11-19713734-A-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_145117.5(NAV2):c.39A>C(p.Gly13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,595,400 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (18 hom.)
• Consequence: NAV2 NM_145117.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.53

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-19713734-A-C is Benign according to our data. Variant chr11-19713734-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2641676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.53 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV2	NM_145117.5	c.39A>C	p.Gly13=	synonymous_variant	1/38	ENST00000349880.9
LEISA1	NR_015384.2	n.939T>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV2	ENST00000349880.9	c.39A>C	p.Gly13=	synonymous_variant	1/38	1	NM_145117.5
NAV2	ENST00000360655.8	c.76-118750A>C		intron_variant		1		P1
NAV2	ENST00000396087.7	c.39A>C	p.Gly13=	synonymous_variant	1/41	5
NAV2	ENST00000396085.6	c.39A>C	p.Gly13=	synonymous_variant	1/39	5

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 380 AN: 152156 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00451

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00224 AC: 541 AN: 241678 Hom.: 4 AF XY: 0.00225 AC XY: 296 AN XY: 131528

Gnomad AFR exome AF: 0.000572

Gnomad AMR exome AF: 0.000687

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000376

Gnomad NFE exome AF: 0.00459

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.00430 AC: 6205 AN: 1443126 Hom.: 18 Cov.: 31 AF XY: 0.00403 AC XY: 2884 AN XY: 714836

Gnomad4 AFR exome AF: 0.000607

Gnomad4 AMR exome AF: 0.000646

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000400

Gnomad4 NFE exome AF: 0.00543

Gnomad4 OTH exome AF: 0.00271

GnomAD4 genome AF: 0.00250 AC: 380 AN: 152274 Hom.: 2 Cov.: 33 AF XY: 0.00235 AC XY: 175 AN XY: 74470

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00451

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00263 Hom.: 1

Bravo AF: 0.00264

EpiCase AF: 0.00383

EpiControl AF: 0.00451

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

NAV2: BP4, BP7, BS2 -

NAV2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as likely 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	-0.59
Cadd	Benign	12
Dann	Benign	0.75

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: rs146393896; hg19: chr11-19735280; COSMIC: COSV100587367; COSMIC: COSV100587367;