Submissions for variant NM_002185.5(IL7R):c.355A>T (p.Lys119Ter)

dbSNP: rs1448018291

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	RCV000796316	SCV004810398	likely pathogenic	Immunodeficiency 104	2024-01-30	reviewed by expert panel	curation	c.355A>T (p.Lys119Ter)(NM_002185.5) variant in IL7R is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 3/8 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1_Met).The variant is absent in gnomAD v4 (PM2_supporting). There are no publications for this variant in the literature. As per the SCID VCEP specifications and the Bayesian interpretation of the ACMG/AMP combining rules, 1 very strong and 1 supporting criteria results in a Likely Pathogenic classification. In summary, this variant meets the criteria to be classified as Likely Pathogenic variant for autosomal recessive severe combined immunodeficiency due to IL7R deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PVS1_Met,PM2_supporting (VCEP specifications version 1).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000796316	SCV000935823	pathogenic	Immunodeficiency 104	2022-11-22	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 642787). This variant has not been reported in the literature in individuals affected with IL7R-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys119*) in the IL7R gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IL7R are known to be pathogenic (PMID: 21664875, 26123418).