rs755849383

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

1
7
11

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

Genome browser will be placed here

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
NAV2NM_145117.5 linkc.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 Appris UniProt
NAV2ENST00000349880.9 linkc.52G>A p.Val18Met missense_variant Exon 1 of 38 1 NM_145117.5 ENSP00000309577.6 Q8IVL1-3
NAV2ENST00000360655.8 linkc.76-118737G>A intron_variant Intron 1 of 37 1 ENSP00000353871.4 Q8IVL1-4
NAV2ENST00000396087.7 linkc.52G>A p.Val18Met missense_variant Exon 1 of 41 5 ENSP00000379396.3 Q8IVL1-1
NAV2ENST00000396085.6 linkc.52G>A p.Val18Met missense_variant Exon 1 of 39 5 ENSP00000379394.1 Q8IVL1-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000816
AC:
2
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:
8
AN:
1458962
Hom.:
0
Cov.:
31
AF XY:
0.00000965
AC XY:
7
AN XY:
725498
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33426
American (AMR)
AF:
0.00
AC:
0
AN:
44546
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26012
East Asian (EAS)
AF:
0.0000505
AC:
2
AN:
39638
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86024
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52672
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5626
European-Non Finnish (NFE)
AF:
0.00000540
AC:
6
AN:
1110774
Other (OTH)
AF:
0.00
AC:
0
AN:
60244
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000165
AC:
2

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
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.016
.;.;T;.;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.94
D;D;D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.14
T;T;T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
0.90
L;.;.;L;L
PhyloP100
5.0
PrimateAI
Pathogenic
0.85
D
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
D
GERP RS
4.5
PromoterAI
-0.0028
Neutral
Varity_R
0.16
gMVP
0.26
Mutation Taster
=92/8
polymorphism

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

Other links and lift over

dbSNP: rs755849383; hg19: chr11-19735293; API