chr2-102008532-C-A

Variant names:

• chr2-102008532-C-A
• rs200366216
• NM_004633.4:c.-44C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004633.4(IL1R2):​c.-44C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,536,132 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (5 hom.)
• Consequence: IL1R2 NM_004633.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.167
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-102008532-C-A is Benign according to our data. Variant chr2-102008532-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2651210.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	NM_004633.4	MANE Select	c.-44C>A		5_prime_UTR	Exon 2 of 9	NP_004624.1	P27930-1
	IL1R2	NM_001261419.2		c.-44C>A		5_prime_UTR	Exon 2 of 7	NP_001248348.1	P27930-2
	IL1R2	NR_048564.2		n.174C>A		non_coding_transcript_exon	Exon 2 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	ENST00000332549.8	TSL:1 MANE Select	c.-44C>A		5_prime_UTR	Exon 2 of 9	ENSP00000330959.3	P27930-1
	IL1R2	ENST00000393414.6	TSL:1	c.-44C>A		5_prime_UTR	Exon 2 of 9	ENSP00000377066.2	P27930-1
	IL1R2	ENST00000441002.1	TSL:1	c.-44C>A		5_prime_UTR	Exon 1 of 6	ENSP00000414611.1	P27930-2

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 285 AN: 152164 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00197

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00217 AC: 546 AN: 251240 AF XY: 0.00201

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00387

Gnomad ASJ exome AF: 0.0164

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00178

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00180 AC: 2487 AN: 1383850 Hom.: 5 Cov.: 23 AF XY: 0.00177 AC XY: 1224 AN XY: 693006

African (AFR) AF: 0.000377 AC: 12 AN: 31870

American (AMR) AF: 0.00372 AC: 166 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.0180 AC: 462 AN: 25646

East Asian (EAS) AF: 0.00 AC: 0 AN: 39322

South Asian (SAS) AF: 0.000260 AC: 22 AN: 84706

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53374

Middle Eastern (MID) AF: 0.00571 AC: 31 AN: 5428

European-Non Finnish (NFE) AF: 0.00157 AC: 1637 AN: 1041190

Other (OTH) AF: 0.00265 AC: 153 AN: 57698

GnomAD4 genome AF: 0.00186 AC: 284 AN: 152282 Hom.: 1 Cov.: 31 AF XY: 0.00164 AC XY: 122 AN XY: 74460

African (AFR) AF: 0.000553 AC: 23 AN: 41556

American (AMR) AF: 0.00314 AC: 48 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00197 AC: 134 AN: 68028

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00473 Hom.: 0

Bravo AF: 0.00242

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.76
PhyloP100		0.17
PromoterAI		-0.0029	Neutral
Mutation Taster		=300/0	polymorphism

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: rs200366216; hg19: chr2-102624994;