Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002547627 | SCV003264226 | uncertain significance | Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome | 2022-09-23 | criteria provided, single submitter | clinical testing | 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. 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 EDAR protein function. ClinVar contains an entry for this variant (Variation ID: 1049661). This variant has not been reported in the literature in individuals affected with EDAR-related conditions. This variant is present in population databases (rs201793571, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 32 of the EDAR protein (p.Gly32Ser). |
| Ambry Genetics | RCV004034453 | SCV004862565 | uncertain significance | Inborn genetic diseases | 2023-12-07 | criteria provided, single submitter | clinical testing | The c.94G>A (p.G32S) alteration is located in exon 3 (coding exon 2) of the EDAR gene. This alteration results from a G to A substitution at nucleotide position 94, causing the glycine (G) at amino acid position 32 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Department of Pathology and Laboratory Medicine, |
RCV001356060 | SCV001551120 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The EDAR p.G32S variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs201793571) and in control databases in 34 of 282734 chromosomes at a frequency of 0.0001203 (Genome Aggregation Database March 6, 2019, v2.1.1). The p.G32 residue is conserved in mammals and computational analyses (MUT Assesor, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |