11-19713953-C-A

Variant names:

• chr11-19713953-C-A
• rs147977739
• NM_145117.5:c.258C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145117.5(NAV2):​c.258C>A​(p.Phe86Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,612,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.745
• Publications: 4 publications found

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:55264): (lncRNA enhancing IL-6/STAT3 signaling activation 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009785026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5	c.258C>A	p.Phe86Leu	missense_variant	Exon 1 of 38	ENST00000349880.9	NP_660093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV2	ENST00000349880.9	c.258C>A	p.Phe86Leu	missense_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6
NAV2	ENST00000360655.8	c.76-118531C>A		intron_variant	Intron 1 of 37	1		ENSP00000353871.4
NAV2	ENST00000396087.7	c.258C>A	p.Phe86Leu	missense_variant	Exon 1 of 41	5		ENSP00000379396.3
NAV2	ENST00000396085.6	c.258C>A	p.Phe86Leu	missense_variant	Exon 1 of 39	5		ENSP00000379394.1

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 151968 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000141 AC: 35 AN: 248074 AF XY: 0.000119

Gnomad AFR exome AF: 0.00202

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1460814 Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26 AN XY: 726720

African (AFR) AF: 0.00134 AC: 45 AN: 33472

American (AMR) AF: 0.0000895 AC: 4 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111858

Other (OTH) AF: 0.000116 AC: 7 AN: 60356

GnomAD4 genome AF: 0.000447 AC: 68 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74340

African (AFR) AF: 0.00157 AC: 65 AN: 41510

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67960

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000148 Hom.: 0

Bravo AF: 0.000468

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.258C>A (p.F86L) alteration is located in exon 1 (coding exon 1) of the NAV2 gene. This alteration results from a C to A substitution at nucleotide position 258, causing the phenylalanine (F) at amino acid position 86 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	.;.;T;.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.65	T;T;T;T;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.0098	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.;N;N
PhyloP100		0.74
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.19	N;.;.;N;N
REVEL	Benign	0.15
Sift	Benign	0.93	T;.;.;T;T
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		0.0010	.;.;.;B;.
Vest4		0.15
MutPred		0.50		Gain of catalytic residue at F86 (P = 0.0091);Gain of catalytic residue at F86 (P = 0.0091);Gain of catalytic residue at F86 (P = 0.0091);Gain of catalytic residue at F86 (P = 0.0091);Gain of catalytic residue at F86 (P = 0.0091);
MVP		0.10
MPC		0.18
ClinPred		0.043	T
GERP RS		0.31
PromoterAI		-0.050	Neutral
Varity_R		0.073
gMVP		0.49
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147977739; hg19: chr11-19735499;