16-47109524-C-A

Variant names:

• chr16-47109524-C-A
• rs1384956543
• NM_018092.5:c.842G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018092.5(NETO2):​c.842G>T​(p.Arg281Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R281Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NETO2 NM_018092.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NETO2	NM_018092.5	MANE Select	c.842G>T	p.Arg281Leu	missense	Exon 7 of 9	NP_060562.3
	NETO2	NM_001201477.2		c.821G>T	p.Arg274Leu	missense	Exon 7 of 9	NP_001188406.1	Q8NC67-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NETO2	ENST00000562435.6	TSL:1 MANE Select	c.842G>T	p.Arg281Leu	missense	Exon 7 of 9	ENSP00000455169.1	Q8NC67-1
	NETO2	ENST00000303155.9	TSL:5	c.821G>T	p.Arg274Leu	missense	Exon 7 of 9	ENSP00000306726.5	Q8NC67-3
	NETO2	ENST00000878303.1		c.797G>T	p.Arg266Leu	missense	Exon 6 of 8	ENSP00000548362.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.54	N
REVEL	Uncertain	0.52
Sift	Benign	0.39	T
Sift4G	Uncertain	0.023	D
Polyphen		0.91	P
Vest4		0.70
MutPred		0.56		Loss of MoRF binding (P = 0.0199)
MVP		0.54
MPC		1.0
ClinPred		0.86	D
GERP RS		5.5
PromoterAI		-0.050	Neutral
Varity_R		0.15
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: 7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1384956543; hg19: chr16-47143435;