NM_000206.3(IL2RG):c.186T>A (p.Cys62Ter) AND X-linked severe combined immunodeficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 1, 2024
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000010702.5

Allele description [Variation Report for NM_000206.3(IL2RG):c.186T>A (p.Cys62Ter)]

NM_000206.3(IL2RG):c.186T>A (p.Cys62Ter)

Gene:

IL2RG:interleukin 2 receptor subunit gamma [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq13.1

Genomic location:

Preferred name:

NM_000206.3(IL2RG):c.186T>A (p.Cys62Ter)

Other names:

NM_000206.3(IL2RG):c.186T>A; p.Cys62Ter

HGVS:

NC_000023.11:g.71110980A>T
NG_009088.1:g.5574T>A
NG_021141.1:g.809T>A
NM_000206.3:c.186T>AMANE SELECT
NP_000197.1:p.Cys62Ter
LRG_150:g.5574T>A
NC_000023.10:g.70330830A>T

Protein change:

C62*; CYS62TER

Links:

OMIM: 308380.0004; dbSNP: rs111033619

NCBI 1000 Genomes Browser:

rs111033619

Molecular consequence:

NM_000206.3:c.186T>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000030928	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 1993)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004809088	ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen SCID ACMG Specifications IL2RG V1.0.0)	Pathogenic (Feb 1, 2024)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000030928

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 1993)

germline

literature only

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

SCV004809088

ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(ClinGen SCID ACMG Specifications IL2RG V1.0.0)

Pathogenic
(Feb 1, 2024)

germline

curation

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.

Puck JM, Deschênes SM, Porter JC, Dutra AS, Brown CJ, Willard HF, Henthorn PS.

Hum Mol Genet. 1993 Aug;2(8):1099-104.

PubMed [citation]

PMID:: 8401490

Details of each submission

From OMIM, SCV000030928.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with X-linked SCID (300400), Puck et al. (1993) identified a 200T-A transversion in exon 2 of the IL2RG gene, resulting in a cys62-to-ter (C62X) substitution.

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

From ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen, SCV004809088.1

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

Description

The c.186T>A (p.Cys62Ter) (NM_000206.3) variant in IL2RG is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 2/8 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1 Met).The variant is absent in gnomAD v4 (PM2_supporting). Male patient (0.5 pt.), Absent CD132 expression (demonstrated by RT-PCR) (1 pt.) total :1.5 pts (PP4) (PMID: 8462096). In summary, this variant meets the criteria to be classified as a Pathogenic variant for X-linked severe combined immunodeficiency due to IL2RG deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PVS1 Met,PP4,PM2_supporting (VCEP specifications version 1).

#	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: Apr 15, 2024

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