11-19832549-C-T

Variant names:

• chr11-19832549-C-T
• rs148087344
• NM_145117.5:c.333C>T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_145117.5(NAV2):​c.333C>T​(p.Leu111Leu) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.0170

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.017 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5	c.333C>T	p.Leu111Leu	synonymous_variant	Exon 2 of 38	ENST00000349880.9	NP_660093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV2	ENST00000349880.9	c.333C>T	p.Leu111Leu	synonymous_variant	Exon 2 of 38	1	NM_145117.5	ENSP00000309577.6

Frequencies

GnomAD3 genomes AF: 0.00497 AC: 757 AN: 152186 Hom.: 8 Cov.: 33

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

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

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 AF: 0.00497 AC: 757 AN: 152304 Hom.: 8 Cov.: 33 AF XY: 0.00525 AC XY: 391 AN XY: 74466

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: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NAV2: BP4, BP7 -

NAV2-related disorder Benign:1

Feb 04, 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	-0.27
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

Other links and lift over

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