X-115005294-G-C

Variant names:

• chrX-115005294-G-C
• NM_000640.3:c.1019C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000640.3(IL13RA2):​c.1019C>G​(p.Thr340Ser) 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 benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: IL13RA2 NM_000640.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.304

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049947202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13RA2	NM_000640.3	c.1019C>G	p.Thr340Ser	missense_variant	Exon 9 of 10	ENST00000243213.2	NP_000631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL13RA2	ENST00000243213.2	c.1019C>G	p.Thr340Ser	missense_variant	Exon 9 of 10	1	NM_000640.3	ENSP00000243213.1
IL13RA2	ENST00000371936.5	c.1019C>G	p.Thr340Ser	missense_variant	Exon 10 of 11	5		ENSP00000361004.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1019C>G (p.T340S) alteration is located in exon 9 (coding exon 8) of the IL13RA2 gene. This alteration results from a C to G substitution at nucleotide position 1019, causing the threonine (T) at amino acid position 340 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	0.079
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.21
DANN	Benign	0.20
DEOGEN2	Benign	0.14	T;T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.24	.;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.53	N;N
REVEL	Benign	0.13
Sift	Benign	0.90	T;T
Sift4G	Benign	0.85	T;T
Polyphen		0.0020	B;B
Vest4		0.20
MutPred		0.31		Gain of disorder (P = 0.0348);Gain of disorder (P = 0.0348);
MVP		0.067
MPC		0.22
ClinPred		0.035	T
GERP RS		1.1
Varity_R		0.036
gMVP		0.15

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-114239857;