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.292A>G (p.Lys98Glu)

CA10443891

804024 (ClinVar)

Gene: IL2RG

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

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 6d7accf0-655c-4f28-83ba-f6e2e0830f90

HGVS expressions

NM_000206.3:c.292A>G

NM_000206.3(IL2RG):c.292A>G (p.Lys98Glu)

NC_000023.11:g.71110666T>C

CM000685.2:g.71110666T>C

NC_000023.10:g.70330516T>C

CM000685.1:g.70330516T>C

NC_000023.9:g.70247241T>C

NG_009088.1:g.5888A>G

NG_021141.1:g.1123A>G

ENST00000374202.7:c.292A>G

ENST00000642473.1:n.656A>G

ENST00000644022.1:n.698A>G

ENST00000644708.1:n.698A>G

ENST00000644911.1:n.698A>G

ENST00000645266.1:c.292A>G

ENST00000645518.1:c.292A>G

ENST00000646106.1:c.292A>G

ENST00000646505.1:c.292A>G

ENST00000647492.1:c.292A>G

ENST00000276110.6:n.677A>G

ENST00000374188.7:c.-425A>G

ENST00000374202.6:c.292A>G

ENST00000456850.6:c.24+759A>G

ENST00000464642.5:c.160A>G

ENST00000473378.1:c.229A>G

ENST00000487883.1:c.256A>G

ENST00000512747.3:n.359A>G

NM_000206.2:c.292A>G

Uncertain Significance

PP4_Moderate

PM2

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.292A>G is a missense variant predicted to cause substitution of Lysine by Glutamic Acid at amino acid 98 (p.Lys98Glu). The filtering allele frequency (the upper threshold of the 95% CI of 55/893392) of the 292A>G variant in IL2RG is 0.00004918 for European Non-Finnish chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.000124 ) for PM2_Supporting. However, 14 hemizygotes have been observed in gnomAD. (PM2_not met). 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) (PMID: 10794430). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for X-linked severe combined immunodeficiency due to IL2RG deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PP4_Moderate (VCEP specifications version 1).

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) (PMID: 10794430).

PM2

The filtering allele frequency (the upper threshold of the 95% CI of 55/893392) of the 292A>G variant in IL2RG is 0.00004918 for European Non-Finnish chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.000124 ) for PM2_Supporting. However, 14 hemizygotes have been observed in gnomAD. (PM2_not met)

Approved on: 2024-01-10

Published on: 2024-01-10

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