rs752423140
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000417.3(IL2RA):c.517G>A(p.Gly173Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000417.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL2RA | NM_000417.3 | c.517G>A | p.Gly173Arg | missense_variant | Exon 4 of 8 | ENST00000379959.8 | NP_000408.1 | |
IL2RA | NM_001308242.2 | c.368-1603G>A | intron_variant | Intron 3 of 6 | NP_001295171.1 | |||
IL2RA | NM_001308243.2 | c.368-2045G>A | intron_variant | Intron 3 of 5 | NP_001295172.1 | |||
LOC124902368 | XR_007062042.1 | n.*50C>T | downstream_gene_variant |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152070Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251492Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135920
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461882Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11AN XY: 727238
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152070Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74302
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.517G>A (p.G173R) alteration is located in exon 4 (coding exon 4) of the IL2RA gene. This alteration results from a G to A substitution at nucleotide position 517, causing the glycine (G) at amino acid position 173 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Immunodeficiency due to CD25 deficiency Uncertain:1
This sequence change replaces glycine with arginine at codon 173 of the IL2RA protein (p.Gly173Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs752423140, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with IL2RA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at