NM_145117.5:c.2779A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145117.5(NAV2):​c.2779A>G​(p.Ser927Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

NAV2
NM_145117.5 missense

Scores

8
6
5

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.56
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAV2NM_145117.5 linkc.2779A>G p.Ser927Gly missense_variant Exon 12 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.2779A>G p.Ser927Gly missense_variant Exon 12 of 38 1 NM_145117.5 ENSP00000309577.6 Q8IVL1-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

NAV2-related disorder Uncertain:1
Jun 20, 2024
PreventionGenetics, part of Exact Sciences
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

The NAV2 c.2848A>G variant is predicted to result in the amino acid substitution p.Ser950Gly. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
.;.;.;T;.;D;.;T;T
Eigen
Uncertain
0.68
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Benign
0.56
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.058
D
MetaRNN
Uncertain
0.48
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Pathogenic
3.0
.;.;.;.;.;M;.;.;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-2.7
D;D;.;N;D;D;D;D;D
REVEL
Benign
0.28
Sift
Pathogenic
0.0
D;D;.;D;D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D;D;D;D
Polyphen
0.99
D;.;.;.;D;.;P;P;.
Vest4
0.64
MutPred
0.17
.;.;.;.;.;.;Loss of phosphorylation at S13 (P = 0.0202);Loss of phosphorylation at S13 (P = 0.0202);Loss of phosphorylation at S13 (P = 0.0202);
MVP
0.47
MPC
0.63
ClinPred
0.99
D
GERP RS
5.9
Varity_R
0.75
gMVP
0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-20057515; API