Submissions for variant NM_147127.5(EVC2):c.3544G>T (p.Val1182Leu)

dbSNP: rs144511301

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000497426	SCV000590433	uncertain significance	not provided	2017-06-20	criteria provided, single submitter	clinical testing	The V1182L variant in the EVC2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is observed in 1/10936 (0.01%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). The V1182L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret V1182L as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002524091	SCV003280401	uncertain significance	Ellis-van Creveld syndrome; Curry-Hall syndrome	2024-07-10	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1182 of the EVC2 protein (p.Val1182Leu). This variant is present in population databases (rs144511301, gnomAD 0.02%). 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: 432680). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Ambry Genetics	RCV004619306	SCV005113338	likely benign	Inborn genetic diseases	2024-03-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV004751571	SCV005351719	uncertain significance	EVC2-related disorder	2024-06-14	no assertion criteria provided	clinical testing	The EVC2 c.3544G>T variant is predicted to result in the amino acid substitution p.Val1182Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.015% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.