rs193920943

Positions:

• chr16-47083267-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018092.5(NETO2):​c.1532G>C​(p.Arg511Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NETO2 NM_018092.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.09

Genes affected

NETO2 (HGNC:14644): (neuropilin and tolloid like 2) This gene encodes a predicted transmembrane protein containing two extracellular CUB domains followed by a low-density lipoprotein class A (LDLa) domain. A similar gene in rats encodes a protein that modulates glutamate signaling in the brain by regulating kainate receptor function. Expression of this gene may be a biomarker for proliferating infantile hemangiomas. A pseudogene of this gene is located on the long arm of chromosome 8. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NETO2	NM_018092.5	c.1532G>C	p.Arg511Thr	missense_variant	9/9	ENST00000562435.6	NP_060562.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NETO2	ENST00000562435.6	c.1532G>C	p.Arg511Thr	missense_variant	9/9	1	NM_018092.5	ENSP00000455169.1
NETO2	ENST00000303155.9	c.1511G>C	p.Arg504Thr	missense_variant	9/9	5		ENSP00000306726.5
NETO2	ENST00000562559.5	c.1049G>C	p.Arg350Thr	missense_variant	5/5	3		ENSP00000454213.1
NETO2	ENST00000564667.1	c.638G>C	p.Arg213Thr	missense_variant	2/2	4		ENSP00000457133.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.26
Sift	Benign	0.080	T;T
Sift4G	Benign	0.13	T;T
Polyphen		1.0	D;.
Vest4		0.63
MutPred		0.48		Gain of sheet (P = 0.0827);.;
MVP		0.54
MPC		1.2
ClinPred		0.89	D
GERP RS		5.0
Varity_R		0.34
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs193920943; hg19: chr16-47117178; COSMIC: COSV57455978; COSMIC: COSV57455978;