NM_000640.3:c.436G>T

Variant names:

• chrX-115013854-C-A
• rs199942421
• NM_000640.3:c.436G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 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
• 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 1 ACMG points.

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

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.436G>T	p.Val146Leu	missense	Exon 5 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.436G>T	p.Val146Leu	missense	Exon 5 of 10	ENSP00000243213.1	Q14627
	IL13RA2	ENST00000371936.5	TSL:5	c.436G>T	p.Val146Leu	missense	Exon 6 of 11	ENSP00000361004.1	Q14627
	IL13RA2	ENST00000958003.1		c.436G>T	p.Val146Leu	missense	Exon 5 of 10	ENSP00000628062.1

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

African (AFR) AF: 0.00 AC: 0 AN: 22036

American (AMR) AF: 0.0000291 AC: 1 AN: 34351

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18059

East Asian (EAS) AF: 0.00 AC: 0 AN: 29051

South Asian (SAS) AF: 0.00 AC: 0 AN: 49041

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3723

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 656870

Other (OTH) AF: 0.00 AC: 0 AN: 39389

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-2.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.40
Sift	Benign	0.039	D
Sift4G	Benign	0.11	T
Polyphen		0.29	B
Vest4		0.18
MutPred		0.62		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
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs199942421; hg19: chrX-114248417;