2-102192104-C-T

Variant names:

• chr2-102192104-C-T
• rs1202931052
• NM_003854.4:c.473C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003854.4(IL1RL2):​c.473C>T​(p.Pro158Leu) 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. 15/24 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P158Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL1RL2 NM_003854.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL2	NM_003854.4	MANE Select	c.473C>T	p.Pro158Leu	missense	Exon 4 of 12	NP_003845.2
	IL1RL2	NM_001351446.2		c.473C>T	p.Pro158Leu	missense	Exon 4 of 12	NP_001338375.1	Q9HB29-1
	IL1RL2	NM_001351447.1		c.138+4179C>T		intron	N/A	NP_001338376.1	Q9HB29-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL2	ENST00000264257.7	TSL:1 MANE Select	c.473C>T	p.Pro158Leu	missense	Exon 4 of 12	ENSP00000264257.2	Q9HB29-1
	IL1RL2	ENST00000441515.3	TSL:1	c.138+4179C>T		intron	N/A	ENSP00000413348.2	Q9HB29-2
	IL1RL2	ENST00000908896.1		c.680C>T	p.Pro227Leu	missense	Exon 4 of 12	ENSP00000578955.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.8
DANN	Benign	0.41
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.61
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.066
Sift	Benign	0.12	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.096
MutPred		0.56		Loss of methylation at K163 (P = 0.093)
MVP		0.27
MPC		0.15
ClinPred		0.099	T
GERP RS		1.3
Varity_R		0.068
gMVP		0.32
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: 16

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

Other links and lift over

dbSNP: rs1202931052; hg19: chr2-102808564;