rs2302612

Variant names:

• chr2-102235248-T-A
• NM_003854.4:c.1649T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-102235248-T-A
• chr2-102235248-T-C
• chr2-102235248-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003854.4(IL1RL2):​c.1649T>A​(p.Leu550Gln) 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. 14/21 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. L550P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09561986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL2	NM_003854.4	c.1649T>A	p.Leu550Gln	missense_variant	Exon 11 of 12	ENST00000264257.7	NP_003845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL2	ENST00000264257.7	c.1649T>A	p.Leu550Gln	missense_variant	Exon 11 of 12	1	NM_003854.4	ENSP00000264257.2
IL1RL2	ENST00000441515.3	c.1295T>A	p.Leu432Gln	missense_variant	Exon 9 of 10	1		ENSP00000413348.2
IL1RL2	ENST00000481806.1	n.1311T>A		non_coding_transcript_exon_variant	Exon 9 of 10	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.053	T;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.081
Sift	Benign	0.032	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.88	P;.
Vest4		0.21
MutPred		0.27		Gain of phosphorylation at T553 (P = 0.1169);.;
MVP		0.12
MPC		0.16
ClinPred		0.31	T
GERP RS		1.0
Varity_R		0.087
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-102851708;