rs201105599
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000417.3(IL2RA):c.297A>T(p.Glu99Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL2RA | NM_000417.3 | c.297A>T | p.Glu99Asp | missense_variant | 3/8 | ENST00000379959.8 | |
IL2RA | NM_001308242.2 | c.297A>T | p.Glu99Asp | missense_variant | 3/7 | ||
IL2RA | NM_001308243.2 | c.297A>T | p.Glu99Asp | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL2RA | ENST00000379959.8 | c.297A>T | p.Glu99Asp | missense_variant | 3/8 | 1 | NM_000417.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251480Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135918
GnomAD4 exome AF: 0.0000780 AC: 114AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.0000756 AC XY: 55AN XY: 727226
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74358
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2022 | The c.297A>T (p.E99D) alteration is located in exon 3 (coding exon 3) of the IL2RA gene. This alteration results from a A to T substitution at nucleotide position 297, causing the glutamic acid (E) at amino acid position 99 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Immunodeficiency due to CD25 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 99 of the IL2RA protein (p.Glu99Asp). This variant is present in population databases (rs201105599, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with IL2RA-related conditions. ClinVar contains an entry for this variant (Variation ID: 577868). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt IL2RA protein function with a negative predictive value of 80%. 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