Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000206.3(IL2RG):c.184T>C (p.Cys62Arg)

CA413497163

1066149 (ClinVar)

Gene: IL2RG

Condition: T-B+ severe combined immunodeficiency due to gamma chain deficiency

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: a02c3b22-ff9e-46c7-8d9b-f6626fccdd0d

Approved on: 2024-06-12

Published on: 2024-06-12

HGVS expressions

NM_000206.3:c.184T>C

NM_000206.3(IL2RG):c.184T>C (p.Cys62Arg)

NC_000023.11:g.71110982A>G

CM000685.2:g.71110982A>G

NC_000023.10:g.70330832A>G

CM000685.1:g.70330832A>G

NC_000023.9:g.70247557A>G

NG_009088.1:g.5572T>C

NG_021141.1:g.807T>C

ENST00000482750.6:c.184T>C

ENST00000696903.1:n.235T>C

ENST00000374202.7:c.184T>C

ENST00000642473.1:n.548T>C

ENST00000644022.1:n.590T>C

ENST00000644708.1:n.590T>C

ENST00000644911.1:n.590T>C

ENST00000645266.1:c.184T>C

ENST00000645518.1:c.184T>C

ENST00000646106.1:c.184T>C

ENST00000646505.1:c.184T>C

ENST00000647492.1:c.184T>C

ENST00000276110.6:n.569T>C

ENST00000374188.7:c.-533T>C

ENST00000374202.6:c.184T>C

ENST00000456850.6:c.24+443T>C

ENST00000464642.5:c.52T>C

ENST00000473378.1:c.121T>C

ENST00000487883.1:c.148T>C

ENST00000512747.3:n.251T>C

NM_000206.2:c.184T>C

Pathogenic

PM1_Strong PS4_Supporting PM5 PP4_Moderate PM2_Supporting

Evidence Links 0

Expert Panel

Severe Combined Immunodeficiency Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for IL2RG Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_000206.3(IL2RG):c.184T>C is a missense variant predicted to cause substitution of Cysteine by Arginine at amino acid 62 (p.Cys62Arg). This mutation affects conserved cysteine residue i.e. Cys62 (PM1_strong). The variant is absent in gnomAD v4 (PM2_supporting). Male patient (0.5 pt.) with SCID (0.5 pt.), genome sequencing conducted (1 pt.),T-B+NK- lymphocyte subset profile (0.5 pt.); total : 2.5 pts (PP4_Moderate) (Invitae).Another missense variant [NM_000206.3(IL2RG):c.186T>A (p.Cys62Ter)] in the same codon has been reported (classified as pathogenic by SCID VCEP) (PM5 met).The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (Invitae, PMID: 27484032) (PS4_supporting). 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: PM1_strong, PM2_supporting, PP4_Moderate,PM5 met,PS4_supporting (VCEP specifications version 1).

PM1_Strong

This mutation affects conserved cysteine residue i.e. Cys62 (PM1_strong).

PS4_Supporting

The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (Invitae, PMID: 27484032) (PS4_supporting).

PM5

Another missense variant [NM_000206.3(IL2RG):c.186T>A (p.Cys62Ter)] in the same codon has been reported (classified as pathogenic by SCID VCEP) (PM5 met).

PP4_Moderate

Male patient (0.5 pt.) with SCID (0.5 pt.), genome sequencing conducted (1 pt.),T-B+NK- lymphocyte subset profile (0.5 pt.); total : 2.5 pts (PP4_Moderate) (Invitae).

PM2_Supporting

The variant is absent in gnomAD v4 (PM2_supporting).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.