2-102219021-G-T

Variant names:

• chr2-102219021-G-T
• NM_003854.4:c.793G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003854.4(IL1RL2):​c.793G>T​(p.Val265Phe) 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. 13/21 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: 2.34

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.346903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL2	NM_003854.4	c.793G>T	p.Val265Phe	missense_variant	Exon 7 of 12	ENST00000264257.7	NP_003845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL2	ENST00000264257.7	c.793G>T	p.Val265Phe	missense_variant	Exon 7 of 12	1	NM_003854.4	ENSP00000264257.2
IL1RL2	ENST00000441515.3	c.439G>T	p.Val147Phe	missense_variant	Exon 5 of 10	1		ENSP00000413348.2
IL1RL2	ENST00000481806.1	n.455G>T		non_coding_transcript_exon_variant	Exon 5 of 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

Feb 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.793G>T (p.V265F) alteration is located in exon 7 (coding exon 6) of the IL1RL2 gene. This alteration results from a G to T substitution at nucleotide position 793, causing the valine (V) at amino acid position 265 to be replaced by a phenylalanine (F). 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	0.26
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.098	T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.092
Sift	Benign	0.095	T;T
Sift4G	Benign	0.74	T;T
Polyphen		0.21	B;.
Vest4		0.58
MutPred		0.47		Gain of sheet (P = 0.1208);.;
MVP		0.15
MPC		0.47
ClinPred		0.50	T
GERP RS		3.9
Varity_R		0.12
gMVP		0.68

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: chr2-102835481;