NM_000206.3(IL2RG):c.720G>A (p.Trp240Ter) AND X-linked severe combined immunodeficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 1, 2016
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:: RCV000538891.5

Allele description [Variation Report for NM_000206.3(IL2RG):c.720G>A (p.Trp240Ter)]

NM_000206.3(IL2RG):c.720G>A (p.Trp240Ter)

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.720G>A (p.Trp240Ter)

HGVS:

NC_000023.11:g.71109265C>T
NG_009088.1:g.7289G>A
NG_021141.1:g.2524G>A
NM_000206.3:c.720G>AMANE SELECT
NP_000197.1:p.Trp240Ter
NP_000197.1:p.Trp240Ter
LRG_150t1:c.720G>A
LRG_150:g.7289G>A
LRG_150p1:p.Trp240Ter
NC_000023.10:g.70329115C>T
NM_000206.2:c.720G>A

Protein change:

W240*

Links:

dbSNP: rs1556330234

NCBI 1000 Genomes Browser:

rs1556330234

Molecular consequence:

NM_000206.3:c.720G>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

Recent activity

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Mus musculus adaptor-related protein complex 2, beta 1 subunit (Ap2b1), transcri...
Mus musculus adaptor-related protein complex 2, beta 1 subunit (Ap2b1), transcript variant 2, mRNA
gi|78711839|ref|NM_027915.2|

Nucleotide
Mus musculus histone cluster 1, H1e, mRNA (cDNA clone MGC:107634 IMAGE:6745595),...
Mus musculus histone cluster 1, H1e, mRNA (cDNA clone MGC:107634 IMAGE:6745595), complete cds
gi|59809089|gb|BC089600.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000637250	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 1, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9058718, 10794430, 28492532 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000637250

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 1, 2016)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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, SCV000637250.3

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

Description

A different variant, c.719G>A, which results in the same truncating effect (p.Trp240*) on the protein and absent IL2RG expression, has been observed in a patient affected with classic X-linked SCID (IL2RGbase, http://research.nhgri.nih.gov/scid/IL2RGbase.shtml). In addition, fourteen unrelated patients with classic X-linked SCID have been observed in IL2RGbase with truncating mutations in exon 5 showing nonsense-mediated decay and absence of IL2RG mRNA (Personal communication, Dr. Jennifer Puck). For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, truncating variants in IL2RG are known to be pathogenic (PMID: 9058718, 10794430). This sequence change creates a premature translational stop signal at codon 240 (p.Trp240*) of the IL2RG gene. It is expected to result in an absent or disrupted protein product.

#	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 28, 2024

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