2-102212160-T-C

Position:

• chr2-102212160-T-C

Variant summary

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

The NM_003854.4(IL1RL2):​c.710T>C​(p.Ile237Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00159 in 1,611,270 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0080 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (22 hom.)
• Consequence: IL1RL2 NM_003854.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.67

Genes affected

IL1RL2 (HGNC:5999): (interleukin 1 receptor like 2) The protein encoded by this gene is a member of the interleukin 1 receptor family. An experiment with transient gene expression demonstrated that this receptor was incapable of binding to interleukin 1 alpha and interleukin 1 beta with high affinity. This gene and four other interleukin 1 receptor family genes, including interleukin 1 receptor, type I (IL1R1), interleukin 1 receptor, type II (IL1R2), interleukin 1 receptor-like 1 (IL1RL1), and interleukin 18 receptor 1 (IL18R1), form a cytokine receptor gene cluster in a region mapped to chromosome 2q12. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009036064).
• BP6: Variant 2-102212160-T-C is Benign according to our data. Variant chr2-102212160-T-C is described in ClinVar as [Benign]. Clinvar id is 787240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00803 (1223/152326) while in subpopulation AFR AF= 0.0273 (1134/41564). AF 95% confidence interval is 0.026. There are 15 homozygotes in gnomad4. There are 594 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL2	NM_003854.4	c.710T>C	p.Ile237Thr	missense_variant	6/12	ENST00000264257.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL2	ENST00000264257.7	c.710T>C	p.Ile237Thr	missense_variant	6/12	1	NM_003854.4	P1
IL1RL2	ENST00000441515.3	c.356T>C	p.Ile119Thr	missense_variant	4/10	1
IL1RL2	ENST00000481806.1	n.372T>C		non_coding_transcript_exon_variant	4/10	5

Frequencies

GnomAD3 genomes AF: 0.00804 AC: 1223 AN: 152208 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00910

GnomAD3 exomes AF: 0.00217 AC: 546 AN: 251250 Hom.: 4 AF XY: 0.00169 AC XY: 230 AN XY: 135788

Gnomad AFR exome AF: 0.0281

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.000921 AC: 1343 AN: 1458944 Hom.: 22 Cov.: 28 AF XY: 0.000831 AC XY: 603 AN XY: 725956

Gnomad4 AFR exome AF: 0.0298

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000111

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.00803 AC: 1223 AN: 152326 Hom.: 15 Cov.: 32 AF XY: 0.00797 AC XY: 594 AN XY: 74494

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00181 Hom.: 4

Bravo AF: 0.00900

ESP6500AA AF: 0.0245 AC: 108

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00249 AC: 302

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

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 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;T
MetaRNN	Benign	0.0090	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.035	D;T
Polyphen		0.99	D;.
Vest4		0.69
MVP		0.31
MPC		0.36
ClinPred		0.055	T
GERP RS		4.3
Varity_R		0.26
gMVP		0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs13405631; hg19: chr2-102828620;