ClinVar

Description

The BRCA2 p.Gln2491* variant was identified in 2 of 1500 proband chromosomes (frequency: 0.001) from individuals or families with breast or ovarian cancer (Kwong 2012, Machackova 2008). The variant was also identified in dbSNP (ID: rs80358971) as "With Pathogenic allele", ClinVar (classified as pathogenic by ENIGMA, Ambry Genetics and three other submitters), COGR, LOVD 3.0 (4x ), UMD-LSDB (1x as causal), BIC Database (2x with clinical importance), ARUP Laboratories (definitely pathogenic), and in Zhejiang University Database. The variant was not identified in Cosmic, or MutDB databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Gln2491* variant leads to a premature stop codon at position 2491 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in breast or 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.