Genetic Variant IL13RA2:p.Glu29Lys (chrX-115017185-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.85G>A(p.Glu29Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 808,520 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000055 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000019 ( 0 hom. 6 hem. )

Consequence

IL13RA2
NM_000640.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.569

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=0.062325686).

BP6

Variant X-115017185-C-T is Benign according to our data. Variant chrX-115017185-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3528547.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.85G>A	p.Glu29Lys	missense	Exon 2 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.85G>A	p.Glu29Lys	missense	Exon 2 of 10	ENSP00000243213.1	Q14627
IL13RA2	ENST00000371936.5	TSL:5	c.85G>A	p.Glu29Lys	missense	Exon 3 of 11	ENSP00000361004.1	Q14627
IL13RA2	ENST00000958003.1		c.85G>A	p.Glu29Lys	missense	Exon 2 of 10	ENSP00000628062.1

Frequencies

GnomAD3 genomes

AF:

0.0000545

AC:

AN:

110057

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000283

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000758

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000177

AC:

AN:

169509

AF XY:

0.0000179

show subpopulations

Gnomad AFR exome

AF:

0.0000810

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000258

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

698463

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

212925

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18468

American (AMR)

AF:

0.00

AC:

AN:

33100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16697

East Asian (EAS)

AF:

0.00

AC:

AN:

27787

South Asian (SAS)

AF:

0.00

AC:

AN:

44247

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3410

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

481820

Other (OTH)

AF:

0.00

AC:

AN:

32688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.0000545

AC:

AN:

110057

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

32381

show subpopulations

African (AFR)

AF:

0.0000331

AC:

AN:

30215

American (AMR)

AF:

0.00

AC:

AN:

10235

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2633

East Asian (EAS)

AF:

0.000283

AC:

AN:

3531

South Asian (SAS)

AF:

0.00

AC:

AN:

2490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5801

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.0000758

AC:

AN:

52775

Other (OTH)

AF:

0.00

AC:

AN:

1462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

0.076

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.37

CADD

Benign

7.5

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.13

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.58

M_CAP

Benign

0.037

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.41

PhyloP100

0.57

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.71

REVEL

Benign

0.14

Sift

Benign

0.14

Sift4G

Benign

0.18

Polyphen

0.010

Vest4

0.16

MVP

0.10

MPC

0.26

ClinPred

0.044

GERP RS

2.3

PromoterAI

-0.037

Neutral

(source)

Varity_R

0.095

gMVP

0.42

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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