rs142963191

Variant names:

• chr2-102009812-C-T
• rs142963191
• NM_004633.4:c.318C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004633.4(IL1R2):​c.318C>T​(p.Tyr106Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,614,150 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (8 hom.)
• Consequence: IL1R2 NM_004633.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0680
• Publications: 5 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 2-102009812-C-T is Benign according to our data. Variant chr2-102009812-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2651211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.068 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 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.318C>T	p.Tyr106Tyr	synonymous	Exon 3 of 9	NP_004624.1	P27930-1
	IL1R2	NM_001261419.2		c.318C>T	p.Tyr106Tyr	synonymous	Exon 3 of 7	NP_001248348.1	P27930-2
	IL1R2	NR_048564.2		n.535C>T		non_coding_transcript_exon	Exon 3 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	ENST00000332549.8	TSL:1 MANE Select	c.318C>T	p.Tyr106Tyr	synonymous	Exon 3 of 9	ENSP00000330959.3	P27930-1
	IL1R2	ENST00000393414.6	TSL:1	c.318C>T	p.Tyr106Tyr	synonymous	Exon 3 of 9	ENSP00000377066.2	P27930-1
	IL1R2	ENST00000441002.1	TSL:1	c.318C>T	p.Tyr106Tyr	synonymous	Exon 2 of 6	ENSP00000414611.1	P27930-2

Frequencies

GnomAD3 genomes AF: 0.00208 AC: 316 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00300

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00248 AC: 620 AN: 250300 AF XY: 0.00263

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00874

Gnomad NFE exome AF: 0.00343

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00272 AC: 3982 AN: 1461838 Hom.: 8 Cov.: 31 AF XY: 0.00257 AC XY: 1867 AN XY: 727228

African (AFR) AF: 0.000657 AC: 22 AN: 33480

American (AMR) AF: 0.000358 AC: 16 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00876 AC: 468 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00301 AC: 3351 AN: 1111980

Other (OTH) AF: 0.00177 AC: 107 AN: 60396

GnomAD4 genome AF: 0.00207 AC: 316 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.00220 AC XY: 164 AN XY: 74492

African (AFR) AF: 0.000529 AC: 22 AN: 41560

American (AMR) AF: 0.000523 AC: 8 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00753 AC: 80 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00300 AC: 204 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00235 Hom.: 0

Bravo AF: 0.00176

EpiCase AF: 0.00202

EpiControl AF: 0.00237

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	-0.38
CADD	Benign	5.4
DANN	Benign	0.55
PhyloP100		0.068
Mutation Taster		=99/1	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: rs142963191; hg19: chr2-102626274; COSMIC: COSV60208389;