Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000160148 | SCV000210462 | uncertain significance | not provided | 2014-06-12 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.8140C>G at the cDNA level, p.Gln2714Glu (Q2714E) at the protein level, and results in the change of a Glutamine to a Glutamic Acid (CAA>GAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Gln2714Glu 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 Glutamine and Glutamic Acid differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Gln2714Glu occurs at a position that is variable across species and is located in a DNA binding domain (Borg 2010). In addition, 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 Gln2714Glu is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Baylor Genetics | RCV003462080 | SCV004216103 | uncertain significance | Familial cancer of breast | 2023-05-30 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003644917 | SCV004456299 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-04-09 | criteria provided, single submitter | clinical testing | 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: 182249). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 2714 of the BRCA2 protein (p.Gln2714Glu). |