ClinVar

Description

The BRCA2 p.Met192ValfsX13 variant was identified in 3 of 2638 proband chromosomes (frequency: 0.0011) from individuals or families with hereditary breast and ovarian cancer (Evans 2003, Litton 2011, Safra 2013). The variant was also identified in dbSNP (ID: rs587782398) with no classification, ClinVar (11x as pathogenic, reviewed by expert panel), LOVD 3.0 (3x), UMD-LSDB (9x as causal), BIC Database (30x as pathogenic), and ARUP Laboratories (as definitely pathogenic). The variant was not identified in Cosmic, MutDB, Zhejiang Colon Cancer databases. The variant was not identified in the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project or the Exome Aggregation Consortium (August 8th 2016) control databases. The p.Met192ValfsX13 variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 192 and leads to a premature stop codon at position 204. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.