11-19713850-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_145117.5(NAV2):c.155A>G(p.Tyr52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,613,580 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 1 hom. )

Consequence

NAV2
NM_145117.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.20

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:

LEISA1 (HGNC:):

LEISA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02209562).

BP6

Variant 11-19713850-A-G is Benign according to our data. Variant chr11-19713850-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3042108.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV2	NM_145117.5 linkuse as main transcript	c.155A>G	p.Tyr52Cys	missense_variant	1/38	ENST00000349880.9
LEISA1	NR_015384.2 linkuse as main transcript	n.823T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV2	ENST00000349880.9 linkuse as main transcript	c.155A>G	p.Tyr52Cys	missense_variant	1/38	1	NM_145117.5		Q8IVL1-3
NAV2	ENST00000360655.8 linkuse as main transcript	c.76-118634A>G		intron_variant		1		P1	Q8IVL1-4
NAV2	ENST00000396087.7 linkuse as main transcript	c.155A>G	p.Tyr52Cys	missense_variant	1/41	5			Q8IVL1-1
NAV2	ENST00000396085.6 linkuse as main transcript	c.155A>G	p.Tyr52Cys	missense_variant	1/39	5			Q8IVL1-2

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

229

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00127

AC:

315

AN:

247790

Hom.:

AF XY:

0.00135

AC XY:

182

AN XY:

134520

show subpopulations

Gnomad AFR exome

AF:

0.000436

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000931

Gnomad NFE exome

AF:

0.00210

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00193

AC:

2821

AN:

1461290

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

1348

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000755

Gnomad4 NFE exome

AF:

0.00235

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00150

AC:

229

AN:

152290

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00240

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00170

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00210

AC:

ExAC

AF:

0.00148

AC:

180

EpiCase

AF:

0.00196

EpiControl

AF:

0.00261

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NAV2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2023

This variant is classified as likely 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

0.084

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.0079

Eigen_PC

Benign

0.033

FATHMM_MKL

Benign

0.55

LIST_S2

Uncertain

0.87

D;D;D;D;D

M_CAP

Benign

0.047

MetaRNN

Benign

0.022

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

N;.;.;N;N

MutationTaster

Benign

0.96

D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.070

N;.;.;N;N

REVEL

Benign

0.28

Sift

Uncertain

0.0080

D;.;.;D;D

Sift4G

Benign

0.069

T;T;T;T;T

Polyphen

0.99

.;.;.;D;.

Vest4

0.73

MVP

0.043

MPC

0.75

ClinPred

0.034

GERP RS

2.9

Varity_R

0.10

gMVP

0.59

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