individuals and were comprehensively analyzed by using bioinformatics tools and databases. A total of 96 variants (59 coding and 37 non-coding) including 7 novel variants were identified and analyzed for their functional importance. We identified 11 missense variants that potentially affect protein function; 22 variants were likely to alter different types of posttranslational modifications. Also, multiple non-coding BRCA1/2 variants were found to reside in the critical regulatory regions that have the potential to act as eQTLs and affect alternative splicing. The results of our study shed light on the possible contributions of not only coding variants but also non-coding BRCA1/2 variants in BRCRA-related cancers. Further investigation is required to fully understand their potential associations with phenotypes which may ultimately lead their utilization on cancer management as a biomarker.