rs2302612

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003854.4(IL1RL2):ā€‹c.1649T>Cā€‹(p.Leu550Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,652 control chromosomes in the GnomAD database, including 45,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.30 ( 8301 hom., cov: 33)
Exomes š‘“: 0.21 ( 36802 hom. )

Consequence

IL1RL2
NM_003854.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0410
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=4.3625725E-5).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL1RL2NM_003854.4 linkuse as main transcriptc.1649T>C p.Leu550Pro missense_variant 11/12 ENST00000264257.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1RL2ENST00000264257.7 linkuse as main transcriptc.1649T>C p.Leu550Pro missense_variant 11/121 NM_003854.4 P1Q9HB29-1
IL1RL2ENST00000441515.3 linkuse as main transcriptc.1295T>C p.Leu432Pro missense_variant 9/101 Q9HB29-2
IL1RL2ENST00000481806.1 linkuse as main transcriptn.1311T>C non_coding_transcript_exon_variant 9/105

Frequencies

GnomAD3 genomes
AF:
0.296
AC:
45020
AN:
152014
Hom.:
8267
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.497
Gnomad AMI
AF:
0.315
Gnomad AMR
AF:
0.397
Gnomad ASJ
AF:
0.171
Gnomad EAS
AF:
0.290
Gnomad SAS
AF:
0.109
Gnomad FIN
AF:
0.145
Gnomad MID
AF:
0.256
Gnomad NFE
AF:
0.195
Gnomad OTH
AF:
0.291
GnomAD3 exomes
AF:
0.255
AC:
64028
AN:
250910
Hom.:
11262
AF XY:
0.232
AC XY:
31482
AN XY:
135636
show subpopulations
Gnomad AFR exome
AF:
0.509
Gnomad AMR exome
AF:
0.545
Gnomad ASJ exome
AF:
0.179
Gnomad EAS exome
AF:
0.292
Gnomad SAS exome
AF:
0.102
Gnomad FIN exome
AF:
0.144
Gnomad NFE exome
AF:
0.194
Gnomad OTH exome
AF:
0.238
GnomAD4 exome
AF:
0.208
AC:
304122
AN:
1461520
Hom.:
36802
Cov.:
35
AF XY:
0.203
AC XY:
147395
AN XY:
727058
show subpopulations
Gnomad4 AFR exome
AF:
0.516
Gnomad4 AMR exome
AF:
0.526
Gnomad4 ASJ exome
AF:
0.175
Gnomad4 EAS exome
AF:
0.251
Gnomad4 SAS exome
AF:
0.107
Gnomad4 FIN exome
AF:
0.149
Gnomad4 NFE exome
AF:
0.195
Gnomad4 OTH exome
AF:
0.221
GnomAD4 genome
AF:
0.297
AC:
45120
AN:
152132
Hom.:
8301
Cov.:
33
AF XY:
0.292
AC XY:
21726
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.497
Gnomad4 AMR
AF:
0.398
Gnomad4 ASJ
AF:
0.171
Gnomad4 EAS
AF:
0.290
Gnomad4 SAS
AF:
0.109
Gnomad4 FIN
AF:
0.145
Gnomad4 NFE
AF:
0.195
Gnomad4 OTH
AF:
0.290
Alfa
AF:
0.219
Hom.:
10620
Bravo
AF:
0.333
TwinsUK
AF:
0.198
AC:
736
ALSPAC
AF:
0.204
AC:
787
ESP6500AA
AF:
0.492
AC:
2167
ESP6500EA
AF:
0.191
AC:
1642
ExAC
AF:
0.248
AC:
30073
Asia WGS
AF:
0.230
AC:
802
AN:
3478
EpiCase
AF:
0.200
EpiControl
AF:
0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.76
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
4.0
DANN
Benign
0.80
DEOGEN2
Benign
0.091
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.086
N
LIST_S2
Benign
0.36
T;T
MetaRNN
Benign
0.000044
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.34
N;.
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.031
Sift
Benign
0.23
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.0070
B;.
Vest4
0.15
MPC
0.24
ClinPred
0.0032
T
GERP RS
1.0
Varity_R
0.093
gMVP
0.42

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.

Other links and lift over

dbSNP: rs2302612; hg19: chr2-102851708; COSMIC: COSV51813459; API