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GeneBe

11-19832549-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_145117.5(NAV2):c.333C>T(p.Leu111=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 1,614,174 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 8 hom., cov: 33)
Exomes 𝑓: 0.0060 ( 39 hom. )

Consequence

NAV2
NM_145117.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0170
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-19832549-C-T is Benign according to our data. Variant chr11-19832549-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2641677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.017 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NAV2NM_145117.5 linkuse as main transcriptc.333C>T p.Leu111= synonymous_variant 2/38 ENST00000349880.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAV2ENST00000349880.9 linkuse as main transcriptc.333C>T p.Leu111= synonymous_variant 2/381 NM_145117.5 Q8IVL1-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00497
AC:
757
AN:
152186
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000989
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00275
Gnomad ASJ
AF:
0.00230
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.0164
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00692
Gnomad OTH
AF:
0.00622
GnomAD3 exomes
AF:
0.00524
AC:
1317
AN:
251480
Hom.:
7
AF XY:
0.00514
AC XY:
699
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00123
Gnomad AMR exome
AF:
0.00124
Gnomad ASJ exome
AF:
0.00149
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00144
Gnomad FIN exome
AF:
0.0156
Gnomad NFE exome
AF:
0.00730
Gnomad OTH exome
AF:
0.00456
GnomAD4 exome
AF:
0.00600
AC:
8766
AN:
1461870
Hom.:
39
Cov.:
32
AF XY:
0.00585
AC XY:
4254
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.00136
Gnomad4 ASJ exome
AF:
0.00107
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00157
Gnomad4 FIN exome
AF:
0.0147
Gnomad4 NFE exome
AF:
0.00673
Gnomad4 OTH exome
AF:
0.00411
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00497
AC:
757
AN:
152304
Hom.:
8
Cov.:
33
AF XY:
0.00525
AC XY:
391
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.000986
Gnomad4 AMR
AF:
0.00275
Gnomad4 ASJ
AF:
0.00230
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.0164
Gnomad4 NFE
AF:
0.00692
Gnomad4 OTH
AF:
0.00616
Alfa
AF:
0.00585
Hom.:
1
Bravo
AF:
0.00394
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00556
EpiControl
AF:
0.00670

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2022NAV2: BP4, BP7 -
NAV2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 04, 2020This 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
-0.27
Cadd
Benign
11
Dann
Benign
0.77

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.

Other links and lift over

dbSNP: rs148087344; hg19: chr11-19854095; COSMIC: COSV100587518; API