Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Genomics, |
RCV000768207 | SCV000898671 | uncertain significance | Lafora disease | 2021-03-30 | criteria provided, single submitter | clinical testing | EPM2A NM_005670.3 exon 3 p.His175Arg (c.524A>G): This variant has not been reported in the literature but is present in 0.006% (1/15304) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/6-145956575-T-C). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Invitae | RCV001205326 | SCV001376575 | uncertain significance | Progressive myoclonic epilepsy | 2022-04-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 626099). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 175 of the EPM2A protein (p.His175Arg). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with EPM2A-related conditions. 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. |