ClinVar Miner

Submissions for variant NM_005670.4(EPM2A):c.776G>A (p.Gly259Glu)

gnomAD frequency: 0.00014  dbSNP: rs200641543
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000427841 SCV000536080 uncertain significance not provided 2017-01-13 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the EPM2A gene. The G259E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G259E variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G259E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000813908 SCV000954290 uncertain significance Progressive myoclonic epilepsy 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 259 of the EPM2A protein (p.Gly259Glu). This variant is present in population databases (rs200641543, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with EPM2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 392758). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 RCV002411416 SCV002674673 uncertain significance Inborn genetic diseases 2019-04-14 criteria provided, single submitter clinical testing The p.G259E variant (also known as c.776G>A), located in coding exon 4 of the EPM2A gene, results from a G to A substitution at nucleotide position 776. The glycine at codon 259 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.