rs766715523

Variant names:

• chr16-47083303-C-A
• NM_018092.5:c.1496G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-47083303-C-A
• chr16-47083303-C-G
• chr16-47083303-C-T

Variant summary

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

The NM_018092.5(NETO2):​c.1496G>T​(p.Arg499Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NETO2 NM_018092.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.70

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 rank	MANE	Protein	UniProt
NETO2	NM_018092.5	c.1496G>T	p.Arg499Leu	missense_variant	Exon 9 of 9	ENST00000562435.6	NP_060562.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NETO2	ENST00000562435.6	c.1496G>T	p.Arg499Leu	missense_variant	Exon 9 of 9	1	NM_018092.5	ENSP00000455169.1
NETO2	ENST00000303155.9	c.1475G>T	p.Arg492Leu	missense_variant	Exon 9 of 9	5		ENSP00000306726.5
NETO2	ENST00000562559.5	c.1013G>T	p.Arg338Leu	missense_variant	Exon 5 of 5	3		ENSP00000454213.1
NETO2	ENST00000564667.1	c.602G>T	p.Arg201Leu	missense_variant	Exon 2 of 2	4		ENSP00000457133.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.26
Sift	Benign	0.032	D;D
Sift4G	Benign	0.065	T;T
Polyphen		0.95	P;.
Vest4		0.60
MutPred		0.41		Gain of sheet (P = 0.0266);.;
MVP		0.60
MPC		0.89
ClinPred		0.96	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.49

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: chr16-47117214; COSMIC: COSV100292507; COSMIC: COSV100292507;