2-102225961-T-C

Variant summary

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

The NM_003854.4(IL1RL2):c.1055T>C(p.Val352Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,412 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. V352I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

IL1RL2
NM_003854.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.865

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:

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=0.051760077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL2	NM_003854.4 linkuse as main transcript	c.1055T>C	p.Val352Ala	missense_variant	9/12	ENST00000264257.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL2	ENST00000264257.7 linkuse as main transcript	c.1055T>C	p.Val352Ala	missense_variant	9/12	1	NM_003854.4	P1	Q9HB29-1
IL1RL2	ENST00000441515.3 linkuse as main transcript	c.701T>C	p.Val234Ala	missense_variant	7/10	1			Q9HB29-2
IL1RL2	ENST00000481806.1 linkuse as main transcript	n.717T>C		non_coding_transcript_exon_variant	7/10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249720

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135110

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1459412

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000110

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

Dec 18, 2023

The c.1055T>C (p.V352A) alteration is located in exon 9 (coding exon 8) of the IL1RL2 gene. This alteration results from a T to C substitution at nucleotide position 1055, causing the valine (V) at amino acid position 352 to be replaced by an alanine (A). 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

0.087

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.71

Cadd

Benign

3.1

Dann

Benign

0.60

DEOGEN2

Benign

0.065

T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.15

N;N

REVEL

Benign

0.016

Sift

Benign

0.47

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.0010

B;.

Vest4

0.065

MutPred

0.38

Gain of sheet (P = 0.0477);.;

MVP

0.048

MPC

0.18

ClinPred

0.042

GERP RS

3.4

Varity_R

0.046

gMVP

0.31

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