Genetic Variant NAV2:p.Pro17Leu (chr11-19713745-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_145117.5(NAV2):c.50C>T(p.Pro17Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P17H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NAV2
NM_145117.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.04

Publications

1 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]

NAV2 links:

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

LEISA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27305377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5 link	c.50C>T	p.Pro17Leu	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.50C>T	p.Pro17Leu	missense_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6	Q8IVL1-3
NAV2	ENST00000360655.8 link	c.76-118739C>T		intron_variant	Intron 1 of 37	1		ENSP00000353871.4	Q8IVL1-4
NAV2	ENST00000396087.7 link	c.50C>T	p.Pro17Leu	missense_variant	Exon 1 of 41	5		ENSP00000379396.3	Q8IVL1-1
NAV2	ENST00000396085.6 link	c.50C>T	p.Pro17Leu	missense_variant	Exon 1 of 39	5		ENSP00000379394.1	Q8IVL1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

244928

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458758

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.0000449

AC:

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26010

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

85998

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52678

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110644

Other (OTH)

AF:

0.00

AC:

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

.;.;T;.;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

D;D;D;D;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.0

L;.;.;L;L

PhyloP100

7.0

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.4

N;.;.;N;N

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;.;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

0.98

.;.;.;D;.

Vest4

0.39

MutPred

0.41

Loss of disorder (P = 0.0246);Loss of disorder (P = 0.0246);Loss of disorder (P = 0.0246);Loss of disorder (P = 0.0246);Loss of disorder (P = 0.0246);

MVP

0.18

MPC

0.67

ClinPred

0.79

GERP RS

5.4

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.28

gMVP

0.46

Mutation Taster

=77/23

polymorphism

(source)

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

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11-19713745-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over