Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000572694 | SCV000673077 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-12-08 | criteria provided, single submitter | clinical testing | The p.E2702Q variant (also known as c.8104G>C), located in coding exon 17 of the BRCA2 gene, results from a G to C substitution at nucleotide position 8104. The glutamic acid at codon 2702 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not 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 |
RCV001037909 | SCV001201345 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-04-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 2702 of the BRCA2 protein (p.Glu2702Gln). This variant is present in population databases (rs186224762, gnomAD 0.003%). 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: 485408). 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, |
RCV004001112 | SCV004845598 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-06-08 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glutamine at codon 2702 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251328 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |