Variant 11-19832542-G-A 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_145117.5(NAV2):c.326G>A(p.Arg109Lys) variant causes a missense change. The variant allele was found at a frequency of 0.33 in 1,613,540 control chromosomes in the GnomAD database, including 93,706 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.42 ( 14997 hom., cov: 32)

Exomes 𝑓: 0.32 ( 78709 hom. )

Consequence

NAV2
NM_145117.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.38

Variant links:

Genes affected

NAV2 (HGNC:15997): (neuron navigator 2) This gene encodes a member of the neuron navigator gene family, which may play a role in cellular growth and migration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

NAV2 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=1.98042E-5).

BP6

Variant 11-19832542-G-A is Benign according to our data. Variant chr11-19832542-G-A is described in ClinVar as [Benign]. Clinvar id is 3058864.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV2	NM_145117.5 linkuse as main transcript	c.326G>A	p.Arg109Lys	missense_variant	2/38	ENST00000349880.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV2	ENST00000349880.9 linkuse as main transcript	c.326G>A	p.Arg109Lys	missense_variant	2/38	1	NM_145117.5		Q8IVL1-3

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63495

AN:

151806

Hom.:

14962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.647

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.448

GnomAD3 exomes

AF:

0.347

AC:

87291

AN:

251430

Hom.:

16545

AF XY:

0.334

AC XY:

45443

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.651

Gnomad AMR exome

AF:

0.386

Gnomad ASJ exome

AF:

0.377

Gnomad EAS exome

AF:

0.411

Gnomad SAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.321

AC:

469123

AN:

1461614

Hom.:

78709

Cov.:

AF XY:

0.318

AC XY:

230912

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.664

Gnomad4 AMR exome

AF:

0.390

Gnomad4 ASJ exome

AF:

0.378

Gnomad4 EAS exome

AF:

0.366

Gnomad4 SAS exome

AF:

0.213

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.418

AC:

63573

AN:

151926

Hom.:

14997

Cov.:

AF XY:

0.413

AC XY:

30681

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.648

Gnomad4 AMR

AF:

0.400

Gnomad4 ASJ

AF:

0.381

Gnomad4 EAS

AF:

0.390

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.307

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.441

Alfa

AF:

0.346

Hom.:

25013

Bravo

AF:

0.445

TwinsUK

AF:

0.311

AC:

1152

ALSPAC

AF:

0.307

AC:

1183

ESP6500AA

AF:

0.656

AC:

2886

ESP6500EA

AF:

0.318

AC:

2734

ExAC

AF:

0.348

AC:

42201

Asia WGS

AF:

0.273

AC:

951

AN:

3478

EpiCase

AF:

0.342

EpiControl

AF:

0.339

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NAV2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Benign

0.72

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.56

T;T;T;T;T;T;T

MetaRNN

Benign

0.000020

T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Uncertain

0.72

PROVEAN

Benign

1.2

N;N;.;.;N;N;.

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;.;.;T;T;.

Sift4G

Benign

1.0

T;T;T;T;T;T;.

Polyphen

0.0

B;.;.;.;B;.;.

Vest4

0.12

MPC

0.16

ClinPred

0.020

GERP RS

5.8

Varity_R

0.064

gMVP

0.45

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