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]

Variant: NM_000206.3(IL2RG):c.455T>G (p.Val152Gly)

CA413496508

624584 (ClinVar)

Gene: IL2RG (HGNC:3561)

Condition: T-B+ severe combined immunodeficiency due to gamma chain deficiency (MONDO:0010315)

Inheritance Mode: X-linked inheritance

UUID: 6b44a96e-4725-4e0f-adb2-46375b66f326

Approved on: 2026-02-20

Published on: 2026-04-24

HGVS expressions

NM_000206.3(IL2RG):c.455T>G (p.Val152Gly)

NM_000206.3:c.455T>G

NC_000023.11:g.71110295A>C

CM000685.2:g.71110295A>C

NC_000023.10:g.70330145A>C

CM000685.1:g.70330145A>C

NC_000023.9:g.70246870A>C

NG_009088.1:g.6259T>G

NG_021141.1:g.1494T>G

ENST00000482750.6:c.455T>G

ENST00000696903.1:n.506T>G

ENST00000374202.7:c.455T>G

ENST00000642473.1:n.819T>G

ENST00000644022.1:n.860+209T>G

ENST00000644708.1:n.861T>G

ENST00000644911.1:n.861T>G

ENST00000645266.1:c.455T>G

ENST00000645518.1:c.455T>G

ENST00000646106.1:c.455T>G

ENST00000646505.1:c.455T>G

ENST00000647492.1:c.455T>G

ENST00000276110.6:n.1048T>G

ENST00000374188.7:c.-262T>G

ENST00000374202.6:c.455T>G

ENST00000456850.6:c.25-905T>G

ENST00000464642.5:c.323T>G

ENST00000487883.1:c.419T>G

ENST00000512747.3:n.521+209T>G

NM_000206.2:c.455T>G

Likely Pathogenic

PP4_Strong PM2_Supporting PM5 PS4_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 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

The NM_000206.3:c.455T>G variant in IL2RG is a missense variant predicted to cause substitution of valine by glycine at amino acid 152 (p.Val152Gly). The variant is absent from gnomAD v4.1.0 (PM2_Supporting). The variant has been reported in two patients meeting the PP4 phenotypic criteria (PMIDs 31031743, 36177038) (PS4_Supporting). One patient was diagnosed with SCID (PMID 36177038). The patient showed a T-B+NK- lymphocyte profile and an absence of STAT5 phosphorylation upon IL-2 stimulation (other possible variants were not excluded). The lymphopenia was resolved by IL2RG gene therapy (CNV testing not reported) (PP4_Strong). Another missense variant c.455T>C (p.Val152Ala) in the same codon has been classified as pathogenic for SCID by the ClinGen SCID VCEP (PM5). In summary, this variant is classified as likely pathogenic for SCID. ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: PP4_Strong, PM2_Supporting, PM5, PS4_Supporting (VCEP specifications version 2.1).

PP4_Strong

One individual with this variant was diagnosed with X-SCID (0.5pt) (PMID 36177038). The patient showed a T-B+NK- lymphocyte profile (0.5pt + 1pt), and an absence of STAT5 phosphorylation upon IL-2 stimulation (other possible variants were not excluded) (1.5pt). The lymphopenia was resolved by IL2RG gene therapy (CNV testing not reported, 4.5pt). 8pt in total, PP4_Strong is met.

PM2_Supporting

This variant is absent from gnomAD v4.1.0. (PM2_Supporting)

PM5

Another missense variant c.455T>C (p.Val152Ala), ClinVar Variation ID 36386, in the same codon has been classified as pathogenic for SCID by the ClinGen SCID VCEP. PM5 is met.

PS4_Supporting

This variant has been reported in 2 patients meeting the PP4 phenotypic criteria (PMIDs 31031743, 36177038). Excluding the proband used to satisfy the PP4 criteria (PMID 36177038), the other patient is counted for PS4. PS4_Supporting is met.

Curation History

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