Variant rs2025345 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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	MANE
IL2RA	NM_000417.3 linkuse as main transcript	c.256+109T>C	intron_variant	ENST00000379959.8
IL2RA	NM_001308242.2 linkuse as main transcript	c.256+109T>C	intron_variant
IL2RA	NM_001308243.2 linkuse as main transcript	c.256+109T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RA	ENST00000379959.8 linkuse as main transcript	c.256+109T>C		intron_variant		1	NM_000417.3	P1

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

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.579

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.324

Gnomad4 NFE exome

AF:

0.371

Gnomad4 OTH exome

AF:

0.351

GnomAD4 genome

AF:

0.314

AC:

47691

AN:

151938

Hom.:

8522

Cov.:

AF XY:

0.316

AC XY:

23456

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.456

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.395

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.368

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.371

Hom.:

15638

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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

DANN

Benign

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over