2-102235248-T-C

Position:

• chr2-102235248-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003854.4(IL1RL2):​c.1649T>C​(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: 𝑓 0.30 (8301 hom., cov: 33)
  • Exomes 𝑓: 0.21 (36802 hom.)
• Consequence: IL1RL2 NM_003854.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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]

ACMG classification

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
IL1RL2	NM_003854.4	c.1649T>C	p.Leu550Pro	missense_variant	11/12	ENST00000264257.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL2	ENST00000264257.7	c.1649T>C	p.Leu550Pro	missense_variant	11/12	1	NM_003854.4	P1
IL1RL2	ENST00000441515.3	c.1295T>C	p.Leu432Pro	missense_variant	9/10	1
IL1RL2	ENST00000481806.1	n.1311T>C		non_coding_transcript_exon_variant	9/10	5

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45020 AN: 152014 Hom.: 8267 Cov.: 33

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

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

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

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

Other links and lift over

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