NM_022336.4(EDAR):c.1151_1154dup (p.Asp386fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 15, 2021
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:: RCV001896839.4

Allele description [Variation Report for NM_022336.4(EDAR):c.1151_1154dup (p.Asp386fs)]

NM_022336.4(EDAR):c.1151_1154dup (p.Asp386fs)

Genes:

RANBP2:RAN binding protein 2 [Gene - OMIM - HGNC]
EDAR:ectodysplasin A receptor [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

2q13

Genomic location:

Preferred name:

NM_022336.4(EDAR):c.1151_1154dup (p.Asp386fs)

HGVS:

NC_000002.12:g.108897100CT[4]
NG_008257.1:g.97270AG[4]
NM_022336.4:c.1151_1154dupMANE SELECT
NP_071731.1:p.Asp386fs
NC_000002.11:g.109513555_109513556insCTCT
NC_000002.11:g.109513556CT[4]

Protein change:

D386fs

Links:

dbSNP: rs2105371643

NCBI 1000 Genomes Browser:

rs2105371643

Molecular consequence:

NM_022336.4:c.1151_1154dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (ECTD10A)
Synonyms:: Ectodermal Dysplasia 3, Anhidrotic
Identifiers:: MONDO: MONDO:0007509; MedGen: C3888065; Orphanet: 1810; Orphanet: 238468; OMIM: 129490

Name:: Autosomal recessive hypohidrotic ectodermal dysplasia syndrome
Synonyms:: Autosomal recessive hypohidrotic ectodermal dysplasia
Identifiers:: MONDO: MONDO:0016619; MedGen: C0406702

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002175452	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 15, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21771270, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002175452

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 15, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Two novel mutations in the gene EDAR causing autosomal recessive hypohidrotic ectodermal dysplasia.

Naqvi SK, Wasif N, Javaid H, Ahmad W.

Orthod Craniofac Res. 2011 Aug;14(3):156-9. doi: 10.1111/j.1601-6343.2011.01521.x. Epub 2011 Jul 14.

PubMed [citation]

PMID:: 21771270

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002175452.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the EDAR protein in which other variant(s) (p.Ile388Thr) have been determined to be pathogenic (PMID: 21771270). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with EDAR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp386Glufs*3) in the EDAR gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 63 amino acid(s) of the EDAR protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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