Genetic Variant NM_003854.4:c.710T>C (chr2-102212160-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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 (★★).

Frequency

Genomes: 𝑓 0.0080 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 22 hom. )

Consequence

IL1RL2
NM_003854.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.67

Publications

4 publications found

Variant links:

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]

IL1RL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 787240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003854.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL1RL2	NM_003854.4	MANE Select	c.710T>C	p.Ile237Thr	missense	Exon 6 of 12	NP_003845.2
IL1RL2	NM_001351446.2		c.710T>C	p.Ile237Thr	missense	Exon 6 of 12	NP_001338375.1	Q9HB29-1
IL1RL2	NM_001351447.1		c.356T>C	p.Ile119Thr	missense	Exon 4 of 10	NP_001338376.1	Q9HB29-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL1RL2	ENST00000264257.7	TSL:1 MANE Select	c.710T>C	p.Ile237Thr	missense	Exon 6 of 12	ENSP00000264257.2	Q9HB29-1
IL1RL2	ENST00000441515.3	TSL:1	c.356T>C	p.Ile119Thr	missense	Exon 4 of 10	ENSP00000413348.2	Q9HB29-2
IL1RL2	ENST00000908896.1		c.917T>C	p.Ile306Thr	missense	Exon 6 of 12	ENSP00000578955.1

Frequencies

GnomAD3 genomes

AF:

0.00804

AC:

1223

AN:

152208

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00217

AC:

546

AN:

251250

AF XY:

0.00169

show subpopulations

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 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.:

Cov.:

AF XY:

0.000831

AC XY:

603

AN XY:

725956

show subpopulations

African (AFR)

AF:

0.0298

AC:

995

AN:

33404

American (AMR)

AF:

0.00181

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39642

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53342

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000111

AC:

123

AN:

1109462

Other (OTH)

AF:

0.00222

AC:

134

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

108

163

217

271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00803

AC:

1223

AN:

152326

Hom.:

Cov.:

AF XY:

0.00797

AC XY:

594

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0273

AC:

1134

AN:

41564

American (AMR)

AF:

0.00392

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68034

Other (OTH)

AF:

0.00900

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00298

Hom.:

Bravo

AF:

0.00900

ESP6500AA

AF:

0.0245

AC:

108

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00249

AC:

302

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0090

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

3.7

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.20

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.035

Polyphen

0.99

Vest4

0.69

MVP

0.31

MPC

0.36

ClinPred

0.055

GERP RS

4.3

Varity_R

0.26

gMVP

0.65

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over