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))

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

Approved on: 2024-01-17

Published on: 2024-01-17

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

• Met criteria codes: BS2

• Not Met criteria codes: PM5 PM2 BS1

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

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).

Met criteria codes

• BS2: 3 adult hemizygous males with this variant are present in the East Asian population in gnomADv2.1.1

Not Met criteria codes

• 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.