Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000160190 | SCV000210535 | uncertain significance | not provided | 2014-10-07 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.7185C>A at the cDNA level, p.His2395Gln (H2395Q) at the protein level, and results in the change of a Histidine to a Glutamine (CAC>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 His2395Gln 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 Histidine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 His2395Gln occurs at a position that is moderately conserved across species and is located within 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 His2395Gln is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV001051969 | SCV001216154 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-05-11 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2395 of the BRCA2 protein (p.His2395Gln). 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: 182272). 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. 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. |