Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000205144 | SCV000260726 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 28 of the BRCA2 protein (p.Ser28Gly). 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: 220292). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| St. |
RCV002291594 | SCV002584591 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2022-08-30 | criteria provided, single submitter | clinical testing | The BRCA2 c.82A>G (p.Ser28Gly) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with hereditary breast and ovarian cancer or Fanconi anemia. In summary, the evidence currently available is insufficient to determine the role of this variant in hereditary breast and ovarian cancer and/or Fanconi anemia. It has therefore been classified as of uncertain significance. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477691 | SCV004220596 | uncertain significance | not provided | 2023-06-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| All of Us Research Program, |
RCV004804844 | SCV005424232 | uncertain significance | BRCA2-related cancer predisposition | 2024-05-14 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with glycine at codon 28 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 BRCA2-related disorders 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. |