Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129493 | SCV000184265 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-10 | criteria provided, single submitter | clinical testing | The p.A3148V variant (also known as c.9443C>T), located in coding exon 24 of the BRCA2 gene, results from a C to T substitution at nucleotide position 9443. The alanine at codon 3148 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV000160170 | SCV000210507 | uncertain significance | not provided | 2014-06-09 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.9443C>T at the cDNA level, p.Ala3148Val (A3148V) at the protein level, and results in the change of an Alanine to a Valine (GCT>GTT). Of note, this variant is also known as BRCA2 c.9671C>T by alternate nomenclature. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant 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 Alanine and Valine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Ala3148Val occurs at a position that is well conserved across species and is not located in a known functional domain. In addition, in silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available information, we consider BRCA2 Ala3148Val to be a variant of uncertain significance.Based on the reported results of this patientÂ’s relativeÂ’s testing, the BRCA2 pathogenic variant and BRCA2 variant of uncertain significance are on the same chromosome (in cis). |
| Color Diagnostics, |
RCV000129493 | SCV000684065 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000695537 | SCV000824044 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-09-11 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3148 of the BRCA2 protein (p.Ala3148Val). 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: 141127). 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. |
| Baylor Genetics | RCV004567086 | SCV005059199 | uncertain significance | Familial cancer of breast | 2023-11-07 | criteria provided, single submitter | clinical testing |