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NM_000206.3(IL2RG):c.655T>C (p.Tyr219His) AND X-linked severe combined immunodeficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 13, 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:
RCV004765356.1

Allele description [Variation Report for NM_000206.3(IL2RG):c.655T>C (p.Tyr219His)]

NM_000206.3(IL2RG):c.655T>C (p.Tyr219His)

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.655T>C (p.Tyr219His)
Other names:
NM_000206.3(IL2RG):c.655T>C; p.Tyr219His
HGVS:
  • NC_000023.11:g.71109330A>G
  • NG_009088.1:g.7224T>C
  • NG_021141.1:g.2459T>C
  • NM_000206.3:c.655T>CMANE SELECT
  • NP_000197.1:p.Tyr219His
  • LRG_150:g.7224T>C
  • NC_000023.10:g.70329180A>G
Protein change:
Y219H
Links:
dbSNP: rs2147748284
NCBI 1000 Genomes Browser:
rs2147748284
Molecular consequence:
  • NM_000206.3:c.655T>C - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005375402ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen SCID ACMG Specifications IL2RG V1.0.0)		Uncertain Significance
(Jun 13, 2024) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen, SCV005375402.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.655T>C (NM_000206.3) variant in IL2RG is a missense variant predicted to cause substitution of Tyrosine by Histidine at amino acid 219 (p.Tyr219His). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in individuals affected with SCID/IL2RG-related conditions or in functional studies. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for X-linked T-B+ severe combined immunodeficiency due to gamma chain deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PM2_Supporting (VCEP specifications version 1).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024