Submissions for variant NM_002185.5(IL7R):c.1043A>C (p.Asn348Thr)

dbSNP: rs41270321

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	RCV000532907	SCV004810392	benign	Immunodeficiency 104	2024-04-03	reviewed by expert panel	curation	The c.1043A>C (NM_002185.5) variant in IL7R is a missense variant predicted to cause substitution of Asparagine by Threonine at amino acid 348 (p.Asn348Thr). The filtering allele frequency (the lower threshold of the 95% CI of 20801/1179968 alleles) of the c.1043A>C variant in IL7R is 0.01743 for European (non-Finnish) chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00566) for BA1, and therefore meets this criterion (BA1). Additionally, 215 adult homozygous occurrences are described in gnomAD (BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000532907	SCV000638914	benign	Immunodeficiency 104	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000532907	SCV001315715	benign	Immunodeficiency 104	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV001572755	SCV001836427	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001572755	SCV005299865	benign	not provided		criteria provided, single submitter	not provided
ITMI	RCV000121221	SCV000085392	not provided	not specified	2013-09-19	no assertion provided	reference population
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572755	SCV001797617	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000121221	SCV001929505	benign	not specified		no assertion criteria provided	clinical testing