Variant 16-47083433-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018092.5(NETO2):c.1366T>A(p.Ser456Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00372 in 1,614,126 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.020 ( 105 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 90 hom. )

Consequence

NETO2
NM_018092.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.95

Variant links:

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]

NETO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018110871).

BP6

Variant 16-47083433-A-T is Benign according to our data. Variant chr16-47083433-A-T is described in ClinVar as [Benign]. Clinvar id is 768776.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NETO2	NM_018092.5 linkuse as main transcript	c.1366T>A	p.Ser456Thr	missense_variant	9/9	ENST00000562435.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NETO2	ENST00000562435.6 linkuse as main transcript	c.1366T>A	p.Ser456Thr	missense_variant	9/9	1	NM_018092.5	P4	Q8NC67-1
NETO2	ENST00000303155.9 linkuse as main transcript	c.1345T>A	p.Ser449Thr	missense_variant	9/9	5		A1	Q8NC67-3
NETO2	ENST00000562559.5 linkuse as main transcript	c.886T>A	p.Ser296Thr	missense_variant	5/5	3
NETO2	ENST00000564667.1 linkuse as main transcript	c.475T>A	p.Ser159Thr	missense_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

3062

AN:

152114

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0697

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00524

AC:

1318

AN:

251488

Hom.:

AF XY:

0.00379

AC XY:

515

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0714

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00200

AC:

2923

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1225

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0697

Gnomad4 AMR exome

AF:

0.00434

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000881

Gnomad4 OTH exome

AF:

0.00445

GnomAD4 genome

AF:

0.0202

AC:

3079

AN:

152232

Hom.:

105

Cov.:

AF XY:

0.0196

AC XY:

1459

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0699

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00615

Hom.:

Bravo

AF:

0.0228

ESP6500AA

AF:

0.0665

AC:

293

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00667

AC:

810

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.46

N;N

Sift

Benign

0.58

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.60

P;.

Vest4

0.11

MVP

0.48

MPC

0.29

ClinPred

0.0084

GERP RS

2.2

Varity_R

0.068

gMVP

0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over