NM_001399.5(EDA):c.1116C>G (p.Asn372Lys) AND Hypohidrotic X-linked ectodermal dysplasia

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 6, 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:: RCV001040957.9

Allele description [Variation Report for NM_001399.5(EDA):c.1116C>G (p.Asn372Lys)]

NM_001399.5(EDA):c.1116C>G (p.Asn372Lys)

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.1116C>G (p.Asn372Lys)

HGVS:

NC_000023.11:g.70035549C>G
NG_009809.2:g.424483C>G
NM_001005609.2:c.1110C>G
NM_001005612.3:c.1101C>G
NM_001399.5:c.1116C>GMANE SELECT
NP_001005609.1:p.Asn370Lys
NP_001005612.2:p.Asn367Lys
NP_001390.1:p.Asn372Lys
NC_000023.10:g.69255399C>G
NM_001399.4:c.1116C>G

Protein change:

N367K

Links:

dbSNP: rs2020255486

NCBI 1000 Genomes Browser:

rs2020255486

Molecular consequence:

NM_001005609.2:c.1110C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001005612.3:c.1101C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001399.5:c.1116C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypohidrotic X-linked ectodermal dysplasia (XHED)
Synonyms:: ECTODERMAL DYSPLASIA, HYPOHIDROTIC, 1; Anhidrotic ectodermal dysplasia X-linked; Christ Siemens Touraine syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010585; MedGen: C0162359; Orphanet: 181; Orphanet: 238468; OMIM: 305100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001204550	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28045201, 28492532
SCV002087208	Natera, Inc.	no assertion criteria provided	Likely pathogenic (Jan 11, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001204550

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 6, 2023)

germline

clinical testing

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

SCV002087208

Natera, Inc.

no assertion criteria provided

Likely pathogenic
(Jan 11, 2021)

germline

clinical testing

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

Mutational spectrum of EDA and EDAR genes in a cohort of Mexican mestizo patients with hypohidrotic ectodermal dysplasia.

Monroy-Jaramillo N, Abad-Flores JD, García-Delgado C, Villaseñor-Domínguez A, Mena-Cedillos C, Toledo-Bahena ME, Valencia-Herrera AM, Sánchez-Boiso A, Akaki-Carreño YI, Del Río Navarro B, Aguirre-Hernández J, López-López M, Cervantes A, Cerbón M, Morán-Barroso VF.

J Eur Acad Dermatol Venereol. 2017 Jul;31(7):e321-e324. doi: 10.1111/jdv.14107. Epub 2017 Feb 17. No abstract available.

PubMed [citation]

PMID:: 28045201

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001204550.5

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

Description

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 372 of the EDA protein (p.Asn372Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypohidrotic ectodermal dysplasia (PMID: 28045201; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 839246). 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 EDA protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

#	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

From Natera, Inc., SCV002087208.1

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

#	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: Feb 20, 2024

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