Submissions for variant NM_002185.5(IL7R):c.41T>C (p.Leu14Ser)

dbSNP: rs1759661333

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	RCV002244108	SCV004810401	uncertain significance	Immunodeficiency 104	2024-04-01	reviewed by expert panel	curation	NM_002185.5(IL7R):c.41T>C is a missense variant predicted to cause substitution of Leucine by Serine at amino acid 14 (p.Leu14Ser). The highest population minor allele frequency in gnomAD v4 is 0.00001160 (1/86214 alleles) in South Asian population, which is lower than the ClinGen SCID VCEP threshold (<0.00004129) for PM2_Supporting, meeting this criterion (PM2_Supporting). Patient P1 was found homozygous for this mutation (0.5 pt.) (PM3_supporting) (PMID: 33599911).Patient with SCID (0.5 pt.) and exome sequencing conducted (0.5 pt.) (total :1 pt.) (PP4) (PMID: 33599911). 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, PM3_supporting, PP4(VCEP specifications version 1).
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002244108	SCV002512389	likely pathogenic	Immunodeficiency 104	2021-12-01	criteria provided, single submitter	clinical testing	ACMG classification criteria: PS4 supporting, PM2 moderate, PM3 moderate, PP4 supporting