Genetic Variant NAV2:p.Pro28Pro (chr11-19713779-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_145117.5(NAV2):c.84C>A(p.Pro28Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00365 in 1,612,914 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.020 ( 105 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 97 hom. )

Consequence

NAV2
NM_145117.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.496

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 11-19713779-C-A is Benign according to our data. Variant chr11-19713779-C-A is described in ClinVar as [Benign]. Clinvar id is 3039323.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.496 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5 link	c.84C>A	p.Pro28Pro	synonymous_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.84C>A	p.Pro28Pro	synonymous_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6	Q8IVL1-3
NAV2	ENST00000360655.8 link	c.76-118705C>A		intron_variant	Intron 1 of 37	1		ENSP00000353871.4	Q8IVL1-4
NAV2	ENST00000396087.7 link	c.84C>A	p.Pro28Pro	synonymous_variant	Exon 1 of 41	5		ENSP00000379396.3	Q8IVL1-1
NAV2	ENST00000396085.6 link	c.84C>A	p.Pro28Pro	synonymous_variant	Exon 1 of 39	5		ENSP00000379394.1	Q8IVL1-2

Frequencies

GnomAD3 genomes

AF:

0.0198

AC:

3019

AN:

152226

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0693

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00582

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00513

AC:

1252

AN:

243876

Hom.:

AF XY:

0.00375

AC XY:

499

AN XY:

132960

show subpopulations

Gnomad AFR exome

AF:

0.0725

Gnomad AMR exome

AF:

0.00294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000166

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.00196

AC:

2863

AN:

1460570

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1211

AN XY:

726570

show subpopulations

Gnomad4 AFR exome

AF:

0.0709

Gnomad4 AMR exome

AF:

0.00331

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.00418

GnomAD4 genome

AF:

0.0198

AC:

3022

AN:

152344

Hom.:

105

Cov.:

AF XY:

0.0195

AC XY:

1449

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0692

Gnomad4 AMR

AF:

0.00581

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00641

Hom.:

Bravo

AF:

0.0222

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NAV2-related disorder

Benign:1

Jan 03, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.86

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

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