Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000801524 | SCV000941301 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-11-01 | criteria provided, single submitter | clinical testing | Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant has not been reported in the literature in individuals with BRCA2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys1565Argfs*3) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002332630 | SCV002633910 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-06-21 | criteria provided, single submitter | clinical testing | The c.4694delA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 4694, causing a translational frameshift with a predicted alternate stop codon (p.K1565Rfs*3). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Department of Pathology and Laboratory Medicine, |
RCV001354286 | SCV001548865 | pathogenic | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA2 p.Lys1565Argfs*3 variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, LOVD 3.0, UMD-LSDB, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.4694del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1565 and leads to a premature stop codon at position 1567. 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 breast and ovarian cancers 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. |