Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000779938 | SCV000916879 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2018-03-08 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.3937delT (p.Tyr1313ThrfsX22) 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 (eg. c.3967A>T, p.Lys1323X; c.3975_3978dupTGCT, p.Ala1327fsX4; c.4003G>T, p.Glu1335X). The variant was absent in 94852 control chromosomes (ExAC). To our knowledge, no occurrence of c.3937delT in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its 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. |
| Labcorp Genetics |
RCV000779938 | SCV001396790 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-06-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 632695). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr1313Thrfs*22) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV003344038 | SCV004052536 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-07-06 | criteria provided, single submitter | clinical testing | The c.3937delT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 3937, causing a translational frameshift with a predicted alternate stop codon (p.Y1313Tfs*22). 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. |