Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000486534 | SCV000569577 | uncertain significance | not provided | 2016-11-30 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.9191A>G at the cDNA level, p.Asp3064Gly (D3064G) at the protein level, and results in the change of an Aspartic Acid to a Glycine (GAC>GGC). Using alternate nomenclature, this variant would be defined as BRCA2 9419A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asp3064Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting 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 Asp3064Gly occurs at a position that is not conserved and is located within the DNA binding domain (Yang 2002). In silico analyses are inconsistent regarding the effect this variant may have on protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Asp3064Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV002526582 | SCV003351408 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-12-06 | 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 3064 of the BRCA2 protein (p.Asp3064Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 30362333). ClinVar contains an entry for this variant (Variation ID: 420651). 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 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. |
| All of Us Research Program, |
RCV004003330 | SCV004833811 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-05-08 | criteria provided, single submitter | clinical testing |