rs2228150

Positions:

chr10-6026006-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000417.3(IL2RA):c.84G>A(p.Pro28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,613,062 control chromosomes in the GnomAD database, including 2,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 954 hom., cov: 33)

Exomes 𝑓: 0.034 ( 1643 hom. )

Consequence

IL2RA
NM_000417.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.67

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-6026006-C-T is Benign according to our data. Variant chr10-6026006-C-T is described in ClinVar as [Benign]. Clinvar id is 300261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IL2RA	NM_000417.3 linkuse as main transcript	c.84G>A	p.Pro28=	synonymous_variant	2/8	ENST00000379959.8	NP_000408.1
IL2RA	NM_001308242.2 linkuse as main transcript	c.84G>A	p.Pro28=	synonymous_variant	2/7		NP_001295171.1
IL2RA	NM_001308243.2 linkuse as main transcript	c.84G>A	p.Pro28=	synonymous_variant	2/6		NP_001295172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8 linkuse as main transcript	c.84G>A	p.Pro28=	synonymous_variant	2/8	1	NM_000417.3	ENSP00000369293	P1
	ENST00000440436.1 linkuse as main transcript	n.29C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0785

AC:

11935

AN:

152040

Hom.:

954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.0511

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0605

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0292

Gnomad OTH

AF:

0.0718

GnomAD3 exomes

AF:

0.0423

AC:

10638

AN:

251410

Hom.:

521

AF XY:

0.0415

AC XY:

5639

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.0286

Gnomad ASJ exome

AF:

0.0338

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.0656

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.0299

Gnomad OTH exome

AF:

0.0397

GnomAD4 exome

AF:

0.0340

AC:

49701

AN:

1460902

Hom.:

1643

Cov.:

AF XY:

0.0348

AC XY:

25270

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.0297

Gnomad4 ASJ exome

AF:

0.0337

Gnomad4 EAS exome

AF:

0.000857

Gnomad4 SAS exome

AF:

0.0676

Gnomad4 FIN exome

AF:

0.0147

Gnomad4 NFE exome

AF:

0.0279

Gnomad4 OTH exome

AF:

0.0414

GnomAD4 genome

AF:

0.0785

AC:

11938

AN:

152160

Hom.:

954

Cov.:

AF XY:

0.0771

AC XY:

5735

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.0508

Gnomad4 ASJ

AF:

0.0302

Gnomad4 EAS

AF:

0.00250

Gnomad4 SAS

AF:

0.0602

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.0292

Gnomad4 OTH

AF:

0.0710

Alfa

AF:

0.0580

Hom.:

307

Bravo

AF:

0.0859

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0304

EpiControl

AF:

0.0327

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.41

DANN

Benign

0.71

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