Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000113268 | SCV000300702 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2016-09-08 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Ambry Genetics | RCV000218617 | SCV000277020 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-07-21 | criteria provided, single submitter | clinical testing | The c.4048_4051delCATA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of 4 nucleotides at nucleotide positions 4048 to 4051, causing a translational frameshift with a predicted alternate stop codon (p.H1350Kfs*23). 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. |
| Color Diagnostics, |
RCV000218617 | SCV001340016 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-09-10 | criteria provided, single submitter | clinical testing | This variant deletes 4 nucleotides 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. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. 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. Based on the available evidence, this variant is classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001358766 | SCV001554636 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.4048_4051delCATA (p.His1350LysfsX23) 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. The variant was absent in 239668 control chromosomes. To our knowledge, no occurrence of c.4048_4051delCATA in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters, including an expert panel (ENIGMA), have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV001358766 | SCV004517548 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.His1350Lysfs*23) 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: 51587). For these reasons, this variant has been classified as Pathogenic. |
| Breast Cancer Information Core |
RCV000113268 | SCV000146365 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing |