Variant: NM_002185.5(IL7R):c.539A>C (p.His180Pro)

CA214046

36393 (ClinVar)

Gene: IL7R

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

Inheritance Mode: Autosomal recessive inheritance

UUID: 885a0746-b415-4282-8d33-765d38662073

Approved on: 2024-01-24

Published on: 2024-01-24

HGVS expressions

NM_002185.5:c.539A>C
NM_002185.5(IL7R):c.539A>C (p.His180Pro)
NC_000005.10:g.35873481A>C
CM000667.2:g.35873481A>C
NC_000005.9:g.35873583A>C
CM000667.1:g.35873583A>C
NC_000005.8:g.35909340A>C
NG_009567.1:g.21593A>C
ENST00000303115.8:c.539A>C
ENST00000303115.7:c.539A>C
ENST00000506850.5:c.539A>C
ENST00000509668.1:n.281A>C
ENST00000514217.5:c.538-2031A>C
NM_002185.3:c.539A>C
NR_120485.1:n.641-2031A>C
NM_002185.4:c.539A>C
NR_120485.2:n.667-2031A>C
NR_120485.3:n.625-2031A>C

Uncertain Significance

• Not Met criteria codes: PM2 PP4

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.539A>C is a missense variant predicted to cause substitution of Histidine by Proline at amino acid 180 (p.His180Pro). The highest population minor allele frequency in gnomAD v4 is 0.0002710 (16/59030 alleles) in Admixed American population (PM2_Supporting, BS1, and BA1 are not met). 2 patients (PMID: 23810098) with SCID (0.5 pt.) having T-B+NK+ lymphocyte subset profile (0.25 pt.) (Total :0.75 pts.) (PP4 not met). Both patients had maternal cell engraftment. One patient (PMID: 23810098) was found heterozygous for H180P & F71S (pre-curated as VUS) and another patient (PMID: 23810098) was found heterozygous for H180P & I94fs (not classified by SCID VCEP) (0.25 pt.). 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: No criteria met (VCEP specifications version 1).

Not Met criteria codes

• PM2: The highest population minor allele frequency in gnomAD v4 is 0.0002710 (16/59030 alleles) in Admixed American population (PM2_Supporting, BS1, and BA1 are not met)
• PP4: 2 patients (PMID: 23810098) with SCID (0.5 pt.) having T-B+NK+ lymphocyte subset profile (0.25 pt.) (Total :0.75 pts.) (PP4 not met). Both patients had maternal cell engraftment.