chr11-19713846-A-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145117.5(NAV2):​c.151A>C​(p.Thr51Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T51S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NAV2
NM_145117.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.553

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: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.051371366).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAV2NM_145117.5 linkc.151A>C p.Thr51Pro 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.151A>C p.Thr51Pro missense_variant Exon 1 of 38 1 NM_145117.5 ENSP00000309577.6 Q8IVL1-3
NAV2ENST00000360655.8 linkc.76-118638A>C intron_variant Intron 1 of 37 1 ENSP00000353871.4 Q8IVL1-4
NAV2ENST00000396087.7 linkc.151A>C p.Thr51Pro missense_variant Exon 1 of 41 5 ENSP00000379396.3 Q8IVL1-1
NAV2ENST00000396085.6 linkc.151A>C p.Thr51Pro missense_variant Exon 1 of 39 5 ENSP00000379394.1 Q8IVL1-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461178
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726886
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86248
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52914
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111868
Other (OTH)
AF:
0.00
AC:
0
AN:
60356
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
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.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
14
DANN
Benign
0.95
DEOGEN2
Benign
0.010
.;.;T;.;T
Eigen
Benign
-0.97
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.59
T;T;T;T;T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.051
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.;.;N;N
PhyloP100
-0.55
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.42
N;.;.;N;N
REVEL
Benign
0.016
Sift
Benign
0.047
D;.;.;D;D
Sift4G
Benign
0.13
T;T;T;T;T
Polyphen
0.060
.;.;.;B;.
Vest4
0.14
MutPred
0.26
Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP
0.10
MPC
0.22
ClinPred
0.047
T
GERP RS
-0.60
PromoterAI
0.0090
Neutral
Varity_R
0.13
gMVP
0.34
Mutation Taster
=90/10
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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: rs756079268; hg19: chr11-19735392; API