Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000255133 | SCV000225692 | pathogenic | not provided | 2014-10-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000255133 | SCV000321591 | pathogenic | not provided | 2015-05-28 | criteria provided, single submitter | clinical testing | The G382S missense variant in the EDAR gene has been reported previously in association with autosomal recessive hypohidrotic ectodermal dysplasia (Naeem et al., 2005; Bashyam et al., 2012; Bibi et al., 2011). It 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. G382S 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 that is conserved across species and in-silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (T373M, R375H, L377F, E379K, I388T, M391K) have been reported in the Human Gene Mutation Database in association with EDAR-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In addition, studies of the G382S variant in the death domain of the EDAR gene have shown that it is expected to disrupt stability and reduce affinity to EDARADD, resulting in impaired activation of nuclear factor kappa-B (Bashyam et al., 2012; Bibi et al., 2011). We interpret the G382S variant as pathogenic. |
Invitae | RCV001384049 | SCV001583420 | pathogenic | Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome | 2023-08-09 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 194115). 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 expected to disrupt EDAR protein function. For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individuals with autosomal recessive hypohidrotic ectodermal dysplasia (PMID: 16029325, 22032522). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs747806672, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 382 of the EDAR protein (p.Gly382Ser). |