Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000574414 | SCV000666050 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-10 | criteria provided, single submitter | clinical testing | The p.V2747I variant (also known as c.8239G>A), located in coding exon 17 of the BRCA2 gene, results from a G to A substitution at nucleotide position 8239. The valine at codon 2747 is replaced by isoleucine, an amino acid with highly similar properties. This variant was non-functional in a homology-directed DNA repair (HDR) assay (Ambry internal data). This amino acid position is 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. |
| Color Diagnostics, |
RCV000574414 | SCV001350580 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-05 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with isoleucine at codon 2747 of the BRCA2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. 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). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV001206143 | SCV001377438 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2747 of the BRCA2 protein (p.Val2747Ile). 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: 38145). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV002508189 | SCV002817992 | uncertain significance | not provided | 2022-06-30 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 8467G>A; This variant is associated with the following publications: (PMID: 12228710) |
| Baylor Genetics | RCV003460532 | SCV004213661 | uncertain significance | Familial cancer of breast | 2023-08-18 | criteria provided, single submitter | clinical testing | |
| Clinical Genetics Laboratory, |
RCV002508189 | SCV005199833 | uncertain significance | not provided | 2022-05-27 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004700293 | SCV005205285 | uncertain significance | not specified | 2024-06-05 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.8239G>A (p.Val2747Ile) results in a conservative amino acid change located in the BRCA2, OB1 domain (IPR015187) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 249070 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.8239G>A in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 38145). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Sharing Clinical Reports Project |
RCV000031728 | SCV000054335 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2007-05-23 | no assertion criteria provided | clinical testing |