dbSNP rs199942421: IL13RA2:p.Val146Ile (chrX-115013854-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000640.3(IL13RA2):c.436G>A(p.Val146Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,004,779 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 39 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.00012 ( 0 hom. 35 hem. )

Consequence

IL13RA2
NM_000640.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.30

Publications

0 publications found

Variant links:

Genes affected

IL13RA2 (HGNC:5975): (interleukin 13 receptor subunit alpha 2) The protein encoded by this gene is closely related to Il13RA1, a subuint of the interleukin 13 receptor complex. This protein binds IL13 with high affinity, but lacks cytoplasmic domain, and does not appear to function as a signal mediator. It is reported to play a role in the internalization of IL13. [provided by RefSeq, Jul 2008]

IL13RA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06235054).

BP6

Variant X-115013854-C-T is Benign according to our data. Variant chrX-115013854-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3528546.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000640.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13RA2	NM_000640.3	MANE Select	c.436G>A	p.Val146Ile	missense	Exon 5 of 10	NP_000631.1	Q14627

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL13RA2	ENST00000243213.2	TSL:1 MANE Select	c.436G>A	p.Val146Ile	missense	Exon 5 of 10	ENSP00000243213.1	Q14627
IL13RA2	ENST00000371936.5	TSL:5	c.436G>A	p.Val146Ile	missense	Exon 6 of 11	ENSP00000361004.1	Q14627
IL13RA2	ENST00000958003.1		c.436G>A	p.Val146Ile	missense	Exon 5 of 10	ENSP00000628062.1

Frequencies

GnomAD3 genomes

AF:

0.0000536

AC:

AN:

111859

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000113

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000564

AC:

AN:

177288

AF XY:

0.0000965

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000385

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000999

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.000118

AC:

105

AN:

892920

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

254600

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22036

American (AMR)

AF:

0.000146

AC:

AN:

34351

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18059

East Asian (EAS)

AF:

0.0000688

AC:

AN:

29051

South Asian (SAS)

AF:

0.00

AC:

AN:

49042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3723

European-Non Finnish (NFE)

AF:

0.000134

AC:

AN:

656855

Other (OTH)

AF:

0.000254

AC:

AN:

39389

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000536

AC:

AN:

111859

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

34041

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30802

American (AMR)

AF:

0.00

AC:

AN:

10499

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3598

South Asian (SAS)

AF:

0.00

AC:

AN:

2668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6057

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53156

Other (OTH)

AF:

0.00

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<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:

0.000142

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0040

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.30

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.52

M_CAP

Benign

0.064

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.20

PhyloP100

-2.3

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.22

REVEL

Benign

0.24

Sift

Benign

1.0

Sift4G

Benign

0.75

Polyphen

0.010

Vest4

0.073

MutPred

0.58

Loss of sheet (P = 0.1398)

MVP

0.10

MPC

0.27

ClinPred

0.019

GERP RS

-6.2

Varity_R

0.045

gMVP

0.33

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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