11-19713779-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_145117.5(NAV2):c.84C>A(p.Pro28=) 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 (★).

• Frequency:
  • Genomes: 𝑓 0.020 (105 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (97 hom.)
• Consequence: NAV2 NM_145117.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.496

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]

LEISA1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 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 criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
NAV2	NM_145117.5	c.84C>A	p.Pro28=	synonymous_variant	1/38	ENST00000349880.9
LEISA1	NR_015384.2	n.894G>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV2	ENST00000349880.9	c.84C>A	p.Pro28=	synonymous_variant	1/38	1	NM_145117.5
NAV2	ENST00000360655.8	c.76-118705C>A		intron_variant		1		P1
NAV2	ENST00000396087.7	c.84C>A	p.Pro28=	synonymous_variant	1/41	5
NAV2	ENST00000396085.6	c.84C>A	p.Pro28=	synonymous_variant	1/39	5

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3019 AN: 152226 Hom.: 105 Cov.: 33

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.: 37 AF XY: 0.00375 AC XY: 499 AN XY: 132960

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.: 97 Cov.: 31 AF XY: 0.00167 AC XY: 1211 AN XY: 726570

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.: 33 AF XY: 0.0195 AC XY: 1449 AN XY: 74486

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.: 5

Bravo AF: 0.0222

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NAV2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 03, 2020

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	14
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

Other links and lift over

dbSNP: rs11828836; hg19: chr11-19735325;