chr2-102201580-C-G

Variant names:

• chr2-102201580-C-G
• rs184118101
• NM_003854.4:c.514C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003854.4(IL1RL2):​c.514C>G​(p.Arg172Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL1RL2 NM_003854.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.432

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL2	NM_003854.4	c.514C>G	p.Arg172Gly	missense_variant	Exon 5 of 12	ENST00000264257.7	NP_003845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL2	ENST00000264257.7	c.514C>G	p.Arg172Gly	missense_variant	Exon 5 of 12	1	NM_003854.4	ENSP00000264257.2
IL1RL2	ENST00000441515.3	c.163C>G	p.Arg55Gly	missense_variant	Exon 3 of 10	1		ENSP00000413348.2
IL1RL2	ENST00000421464.1	c.514C>G	p.Arg172Gly	missense_variant, splice_region_variant	Exon 5 of 5	5		ENSP00000387611.1
IL1RL2	ENST00000481806.1	n.176C>G		non_coding_transcript_exon_variant	Exon 3 of 10	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.514C>G (p.R172G) alteration is located in exon 5 (coding exon 4) of the IL1RL2 gene. This alteration results from a C to G substitution at nucleotide position 514, causing the arginine (R) at amino acid position 172 to be replaced by a glycine (G). 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	0.24
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T;.;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.5	D;D;N
REVEL	Benign	0.23
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.024	D;D;D
Polyphen		0.88	P;.;.
Vest4		0.33
MutPred		0.55		Gain of sheet (P = 0.0477);.;Gain of sheet (P = 0.0477);
MVP		0.86
MPC		0.51
ClinPred		0.87	D
GERP RS		-1.7
Varity_R		0.62
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.38		Position offset: -24

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs184118101; hg19: chr2-102818040; COSMIC: COSV99960128;