Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000582650 | SCV000689097 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-03 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000802730 | SCV000942573 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2702 of the BRCA2 protein (p.Glu2702Lys). 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: 491345). 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. |
| Ambry Genetics | RCV000582650 | SCV001189697 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-25 | criteria provided, single submitter | clinical testing | The p.E2702K variant (also known as c.8104G>A), located in coding exon 17 of the BRCA2 gene, results from a G to A substitution at nucleotide position 8104. The glutamic acid at codon 2702 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved through mammals but not in all 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 |
RCV001584401 | SCV001814118 | uncertain significance | not provided | 2022-07-29 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Not observed in large population cohorts (gnomAD); Also known as 8332G>A; This variant is associated with the following publications: (PMID: 12228710) |
| Department of Pathology and Laboratory Medicine, |
RCV001354239 | SCV001548801 | uncertain significance | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA2 p.Glu2702Lys variant was not identified in the literature nor was it identified in the dbSNP, COGR, Cosmic, MutDB, LOVD 3.0, UMD-LSDB, BIC Database, ARUP Laboratories, or Zhejiang University databases. The variant was identified in ClinVar database (classified as uncertain significance by Color Genomics). The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Glu2702Lys residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |