rs199942421

Variant names:

• chrX-115013854-C-A
• NM_000640.3:c.436G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-115013854-C-A
• chrX-115013854-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000640.3(IL13RA2):​c.436G>T​(p.Val146Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000112 in 892,934 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 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. V146I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000011 (0 hom. 0 hem.)
• Consequence: IL13RA2 NM_000640.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27382725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13RA2	NM_000640.3	c.436G>T	p.Val146Leu	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.436G>T	p.Val146Leu	missense_variant	Exon 5 of 10	1	NM_000640.3	ENSP00000243213.1
IL13RA2	ENST00000371936.5	c.436G>T	p.Val146Leu	missense_variant	Exon 6 of 11	5		ENSP00000361004.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000112 AC: 1 AN: 892934 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 254612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000291

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.57
DANN	Benign	0.86
DEOGEN2	Uncertain	0.57	D;D
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.70	.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.40
Sift	Benign	0.039	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.29	B;B
Vest4		0.18
MutPred		0.62		Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);
MVP		0.14
MPC		0.72
ClinPred		0.70	D
GERP RS		-6.2
Varity_R		0.24
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-114248417;