chr10-6024237-C-G

Variant names:

Variant summary

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

The NM_000417.3(IL2RA):c.367+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,585,976 control chromosomes in the GnomAD database, including 41,976 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3284 hom., cov: 33)

Exomes 𝑓: 0.23 ( 38692 hom. )

Consequence

IL2RA
NM_000417.3 splice_region, intron

Scores

Splicing: ADA: 0.00004377

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.0900

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-6024237-C-G is Benign according to our data. Variant chr10-6024237-C-G is described in ClinVar as [Benign]. Clinvar id is 300259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL2RA	NM_000417.3 link	c.367+7G>C	splice_region_variant, intron_variant	Intron 3 of 7	ENST00000379959.8	NP_000408.1	P01589
IL2RA	NM_001308242.2 link	c.367+7G>C	splice_region_variant, intron_variant	Intron 3 of 6		NP_001295171.1	P01589Q5W005
IL2RA	NM_001308243.2 link	c.367+7G>C	splice_region_variant, intron_variant	Intron 3 of 5		NP_001295172.1	P01589H0Y5Z0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RA	ENST00000379959.8 link	c.367+7G>C		splice_region_variant, intron_variant	Intron 3 of 7	1	NM_000417.3	ENSP00000369293.3		P01589

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28526

AN:

152094

Hom.:

3278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0824

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.176

GnomAD3 exomes

AF:

0.211

AC:

52998

AN:

251124

Hom.:

6155

AF XY:

0.217

AC XY:

29434

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.0806

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.249

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.227

AC:

325798

AN:

1433764

Hom.:

38692

Cov.:

AF XY:

0.228

AC XY:

163003

AN XY:

715178

show subpopulations

Gnomad4 AFR exome

AF:

0.0752

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.188

AC:

28545

AN:

152212

Hom.:

3284

Cov.:

AF XY:

0.191

AC XY:

14226

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0825

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.247

Gnomad4 SAS

AF:

0.241

Gnomad4 FIN

AF:

0.333

Gnomad4 NFE

AF:

0.233

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.186

Hom.:

1002

Bravo

AF:

0.166

Asia WGS

AF:

0.259

AC:

903

AN:

3478

EpiCase

AF:

0.219

EpiControl

AF:

0.216

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency due to CD25 deficiency

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Nov 12, 2023

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 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

not provided

Benign:1Other:1

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.2

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.0

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