ClinVar

Description

BRCA2, EXON11, c.3860del, p.Asn1287Ilefs*6, Heterozygous, PathogenicrnThe BRCA2 p.Asn1287Ilefs*6 variant was identified in 8 of 830 proband chromosomes (frequency: 0.01) from African-American, Polish, Italian and Austrian individuals or families with breast or ovarian cancer and was not identified in 326 control chromosomes from healthy individuals (Kanaan 2003, Perkowska 2003, Papi 2009, Singer 2014). The variant was also identified in dbSNP (ID: rs80359406) as “With Pathogenic allele”, ClinVar (classified as pathogenic by an ENIGMA expert panel (2016), Ambry Genetics, Invitae, GeneDx, CIMBA and 10 other submitters), LOVD 3.0, and UMD-LSDB (classified as 5-causal). 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 c.3860del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1287 and leads to a premature stop codon at position 1292. 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. Assessment Date: 2019/07/15. References (PMIDs): 12942367, 18821011, 12673801, 23772696.