11-19713721-A-C

Variant summary

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

The NM_145117.5(NAV2):c.26A>C(p.Lys9Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000147 in 1,428,848 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: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.37

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=0.2297703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV2	NM_145117.5	c.26A>C	p.Lys9Thr	missense_variant	1/38	ENST00000349880.9
LEISA1	NR_015384.2	n.952T>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV2	ENST00000349880.9	c.26A>C	p.Lys9Thr	missense_variant	1/38	1	NM_145117.5
NAV2	ENST00000360655.8	c.76-118763A>C		intron_variant		1		P1
NAV2	ENST00000396087.7	c.26A>C	p.Lys9Thr	missense_variant	1/41	5
NAV2	ENST00000396085.6	c.26A>C	p.Lys9Thr	missense_variant	1/39	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000852 AC: 2 AN: 234704 Hom.: 0 AF XY: 0.0000156 AC XY: 2 AN XY: 127872

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000697

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000147 AC: 21 AN: 1428848 Hom.: 0 Cov.: 31 AF XY: 0.0000213 AC XY: 15 AN XY: 705390

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000714

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000128

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000285 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Nov 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.30
Cadd	Pathogenic	26
Dann	Uncertain	1.0
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	T;T;D;T;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;.;.;L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.5	N;.;.;N;N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;.;.;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D
Polyphen		0.92	.;.;.;P;.
Vest4		0.51
MutPred		0.31		Loss of MoRF binding (P = 0.007);Loss of MoRF binding (P = 0.007);Loss of MoRF binding (P = 0.007);Loss of MoRF binding (P = 0.007);Loss of MoRF binding (P = 0.007);
MVP		0.068
MPC		0.72
ClinPred		0.64	D
GERP RS		5.4
Varity_R		0.48
gMVP		0.39

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: rs1288286466; hg19: chr11-19735267;