Genetic Variant IL1RL2:p.Pro158Gln (chr2-102192104-C-A) – 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_003854.4(IL1RL2):c.473C>A(p.Pro158Gln) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL1RL2
NM_003854.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.606

Publications

0 publications found

Variant links:

Genes affected

IL1RL2 (HGNC:5999): (interleukin 1 receptor like 2) The protein encoded by this gene is a member of the interleukin 1 receptor family. An experiment with transient gene expression demonstrated that this receptor was incapable of binding to interleukin 1 alpha and interleukin 1 beta with high affinity. This gene and four other interleukin 1 receptor family genes, including interleukin 1 receptor, type I (IL1R1), interleukin 1 receptor, type II (IL1R2), interleukin 1 receptor-like 1 (IL1RL1), and interleukin 18 receptor 1 (IL18R1), form a cytokine receptor gene cluster in a region mapped to chromosome 2q12. [provided by RefSeq, Jul 2008]

IL1RL2 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=0.090239555).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003854.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL1RL2	NM_003854.4	MANE Select	c.473C>A	p.Pro158Gln	missense	Exon 4 of 12	NP_003845.2
IL1RL2	NM_001351446.2		c.473C>A	p.Pro158Gln	missense	Exon 4 of 12	NP_001338375.1	Q9HB29-1
IL1RL2	NM_001351447.1		c.138+4179C>A		intron	N/A	NP_001338376.1	Q9HB29-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL1RL2	ENST00000264257.7	TSL:1 MANE Select	c.473C>A	p.Pro158Gln	missense	Exon 4 of 12	ENSP00000264257.2	Q9HB29-1
IL1RL2	ENST00000441515.3	TSL:1	c.138+4179C>A		intron	N/A	ENSP00000413348.2	Q9HB29-2
IL1RL2	ENST00000908896.1		c.680C>A	p.Pro227Gln	missense	Exon 4 of 12	ENSP00000578955.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1434742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713138

African (AFR)

AF:

0.00

AC:

AN:

31616

American (AMR)

AF:

0.00

AC:

AN:

37196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25252

East Asian (EAS)

AF:

0.00

AC:

AN:

38552

South Asian (SAS)

AF:

0.00

AC:

AN:

80886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103066

Other (OTH)

AF:

0.00

AC:

AN:

59330

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.040

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.69

M_CAP

Benign

0.0046

MetaRNN

Benign

0.090

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.64

PhyloP100

0.61

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.14

REVEL

Benign

0.037

Sift

Benign

0.18

Sift4G

Benign

0.59

Polyphen

0.0010

Vest4

0.27

MutPred

0.49

Gain of sheet (P = 0.0827)

MVP

0.19

MPC

0.15

ClinPred

0.17

GERP RS

1.3

Varity_R

0.090

gMVP

0.24

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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