Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520119 | SCV000620882 | uncertain significance | not provided | 2017-09-25 | criteria provided, single submitter | clinical testing | The E553G variant in the EVC2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E553G variant is observed in 2/66724 (0.003%) alleles from individuals of non-Finnish background, in the ExAC dataset (Lek et al., 2016). The E553G 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. This substitution occurs at a position where amino acids with similar properties to Glutamic acid are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret E553G as a variant of uncertain significance. |
Labcorp Genetics |
RCV002527637 | SCV003467358 | uncertain significance | Ellis-van Creveld syndrome; Curry-Hall syndrome | 2022-06-27 | 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 553 of the EVC2 protein (p.Glu553Gly). This variant is present in population databases (rs766349604, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with EVC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 452105). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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. |