Genetic Variant NM_145117.5:c.52G>A (chr11-19713747-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145117.5(NAV2):c.52G>A(p.Val18Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,458,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

NAV2
NM_145117.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Publications

0 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:

LEISA1 (HGNC:55264): (lncRNA enhancing IL-6/STAT3 signaling activation 1)

LEISA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14416692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5 link	c.52G>A	p.Val18Met	missense_variant	Exon 1 of 38	ENST00000349880.9	NP_660093.2	Q8IVL1-3A7E2D6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NAV2	ENST00000349880.9 link	c.52G>A	p.Val18Met	missense_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6	Q8IVL1-3
NAV2	ENST00000360655.8 link	c.76-118737G>A		intron_variant	Intron 1 of 37	1		ENSP00000353871.4	Q8IVL1-4
NAV2	ENST00000396087.7 link	c.52G>A	p.Val18Met	missense_variant	Exon 1 of 41	5		ENSP00000379396.3	Q8IVL1-1
NAV2	ENST00000396085.6 link	c.52G>A	p.Val18Met	missense_variant	Exon 1 of 39	5		ENSP00000379394.1	Q8IVL1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000816

AC:

AN:

244992

AF XY:

0.00000751

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1458962

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.00

AC:

AN:

44546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39638

South Asian (SAS)

AF:

0.00

AC:

AN:

86024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52672

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1110774

Other (OTH)

AF:

0.00

AC:

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 07, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.52G>A (p.V18M) alteration is located in exon 1 (coding exon 1) of the NAV2 gene. This alteration results from a G to A substitution at nucleotide position 52, causing the valine (V) at amino acid position 18 to be replaced by a methionine (M). 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

0.30

BayesDel_addAF

Benign

0.0074

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

.;.;T;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

D;D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.90

L;.;.;L;L

PhyloP100

5.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.65

N;.;.;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;.;.;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D

Polyphen

1.0

.;.;.;D;.

Vest4

0.34

MutPred

0.17

Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);

MVP

0.21

MPC

0.66

ClinPred

0.67

GERP RS

4.5

PromoterAI

-0.0028

Neutral

(source)

Varity_R

0.16

gMVP

0.26

Mutation Taster

=92/8

polymorphism

(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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NM_145117.5:c.52G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over