ClinVar Miner

Submissions for variant NM_022336.4(EDAR):c.259T>C (p.Cys87Arg)

gnomAD frequency: 0.00001  dbSNP: rs121908451
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000006209 SCV000914859 uncertain significance Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive 2017-04-28 criteria provided, single submitter clinical testing The EDAR c.259T>C (p.Cys87Arg) variant has been reported in one study in which it is found in a homozygous state in one individual with autosomal recessive hypohidrotic ectodermal dysplasia and in a heterozygous state in both unaffected parents (Monreal et al. 1999). The p.Cys87Arg variant was absent from 100 control chromosomes but is reported at a frequency of 0.00003 in the European (non-Finnish) population of the Exome Aggregation Consortium. This is based on two alleles only in a region of good sequence coverage so the variant is presumed to be rare. In vitro expression testing found that the p.Cys87Arg variant abolished EDAR binding to EDA-A1 and had a low yield recovery indicating defective folding or solubility (Schneider et al. 2001). Based on the evidence, the p.Cys87Arg variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive hypohidrotic ectodermal dysplasia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV003764531 SCV000937773 uncertain significance Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome 2023-09-10 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with hypohidrotic ectodermal dysplasia (PMID: 10431241). This variant is present in population databases (rs121908451, gnomAD 0.004%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 87 of the EDAR protein (p.Cys87Arg). ClinVar contains an entry for this variant (Variation ID: 5851). 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. Experimental studies have shown that this missense change affects EDAR function (PMID: 11279189). 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.
OMIM RCV000006209 SCV000026391 pathogenic Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive 1999-08-01 no assertion criteria provided literature only

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