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NM_001399.5(EDA):c.457C>T (p.Arg153Cys) AND Anhidrotic ectodermal dysplasia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 17, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003478983.1

Allele description [Variation Report for NM_001399.5(EDA):c.457C>T (p.Arg153Cys)]

NM_001399.5(EDA):c.457C>T (p.Arg153Cys)

Gene:
EDA:ectodysplasin A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq13.1
Genomic location:
Preferred name:
NM_001399.5(EDA):c.457C>T (p.Arg153Cys)
HGVS:
  • NC_000023.11:g.69957087C>T
  • NG_009809.2:g.346021C>T
  • NM_001005609.2:c.457C>T
  • NM_001005612.3:c.457C>T
  • NM_001399.5:c.457C>TMANE SELECT
  • NP_001005609.1:p.Arg153Cys
  • NP_001005612.2:p.Arg153Cys
  • NP_001390.1:p.Arg153Cys
  • NC_000023.10:g.69176937C>T
  • NM_001399.4:c.457C>T
  • Q92838:p.Arg153Cys
  • c.457C>T
Protein change:
R153C
Links:
UniProtKB: Q92838#VAR_054454; dbSNP: rs397516662
NCBI 1000 Genomes Browser:
rs397516662
Molecular consequence:
  • NM_001005609.2:c.457C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005612.3:c.457C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001399.5:c.457C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Anhidrotic ectodermal dysplasia
Identifiers:
MedGen: C1706004; Human Phenotype Ontology: HP:0007476

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004222819Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Nov 17, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population.

Martínez-Romero MC, Ballesta-Martínez MJ, López-González V, Sánchez-Soler MJ, Serrano-Antón AT, Barreda-Sánchez M, Rodriguez-Peña L, Martínez-Menchon MT, Frías-Iniesta J, Sánchez-Pedreño P, Carbonell-Meseguer P, Glover-López G, Guillén-Navarro E; GIEDE (Spanish multidisciplinary research group for ectodermal dysplasia).

Orphanet J Rare Dis. 2019 Dec 3;14(1):281. doi: 10.1186/s13023-019-1251-x.

PubMed [citation]
PMID:
31796081
PMCID:
PMC6892193

Mutations leading to X-linked hypohidrotic ectodermal dysplasia affect three major functional domains in the tumor necrosis factor family member ectodysplasin-A.

Schneider P, Street SL, Gaide O, Hertig S, Tardivel A, Tschopp J, Runkel L, Alevizopoulos K, Ferguson BM, Zonana J.

J Biol Chem. 2001 Jun 1;276(22):18819-27. Epub 2001 Mar 14.

PubMed [citation]
PMID:
11279189
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004222819.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: EDA c.457C>T (p.Arg153Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 182427 control chromosomes (gnomAD). c.457C>T has been reported in the literature in multiple individuals affected with Hypohidrotic Ectodermal Dysplasia (e.g. Schneider_2001, Burger_2014, Wolfhart_2016, Martinez-Romero_2019), and at least one case was reported as having a de novo origin. These data indicate that the variant is very likely to be associated with disease. At least two publications reports experimental evidence evaluating an impact on protein function (Schneider_2001, Chen_2001), finding that the variant interferes with proteolytic processing. The following publications have been ascertained in the context of this evaluation (PMID: 11279189, 11416205, 24715423, 27305980, 31796081). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024