2-102009746-A-G

Position:

• chr2-102009746-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004633.4(IL1R2):​c.252A>G​(p.Thr84=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 1,614,188 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (36 hom.)
• Consequence: IL1R2 NM_004633.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.39

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-102009746-A-G is Benign according to our data. Variant chr2-102009746-A-G is described in ClinVar as [Benign]. Clinvar id is 721339.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.39 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R2	NM_004633.4	c.252A>G	p.Thr84=	synonymous_variant	3/9	ENST00000332549.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R2	ENST00000332549.8	c.252A>G	p.Thr84=	synonymous_variant	3/9	1	NM_004633.4	P1

Frequencies

GnomAD3 genomes AF: 0.00345 AC: 525 AN: 152180 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00619

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00362 AC: 910 AN: 251422 Hom.: 6 AF XY: 0.00344 AC XY: 467 AN XY: 135892

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00749

Gnomad NFE exome AF: 0.00566

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00520 AC: 7596 AN: 1461890 Hom.: 36 Cov.: 32 AF XY: 0.00500 AC XY: 3634 AN XY: 727244

Gnomad4 AFR exome AF: 0.000687

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.00199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00769

Gnomad4 NFE exome AF: 0.00607

Gnomad4 OTH exome AF: 0.00485

GnomAD4 genome AF: 0.00345 AC: 525 AN: 152298 Hom.: 1 Cov.: 32 AF XY: 0.00353 AC XY: 263 AN XY: 74476

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.00619

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00538 Hom.: 2

Bravo AF: 0.00312

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00594

EpiControl AF: 0.00539

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.057
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143906708; hg19: chr2-102626208;