Genetic Variant IL13RA2:p.Leu362Ile (chrX-115005229-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000640.3(IL13RA2):c.1084C>A(p.Leu362Ile) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L362F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

IL13RA2
NM_000640.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11219859).

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.1084C>A	p.Leu362Ile	missense	Exon 9 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.1084C>A	p.Leu362Ile	missense	Exon 9 of 10	ENSP00000243213.1	Q14627
IL13RA2	ENST00000371936.5	TSL:5	c.1084C>A	p.Leu362Ile	missense	Exon 10 of 11	ENSP00000361004.1	Q14627
IL13RA2	ENST00000958003.1		c.1084C>A	p.Leu362Ile	missense	Exon 9 of 10	ENSP00000628062.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

990644

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

297796

African (AFR)

AF:

0.00

AC:

AN:

24323

American (AMR)

AF:

0.00

AC:

AN:

35042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18725

East Asian (EAS)

AF:

0.00

AC:

AN:

29700

South Asian (SAS)

AF:

0.00

AC:

AN:

51788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3859

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

744263

Other (OTH)

AF:

0.00

AC:

AN:

42460

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.024

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.17

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.30

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.8

PhyloP100

-1.6

PrimateAI

Benign

0.35

PROVEAN

Benign

0.14

REVEL

Benign

0.29

Sift

Benign

0.48

Sift4G

Benign

0.45

Polyphen

0.59

Vest4

0.13

MutPred

0.38

Loss of helix (P = 0.0558)

MVP

0.10

MPC

0.25

ClinPred

0.11

GERP RS

-4.7

Varity_R

0.066

gMVP

0.17

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over