Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001181299 | SCV001346411 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194024 | SCV001363259 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-02-27 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.6244delG (p.Glu2082AsnfsX4) 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 293432 control chromosomes. c.6244delG has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Momozawa_2018, Villarreal-Garza_2015, Millan_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV001194024 | SCV001582063 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu2082Asnfs*4) 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 premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 25236687, 31454914). ClinVar contains an entry for this variant (Variation ID: 921737). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV001181299 | SCV002656411 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-08-22 | criteria provided, single submitter | clinical testing | The c.6244delG pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 6244, causing a translational frameshift with a predicted alternate stop codon (p.E2082Nfs*4). This variant has been reported in an individual with ovarian cancer in a cohort of breast and ovarian cancer patients in Mexico (Villarreal-Garza C et al. Cancer, 2015 Feb;121:372-8). This alteration has also been reported with a carrier frequency of 0.00014 in 7051 unselected breast cancer patients and 0 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). 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. |
| Baylor Genetics | RCV003462653 | SCV004214583 | pathogenic | Familial cancer of breast | 2021-04-23 | criteria provided, single submitter | clinical testing |