ClinVar

Description

The BRCA2 c.6405_6409delCTTAA variant (rs80359584) is reported in the medical literature in individuals with breast cancer or hereditary breast and ovarian cancer (Alemar 2016, Momozawa 2018, Wen 2018, Whitworth 2018). The variant is described as pathogenic by several sources in the ClinVar database (Variation ID: 38043) and is described in the general population with an allele frequency of 0.0004% (1/240630 alleles) in the Genome Aggregation Database. This variant causes a frameshift by deleting 5 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Considering available information, this variant is classified as pathogenic. References: Alemar B et al. Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations. Cancer Genet. 2016 Sep;209(9):417-422. Momozawa Y et al. Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8. Wen WX et al. Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia. J Med Genet. 2018 Feb;55(2):97-103. Whitworth J et al. Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes. Am J Hum Genet. 2018 Jul 5;103(1):3-18.