Variant: NM_000206.3(IL2RG):c.202G>A (p.Glu68Lys)

CA16608976

379561 (ClinVar)

Gene: IL2RG

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

Inheritance Mode: X-linked inheritance

UUID: 2777e3d3-64d9-471a-a3d8-c36d5f50889d

HGVS expressions

NM_000206.3:c.202G>A
NM_000206.3(IL2RG):c.202G>A (p.Glu68Lys)
NC_000023.11:g.71110964C>T
CM000685.2:g.71110964C>T
NC_000023.10:g.70330814C>T
CM000685.1:g.70330814C>T
NC_000023.9:g.70247539C>T
NG_009088.1:g.5590G>A
NG_021141.1:g.825G>A
ENST00000374202.7:c.202G>A
ENST00000642473.1:n.566G>A
ENST00000644022.1:n.608G>A
ENST00000644708.1:n.608G>A
ENST00000644911.1:n.608G>A
ENST00000645266.1:c.202G>A
ENST00000645518.1:c.202G>A
ENST00000646106.1:c.202G>A
ENST00000646505.1:c.202G>A
ENST00000647492.1:c.202G>A
ENST00000276110.6:n.587G>A
ENST00000374188.7:c.-515G>A
ENST00000374202.6:c.202G>A
ENST00000456850.6:c.24+461G>A
ENST00000464642.5:c.70G>A
ENST00000473378.1:c.139G>A
ENST00000487883.1:c.166G>A
ENST00000512747.3:n.269G>A
NM_000206.2:c.202G>A

Pathogenic

• Met criteria codes: PM2_Supporting PS4 PP4_Moderate

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

NM_000206.3(IL2RG):c.202G>A is a missense variant predicted to cause substitution of Glutamic Acid by Lysine at amino acid 68 (p.Glu68Lys). The variant is absent in gnomAD v4 (PM2_supporting). Male patient (0.5 pt.) with SCID (0.5 pt.), genome sequencing conducted (1 pt.), Absent CD132 expression (1 pt.), T-B+NK- lymphocyte subset profile (0.5 pt.); total :3.5 pts PMID: 30778343 (PP4_moderate). This variant is found in multiple unrelated affected probands (total pts. >16) (PS4_very strong) (PMIDs: 9058718, 24534054,11129345, 32477911,31456805, 27484032,31031743,30778343). As per the SCID VCEP specifications and the Bayesian interpretation of the ACMG/AMP combining rules, 1 Very Strong,1 Moderate and 1 Supporting criteria results in a Pathogenic classification. In summary, this variant meets the criteria to be classified as Pathogenic for X-linked severe combined immunodeficiency due to IL2RG deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PM2_supporting,PP4_moderate,PS4_very strong (VCEP specifications version 1).

Met criteria codes

• PM2_Supporting: The variant is absent in gnomAD v4 (PM2_supporting).
• PS4: This variant is found in multiple unrelated affected probands (total pts. >16) (PS4_very strong) (PMIDs: 9058718, 24534054,11129345, 32477911,31456805, 27484032,31031743,30778343)
• PP4_Moderate: Male patient (0.5 pt.) with SCID (0.5 pt.), genome sequencing conducted (1 pt.), Absent CD132 expression (1 pt.), T-B+NK- lymphocyte subset profile (0.5 pt.); total :3.5 pts PMID: 30778343 (PP4_moderate).

Approved on: 2024-01-31

Published on: 2024-01-31