X-115013854-C-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.30
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 3528546.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL13RA2NM_000640.3 linkc.436G>A p.Val146Ile missense_variant Exon 5 of 10 ENST00000243213.2 NP_000631.1 Q14627

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL13RA2ENST00000243213.2 linkc.436G>A p.Val146Ile missense_variant Exon 5 of 10 1 NM_000640.3 ENSP00000243213.1 Q14627
IL13RA2ENST00000371936.5 linkc.436G>A p.Val146Ile missense_variant Exon 6 of 11 5 ENSP00000361004.1 Q14627

Frequencies

GnomAD3 genomes
AF:
0.0000536
AC:
6
AN:
111859
Hom.:
0
Cov.:
23
AF XY:
0.000118
AC XY:
4
AN XY:
34041
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
GnomAD3 exomes
AF:
0.0000564
AC:
10
AN:
177288
Hom.:
0
AF XY:
0.0000965
AC XY:
6
AN XY:
62204
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 SAS 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.:
0
Cov.:
17
AF XY:
0.000137
AC XY:
35
AN XY:
254600
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000146
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000688
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000134
Gnomad4 OTH exome
AF:
0.000254
GnomAD4 genome
AF:
0.0000536
AC:
6
AN:
111859
Hom.:
0
Cov.:
23
AF XY:
0.000118
AC XY:
4
AN XY:
34041
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:
0.000113
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
1
Bravo
AF:
0.0000604
ExAC
AF:
0.0000824
AC:
10

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Oct 08, 2024
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
0.064
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.0040
DANN
Benign
0.57
DEOGEN2
Benign
0.30
T;T
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.52
.;T
M_CAP
Benign
0.064
D
MetaRNN
Benign
0.062
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
0.20
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.22
N;N
REVEL
Benign
0.24
Sift
Benign
1.0
T;T
Sift4G
Benign
0.75
T;T
Polyphen
0.010
B;B
Vest4
0.073
MutPred
0.58
Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);
MVP
0.10
MPC
0.27
ClinPred
0.019
T
GERP RS
-6.2
Varity_R
0.045
gMVP
0.33

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

LitVar

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

Other links and lift over

dbSNP: rs199942421; hg19: chrX-114248417; API