Variant: NM_002185.5(IL7R):c.212T>C (p.Phe71Ser)

CA3231862

418257 (ClinVar)

Gene: IL7R

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

Inheritance Mode: Autosomal recessive inheritance

UUID: 22d69319-3a7f-4087-99c8-a6726ddb5e3e

Approved on: 2024-06-17

Published on: 2024-06-17

HGVS expressions

NM_002185.5:c.212T>C
NM_002185.5(IL7R):c.212T>C (p.Phe71Ser)
NC_000005.10:g.35860981T>C
CM000667.2:g.35860981T>C
NC_000005.9:g.35861083T>C
CM000667.1:g.35861083T>C
NC_000005.8:g.35896840T>C
NG_009567.1:g.9093T>C
ENST00000303115.8:c.212T>C
ENST00000303115.7:c.212T>C
ENST00000506850.5:c.212T>C
ENST00000511031.1:n.346T>C
ENST00000511982.1:c.212T>C
ENST00000514217.5:c.212T>C
NM_002185.3:c.212T>C
NR_120485.1:n.315T>C
NM_002185.4:c.212T>C
NR_120485.2:n.341T>C
NR_120485.3:n.299T>C

Uncertain Significance

• Met criteria codes: PM2_Supporting

• Not Met criteria codes: PM3

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.212T>C is a missense variant predicted to cause substitution of Phenylalanine by Serine at amino acid 71 (p.Phe71Ser).The filtering allele frequency of the c.212T>C variant in IL7R is 0 by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.00004129) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). One patient (PMID: 23810098) was found heterozygous for F71S & H180P (pre-curated as VUS) (0.25 pt.) (PM3 not met). 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 filtering allele frequency of the c.212T>C variant in IL7R is 0 by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.00004129) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).

Not Met criteria codes

• PM3: One patient (PMID: 23810098) was found heterozygous for F71S & H180P (pre-curated as VUS) (0.25 pt.).