2-102225975-A-C

Position:

• chr2-102225975-A-C

Variant summary

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

The NM_003854.4(IL1RL2):​c.1069A>C​(p.Asn357His) 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. 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: 1.33

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=0.110070825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL2	NM_003854.4	c.1069A>C	p.Asn357His	missense_variant	9/12	ENST00000264257.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL2	ENST00000264257.7	c.1069A>C	p.Asn357His	missense_variant	9/12	1	NM_003854.4	P1
IL1RL2	ENST00000441515.3	c.715A>C	p.Asn239His	missense_variant	7/10	1
IL1RL2	ENST00000481806.1	n.731A>C		non_coding_transcript_exon_variant	7/10	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2021

The c.1069A>C (p.N357H) alteration is located in exon 9 (coding exon 8) of the IL1RL2 gene. This alteration results from a A to C substitution at nucleotide position 1069, causing the asparagine (N) at amino acid position 357 to be replaced by a histidine (H). 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	0.065
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.048
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.055	T;T
Polyphen		0.013	B;.
Vest4		0.15
MutPred		0.52		Loss of sheet (P = 0.1398);.;
MVP		0.23
MPC		0.15
ClinPred		0.10	T
GERP RS		1.8
Varity_R		0.086
gMVP		0.33

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: rs1690573653; hg19: chr2-102842435;