2-102225960-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003854.4(IL1RL2):c.1054G>A(p.Val352Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,611,318 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V352A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.016 (65 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (80 hom.)
• Consequence: IL1RL2 NM_003854.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0460

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=0.0025072396).
• BP6: Variant 2-102225960-G-A is Benign according to our data. Variant chr2-102225960-G-A is described in ClinVar as [Benign]. Clinvar id is 786485.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL2	NM_003854.4	c.1054G>A	p.Val352Ile	missense_variant	9/12	ENST00000264257.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL2	ENST00000264257.7	c.1054G>A	p.Val352Ile	missense_variant	9/12	1	NM_003854.4	P1
IL1RL2	ENST00000441515.3	c.700G>A	p.Val234Ile	missense_variant	7/10	1
IL1RL2	ENST00000481806.1	n.716G>A		non_coding_transcript_exon_variant	7/10	5

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2453 AN: 152072 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0101

GnomAD3 exomes AF: 0.00407 AC: 1015 AN: 249506 Hom.: 28 AF XY: 0.00310 AC XY: 418 AN XY: 135028

Gnomad AFR exome AF: 0.0567

Gnomad AMR exome AF: 0.00222

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000987

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00160 AC: 2331 AN: 1459128 Hom.: 80 Cov.: 30 AF XY: 0.00140 AC XY: 1017 AN XY: 725946

Gnomad4 AFR exome AF: 0.0577

Gnomad4 AMR exome AF: 0.00264

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.00357

GnomAD4 genome AF: 0.0162 AC: 2458 AN: 152190 Hom.: 65 Cov.: 32 AF XY: 0.0159 AC XY: 1180 AN XY: 74414

Gnomad4 AFR AF: 0.0566

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00996

Alfa AF: 0.00311 Hom.: 16

Bravo AF: 0.0186

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00538 AC: 653

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0000550

EpiControl AF: 0.000239

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	0.083
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.1
Dann	Benign	0.72
DEOGEN2	Benign	0.061	T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.63	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.028
Sift	Benign	0.47	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.0040	B;.
Vest4		0.10
MVP		0.17
MPC		0.12
ClinPred		0.0061	T
GERP RS		2.8
Varity_R		0.025
gMVP		0.19

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: rs33946385; hg19: chr2-102842420;