rs2025345
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000417.3(IL2RA):c.256+109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,028,996 control chromosomes in the GnomAD database, including 70,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.31 ( 8522 hom., cov: 32)
Exomes 𝑓: 0.37 ( 61518 hom. )
Consequence
IL2RA
NM_000417.3 intron
NM_000417.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.189
Genes affected
IL2RA (HGNC:6008): (interleukin 2 receptor subunit alpha) The interleukin 2 (IL2) receptor alpha (IL2RA) and beta (IL2RB) chains, together with the common gamma chain (IL2RG), constitute the high-affinity IL2 receptor. Homodimeric alpha chains (IL2RA) result in low-affinity receptor, while homodimeric beta (IL2RB) chains produce a medium-affinity receptor. Normally an integral-membrane protein, soluble IL2RA has been isolated and determined to result from extracellular proteolyisis. Alternately-spliced IL2RA mRNAs have been isolated, but the significance of each is presently unknown. Mutations in this gene are associated with interleukin 2 receptor alpha deficiency. Patients with severe Coronavirus Disease 2019 (COVID-19), the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have significantly elevated levels of IL2R in their plasma. Similarly, serum IL-2R levels are found to be elevated in patients with different types of carcinomas. Certain IL2RA and IL2RB gene polymorphisms have been associated with lung cancer risk. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 10-6025725-A-G is Benign according to our data. Variant chr10-6025725-A-G is described in ClinVar as [Benign]. Clinvar id is 2688212.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL2RA | NM_000417.3 | c.256+109T>C | intron_variant | ENST00000379959.8 | |||
IL2RA | NM_001308242.2 | c.256+109T>C | intron_variant | ||||
IL2RA | NM_001308243.2 | c.256+109T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL2RA | ENST00000379959.8 | c.256+109T>C | intron_variant | 1 | NM_000417.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.314 AC: 47656AN: 151824Hom.: 8506 Cov.: 32
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GnomAD4 exome AF: 0.367 AC: 322098AN: 877058Hom.: 61518 AF XY: 0.364 AC XY: 166469AN XY: 457254
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GnomAD4 genome ? AF: 0.314 AC: 47691AN: 151938Hom.: 8522 Cov.: 32 AF XY: 0.316 AC XY: 23456AN XY: 74234
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at