ClinVar

Description

The BRCA2 c.9353T>C variant is predicted to result in the amino acid substitution p.Met3118Thr. This variant was reported in an individual with breast cancer and osteosarcoma and a family history of breast cancer (Katagiri et al 1998. PubMed ID: 9609997). Of note, there was no mention of additional genetic testing beyond BRCA1 and BRCA2 analysis, for this family. A bioinformatics analysis utilizing protein likelihood ratios predicted that the p.Met3118 variant would have a neutral impact on protein function (Supplementary Table 1, Karchin R et al 2008. PubMed ID: 19043619). This variant was interpreted as a variant of uncertain significance in a study of incidental findings in participants’ exomes (Table S1, Dorschner et al 2013. PubMed ID: 24055113; Amendola et al 2015. PubMed ID: 25637381). This variant has been reported twice in the Breast Cancer Information Core database with uncertain clinical significance (https://research.nhgri.nih.gov/bic/). This variant is reported in 0.025% of alleles in individuals of African descent in gnomAD and has conflicting interpretations in the ClinVar database, ranging from likely benign to uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/38232/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.