11-20044108-C-G

Variant names:

• chr11-20044108-C-G
• rs1191136296
• NM_145117.5:c.3035C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145117.5(NAV2):​c.3035C>G​(p.Pro1012Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.40

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]

NAV2-AS2 (HGNC:40743): (NAV2 antisense RNA 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.407993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5	c.3035C>G	p.Pro1012Arg	missense_variant	Exon 13 of 38	ENST00000349880.9	NP_660093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV2	ENST00000349880.9	c.3035C>G	p.Pro1012Arg	missense_variant	Exon 13 of 38	1	NM_145117.5	ENSP00000309577.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3035C>G (p.P1012R) alteration is located in exon 13 (coding exon 13) of the NAV2 gene. This alteration results from a C to G substitution at nucleotide position 3035, causing the proline (P) at amino acid position 1012 to be replaced by an arginine (R). 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	0.51
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.025	.;.;.;T;.;T;.;T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.41	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	.;.;.;.;.;N;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.7	N;N;.;.;N;N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.50	T;T;.;.;T;T;T;T;T
Sift4G	Benign	0.19	T;T;T;T;T;T;T;T;T
Polyphen		1.0	D;.;.;.;D;D;D;D;.
Vest4		0.79
MutPred		0.19		.;.;.;Gain of MoRF binding (P = 0.0068);.;Gain of MoRF binding (P = 0.0068);.;.;.;
MVP		0.27
MPC		0.68
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.081
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: rs1191136296; hg19: chr11-20065654;