Genetic Variant NAV2:p.His26Tyr (chr11-19713771-C-T) – ACMG Classification: Uncertain_significance (1 pts)

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

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]

NAV2 links:

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

LEISA1 links:

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
NAV2	NM_145117.5 link	c.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	UniProt
NAV2	ENST00000349880.9 link	c.76C>T	p.His26Tyr	missense_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6	Q8IVL1-3
NAV2	ENST00000360655.8 link	c.76-118713C>T		intron_variant	Intron 1 of 37	1		ENSP00000353871.4	Q8IVL1-4
NAV2	ENST00000396087.7 link	c.76C>T	p.His26Tyr	missense_variant	Exon 1 of 41	5		ENSP00000379396.3	Q8IVL1-1
NAV2	ENST00000396085.6 link	c.76C>T	p.His26Tyr	missense_variant	Exon 1 of 39	5		ENSP00000379394.1	Q8IVL1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000818

AC:

AN:

244412

Hom.:

AF XY:

0.00000751

AC XY:

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:

AN:

1460508

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

.;.;T;.;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.40

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

N;.;.;N;N

PrimateAI

Uncertain

0.79

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over