Submissions for variant NM_000417.3(IL2RA):c.272C>T (p.Thr91Met)

gnomAD frequency: 0.00183  dbSNP: rs72650666

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000498899	SCV000590656	uncertain significance	not provided	2017-06-21	criteria provided, single submitter	clinical testing	The T91M variant in the IL2RA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T91M variant is observed in 53/6,604 (0.8%) alleles from individuals of Finnish background and 147/66,618 (0.2%) alleles from individuals of European (non-Finnish) background in the ExAC dataset (Lek et al., 2016). The T91M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret T91M as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083317	SCV000641195	benign	Immunodeficiency due to CD25 deficiency	2025-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001083317	SCV001263551	likely benign	Immunodeficiency due to CD25 deficiency	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000498899	SCV001745994	uncertain significance	not provided	2021-06-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925437	SCV004738373	likely benign	IL2RA-related disorder	2022-11-21	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).