U.S. flag

An official website of the United States government

NM_022336.4(EDAR):c.259T>C (p.Cys87Arg) AND Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Apr 28, 2017
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:
RCV000006209.7

Allele description [Variation Report for NM_022336.4(EDAR):c.259T>C (p.Cys87Arg)]

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

Genes:
RANBP2:RAN binding protein 2 [Gene - OMIM - HGNC]
EDAR:ectodysplasin A receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q13
Genomic location:
Preferred name:
NM_022336.4(EDAR):c.259T>C (p.Cys87Arg)
HGVS:
  • NC_000002.12:g.108929295A>G
  • NG_008257.1:g.65078T>C
  • NM_022336.4:c.259T>CMANE SELECT
  • NP_071731.1:p.Cys87Arg
  • NC_000002.11:g.109545751A>G
  • NM_022336.3:c.259T>C
  • Q9UNE0:p.Cys87Arg
Protein change:
C87R; CYS87ARG
Links:
UniProtKB: Q9UNE0#VAR_013448; OMIM: 604095.0004; dbSNP: rs121908451
NCBI 1000 Genomes Browser:
rs121908451
Molecular consequence:
  • NM_022336.4:c.259T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive
Synonyms:
Anhidrotic ectodermal dysplasia, autosomal recessive; Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive; Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal
Identifiers:
MONDO: MONDO:0009147; MedGen: C3887494; Orphanet: 238468; Orphanet: 248; OMIM: 224900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000026391OMIM
no assertion criteria provided
Pathogenic
(Aug 1, 1999) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000914859Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)		Uncertain significance
(Apr 28, 2017) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.

Monreal AW, Ferguson BM, Headon DJ, Street SL, Overbeek PA, Zonana J.

Nat Genet. 1999 Aug;22(4):366-9.

PubMed [citation]
PMID:
10431241

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

Details of each submission

From OMIM, SCV000026391.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a family with autosomal recessive hypohidrotic ectodermal dysplasia (ECTD10B; 224900), Monreal et al. (1999) identified a homozygous T-to-C transition at nucleotide 259 of the EDAR gene resulting in a cys-to-arg substitution at codon 87 (C87R) in affected individuals. The mutation resulted in a nonconservative change in the extracellular domain, possibly affecting intra- or interchain disulfide bond formation.

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

From Illumina Laboratory Services, Illumina, SCV000914859.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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.

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

Last Updated: Oct 13, 2024