Variant 11-19880003-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145117.5(NAV2):c.646G>A(p.Ala216Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,613,724 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A216G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

NAV2
NM_145117.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.119

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0069845617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV2	NM_145117.5 linkuse as main transcript	c.646G>A	p.Ala216Thr	missense_variant	5/38	ENST00000349880.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV2	ENST00000349880.9 linkuse as main transcript	c.646G>A	p.Ala216Thr	missense_variant	5/38	1	NM_145117.5		Q8IVL1-3

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000220

AC:

AN:

249698

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

135088

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00279

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000711

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000135

AC:

197

AN:

1461564

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00291

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000269

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000241

Hom.:

Bravo

AF:

0.000427

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.646G>A (p.A216T) alteration is located in exon 5 (coding exon 5) of the NAV2 gene. This alteration results from a G to A substitution at nucleotide position 646, causing the alanine (A) at amino acid position 216 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.86

D;D;D;D;D;D

M_CAP

Benign

0.0052

MetaRNN

Benign

0.0070

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

D;D;D;D;D;D

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.55

N;N;.;.;N;N

REVEL

Benign

0.026

Sift

Benign

0.45

T;T;.;.;T;T

Sift4G

Benign

0.20

T;T;T;T;T;T

Polyphen

0.034

B;.;.;.;B;.

Vest4

0.13

MVP

0.22

MPC

0.15

ClinPred

0.020

GERP RS

3.9

Varity_R

0.042

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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