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.1105A>G (p.Thr369Ala)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10443749

837417 (ClinVar)

Gene: IL2RG

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

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: ac65b97f-ddcc-43fa-a9b0-d817bd4ee123

Approved on: 2024-01-17

Published on: 2024-01-17

HGVS expressions

NM_000206.3:c.1105A>G

NM_000206.3(IL2RG):c.1105A>G (p.Thr369Ala)

NC_000023.11:g.71107741T>C

CM000685.2:g.71107741T>C

NC_000023.10:g.70327591T>C

CM000685.1:g.70327591T>C

NC_000023.9:g.70244316T>C

NG_009088.1:g.8813A>G

NG_021141.1:g.4048A>G

ENST00000374202.7:c.1105A>G

ENST00000642473.1:n.1288+536A>G

ENST00000644022.1:n.1190+536A>G

ENST00000644708.1:n.1302+112A>G

ENST00000644911.1:n.1399+112A>G

ENST00000645266.1:c.924+536A>G

ENST00000645518.1:c.924+536A>G

ENST00000646106.1:c.993+112A>G

ENST00000646505.1:c.924+536A>G

ENST00000647492.1:c.924+536A>G

ENST00000276110.6:n.1698A>G

ENST00000374188.7:c.292A>G

ENST00000374202.6:c.1105A>G

ENST00000456850.6:c.535A>G

ENST00000482750.5:c.421A>G

ENST00000512747.3:n.1639A>G

NM_000206.2:c.1105A>G

Uncertain Significance

BS2_Supporting

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.1105A>G (p.Thr369Ala) is a missense variant that has been reported in ClinVar, without patient information, however it has not been reported in the literature to our knowledge. It occurs at a low allele frequency in gnomAD v2.1. of 0.00002258 which is below the SCID VCEP established threshold of <0.000124, however this includes two adult hemizygotes (PM2_NotMet, BS2_Supporting). In summary, this variant is classified as uncertain significance due to insufficient information. Criteria applied: BS2_supporting (VCEP specifications version 1).

BS2_Supporting

Two adult hemizygous males with this variant are present in gnomADv2.1.1 in the non-Finnish European population (BS2_Supporting).

PM2

The popmax filtering allele frequency in gnomAD v2.1. is 0.00002258 (based on 5/70540 alleles in the non-Finnish European population) which is below the SCID VCEP established threshold of <0.000124, however this includes two adult hemizygotes.

Curation History

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