Genetic Variant IL2RB:p.Glu507Lys (chr22-37128233-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000878.5(IL2RB):c.1519G>A(p.Glu507Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL2RB
NM_000878.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.155

Publications

0 publications found

Variant links:

Genes affected

IL2RB (HGNC:6009): (interleukin 2 receptor subunit beta) The interleukin 2 receptor, which is involved in T cell-mediated immune responses, is present in 3 forms with respect to ability to bind interleukin 2. The low affinity form is a monomer of the alpha subunit and is not involved in signal transduction. The intermediate affinity form consists of an alpha/beta subunit heterodimer, while the high affinity form consists of an alpha/beta/gamma subunit heterotrimer. Both the intermediate and high affinity forms of the receptor are involved in receptor-mediated endocytosis and transduction of mitogenic signals from interleukin 2. The protein encoded by this gene represents the beta subunit and is a type I membrane protein. The use of alternative promoters results in multiple transcript variants encoding the same protein. The protein is primarily expressed in the hematopoietic system. The use by some variants of an alternate promoter in an upstream long terminal repeat (LTR) results in placenta-specific expression. [provided by RefSeq, Sep 2016]

IL2RB Gene-Disease associations (from GenCC):

immunodeficiency 63 with lymphoproliferation and autoimmunity
Inheritance: AR Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

IL2RB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1538598).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000878.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL2RB	NM_000878.5	MANE Select	c.1519G>A	p.Glu507Lys	missense	Exon 10 of 10	NP_000869.1	P14784
IL2RB	NM_001346222.1		c.1519G>A	p.Glu507Lys	missense	Exon 10 of 10	NP_001333151.1	P14784
IL2RB	NM_001346223.2		c.1519G>A	p.Glu507Lys	missense	Exon 10 of 10	NP_001333152.1	P14784

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL2RB	ENST00000216223.10	TSL:1 MANE Select	c.1519G>A	p.Glu507Lys	missense	Exon 10 of 10	ENSP00000216223.5	P14784
IL2RB	ENST00000698894.2		c.1537G>A	p.Glu513Lys	missense	Exon 10 of 10	ENSP00000514013.1	A0A8V8TMD3
IL2RB	ENST00000429622.6	TSL:4	c.1519G>A	p.Glu507Lys	missense	Exon 10 of 10	ENSP00000402685.2	P14784

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1355776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

663682

African (AFR)

AF:

0.00

AC:

AN:

29760

American (AMR)

AF:

0.00

AC:

AN:

27366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19770

East Asian (EAS)

AF:

0.00

AC:

AN:

37440

South Asian (SAS)

AF:

0.00

AC:

AN:

69096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49696

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1061782

Other (OTH)

AF:

0.00

AC:

AN:

55586

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.64

M_CAP

Benign

0.0093

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

PhyloP100

0.15

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.2

REVEL

Benign

0.14

Sift

Uncertain

0.019

Sift4G

Benign

0.14

Polyphen

0.62

Vest4

0.16

MutPred

0.22

Gain of ubiquitination at E507 (P = 0.0039)

MVP

0.23

MPC

0.29

ClinPred

0.58

GERP RS

1.2

Varity_R

0.086

gMVP

0.15

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over