chrX-115013812-C-T

Variant names:

• chrX-115013812-C-T
• rs1276432976
• NM_000640.3:c.478G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_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 (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: IL13RA2 NM_000640.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13RA2	NM_000640.3	c.478G>A	p.Gly160Ser	missense_variant	Exon 5 of 10	ENST00000243213.2	NP_000631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL13RA2	ENST00000243213.2	c.478G>A	p.Gly160Ser	missense_variant	Exon 5 of 10	1	NM_000640.3	ENSP00000243213.1
IL13RA2	ENST00000371936.5	c.478G>A	p.Gly160Ser	missense_variant	Exon 6 of 11	5		ENSP00000361004.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 941122 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 268238

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.478G>A (p.G160S) alteration is located in exon 5 (coding exon 4) of the IL13RA2 gene. This alteration results from a G to A substitution at nucleotide position 478, causing the glycine (G) at amino acid position 160 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D;D
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.82	.;T
M_CAP	Pathogenic	0.70	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Uncertain	0.72	D
MutationAssessor	Pathogenic	3.5	H;H
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.49	P;P
Vest4		0.40
MutPred		0.85		Gain of glycosylation at G160 (P = 0.0466);Gain of glycosylation at G160 (P = 0.0466);
MVP		0.28
MPC		0.82
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.89
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs1276432976; hg19: chrX-114248375;