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.325G>A (p.Glu109Lys)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10443889

368619 (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: 665bca67-f957-4531-87d1-b052b7e0f034

Approved on: 2024-01-17

Published on: 2024-01-17

HGVS expressions

NM_000206.3:c.325G>A

NM_000206.3(IL2RG):c.325G>A (p.Glu109Lys)

NC_000023.11:g.71110633C>T

CM000685.2:g.71110633C>T

NC_000023.10:g.70330483C>T

CM000685.1:g.70330483C>T

NC_000023.9:g.70247208C>T

NG_009088.1:g.5921G>A

NG_021141.1:g.1156G>A

ENST00000374202.7:c.325G>A

ENST00000642473.1:n.689G>A

ENST00000644022.1:n.731G>A

ENST00000644708.1:n.731G>A

ENST00000644911.1:n.731G>A

ENST00000645266.1:c.325G>A

ENST00000645518.1:c.325G>A

ENST00000646106.1:c.325G>A

ENST00000646505.1:c.325G>A

ENST00000647492.1:c.325G>A

ENST00000276110.6:n.710G>A

ENST00000374188.7:c.-392G>A

ENST00000374202.6:c.325G>A

ENST00000456850.6:c.24+792G>A

ENST00000464642.5:c.193G>A

ENST00000473378.1:c.262G>A

ENST00000487883.1:c.289G>A

ENST00000512747.3:n.392G>A

NM_000206.2:c.325G>A

Benign

BS2 BS1

PM2 BP4

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.325G>A (p.Glu109Lys) 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 0.0006719 (based on 74/92629 alleles in the non-Finnish European population) which is below the SCID VCEP established threshold of >0.00249 for BS1 and above the PM2 threshold of <0.000124. However, the highest MAF is in the Finnish population at 0.004561 (85/18638 alleles, 28 hemizygotes and 1 homozygote) which is above the SCID VCEP established threshold of >0.00249. As this population is not known to have a higher prevalence of this is considered to meet BS1. Sixty-two adult hemizygous males with this variant are present in the gnomADv2.1.1 dataset as well as a homozygous female (BS2). In summary, this variant is classified as Benign. Criteria applied: BS1, BS2 (VCEP specifications version 1).

BS2

62 adult hemizygous males with this variant are present in gnomADv2.1.1 (23 in the non-Finnish European population) plus a homozygous female in the Finnish population (BS2).

BS1

The popmax filtering allele frequency in gnomAD v2.1. is 0.0006719 (based on 74/92629 alleles in the non-Finnish European population) which is below the SCID VCEP established threshold of >0.00249. However, the highest MAF is in the Finnish population at 0.004561 (85/18638 alleles, 28 hemizygotes and 1 homozygote) which is above the SCID VCEP established threshold of >0.00249. As this population is not known to have a higher prevalence of disease this is considered to meet BS1.

PM2

The popmax filtering allele frequency in gnomAD v2.1. is 0.0006719 (based on 74/92629 alleles in the non-Finnish European population) which is above the SCID VCEP established threshold of <0.000124. Additionally, 62 hemizygotes are observed in gnomAD.

BP4

REVEL score of 0.278 predicts no impact on the gene product. Not considered for this gene.

Curation History

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