Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000484683 | SCV000568119 | uncertain significance | not provided | 2018-03-26 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.8305G>C at the cDNA level, p.Glu2769Gln (E2769Q) at the protein level, and results in the change of a Glutamic Acid to a Glutamine (GAA>CAA). Using alternate nomenclature, this variant would be defined as BRCA2 8533G>C. This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. BRCA2 Glu2769Gln was not observed in large population cohorts (Lek 2016). This variant is located in the DNA binding domain (Yang 2002). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Glu2769Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Ambry Genetics | RCV000563964 | SCV000664591 | likely benign | Hereditary cancer-predisposing syndrome | 2022-01-09 | 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. |
| Labcorp Genetics |
RCV001068956 | SCV001234093 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2025-02-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 2769 of the BRCA2 protein (p.Glu2769Gln). 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: 419918). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA2 protein function. 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. |
| All of Us Research Program, |
RCV004003313 | SCV004825879 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-08-15 | criteria provided, single submitter | clinical testing |