Variant chr9-132166965-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM1BP4_StrongBP6_Very_StrongBS2

The NM_032536.4(NTNG2):c.134G>A(p.Arg45His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00724 in 1,614,232 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 63 hom. )

Consequence

NTNG2
NM_032536.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.22

Variant links:

Genes affected

NTNG2 (HGNC:14288): (netrin G2) Predicted to be involved in several processes, including basement membrane assembly; cell morphogenesis involved in differentiation; and regulation of cell projection organization. Located in Flemming body; intercellular bridge; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

NTNG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM1

In a domain Laminin N-terminal (size 251) in uniprot entity NTNG2_HUMAN there are 8 pathogenic changes around while only 1 benign (89%) in NM_032536.4

BP4

Computational evidence support a benign effect (MetaRNN=0.0054740906).

BP6

Variant 9-132166965-G-A is Benign according to our data. Variant chr9-132166965-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 777189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTNG2	NM_032536.4 linkuse as main transcript	c.134G>A	p.Arg45His	missense_variant	2/8	ENST00000393229.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTNG2	ENST00000393229.4 linkuse as main transcript	c.134G>A	p.Arg45His	missense_variant	2/8	1	NM_032536.4	P1	Q96CW9-1

Frequencies

GnomAD3 genomes

AF:

0.00558

AC:

850

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00804

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00738

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00599

AC:

1507

AN:

251446

Hom.:

AF XY:

0.00603

AC XY:

820

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00298

Gnomad ASJ exome

AF:

0.0158

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00905

Gnomad NFE exome

AF:

0.00831

Gnomad OTH exome

AF:

0.00750

GnomAD4 exome

AF:

0.00742

AC:

10845

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00718

AC XY:

5223

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.0183

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.00812

Gnomad4 OTH exome

AF:

0.00786

GnomAD4 genome

AF:

0.00557

AC:

849

AN:

152350

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

418

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00803

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00942

Gnomad4 NFE

AF:

0.00738

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00671

Hom.:

Bravo

AF:

0.00509

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.00643

AC:

781

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00782

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	NTNG2: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.94

N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.10

Sift

Benign

0.14

T;T

Sift4G

Benign

0.090

T;D

Polyphen

0.93

.;P

Vest4

0.32

MVP

0.37

MPC

1.9

ClinPred

0.011

GERP RS

5.7

Varity_R

0.12

gMVP

0.72

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