Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781068 | SCV000918872 | uncertain significance | not specified | 2018-03-20 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.9748T>A (p.Ser3250Thr) results in a conservative amino acid change in the encoded protein sequence. The variant is located outside of any known functional domain or repeat and five of five in-silico tools predict a benign effect of the variant on protein function. The variant is absent from 246130 control chromosomes of gnomAD dataset. 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.9748T>A 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. |
| Labcorp Genetics |
RCV002535688 | SCV003302101 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-08-18 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 3250 of the BRCA2 protein (p.Ser3250Thr). This missense change has been observed in individual(s) with breast cancer (PMID: 33646313). 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: 633108). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478483 | SCV004220667 | uncertain significance | not provided | 2022-11-04 | criteria provided, single submitter | clinical testing | It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in an individual with breast cancer (PMID: 33646313 (2021)). Analysis of this variant using a bioinformatics tool for the prediction of the effect of amino acid changes on protein structure and function yielded a prediction that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Ambry Genetics | RCV004027322 | SCV005032079 | likely benign | Hereditary cancer-predisposing syndrome | 2024-03-14 | 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. |
| Baylor Genetics | RCV004569488 | SCV005059172 | uncertain significance | Familial cancer of breast | 2023-11-29 | criteria provided, single submitter | clinical testing |