Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Pathology and Laboratory Medicine, |
RCV001356937 | SCV001552238 | pathogenic | not provided | no assertion criteria provided | clinical testing | The BRCA2 c.8332-?_8632+?dup variant (chr13.hg19.g.32944559-?_32945161+?dup) results in a duplication of exons 19 and 20, although the precise breakpoints of this duplication were not determined, nor were the effects of this variant on the resulting mRNA or protein product determined. The variant was identified in 3 of 4418 proband chromosomes (frequency: 0.001) from individuals or families with breast or ovarian cancer (Caux-Moncoutier 2011, de la Hoya 2006, Walsh 2006), and was also identified in HGMD and UMD (2X as a causal variant). The variant is predicted to cause a frameshift, which alters the protein's amino acid sequence and leads to a premature stop codon, 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 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. |