rs12358961

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000417.3(IL2RA):c.367+12A>T 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 1,567,342 control chromosomes in the GnomAD database, including 105,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8576 hom., cov: 32)

Exomes 𝑓: 0.36 ( 96861 hom. )

Consequence

IL2RA
NM_000417.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.04

Variant links:

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]

IL2RA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-6024232-T-A is Benign according to our data. Variant chr10-6024232-T-A is described in ClinVar as [Benign]. Clinvar id is 300258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-6024232-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
IL2RA	NM_000417.3 linkuse as main transcript	c.367+12A>T	intron_variant	ENST00000379959.8	NP_000408.1
IL2RA	NM_001308242.2 linkuse as main transcript	c.367+12A>T	intron_variant		NP_001295171.1
IL2RA	NM_001308243.2 linkuse as main transcript	c.367+12A>T	intron_variant		NP_001295172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8 linkuse as main transcript	c.367+12A>T		intron_variant		1	NM_000417.3	ENSP00000369293	P1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47798

AN:

152028

Hom.:

8561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.356

GnomAD3 exomes

AF:

0.375

AC:

94088

AN:

250952

Hom.:

19245

AF XY:

0.368

AC XY:

49971

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.407

Gnomad EAS exome

AF:

0.385

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.331

Gnomad NFE exome

AF:

0.369

Gnomad OTH exome

AF:

0.375

GnomAD4 exome

AF:

0.363

AC:

514255

AN:

1415196

Hom.:

96861

Cov.:

AF XY:

0.362

AC XY:

255922

AN XY:

707140

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.584

Gnomad4 ASJ exome

AF:

0.405

Gnomad4 EAS exome

AF:

0.431

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.325

Gnomad4 NFE exome

AF:

0.367

Gnomad4 OTH exome

AF:

0.347

GnomAD4 genome

AF:

0.314

AC:

47831

AN:

152146

Hom.:

8576

Cov.:

AF XY:

0.316

AC XY:

23527

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.408

Gnomad4 EAS

AF:

0.397

Gnomad4 SAS

AF:

0.293

Gnomad4 FIN

AF:

0.332

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.350

Hom.:

1946

Bravo

AF:

0.324

Asia WGS

AF:

0.298

AC:

1038

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency due to CD25 deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 79% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.053

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over