rs12244380
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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.*1461T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,174 control chromosomes in the GnomAD database, including 13,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.41 ( 13186 hom., cov: 32)
Exomes 𝑓: 0.42 ( 9 hom. )
Consequence
IL2RA
NM_000417.3 3_prime_UTR
NM_000417.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.638
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=-0.9).
BP6
?
Variant 10-6011411-A-G is Benign according to our data. Variant chr10-6011411-A-G is described in ClinVar as [Benign]. Clinvar id is 300224.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL2RA | NM_000417.3 | c.*1461T>C | 3_prime_UTR_variant | 8/8 | ENST00000379959.8 | ||
IL2RA | NM_001308242.2 | c.*1461T>C | 3_prime_UTR_variant | 7/7 | |||
IL2RA | NM_001308243.2 | c.*1461T>C | 3_prime_UTR_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL2RA | ENST00000379959.8 | c.*1461T>C | 3_prime_UTR_variant | 8/8 | 1 | NM_000417.3 | P1 | ||
IL2RA | ENST00000649218.1 | n.2095T>C | non_coding_transcript_exon_variant | 4/4 |
Frequencies
GnomAD3 genomes ? AF: 0.408 AC: 61953AN: 151946Hom.: 13179 Cov.: 32
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GnomAD4 exome AF: 0.418 AC: 46AN: 110Hom.: 9 Cov.: 0 AF XY: 0.424 AC XY: 28AN XY: 66
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GnomAD4 genome ? AF: 0.408 AC: 61997AN: 152064Hom.: 13186 Cov.: 32 AF XY: 0.409 AC XY: 30412AN XY: 74338
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Immunodeficiency due to CD25 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
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