Bioinformatics analyses of identified variants in the brca1 and brca2 genes by next generation sequencing: Retrospective study

The BRCA1 and BRCA2 genes play an important role in DNA damage and repair as tumor suppressor genes. The BRCA1 gene consists of 24 exons and encodes a protein containing 1863 amino acids. The BRCA2 gene has 27 exons and encodes a 3418 amino acid BRCA2 protein. The germline mutations in the BRCA1 and BRCA2 genes have been associated with breast and ovarian cancer so BRCA1 and BRCA2 gene scans are of great importance in the risk, prognosis and diagnosis of breast and ovarian cancer. The data used in this study were obtained from the genotype results of 125 individuals who applied to Bursa Uludag Unıversıty, Department of Medical Genetics created by the next generation sequencing method. As a result of the next generation sequencing, the variants were evaluated by various databases and in silico tools in terms of pathogenicity, minor allele frequencies, regulator importance and impacts on post-translational modifications. As a result of our study, a total of 96 variants were found in the BRCA1 and BRCA2 genes of which 16 were not previously found in the sequencing projects (1000G, ExAC, gnomAD). In addition, three of our novel variants were located in the coding region and the others were located in the intronic region. In this study, we both show several variants that may affect the protein functions and associated with breast and ovarian cancer and also multiple variants were shown to potential role in gene regulation.