Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000697931 | SCV000826565 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-06-27 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 126139). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 2502 of the BRCA2 protein (p.Arg2502Pro). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781093 | SCV000918911 | uncertain significance | not specified | 2018-06-22 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.7505G>C (p.Arg2502Pro) results in a non-conservative amino acid change located in the Breast cancer type 2 susceptibility protein, helical domain (IPR015252) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 246182 control chromosomes (gnomAD). 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.7505G>C 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 uncertain significance. |
| Ambry Genetics | RCV002390253 | SCV002672622 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-31 | criteria provided, single submitter | clinical testing | The p.R2502P variant (also known as c.7505G>C), located in coding exon 14 of the BRCA2 gene, results from a G to C substitution at nucleotide position 7505. The arginine at codon 2502 is replaced by proline, an amino acid with dissimilar properties. Using a computational method that produces a probabilistic likelihood ratio predictive of whether a missense variant impairs protein function, this alteration is predicted to be neutral (Karchin R et al. Cancer Inform. 2008;6:203-16). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV002390253 | SCV004362211 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-07 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with proline at codon 2502 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported 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. |
| Breast Cancer Information Core |
RCV000113770 | SCV000147110 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2001-10-29 | no assertion criteria provided | clinical testing |