NM_001099857.5(IKBKG):c.337G>A (p.Asp113Asn) AND Ectodermal dysplasia and immunodeficiency 1

Germline classification:: Likely benign (1 submission)
Last evaluated:: May 6, 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:: RCV002470750.9

Allele description [Variation Report for NM_001099857.5(IKBKG):c.337G>A (p.Asp113Asn)]

NM_001099857.5(IKBKG):c.337G>A (p.Asp113Asn)

Gene:

IKBKG:inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001099857.5(IKBKG):c.337G>A (p.Asp113Asn)

HGVS:

NC_000023.11:g.154556314G>A
NG_009896.1:g.19071G>A
NM_001099856.6:c.541G>A
NM_001099857.5:c.337G>AMANE SELECT
NM_001145255.4:c.337G>A
NM_001321396.3:c.337G>A
NM_001321397.3:c.337G>A
NM_001377312.1:c.337G>A
NM_001377313.1:c.337G>A
NM_001377314.1:c.337G>A
NM_001377315.1:c.337G>A
NM_003639.4:c.337G>A
NP_001093326.2:p.Asp181Asn
NP_001093327.1:p.Asp113Asn
NP_001138727.1:p.Asp113Asn
NP_001308325.1:p.Asp113Asn
NP_001308326.1:p.Asp113Asn
NP_001364241.1:p.Asp113Asn
NP_001364242.1:p.Asp113Asn
NP_001364243.1:p.Asp113Asn
NP_001364244.1:p.Asp113Asn
NP_003630.1:p.Asp113Asn
LRG_70t1:c.337G>A
LRG_70:g.19071G>A
NC_000023.10:g.153784529G>A
NM_001099856.3:c.541G>A
NM_001099857.2:c.337G>A
NM_003639.3:c.337G>A
NR_165197.1:n.478G>A
Q9Y6K9:p.Asp113Asn

Protein change:

D113N; ASP113ASN

Links:

UniProtKB: Q9Y6K9#VAR_026493; UniProtKB/Swiss-Prot: VAR_026493; OMIM: 300248.0032; dbSNP: rs179363896

NCBI 1000 Genomes Browser:

rs179363896

Molecular consequence:

NM_001099856.6:c.541G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099857.5:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001145255.4:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001321396.3:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001321397.3:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377312.1:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377313.1:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377314.1:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377315.1:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003639.4:c.337G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_165197.1:n.478G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Ectodermal dysplasia and immunodeficiency 1 (EDAID1)
Synonyms:: Ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis, and lymphedema; ECTODERMAL DYSPLASIA AND IMMUNE DEFICIENCY 1; Hyper-IgM immunodeficiency, X-linked, with hypohidrotic ectodermal dysplasia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0020740; MedGen: C1846008; Orphanet: 238468; Orphanet: 98813; OMIM: 300291

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002769322	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (May 6, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 28993958, 30422821, 31965418, 33224153, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002769322

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(May 6, 2021)

germline

clinical testing

PubMed (5)
[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

Functional Evaluation of an IKBKG Variant Suspected to Cause Immunodeficiency Without Ectodermal Dysplasia.

Frans G, van der Werff Ten Bosch J, Moens L, Gijsbers R, Changi-Ashtiani M, Rokni-Zadeh H, Shahrooei M, Wuyts G, Meyts I, Bossuyt X.

J Clin Immunol. 2017 Nov;37(8):801-810. doi: 10.1007/s10875-017-0448-9. Epub 2017 Oct 10.

PubMed [citation]

PMID:: 28993958

Rescue of recurrent deep intronic mutation underlying cell type-dependent quantitative NEMO deficiency.

Boisson B, Honda Y, Ajiro M, Bustamante J, Bendavid M, Gennery AR, Kawasaki Y, Ichishima J, Osawa M, Nihira H, Shiba T, Tanaka T, Chrabieh M, Bigio B, Hur H, Itan Y, Liang Y, Okada S, Izawa K, Nishikomori R, Ohara O, Heike T, et al.

J Clin Invest. 2019 Feb 1;129(2):583-597. doi: 10.1172/JCI124011. Epub 2018 Dec 18.

PubMed [citation]

PMID:: 30422821
PMCID:: PMC6355244

See all PubMed Citations (5)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002769322.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely benign. Following criteria are met: 0109 - This gene is associated with X-linked recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from aspartic acid to asparagine. (I) 0308 - Population frequency for this variant is out of keeping with known incidence of Immunodeficiency 3 (MIM#3300636) and ectodermal dysplasia and immunodeficiency 1 (MIM#300291). (SB) 0504 - Same amino acid change has been observed in placental mammals. (SB) 0808 - Previous reports of pathogenicity for this variant are conflicting. This variant has previously been reported as likely benign and as a variant of uncertain significance (ClinVar). However, it has more recently been suggested to be non disease-causing due to population frequency (PMID: 33224153; 30422821). In addition, this variant was identified in a patient with recurrent bacterial and viral infections since his third month of life but the variant was also identified is the proband's 40 year old healthy cousin (PMID: 31965418) (I) 1004 - This variant has moderate functional evidence supporting normal protein function (PMID: 28993958). (SB) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	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: Aug 18, 2024

ClinVar

Relating variation to medicine