Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564154 | SCV000661446 | likely benign | Hereditary cancer-predisposing syndrome | 2024-01-03 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Color Diagnostics, |
RCV000564154 | SCV000689044 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-18 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000113750 | SCV000785041 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-03-24 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004562232 | SCV000918883 | uncertain significance | not specified | 2023-11-15 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.7394C>T (p.Ala2465Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251094 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.7394C>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV001296258 | SCV001485217 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-07-27 | 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: 52316). This missense change has been observed in individual(s) with BRCA2-related conditions (PMID: 10923033). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2465 of the BRCA2 protein (p.Ala2465Val). This variant is present in population databases (rs80358960, gnomAD 0.01%). |
| All of Us Research Program, |
RCV000113750 | SCV004844402 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-05-31 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV004700326 | SCV005205583 | likely benign | Hereditary cancer | 2024-09-11 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following: it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease, and/or has normal protein function, and/or has lack of segregation with disease, and/or has been detected in co-occurrence with known pathogenic variant, and/or has lack of disease association in case-control studies, and/or is located in a region inconsistent with a known cause of pathogenicity. |
| Breast Cancer Information Core |
RCV000113750 | SCV000147073 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing |