Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
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Variant: NM_000206.3(IL2RG):c.406C>T (p.Arg136Trp)

CA330970071

532192 (ClinVar)

Gene: IL2RG
Condition: T-B+ severe combined immunodeficiency due to gamma chain deficiency
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 0f2b3d6e-bedd-468a-8855-fba7a4478d7c
Approved on: 2024-06-13
Published on: 2024-06-13

HGVS expressions

NM_000206.3:c.406C>T
NM_000206.3(IL2RG):c.406C>T (p.Arg136Trp)
NC_000023.11:g.71110552G>A
CM000685.2:g.71110552G>A
NC_000023.10:g.70330402G>A
CM000685.1:g.70330402G>A
NC_000023.9:g.70247127G>A
NG_009088.1:g.6002C>T
NG_021141.1:g.1237C>T
ENST00000482750.6:c.406C>T
ENST00000696903.1:n.457C>T
ENST00000374202.7:c.406C>T
ENST00000642473.1:n.770C>T
ENST00000644022.1:n.812C>T
ENST00000644708.1:n.812C>T
ENST00000644911.1:n.812C>T
ENST00000645266.1:c.406C>T
ENST00000645518.1:c.406C>T
ENST00000646106.1:c.406C>T
ENST00000646505.1:c.406C>T
ENST00000647492.1:c.406C>T
ENST00000276110.6:n.791C>T
ENST00000374188.7:c.-311C>T
ENST00000374202.6:c.406C>T
ENST00000456850.6:c.24+873C>T
ENST00000464642.5:c.274C>T
ENST00000487883.1:c.370C>T
ENST00000512747.3:n.473C>T
NM_000206.2:c.406C>T

Likely Benign

Met criteria codes 1
BS2
Not Met criteria codes 1
PM2

Evidence Links 0

Expert Panel

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
The c.406C>T (NM_000206.3) variant in IL2RG is a missense variant predicted to cause the substitution of Arginine by Tryptophan at amino acid 136 (p.Arg136Trp). The filtering allele frequency (the upper threshold of the 95% CI of 5/57157 alleles) of the c.406C>T variant in IL2RG is 0.00003386 for African/African American chromosomes by gnomAD v4.1.0, which is lower than the ClinGen SCID VCEP threshold (<0.000124) for PM2_Supporting. However, 04 hemizygotes were observed in gnomAD; thus, PM2 was not met, and BS2 is applicable. In summary, this variant meets the criteria to be classified as Likely Benign 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. Criteria applied: BS2 (VCEP specifications version 1.0).
Met criteria codes
BS2
04 hemizygotes have been observed in gnomAD v.4.1.0, BS2_Strong.
Not Met criteria codes
PM2
The filtering allele frequency (the upper threshold of the 95% CI of 5/57157 alleles) of the c.406C>T variant in IL2RG is 0.00003386 for African/African American chromosomes by gnomAD v4.1.0, which is lower than the ClinGen SCID VCEP threshold (<0.000124) for PM2_Supporting. However, 04 hemizygotes were observed in gnomAD; thus, PM2 was not met.
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