chr2-102022183-T-G

Position:

• chr2-102022183-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004633.4(IL1R2):​c.689-4T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,611,470 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (10 hom., cov: 33)
  • Exomes 𝑓: 0.00062 (8 hom.)
• Consequence: IL1R2 NM_004633.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00005177
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.348

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-102022183-T-G is Benign according to our data. Variant chr2-102022183-T-G is described in ClinVar as [Benign]. Clinvar id is 711332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00616 (937/152158) while in subpopulation AFR AF= 0.0214 (889/41504). AF 95% confidence interval is 0.0203. There are 10 homozygotes in gnomad4. There are 449 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R2	NM_004633.4	c.689-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000332549.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R2	ENST00000332549.8	c.689-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004633.4	P1
IL1R2	ENST00000393414.6	c.689-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P1
IL1R2	ENST00000441002.1	c.689-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
IL1R2	ENST00000474085.5	n.121T>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.00618 AC: 940 AN: 152040 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00165 AC: 416 AN: 251382 Hom.: 7 AF XY: 0.00123 AC XY: 167 AN XY: 135860

Gnomad AFR exome AF: 0.0233

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000618 AC: 902 AN: 1459312 Hom.: 8 Cov.: 29 AF XY: 0.000541 AC XY: 393 AN XY: 726188

Gnomad4 AFR exome AF: 0.0218

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000198

Gnomad4 OTH exome AF: 0.00156

GnomAD4 genome AF: 0.00616 AC: 937 AN: 152158 Hom.: 10 Cov.: 33 AF XY: 0.00604 AC XY: 449 AN XY: 74380

Gnomad4 AFR AF: 0.0214

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00322 Hom.: 4

Bravo AF: 0.00768

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.9
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000052
dbscSNV1_RF	Benign	0.0
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: rs3218961; hg19: chr2-102638645;