chr2-102019704-G-A

Position:

chr2-102019704-G-A

Variant summary

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

The NM_004633.4(IL1R2):c.580G>A(p.Val194Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,613,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

IL1R2
NM_004633.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.282

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:

IL1R2 (HGNC:):

IL1R2 links:

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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=0.02758953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1R2	NM_004633.4 linkuse as main transcript	c.580G>A	p.Val194Ile	missense_variant	5/9	ENST00000332549.8	NP_004624.1	P27930-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL1R2	ENST00000332549.8 linkuse as main transcript	c.580G>A	p.Val194Ile	missense_variant	5/9	1	NM_004633.4	ENSP00000330959.3	P27930-1
IL1R2	ENST00000393414.6 linkuse as main transcript	c.580G>A	p.Val194Ile	missense_variant	5/9	1		ENSP00000377066.2	P27930-1
IL1R2	ENST00000441002.1 linkuse as main transcript	c.580G>A	p.Val194Ile	missense_variant	4/6	1		ENSP00000414611.1	P27930-2
IL1R2	ENST00000457817.5 linkuse as main transcript	c.580G>A	p.Val194Ile	missense_variant	5/5	2		ENSP00000408415.1	C9JNR0

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251276

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000114

AC:

167

AN:

1461508

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.43

DANN

Benign

0.12

DEOGEN2

Benign

0.12

T;T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.45

.;T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.028

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.63

N;N;.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.48

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0040

B;B;.;.

Vest4

0.071

MVP

0.21

MPC

0.077

ClinPred

0.010

GERP RS

-0.77

Varity_R

0.054

gMVP

0.38

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