Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000477598 | SCV000549862 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-12-18 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000567451 | SCV000661255 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-02 | criteria provided, single submitter | clinical testing | The p.V1988I variant (also known as c.5962G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 5962. The valine at codon 1988 is replaced by isoleucine, an amino acid with highly similar properties. This alteration was classified as likely benign by one study that evaluated multiple lines of evidence, including population data, functional evidence, in silico prediction models, segregation with disease and clinical phenotype including tumor characteristics (Tsai GJ et al. Genet Med, 2019 06;21:1435-1442). This variant has also been reported in the literature in at least one individual diagnosed with breast cancer, however it was not reported whether the variant was germline or somatic in origin, and no strong evidence for causality was indicated (Trivedi H et al. Acta Med Acad, 2019 04; 48:105-115). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| University of Washington Department of Laboratory Medicine, |
RCV000477598 | SCV000886452 | likely benign | Hereditary breast ovarian cancer syndrome | 2018-05-29 | criteria provided, single submitter | research | The BRCA2 variant designated as NM_000059.3: c.5962G>A (p.Val1988Ile) is classified as likely benign. This variant is listed in population databases and is found in 1 out of 1250 individuals with Finnish ancestry. Computer software programs predict that this variant is likely to be benign. This variant is found in exon 11, in a domain where non-truncating mutations are usually benign. Cosegregation analysis of one observed family was performed using analyze.myvariant.org (Rañola et al, 2018, PMID:28965303) and yielding a likelihood ratio of pathogenicity of 0.14 to 1 (Thompson, et al., 2003, PMID:2900794) providing evidence that this allele is less likely to cause cancer. Bayesian analysis integrating all of this data (Tavtigian et al, 2018, PMID: 29300386) gives about 1% probability of pathogenicity, which is consistent with a classification of likely benign. This variant is not predicted to alter BRCA2 function or modify cancer risk. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study. |
| Fulgent Genetics, |
RCV000763891 | SCV000894826 | uncertain significance | Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| University of Washington Department of Laboratory Medicine, |
RCV000567451 | SCV003850817 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
| Sharing Clinical Reports Project |
RCV000076947 | SCV000108744 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2011-01-06 | no assertion criteria provided | clinical testing |