2-102005914-A-G

Position:

• chr2-102005914-A-G

Variant summary

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

The NM_004633.4(IL1R2):​c.-61-2601A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,150 control chromosomes in the GnomAD database, including 31,973 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31973 hom., cov: 32)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695

Genes affected

IL1R2 (HGNC:5994): (interleukin 1 receptor type 2) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This protein binds interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA), and acts as a decoy receptor that inhibits the activity of its ligands. Interleukin 4 (IL4) is reported to antagonize the activity of interleukin 1 by inducing the expression and release of this cytokine. This gene and three other genes form a cytokine receptor gene cluster on chromosome 2q12. Alternative splicing results in multiple transcript variants and protein isoforms. Alternative splicing produces both membrane-bound and soluble proteins. A soluble protein is also produced by proteolytic cleavage. [provided by RefSeq, May 2012]

IL1R2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1R2	NM_004633.4	c.-61-2601A>G		intron_variant		ENST00000332549.8	NP_004624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1R2	ENST00000332549.8	c.-61-2601A>G		intron_variant		1	NM_004633.4	ENSP00000330959.3

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96285 AN: 152032 Hom.: 31915 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.634 AC: 96404 AN: 152150 Hom.: 31973 Cov.: 32 AF XY: 0.644 AC XY: 47910 AN XY: 74368

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.597

Alfa AF: 0.519 Hom.: 40446

Bravo AF: 0.636

Asia WGS AF: 0.755 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.35

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: rs4851527; hg19: chr2-102622376; COSMIC: COSV60206369; COSMIC: COSV60206369;