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

Approved on: 2024-01-10

Published on: 2024-01-10

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)

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.