Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164371 | SCV000215006 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-07-22 | criteria provided, single submitter | clinical testing | The p.E2848D variant (also known as c.8544A>T), located in coding exon 19 of the BRCA2 gene, results from an A to T substitution at nucleotide position 8544. The glutamic acid at codon 2848 is replaced by aspartic acid, an amino acid with highly 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. |
| Labcorp Genetics |
RCV000792993 | SCV000932324 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-11-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 185018). 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. This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 2848 of the BRCA2 protein (p.Glu2848Asp). 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. |