Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480786 | SCV000564958 | likely pathogenic | not provided | 2016-02-04 | criteria provided, single submitter | clinical testing | To our knowledge the A382T likely pathogenic variant in the EDA1 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant. However, it has been observed in the hemizygous state in individuals sent for testing at GeneDx. The A382T variant 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. It 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 in mammals and in silico analysis predicts this variant is probably damaging to the protein structure/function. In addition, the EDA1 gene has a low rate of benign missense variation, with missense variants as a common mechanism of disorder. Therefore, as this individual has two affected male family members and symptoms suggestive of the disorder, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. Of note, females who are heterozygous for EDA1 pathogenic variants can show variable phenotypic expression of the disorder, ranging from being virtually asymptomatic to having full expression of the disease. |
| Labcorp Genetics |
RCV001851133 | SCV002273563 | likely pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2023-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 382 of the EDA protein (p.Ala382Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of ectodermal dysplasia (Invitae). ClinVar contains an entry for this variant (Variation ID: 418174). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on EDA protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |