rs193920943

Variant names:

• chr16-47083267-C-G
• rs193920943
• NM_018092.5:c.1532G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018092.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NETO2	NM_018092.5	MANE Select	c.1532G>C	p.Arg511Thr	missense	Exon 9 of 9	NP_060562.3
	NETO2	NM_001201477.2		c.1511G>C	p.Arg504Thr	missense	Exon 9 of 9	NP_001188406.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NETO2	ENST00000562435.6	TSL:1 MANE Select	c.1532G>C	p.Arg511Thr	missense	Exon 9 of 9	ENSP00000455169.1
	NETO2	ENST00000303155.9	TSL:5	c.1511G>C	p.Arg504Thr	missense	Exon 9 of 9	ENSP00000306726.5
	NETO2	ENST00000562559.5	TSL:3	c.1049G>C	p.Arg350Thr	missense	Exon 5 of 5	ENSP00000454213.1

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

Prostate cancer Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.26
Sift	Benign	0.080	T
Sift4G	Benign	0.13	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

Other links and lift over

dbSNP: rs193920943; hg19: chr16-47117178; COSMIC: COSV57455978; COSMIC: COSV57455978;