dbSNP rs6483617: NAV2:p.Arg109Lys (chr11-19832542-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

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 no assertion criteria provided B:1

Conservation

PhyloP100: 6.38

Publications

29 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
NAV2	NM_145117.5 link	c.326G>A	p.Arg109Lys	missense_variant	Exon 2 of 38	ENST00000349880.9	NP_660093.2	Q8IVL1-3A7E2D6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV2	ENST00000349880.9 link	c.326G>A	p.Arg109Lys	missense_variant	Exon 2 of 38	1	NM_145117.5	ENSP00000309577.6		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

GnomAD2 exomes

AF:

0.347

AC:

87291

AN:

251430

AF XY:

0.334

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 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

African (AFR)

AF:

0.664

AC:

22235

AN:

33476

American (AMR)

AF:

0.390

AC:

17450

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

9875

AN:

26132

East Asian (EAS)

AF:

0.366

AC:

14517

AN:

39696

South Asian (SAS)

AF:

0.213

AC:

18398

AN:

86248

European-Finnish (FIN)

AF:

0.298

AC:

15925

AN:

53406

Middle Eastern (MID)

AF:

0.404

AC:

2329

AN:

5768

European-Non Finnish (NFE)

AF:

0.313

AC:

347953

AN:

1111776

Other (OTH)

AF:

0.338

AC:

20441

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

16550

33100

49649

66199

82749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.418

AC:

63573

AN:

151926

Hom.:

14997

Cov.:

AF XY:

0.413

AC XY:

30681

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.648

AC:

26839

AN:

41428

American (AMR)

AF:

0.400

AC:

6117

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1323

AN:

3468

East Asian (EAS)

AF:

0.390

AC:

2005

AN:

5136

South Asian (SAS)

AF:

0.206

AC:

993

AN:

4810

European-Finnish (FIN)

AF:

0.307

AC:

3246

AN:

10564

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21682

AN:

67926

Other (OTH)

AF:

0.441

AC:

931

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1736

3471

5207

6942

8678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.360

Hom.:

41858

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: no assertion criteria provided

LINK: link

Submissions by phenotype

NAV2-related disorder

Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.0023

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

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

MutationAssessor

Benign

-1.5

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

PhyloP100

6.4

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs6483617

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over