Variant chr10-6011411-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000417.3(IL2RA):c.*1461T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,174 control chromosomes in the GnomAD database, including 13,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13186 hom., cov: 32)

Exomes 𝑓: 0.42 ( 9 hom. )

Consequence

IL2RA
NM_000417.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.638

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-6011411-A-G is Benign according to our data. Variant chr10-6011411-A-G is described in ClinVar as [Benign]. Clinvar id is 300224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
IL2RA	NM_000417.3 linkuse as main transcript	c.*1461T>C	3_prime_UTR_variant	8/8	ENST00000379959.8
IL2RA	NM_001308242.2 linkuse as main transcript	c.*1461T>C	3_prime_UTR_variant	7/7
IL2RA	NM_001308243.2 linkuse as main transcript	c.*1461T>C	3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL2RA	ENST00000379959.8 linkuse as main transcript	c.*1461T>C		3_prime_UTR_variant	8/8	1	NM_000417.3	P1
IL2RA	ENST00000649218.1 linkuse as main transcript	n.2095T>C		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61953

AN:

151946

Hom.:

13179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.427

GnomAD4 exome

AF:

0.418

AC:

AN:

110

Hom.:

Cov.:

AF XY:

0.424

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

0.420

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.400

GnomAD4 genome

AF:

0.408

AC:

61997

AN:

152064

Hom.:

13186

Cov.:

AF XY:

0.409

AC XY:

30412

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.363

Gnomad4 AMR

AF:

0.438

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.455

Gnomad4 FIN

AF:

0.465

Gnomad4 NFE

AF:

0.436

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.433

Hom.:

20978

Bravo

AF:

0.402

Asia WGS

AF:

0.307

AC:

1072

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency due to CD25 deficiency

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

DANN

Benign

0.22

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