11-19713771-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145117.5(NAV2):​c.76C>T​(p.His26Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,460,508 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: 0.0000062 ( 0 hom. )

Consequence

NAV2
NM_145117.5 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04
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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3950079).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAV2NM_145117.5 linkc.76C>T p.His26Tyr 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.76C>T p.His26Tyr missense_variant Exon 1 of 38 1 NM_145117.5 ENSP00000309577.6 Q8IVL1-3
NAV2ENST00000360655.8 linkc.76-118713C>T intron_variant Intron 1 of 37 1 ENSP00000353871.4 Q8IVL1-4
NAV2ENST00000396087.7 linkc.76C>T p.His26Tyr missense_variant Exon 1 of 41 5 ENSP00000379396.3 Q8IVL1-1
NAV2ENST00000396085.6 linkc.76C>T p.His26Tyr missense_variant Exon 1 of 39 5 ENSP00000379394.1 Q8IVL1-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000818
AC:
2
AN:
244412
Hom.:
0
AF XY:
0.00000751
AC XY:
1
AN XY:
133130
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000184
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1460508
Hom.:
0
Cov.:
31
AF XY:
0.00000551
AC XY:
4
AN XY:
726536
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.76C>T (p.H26Y) alteration is located in exon 1 (coding exon 1) of the NAV2 gene. This alteration results from a C to T substitution at nucleotide position 76, causing the histidine (H) at amino acid position 26 to be replaced by a tyrosine (Y). 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
0.19
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.024
.;.;T;.;T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.82
T;T;T;T;T
M_CAP
Uncertain
0.090
D
MetaRNN
Benign
0.40
T;T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.55
N;.;.;N;N
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-0.74
N;.;D;N;N
REVEL
Benign
0.17
Sift
Uncertain
0.0070
D;.;D;D;D
Sift4G
Uncertain
0.011
D;D;D;D;D
Polyphen
0.96
.;.;.;D;.
Vest4
0.66
MutPred
0.28
Gain of phosphorylation at H26 (P = 0.0225);Gain of phosphorylation at H26 (P = 0.0225);Gain of phosphorylation at H26 (P = 0.0225);Gain of phosphorylation at H26 (P = 0.0225);Gain of phosphorylation at H26 (P = 0.0225);
MVP
0.41
MPC
0.69
ClinPred
0.81
D
GERP RS
4.5
Varity_R
0.21
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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.

Other links and lift over

dbSNP: rs770541601; hg19: chr11-19735317; API