Variant: NM_002185.5(IL7R):c.135G>C (p.Gln45His)

CA359426752

1393864 (ClinVar)

Gene: IL7R

Condition: severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive

Inheritance Mode: Autosomal recessive inheritance

UUID: 36f127bb-63e7-4ce2-8931-0545fbf07a93

Approved on: 2024-06-17

Published on: 2024-06-17

HGVS expressions

NM_002185.5:c.135G>C
NM_002185.5(IL7R):c.135G>C (p.Gln45His)
NC_000005.10:g.35860904G>C
CM000667.2:g.35860904G>C
NC_000005.9:g.35861006G>C
CM000667.1:g.35861006G>C
NC_000005.8:g.35896763G>C
NG_009567.1:g.9016G>C
ENST00000303115.8:c.135G>C
ENST00000303115.7:c.135G>C
ENST00000506850.5:c.135G>C
ENST00000508941.5:c.135G>C
ENST00000511031.1:n.269G>C
ENST00000511982.1:c.135G>C
ENST00000514217.5:c.135G>C
ENST00000515665.1:c.135G>C
NM_002185.3:c.135G>C
NR_120485.1:n.238G>C
NM_002185.4:c.135G>C
NR_120485.2:n.264G>C
NR_120485.3:n.222G>C

Uncertain Significance

• Met criteria codes: PM2_Supporting

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 IL7R Version 1.0.0

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_002185.5(IL7R):c.135G>C is a missense variant predicted to cause substitution of Glutamine by Histidine at amino acid 45 (p.Gln45His). The variant is only reported in bottleneck population i.e. Middle Eastern in gnomAD v4 in which the minor allele frequency is 0.0001650 (1/6060) (PM2_Supporting). Another missense variant NM_002185.5(IL7R):c.134A>C (p.Gln45Pro) in the same codon has been reported (PM5 not evaluated). To our knowledge, this variant has not been reported in the literature in individuals affected with IL7R-related conditions or in functional studies. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to IL7R deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PM2_Supporting (VCEP specifications version 1).

Met criteria codes

• PM2_Supporting: The variant is only reported in bottleneck population i.e. Middle Eastern in gnomAD v4 in which the minor allele frequency is 0.0001650 (1/6060) (PM2_Supporting).