Submissions for variant NM_000206.3(IL2RG):c.1061A>G (p.His354Arg)

gnomAD frequency: 0.00002  dbSNP: rs771221019

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	RCV001563869	SCV004242248	likely benign	X-linked severe combined immunodeficiency	2024-01-26	reviewed by expert panel	curation	NM_000206.3(IL2RG):c.1061A>G is a missense variant predicted to cause substitution of Histidine by Arginine at amino acid 354 (p.His354Arg). The filtering allele frequency (the upper threshold of the 95% CI of 7/30447) of the c.1061A>G variant in IL2RG is 0.0001216 for East Asian chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.000124 ) for PM2_Supporting. However, 4 hemizygotes were reported (PM2 not met).The variant is observed in 4 hemizygotes in gnomAD v4 (BS2_Strong). To our knowledge, this variant has not been reported in the literature in individuals affected with IL2RG related conditions or in functional studies. In summary, this variant meets the criteria to be classified as likely benign variant for X-linked severe combined immunodeficiency due to IL2RG deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BS2 (VCEP specifications version 1).
Genome-Nilou Lab	RCV001563868	SCV001786915	uncertain significance	Combined immunodeficiency, X-linked	2021-07-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001563869	SCV001786916	uncertain significance	X-linked severe combined immunodeficiency	2021-07-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001563869	SCV002942607	likely benign	X-linked severe combined immunodeficiency	2023-08-18	criteria provided, single submitter	clinical testing