NM_022336.4(EDAR):c.1214G>C (p.Gly405Ala) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 8, 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:: RCV001058350.6

Allele description [Variation Report for NM_022336.4(EDAR):c.1214G>C (p.Gly405Ala)]

NM_022336.4(EDAR):c.1214G>C (p.Gly405Ala)

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.1214G>C (p.Gly405Ala)

HGVS:

NC_000002.12:g.108897040C>G
NG_008257.1:g.97333G>C
NM_022336.4:c.1214G>CMANE SELECT
NP_071731.1:p.Gly405Ala
NC_000002.11:g.109513496C>G
NM_022336.3:c.1214G>C

Protein change:

G405A

Links:

dbSNP: rs1696610594

NCBI 1000 Genomes Browser:

rs1696610594

Molecular consequence:

NM_022336.4:c.1214G>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001222910	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 8, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001222910

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 8, 2021)

germline

clinical testing

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

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

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, SCV001222910.5

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 405 of the EDAR protein (p.Gly405Ala). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly405 amino acid residue in EDAR. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 853527). This missense change has been observed in individual(s) with clinical features of ectodermal dysplasia (Invitae). This variant is not present in population databases (gnomAD no frequency).

#	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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