10-6025725-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000417.3(IL2RA):c.256+109T>C 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 1,028,996 control chromosomes in the GnomAD database, including 70,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 8522 hom., cov: 32)

Exomes 𝑓: 0.37 ( 61518 hom. )

Consequence

IL2RA
NM_000417.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.189

Publications

27 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 10-6025725-A-G is Benign according to our data. Variant chr10-6025725-A-G is described in ClinVar as Benign. ClinVar VariationId is 2688212.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL2RA	NM_000417.3 link	c.256+109T>C	intron_variant	Intron 2 of 7	ENST00000379959.8	NP_000408.1	P01589
IL2RA	NM_001308242.2 link	c.256+109T>C	intron_variant	Intron 2 of 6		NP_001295171.1	P01589Q5W005
IL2RA	NM_001308243.2 link	c.256+109T>C	intron_variant	Intron 2 of 5		NP_001295172.1	P01589H0Y5Z0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8 link	c.256+109T>C		intron_variant	Intron 2 of 7	1	NM_000417.3	ENSP00000369293.3		P01589

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47656

AN:

151824

Hom.:

8506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.352

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.357

GnomAD4 exome

AF:

0.367

AC:

322098

AN:

877058

Hom.:

61518

AF XY:

0.364

AC XY:

166469

AN XY:

457254

show subpopulations

African (AFR)

AF:

0.138

AC:

3012

AN:

21860

American (AMR)

AF:

0.579

AC:

22894

AN:

39530

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

8973

AN:

22246

East Asian (EAS)

AF:

0.435

AC:

15724

AN:

36176

South Asian (SAS)

AF:

0.284

AC:

20438

AN:

71912

European-Finnish (FIN)

AF:

0.324

AC:

16008

AN:

49386

Middle Eastern (MID)

AF:

0.367

AC:

1225

AN:

3338

European-Non Finnish (NFE)

AF:

0.371

AC:

219394

AN:

591502

Other (OTH)

AF:

0.351

AC:

14430

AN:

41108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

10492

20984

31476

41968

52460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4890

9780

14670

19560

24450

<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:

0.314

AC:

47691

AN:

151938

Hom.:

8522

Cov.:

AF XY:

0.316

AC XY:

23456

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.148

AC:

6143

AN:

41422

American (AMR)

AF:

0.456

AC:

6960

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1417

AN:

3466

East Asian (EAS)

AF:

0.395

AC:

2044

AN:

5176

South Asian (SAS)

AF:

0.292

AC:

1407

AN:

4818

European-Finnish (FIN)

AF:

0.334

AC:

3510

AN:

10500

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.368

AC:

25032

AN:

67978

Other (OTH)

AF:

0.355

AC:

747

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1607

3214

4821

6428

8035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.366

Hom.:

21270

Bravo

AF:

0.322

Asia WGS

AF:

0.297

AC:

1033

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

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: 32. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.8

(source)

DANN

Benign

0.72

PhyloP100

0.19

PromoterAI

0.016

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

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