Genetic Variant IL13RA2:p.Gly160Ser (chrX-115013812-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000640.3(IL13RA2):c.478G>A(p.Gly160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G160G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

IL13RA2
NM_000640.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.939

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.478G>A	p.Gly160Ser	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.478G>A	p.Gly160Ser	missense	Exon 5 of 10	ENSP00000243213.1	Q14627
IL13RA2	ENST00000371936.5	TSL:5	c.478G>A	p.Gly160Ser	missense	Exon 6 of 11	ENSP00000361004.1	Q14627
IL13RA2	ENST00000958003.1		c.478G>A	p.Gly160Ser	missense	Exon 5 of 10	ENSP00000628062.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

941122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

268238

African (AFR)

AF:

0.00

AC:

AN:

23142

American (AMR)

AF:

0.00

AC:

AN:

34102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18415

East Asian (EAS)

AF:

0.00

AC:

AN:

29165

South Asian (SAS)

AF:

0.00

AC:

AN:

49573

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40445

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3798

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

701611

Other (OTH)

AF:

0.00

AC:

AN:

40871

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.19

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.89

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.70

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.72

MutationAssessor

Pathogenic

3.5

PhyloP100

2.2

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.81

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.49

Vest4

0.40

MutPred

0.85

Gain of glycosylation at G160 (P = 0.0466)

MVP

0.28

MPC

0.82

ClinPred

1.0

GERP RS

4.7

Varity_R

0.89

gMVP

0.69

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over