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.720G>A (p.Trp240Ter)

CA413495887

463384 (ClinVar)

Gene: IL2RG

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

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: ac826776-8b82-481a-b8e2-e327f5a382b5

Approved on: 2024-06-13

Published on: 2024-06-13

HGVS expressions

NM_000206.3:c.720G>A

NM_000206.3(IL2RG):c.720G>A (p.Trp240Ter)

NC_000023.11:g.71109265C>T

CM000685.2:g.71109265C>T

NC_000023.10:g.70329115C>T

CM000685.1:g.70329115C>T

NC_000023.9:g.70245840C>T

NG_009088.1:g.7289G>A

NG_021141.1:g.2524G>A

ENST00000482750.6:c.720G>A

ENST00000696903.1:n.771G>A

ENST00000374202.7:c.720G>A

ENST00000642473.1:n.1084G>A

ENST00000644022.1:n.986G>A

ENST00000644708.1:n.1126G>A

ENST00000644911.1:n.1126G>A

ENST00000645266.1:c.720G>A

ENST00000645518.1:c.720G>A

ENST00000646106.1:c.720G>A

ENST00000646505.1:c.720G>A

ENST00000647492.1:c.720G>A

ENST00000276110.6:n.1313G>A

ENST00000374188.7:c.4G>A

ENST00000374202.6:c.720G>A

ENST00000456850.6:c.150G>A

ENST00000464642.5:c.588G>A

ENST00000482750.5:c.133G>A

ENST00000512747.3:n.647G>A

NM_000206.2:c.720G>A

Pathogenic

PVS1 PM2_Supporting PP4_Moderate

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

The c.720G>A (p.Trp240Ter) (NM_000206.3) variant in IL2RG is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 5/8, leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1 Met). This variant is absent from gnomAD v4 (PM2_Supporting). At least one proband in the literature presents: Diagnostic criteria for SCID/Leaky SCID/Omenn syndrome met (0.5 pts) + XY male sex (0.5 pts) + SCID phenotype corrected by IL2RG gene therapy WITHOUT CNV testing reported (1 pt). Total is 2 points, PP4_Moderate. In summary, this variant meets the criteria to be classified as Pathogenic 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: PVS1, PM2_Supporting, and PP4_Moderate (VCEP specifications version 1).

PVS1

PM2_Supporting

This variant is absent from gnomAD v4 (PM2_Supporting).

PP4_Moderate

At least one proband in the literature presents: Diagnostic criteria for SCID/Leaky SCID/Omenn syndrome met (0.5 pts) + XY male sex (0.5 pts) + SCID phenotype corrected by IL2RG gene therapy WITHOUT CNV testing performed (1 pt). Total is 2 points, PP4_Moderate.

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.