dbSNP rs374708050: NAV2:p.Pro29Gln (chr11-19713781-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145117.5(NAV2):c.86C>A(p.Pro29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. P29L) 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: 2.86

Publications

0 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09513223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5 link	c.86C>A	p.Pro29Gln	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.86C>A	p.Pro29Gln	missense_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6	Q8IVL1-3
NAV2	ENST00000360655.8 link	c.76-118703C>A		intron_variant	Intron 1 of 37	1		ENSP00000353871.4	Q8IVL1-4
NAV2	ENST00000396087.7 link	c.86C>A	p.Pro29Gln	missense_variant	Exon 1 of 41	5		ENSP00000379396.3	Q8IVL1-1
NAV2	ENST00000396085.6 link	c.86C>A	p.Pro29Gln	missense_variant	Exon 1 of 39	5		ENSP00000379394.1	Q8IVL1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460376

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.00

AC:

AN:

86118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111618

Other (OTH)

AF:

0.00

AC:

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

.;.;T;.;T

Eigen

Benign

-0.079

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.78

T;T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.095

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;N;N

PhyloP100

2.9

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.45

N;.;.;N;N

REVEL

Benign

0.042

Sift

Uncertain

0.025

D;.;.;D;D

Sift4G

Benign

0.084

T;T;T;T;T

Polyphen

0.28

.;.;.;B;.

Vest4

0.21

MutPred

0.16

Loss of catalytic residue at P28 (P = 0.0096);Loss of catalytic residue at P28 (P = 0.0096);Loss of catalytic residue at P28 (P = 0.0096);Loss of catalytic residue at P28 (P = 0.0096);Loss of catalytic residue at P28 (P = 0.0096);

MVP

0.068

MPC

0.29

ClinPred

0.46

GERP RS

4.4

PromoterAI

0.033

Neutral

(source)

Varity_R

0.15

gMVP

0.11

Mutation Taster

=94/6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over