X-115015770-A-T

Variant names:

• chrX-115015770-A-T
• NM_000640.3:c.146T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000640.3(IL13RA2):​c.146T>A​(p.Leu49His) variant causes a missense change. 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)
• Consequence: IL13RA2 NM_000640.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

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.146T>A	p.Leu49His	missense	Exon 3 of 10	NP_000631.1	Q14627

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13RA2	ENST00000243213.2	TSL:1 MANE Select	c.146T>A	p.Leu49His	missense	Exon 3 of 10	ENSP00000243213.1	Q14627
	IL13RA2	ENST00000371936.5	TSL:5	c.146T>A	p.Leu49His	missense	Exon 4 of 11	ENSP00000361004.1	Q14627
	IL13RA2	ENST00000958003.1		c.146T>A	p.Leu49His	missense	Exon 3 of 10	ENSP00000628062.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.76	D
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.70		Loss of stability (P = 0.0565)
MVP		0.42
MPC		0.97
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.95
gMVP		0.85
Mutation Taster		=44/56	disease causing

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

Other links and lift over

hg19: chrX-114250333;