NM_000206.3(IL2RG):c.758-1G>A AND X-linked severe combined immunodeficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 22, 2019
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:: RCV000553796.10

Allele description [Variation Report for NM_000206.3(IL2RG):c.758-1G>A]

NM_000206.3(IL2RG):c.758-1G>A

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.758-1G>A

HGVS:

NC_000023.11:g.71108696C>T
NG_009088.1:g.7858G>A
NG_021141.1:g.3093G>A
NM_000206.3:c.758-1G>AMANE SELECT
LRG_150t1:c.758-1G>A
LRG_150:g.7858G>A
NC_000023.10:g.70328546C>T
NM_000206.2:c.758-1G>A

Links:

dbSNP: rs886042051

NCBI 1000 Genomes Browser:

rs886042051

Molecular consequence:

NM_000206.3:c.758-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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uncharacterized protein COCSADRAFT_276134 [Bipolaris sorokiniana ND90Pr]
uncharacterized protein COCSADRAFT_276134 [Bipolaris sorokiniana ND90Pr]
gi|628060563|ref|XP_007696258.1|

Protein
mapk6 [Maylandia zebra]
mapk6 [Maylandia zebra]
Gene ID:101465607

Gene
Hypocortisolemia
Hypocortisolemia

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000637251	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 22, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 9058718, 10794430, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000637251

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 22, 2019)

germline

clinical testing

PubMed (4)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000637251.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IL2RG are known to be pathogenic (PMID: 9058718, 10794430). For these reasons, this variant has been classified as Pathogenic. Disruption of this splice site has been¬†has been observed in several individuals affected with severe combined immunodeficiency (PMID: 10794430, Invitae). ClinVar contains an entry for this variant (Variation ID:¬†280937). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 5 of the IL2RG gene. It is expected to disrupt RNA splicing and likely results 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: Jun 23, 2024

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