Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000766430 | SCV000567090 | uncertain significance | not provided | 2015-07-05 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.6209A>G at the cDNA level, p.Glu2070Gly (E2070G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAA>GGA). Using alternate nomenclature, this variant would be defined as BRCA2 6437A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Glu2070Gly 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 Glutamic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Glu2070Gly occurs at a position that is not conserved and is not located in a known functional domain (Borg 2010). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BRCA2 Glu2070Gly is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000509660 | SCV000608272 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-10 | criteria provided, single submitter | clinical testing | The p.E2070G variant (also known as c.6209A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6209. The glutamic acid at codon 2070 is replaced by glycine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0004% (greater than 225000 alleles tested) in our clinical cohort. 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 |
RCV001061542 | SCV001226287 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-02-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2070 of the BRCA2 protein (p.Glu2070Gly). 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: 419352). 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. |
University of Washington Department of Laboratory Medicine, |
RCV000509660 | SCV003852317 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004525943 | SCV005040391 | uncertain significance | not specified | 2024-03-05 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV000766430 | SCV000592035 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The BRCA2 p.Glu2070Gly variant has not been reported in the literature nor previously identified by our laboratory. This is a missese alteration, which changes the residue Glu to Gly in the protein sequence coded by exon 11. Although the SIFT program predicts this variant to be deleterious, this evidence alone is not sufficient for assessing its functional impact. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at the current time. Classified as ACMG-3 |