chr10-6024232-T-A

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.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

Publications

18 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:

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=-0.79).

BP6

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

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 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	Effect	Exon Rank	Protein	UniProt
IL2RA	NM_000417.3	MANE Select	c.367+12A>T	intron	N/A	NP_000408.1	P01589
IL2RA	NM_001308242.2		c.367+12A>T	intron	N/A	NP_001295171.1	Q5W005
IL2RA	NM_001308243.2		c.367+12A>T	intron	N/A	NP_001295172.1	H0Y5Z0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL2RA	ENST00000379959.8	TSL:1 MANE Select	c.367+12A>T	intron	N/A	ENSP00000369293.3	P01589
IL2RA	ENST00000379954.5	TSL:1	c.367+12A>T	intron	N/A	ENSP00000369287.1	Q5W005
IL2RA	ENST00000447847.2	TSL:1	c.367+12A>T	intron	N/A	ENSP00000402024.2	H0Y5Z0

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

GnomAD2 exomes

AF:

0.375

AC:

94088

AN:

250952

AF XY:

0.368

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 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

African (AFR)

AF:

0.131

AC:

4274

AN:

32548

American (AMR)

AF:

0.584

AC:

26089

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

10469

AN:

25828

East Asian (EAS)

AF:

0.431

AC:

16990

AN:

39442

South Asian (SAS)

AF:

0.283

AC:

24182

AN:

85328

European-Finnish (FIN)

AF:

0.325

AC:

17365

AN:

53386

Middle Eastern (MID)

AF:

0.362

AC:

2057

AN:

5678

European-Non Finnish (NFE)

AF:

0.367

AC:

392406

AN:

1069562

Other (OTH)

AF:

0.347

AC:

20423

AN:

58788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

16021

32043

48064

64086

80107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12206

24412

36618

48824

61030

<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:

47831

AN:

152146

Hom.:

8576

Cov.:

AF XY:

0.316

AC XY:

23527

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.148

AC:

6153

AN:

41534

American (AMR)

AF:

0.459

AC:

7018

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

1415

AN:

3468

East Asian (EAS)

AF:

0.397

AC:

2054

AN:

5168

South Asian (SAS)

AF:

0.293

AC:

1412

AN:

4824

European-Finnish (FIN)

AF:

0.332

AC:

3519

AN:

10586

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.369

AC:

25061

AN:

67974

Other (OTH)

AF:

0.354

AC:

747

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1600

3200

4799

6399

7999

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:

0.350

Hom.:

1946

Bravo

AF:

0.324

Asia WGS

AF:

0.298

AC:

1038

AN:

3478

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 provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.053

(source)

DANN

Benign

0.78

PhyloP100

-1.0

Mutation Taster

=99/1

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