rs2228149

Positions:

chr10-6021545-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000417.3(IL2RA):c.516C>T(p.His172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 1,613,992 control chromosomes in the GnomAD database, including 2,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 354 hom., cov: 31)

Exomes 𝑓: 0.043 ( 2550 hom. )

Consequence

IL2RA
NM_000417.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.651

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 10-6021545-G-A is Benign according to our data. Variant chr10-6021545-G-A is described in ClinVar as [Benign]. Clinvar id is 300256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.651 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL2RA	NM_000417.3 linkuse as main transcript	c.516C>T	p.His172=	synonymous_variant	4/8	ENST00000379959.8
IL2RA	NM_001308242.2 linkuse as main transcript	c.368-1604C>T		intron_variant
IL2RA	NM_001308243.2 linkuse as main transcript	c.368-2046C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RA	ENST00000379959.8 linkuse as main transcript	c.516C>T	p.His172=	synonymous_variant	4/8	1	NM_000417.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0548

AC:

8324

AN:

152030

Hom.:

348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.0507

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0795

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0366

Gnomad OTH

AF:

0.0617

GnomAD3 exomes

AF:

0.0697

AC:

17528

AN:

251486

Hom.:

1397

AF XY:

0.0615

AC XY:

8363

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.0353

Gnomad EAS exome

AF:

0.0507

Gnomad SAS exome

AF:

0.0174

Gnomad FIN exome

AF:

0.0792

Gnomad NFE exome

AF:

0.0370

Gnomad OTH exome

AF:

0.0671

GnomAD4 exome

AF:

0.0434

AC:

63379

AN:

1461844

Hom.:

2550

Cov.:

AF XY:

0.0420

AC XY:

30550

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0483

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.0358

Gnomad4 EAS exome

AF:

0.0647

Gnomad4 SAS exome

AF:

0.0172

Gnomad4 FIN exome

AF:

0.0743

Gnomad4 NFE exome

AF:

0.0351

Gnomad4 OTH exome

AF:

0.0454

GnomAD4 genome

AF:

0.0548

AC:

8334

AN:

152148

Hom.:

354

Cov.:

AF XY:

0.0575

AC XY:

4274

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0498

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.0351

Gnomad4 EAS

AF:

0.0510

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0795

Gnomad4 NFE

AF:

0.0366

Gnomad4 OTH

AF:

0.0605

Alfa

AF:

0.0435

Hom.:

386

Bravo

AF:

0.0658

Asia WGS

AF:

0.0340

AC:

118

AN:

3478

EpiCase

AF:

0.0399

EpiControl

AF:

0.0425

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency due to CD25 deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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: 33. Only high quality variants are reported. -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.49

DANN

Benign

0.57

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