Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174765 | SCV001338082 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.534delA (p.Lys178AsnfsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251384 control chromosomes (gnomAD). To our knowledge, no occurrence of c.534delA in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating an impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Ambry Genetics | RCV004950301 | SCV005548631 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-07-19 | criteria provided, single submitter | clinical testing | The c.534delA pathogenic mutation, located in coding exon 6 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 534, causing a translational frameshift with a predicted alternate stop codon (p.K178Nfs*7). 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. |
| Labcorp Genetics |
RCV001174765 | SCV005761475 | pathogenic | Hereditary breast ovarian cancer syndrome | 2024-09-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys178Asnfs*7) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 917654). For these reasons, this variant has been classified as Pathogenic. |