NM_000206.3(IL2RG):c.34_35del (p.Leu12fs) AND X-linked severe combined immunodeficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 13, 2022
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:: RCV003022585.2

Allele description [Variation Report for NM_000206.3(IL2RG):c.34_35del (p.Leu12fs)]

NM_000206.3(IL2RG):c.34_35del (p.Leu12fs)

Genes:

LOC126863274:MED14-independent group 3 enhancer GRCh37_chrX:70330888-70332087 [Gene]
IL2RG:interleukin 2 receptor subunit gamma [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq13.1

Genomic location:

Preferred name:

NM_000206.3(IL2RG):c.34_35del (p.Leu12fs)

HGVS:

NC_000023.11:g.71111505_71111506del
NG_009088.1:g.5048_5049del
NG_021141.1:g.283_284del
NG_087770.1:g.568_569del
NM_000206.3:c.34_35delMANE SELECT
NP_000197.1:p.Leu12Ilefs
NP_000197.1:p.Leu12fs
LRG_150t1:c.34_35del
LRG_150:g.5048_5049del
LRG_150p1:p.Leu12Ilefs
NC_000023.10:g.70331355_70331356del
NM_000206.2:c.34_35delTT

Protein change:

L12fs

Molecular consequence:

NM_000206.3:c.34_35del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: X-linked severe combined immunodeficiency (SCIDX1)
Synonyms:: IMMUNODEFICIENCY 4; X-Linked Combined Immunodeficiency Diseases; Severe combined immunodeficiency, X-linked, T cell-negative, B cell-positive, NK cell-negative; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010315; MedGen: C1279481; Orphanet: 276; OMIM: 300400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003326298	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 13, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9058718, 10794430, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003326298

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 13, 2022)

germline

clinical testing

PubMed (3)
[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

Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency.

Puck JM, Pepper AE, Henthorn PS, Candotti F, Isakov J, Whitwam T, Conley ME, Fischer RE, Rosenblatt HM, Small TN, Buckley RH.

Blood. 1997 Mar 15;89(6):1968-77.

PubMed [citation]

PMID:: 9058718

Efficient detection of thirty-seven new IL2RG mutations in human X-linked severe combined immunodeficiency.

Niemela JE, Puck JM, Fischer RE, Fleisher TA, Hsu AP.

Clin Immunol. 2000 Apr;95(1 Pt 1):33-8.

PubMed [citation]

PMID:: 10794430

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003326298.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Leu12Ilefs*22) in the IL2RG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IL2RG are known to be pathogenic (PMID: 9058718, 10794430). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with IL2RG-related conditions. 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: Feb 20, 2024

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