Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166106 | SCV000216873 | likely benign | Hereditary cancer-predisposing syndrome | 2024-07-06 | 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. |
| Gene |
RCV000481679 | SCV000566501 | uncertain significance | not provided | 2015-05-06 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.7331A>G at the cDNA level, p.Asp2444Gly (D2444G) at the protein level, and results in the change of an Aspartic Acid to a Glycine (GAT>GGT). Using alternate nomenclature, this variant would be defined as BRCA2 7559A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asp2444Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Aspartic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Asp2444Gly occurs at a position that is not conserved and is located in the region of interaction with FANCD2 (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Asp2444Gly is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Counsyl | RCV000082971 | SCV000785001 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-03-07 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001857402 | SCV002311762 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2025-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2444 of the BRCA2 protein (p.Asp2444Gly). 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: 96850). 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. |
| Sharing Clinical Reports Project |
RCV000082971 | SCV000115045 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2010-05-26 | no assertion criteria provided | clinical testing |