Genetic Variant IL13RA2:p.Leu352Ser (chrX-115005258-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_000640.3(IL13RA2):c.1055T>C(p.Leu352Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,150,970 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000022 ( 0 hom. 7 hem. )

Consequence

IL13RA2
NM_000640.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.106

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.097477555).

BP6

Variant X-115005258-A-G is Benign according to our data. Variant chrX-115005258-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3109083.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13RA2	NM_000640.3 link	c.1055T>C	p.Leu352Ser	missense_variant	Exon 9 of 10	ENST00000243213.2	NP_000631.1	Q14627

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL13RA2	ENST00000243213.2 link	c.1055T>C	p.Leu352Ser	missense_variant	Exon 9 of 10	1	NM_000640.3	ENSP00000243213.1		Q14627
IL13RA2	ENST00000371936.5 link	c.1055T>C	p.Leu352Ser	missense_variant	Exon 10 of 11	5		ENSP00000361004.1		Q14627

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

113159

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35293

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:

0.0000374

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

182623

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67199

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000222

AC:

AN:

1037811

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

318847

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000227

GnomAD4 genome

AF:

0.0000177

AC:

AN:

113159

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35293

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000374

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 06, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

1.9

DANN

Benign

0.55

DEOGEN2

Benign

0.22

T;T

FATHMM_MKL

Benign

0.00081

LIST_S2

Benign

0.23

.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.097

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

-1.6

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.92

N;N

REVEL

Uncertain

0.29

Sift

Benign

0.17

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.0010

B;B

Vest4

0.17

MutPred

0.50

Loss of stability (P = 0.0414);Loss of stability (P = 0.0414);

MVP

0.68

MPC

0.32

ClinPred

0.036

GERP RS

-0.88

Varity_R

0.086

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over