Variant 2-102015954-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004633.4(IL1R2):c.416C>T(p.Pro139Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,613,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P139S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

IL1R2
NM_004633.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.72

Variant links:

Genes affected

IL1R2 (HGNC:5994): (interleukin 1 receptor type 2) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This protein binds interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA), and acts as a decoy receptor that inhibits the activity of its ligands. Interleukin 4 (IL4) is reported to antagonize the activity of interleukin 1 by inducing the expression and release of this cytokine. This gene and three other genes form a cytokine receptor gene cluster on chromosome 2q12. Alternative splicing results in multiple transcript variants and protein isoforms. Alternative splicing produces both membrane-bound and soluble proteins. A soluble protein is also produced by proteolytic cleavage. [provided by RefSeq, May 2012]

IL1R2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044814706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R2	NM_004633.4 linkuse as main transcript	c.416C>T	p.Pro139Leu	missense_variant	4/9	ENST00000332549.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R2	ENST00000332549.8 linkuse as main transcript	c.416C>T	p.Pro139Leu	missense_variant	4/9	1	NM_004633.4	P1	P27930-1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251440

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461592

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000204

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000317

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.416C>T (p.P139L) alteration is located in exon 4 (coding exon 3) of the IL1R2 gene. This alteration results from a C to T substitution at nucleotide position 416, causing the proline (P) at amino acid position 139 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.6

DANN

Benign

0.89

DEOGEN2

Benign

0.41

T;T;T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.73

.;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.045

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-4.5

D;D;D;D

REVEL

Benign

0.20

Sift

Benign

0.23

T;T;T;T

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.95

P;P;.;.

Vest4

0.17

MVP

0.52

MPC

0.12

ClinPred

0.12

GERP RS

-0.49

Varity_R

0.11

gMVP

0.54

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