Genetic Variant IL2RA:c.65-9808A>G (chr10-6035833-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000417.3(IL2RA):c.65-9808A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,212 control chromosomes in the GnomAD database, including 39,546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.71 ( 39534 hom., cov: 32)

Exomes 𝑓: 0.64 ( 12 hom. )

Consequence

IL2RA
NM_000417.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

20 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:

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL2RA	NM_000417.3 link	c.65-9808A>G	intron_variant	Intron 1 of 7	ENST00000379959.8	NP_000408.1	P01589
IL2RA-AS1	XR_001747349.2 link	n.424T>C	non_coding_transcript_exon_variant	Exon 1 of 2
IL2RA	NM_001308242.2 link	c.65-9808A>G	intron_variant	Intron 1 of 6		NP_001295171.1	P01589Q5W005
IL2RA	NM_001308243.2 link	c.65-9808A>G	intron_variant	Intron 1 of 5		NP_001295172.1	P01589H0Y5Z0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8 link	c.65-9808A>G		intron_variant	Intron 1 of 7	1	NM_000417.3	ENSP00000369293.3		P01589

Frequencies

GnomAD3 genomes

AF:

0.714

AC:

108593

AN:

152036

Hom.:

39487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.828

Gnomad AMI

AF:

0.703

Gnomad AMR

AF:

0.609

Gnomad ASJ

AF:

0.632

Gnomad EAS

AF:

0.927

Gnomad SAS

AF:

0.810

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.669

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.677

GnomAD4 exome

AF:

0.643

AC:

AN:

Hom.:

AF XY:

0.682

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.650

AC:

AN:

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.714

AC:

108697

AN:

152156

Hom.:

39534

Cov.:

AF XY:

0.715

AC XY:

53197

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.828

AC:

34361

AN:

41510

American (AMR)

AF:

0.609

AC:

9300

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.632

AC:

2192

AN:

3466

East Asian (EAS)

AF:

0.927

AC:

4802

AN:

5182

South Asian (SAS)

AF:

0.811

AC:

3910

AN:

4824

European-Finnish (FIN)

AF:

0.658

AC:

6957

AN:

10576

Middle Eastern (MID)

AF:

0.663

AC:

195

AN:

294

European-Non Finnish (NFE)

AF:

0.660

AC:

44898

AN:

67996

Other (OTH)

AF:

0.682

AC:

1441

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1547

3094

4641

6188

7735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.675

Hom.:

109939

Bravo

AF:

0.708

Asia WGS

AF:

0.854

AC:

2971

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.52

(source)

DANN

Benign

0.19

PhyloP100

-1.0

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

Computational scores

Splicing

Publications

Other links and lift over