2-102187575-C-A

Position:

• chr2-102187575-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003854.4(IL1RL2):​c.-12-281C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,022 control chromosomes in the GnomAD database, including 6,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.26 (6917 hom., cov: 32)
• Consequence: IL1RL2 NM_003854.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.661

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL2	NM_003854.4	c.-12-281C>A		intron_variant		ENST00000264257.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL2	ENST00000264257.7	c.-12-281C>A		intron_variant		1	NM_003854.4	P1
IL1RL2	ENST00000441515.3	c.69-281C>A		intron_variant		1
IL1RL2	ENST00000421464.1	c.-13+233C>A		intron_variant		5
IL1RL2	ENST00000481806.1	n.82-281C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39236 AN: 151904 Hom.: 6900 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.0758

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.258 AC: 39288 AN: 152022 Hom.: 6917 Cov.: 32 AF XY: 0.259 AC XY: 19255 AN XY: 74318

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.0750

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.240

Alfa AF: 0.165 Hom.: 1416

Bravo AF: 0.293

Asia WGS AF: 0.212 AC: 735 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Ascending aortic dissection Other:1

association, no assertion criteria provided

case-control

Beijing Anzhen Hospital, Capital Medical University

Feb 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.56

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: rs2241132; hg19: chr2-102804035;