NM_145117.5:c.2779A>G

Variant names:

• chr11-20035969-A-G
• 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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.56

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]

ACMG classification

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
NAV2	NM_145117.5	c.2779A>G	p.Ser927Gly	missense_variant	Exon 12 of 38	ENST00000349880.9	NP_660093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV2	ENST00000349880.9	c.2779A>G	p.Ser927Gly	missense_variant	Exon 12 of 38	1	NM_145117.5	ENSP00000309577.6

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

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;