rs2228150

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000417.3(IL2RA):c.84G>A(p.Pro28Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,613,062 control chromosomes in the GnomAD database, including 2,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 954 hom., cov: 33)

Exomes 𝑓: 0.034 ( 1643 hom. )

Consequence

IL2RA
NM_000417.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.67

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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
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:

IL2RA-AS1 (HGNC:58167):

IL2RA-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-6026006-C-T is Benign according to our data. Variant chr10-6026006-C-T is described in ClinVar as Benign. ClinVar VariationId is 300261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000417.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL2RA	NM_000417.3	MANE Select	c.84G>A	p.Pro28Pro	synonymous	Exon 2 of 8	NP_000408.1	P01589
IL2RA	NM_001308242.2		c.84G>A	p.Pro28Pro	synonymous	Exon 2 of 7	NP_001295171.1	Q5W005
IL2RA	NM_001308243.2		c.84G>A	p.Pro28Pro	synonymous	Exon 2 of 6	NP_001295172.1	H0Y5Z0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL2RA	ENST00000379959.8	TSL:1 MANE Select	c.84G>A	p.Pro28Pro	synonymous	Exon 2 of 8	ENSP00000369293.3	P01589
IL2RA	ENST00000379954.5	TSL:1	c.84G>A	p.Pro28Pro	synonymous	Exon 2 of 7	ENSP00000369287.1	Q5W005
IL2RA	ENST00000447847.2	TSL:1	c.84G>A	p.Pro28Pro	synonymous	Exon 2 of 6	ENSP00000402024.2	H0Y5Z0

Frequencies

GnomAD3 genomes

AF:

0.0785

AC:

11935

AN:

152040

Hom.:

954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.0511

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0605

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0292

Gnomad OTH

AF:

0.0718

GnomAD2 exomes

AF:

0.0423

AC:

10638

AN:

251410

AF XY:

0.0415

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.0286

Gnomad ASJ exome

AF:

0.0338

Gnomad EAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.0299

Gnomad OTH exome

AF:

0.0397

GnomAD4 exome

AF:

0.0340

AC:

49701

AN:

1460902

Hom.:

1643

Cov.:

AF XY:

0.0348

AC XY:

25270

AN XY:

726748

show subpopulations

African (AFR)

AF:

0.210

AC:

7016

AN:

33442

American (AMR)

AF:

0.0297

AC:

1329

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

881

AN:

26136

East Asian (EAS)

AF:

0.000857

AC:

AN:

39696

South Asian (SAS)

AF:

0.0676

AC:

5826

AN:

86204

European-Finnish (FIN)

AF:

0.0147

AC:

785

AN:

53414

Middle Eastern (MID)

AF:

0.0541

AC:

272

AN:

5028

European-Non Finnish (NFE)

AF:

0.0279

AC:

31064

AN:

1111956

Other (OTH)

AF:

0.0414

AC:

2494

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

2527

5053

7580

10106

12633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1234

2468

3702

4936

6170

<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:

0.0785

AC:

11938

AN:

152160

Hom.:

954

Cov.:

AF XY:

0.0771

AC XY:

5735

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.203

AC:

8404

AN:

41476

American (AMR)

AF:

0.0508

AC:

776

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0302

AC:

105

AN:

3472

East Asian (EAS)

AF:

0.00250

AC:

AN:

5190

South Asian (SAS)

AF:

0.0602

AC:

290

AN:

4820

European-Finnish (FIN)

AF:

0.0111

AC:

118

AN:

10604

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0292

AC:

1987

AN:

68004

Other (OTH)

AF:

0.0710

AC:

150

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

516

1032

1547

2063

2579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0591

Hom.:

319

Bravo

AF:

0.0859

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0304

EpiControl

AF:

0.0327

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency due to CD25 deficiency (2)

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.41

(source)

DANN

Benign

0.71

PhyloP100

-2.7

PromoterAI

-0.0093

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over