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]

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Variant: NM_000206.3(IL2RG):c.332T>C (p.Ile111Thr)

CA10443887

795305 (ClinVar)

Gene: IL2RG

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

Inheritance Mode: X-linked inheritance (recessive (HP:0001419))

Link to MONDO

UUID: 38a702d8-39d4-448e-ac07-e960c1864c73

HGVS expressions

NM_000206.3:c.332T>C

NM_000206.3(IL2RG):c.332T>C (p.Ile111Thr)

NC_000023.11:g.71110626A>G

CM000685.2:g.71110626A>G

NC_000023.10:g.70330476A>G

CM000685.1:g.70330476A>G

NC_000023.9:g.70247201A>G

NG_009088.1:g.5928T>C

NG_021141.1:g.1163T>C

ENST00000374202.7:c.332T>C

ENST00000642473.1:n.696T>C

ENST00000644022.1:n.738T>C

ENST00000644708.1:n.738T>C

ENST00000644911.1:n.738T>C

ENST00000645266.1:c.332T>C

ENST00000645518.1:c.332T>C

ENST00000646106.1:c.332T>C

ENST00000646505.1:c.332T>C

ENST00000647492.1:c.332T>C

ENST00000276110.6:n.717T>C

ENST00000374188.7:c.-385T>C

ENST00000374202.6:c.332T>C

ENST00000456850.6:c.24+799T>C

ENST00000464642.5:c.200T>C

ENST00000473378.1:c.269T>C

ENST00000487883.1:c.296T>C

ENST00000512747.3:n.399T>C

NM_000206.2:c.332T>C

Likely Benign

BS2

PM5 PM2 BS1

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 NM_000206.3(IL2RG):c.332T>C (p.Ile111Thr) 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 an intermediate allele frequency, with a popmax filtering allele frequency in gnomAD v2.1.1 of 0.0001413 (based on 6/14830 alleles in the East Asian population) which is below the SCID VCEP established threshold of >0.00249 for BS1 and above the PM2 threshold of <0.000124. Three adult hemizygous males with this variant are present in the East Asian population in gnomADv2.1.1 (BS2). In summary, this variant is classified as Likely Benign. Criteria applied: BS2 (VCEP specifications version 1).

BS2

3 adult hemizygous males with this variant are present in the East Asian population in gnomADv2.1.1

PM5

Another variant found in the amino acid residue, NM_000206.3(IL2RG):c.333C>G (p.Ile111Met), but classified as LB (ClinVar:1568924).

PM2

The popmax filtering allele frequency in gnomAD v2.1.1 is 0.0001413 (based on 6/14830 alleles in the East Asian population) which is above the SCID VCEP established threshold of <0.000124. Additionally, three hemizygotes are observed in gnomAD.

BS1

The popmax filtering allele frequency in gnomAD v2.1.1 is 0.0001413 (based on 6/14830 alleles in the East Asian population) which is below the SCID VCEP established threshold of >0.00249.

Approved on: 2024-01-17

Published on: 2024-01-17

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