Germ line variants in cancer-related genes of early-onset South African breast cancer patients. UPBRCAFAM1

We evaluated germline variation in DNA damage response associated genes in individuals from hereditary breast cancer families with and without BRCA1/2 truncating variants. Whole exome variant data from eight BRCA negative and four BRCA1/2 mutation-positive individuals was used to investigate mutations in 516 DNA damage detection and repair pathway genes. Truncating and putatively damaging missense alterations were observed in genes associated with processes such as DNA damage signalling, non-homologous end joining, homologous recombination repair, translesion synthesis and mismatch repair. We detected a higher fraction of insertion/deletion variants in BRCA1/2 positive individuals, of which 90% were located in non-coding regions. Overall, BRCAx individuals possessed more truncating and putatively pathogenic nonsynonymous (missense & in-frame insertion/deletion) variants in the coding regions of DNA repair genes.