2-102026557-A-G

Variant names:

• chr2-102026557-A-G
• rs2072472
• NM_004633.4:c.1030+304A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004633.4(IL1R2):​c.1030+304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,082 control chromosomes in the GnomAD database, including 4,930 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 0.24 (4930 hom., cov: 32)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 27 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004633.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	NM_004633.4	MANE Select	c.1030+304A>G		intron	N/A	NP_004624.1
	IL1R2	NR_048564.2		n.1247+304A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	ENST00000332549.8	TSL:1 MANE Select	c.1030+304A>G		intron	N/A	ENSP00000330959.3
	IL1R2	ENST00000393414.6	TSL:1	c.1030+304A>G		intron	N/A	ENSP00000377066.2
	IL1R2	ENST00000474085.5	TSL:2	n.466+304A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36797 AN: 151962 Hom.: 4921 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.242 AC: 36833 AN: 152082 Hom.: 4930 Cov.: 32 AF XY: 0.247 AC XY: 18384 AN XY: 74348

African (AFR) AF: 0.155 AC: 6434 AN: 41504

American (AMR) AF: 0.283 AC: 4329 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3472

East Asian (EAS) AF: 0.261 AC: 1350 AN: 5164

South Asian (SAS) AF: 0.132 AC: 635 AN: 4814

European-Finnish (FIN) AF: 0.412 AC: 4349 AN: 10554

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18199 AN: 67984

Other (OTH) AF: 0.242 AC: 512 AN: 2112

Alfa AF: 0.258 Hom.: 2788

Bravo AF: 0.233

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.63
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2072472; hg19: chr2-102643019;