rs2228149

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000417.3(IL2RA):c.516C>T(p.His172His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 1,613,992 control chromosomes in the GnomAD database, including 2,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 354 hom., cov: 31)

Exomes 𝑓: 0.043 ( 2550 hom. )

Consequence

IL2RA
NM_000417.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.651

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency due to CD25 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
neonatal diabetes mellitus
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
neonatal diabetes mellitus with congenital hypothyroidism
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
type 1 diabetes mellitus 10
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

IL2RA links:

LOC124902368 (HGNC:):

LOC124902368 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 10-6021545-G-A is Benign according to our data. Variant chr10-6021545-G-A is described in ClinVar as Benign. ClinVar VariationId is 300256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.651 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
IL2RA	NM_000417.3 link	c.516C>T	p.His172His	synonymous_variant	Exon 4 of 8	ENST00000379959.8	NP_000408.1
IL2RA	NM_001308242.2 link	c.368-1604C>T		intron_variant	Intron 3 of 6		NP_001295171.1
IL2RA	NM_001308243.2 link	c.368-2046C>T		intron_variant	Intron 3 of 5		NP_001295172.1
LOC124902368	XR_007062042.1 link	n.*51G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8 link	c.516C>T	p.His172His	synonymous_variant	Exon 4 of 8	1	NM_000417.3	ENSP00000369293.3

Frequencies

GnomAD3 genomes

AF:

0.0548

AC:

8324

AN:

152030

Hom.:

348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.0507

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0795

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0366

Gnomad OTH

AF:

0.0617

GnomAD2 exomes

AF:

0.0697

AC:

17528

AN:

251486

AF XY:

0.0615

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.0353

Gnomad EAS exome

AF:

0.0507

Gnomad FIN exome

AF:

0.0792

Gnomad NFE exome

AF:

0.0370

Gnomad OTH exome

AF:

0.0671

GnomAD4 exome

AF:

0.0434

AC:

63379

AN:

1461844

Hom.:

2550

Cov.:

AF XY:

0.0420

AC XY:

30550

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0483

AC:

1618

AN:

33480

American (AMR)

AF:

0.237

AC:

10612

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0358

AC:

936

AN:

26134

East Asian (EAS)

AF:

0.0647

AC:

2567

AN:

39694

South Asian (SAS)

AF:

0.0172

AC:

1480

AN:

86258

European-Finnish (FIN)

AF:

0.0743

AC:

3967

AN:

53418

Middle Eastern (MID)

AF:

0.0688

AC:

397

AN:

5768

European-Non Finnish (NFE)

AF:

0.0351

AC:

39058

AN:

1111974

Other (OTH)

AF:

0.0454

AC:

2744

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3463

6926

10388

13851

17314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1588

3176

4764

6352

7940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0548

AC:

8334

AN:

152148

Hom.:

354

Cov.:

AF XY:

0.0575

AC XY:

4274

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0498

AC:

2068

AN:

41512

American (AMR)

AF:

0.150

AC:

2299

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0351

AC:

122

AN:

3472

East Asian (EAS)

AF:

0.0510

AC:

264

AN:

5172

South Asian (SAS)

AF:

0.0168

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0795

AC:

841

AN:

10580

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0366

AC:

2491

AN:

68000

Other (OTH)

AF:

0.0605

AC:

128

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

375

751

1126

1502

1877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0451

Hom.:

585

Bravo

AF:

0.0658

Asia WGS

AF:

0.0340

AC:

118

AN:

3478

EpiCase

AF:

0.0399

EpiControl

AF:

0.0425

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency due to CD25 deficiency

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 provided

Benign:1Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.49

(source)

DANN

Benign

0.57

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over