11-19713747-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145117.5(NAV2):c.52G>A(p.Val18Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,458,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14416692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV2	NM_145117.5	c.52G>A	p.Val18Met	missense_variant	1/38	ENST00000349880.9
LEISA1	NR_015384.2	n.926C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV2	ENST00000349880.9	c.52G>A	p.Val18Met	missense_variant	1/38	1	NM_145117.5
NAV2	ENST00000360655.8	c.76-118737G>A		intron_variant		1		P1
NAV2	ENST00000396087.7	c.52G>A	p.Val18Met	missense_variant	1/41	5
NAV2	ENST00000396085.6	c.52G>A	p.Val18Met	missense_variant	1/39	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000816 AC: 2 AN: 244992 Hom.: 0 AF XY: 0.00000751 AC XY: 1 AN XY: 133206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1458962 Hom.: 0 Cov.: 31 AF XY: 0.00000965 AC XY: 7 AN XY: 725498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.52G>A (p.V18M) alteration is located in exon 1 (coding exon 1) of the NAV2 gene. This alteration results from a G to A substitution at nucleotide position 52, causing the valine (V) at amino acid position 18 to be replaced by a methionine (M). 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	Benign	0.30
BayesDel_addAF	Benign	0.0074	T
BayesDel_noAF	Benign	-0.23
Cadd	Pathogenic	28
Dann	Uncertain	1.0
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.90	L;.;.;L;L
MutationTaster	Benign	0.89	D;D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.65	N;.;.;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D;.;.;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		1.0	.;.;.;D;.
Vest4		0.34
MutPred		0.17		Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);
MVP		0.21
MPC		0.66
ClinPred		0.67	D
GERP RS		4.5
Varity_R		0.16
gMVP		0.26

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: rs755849383; hg19: chr11-19735293;