NM_145117.5:c.155A>G

Variant names:

• chr11-19713850-A-G
• rs148165391
• NM_145117.5:c.155A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_145117.5(NAV2):​c.155A>G​(p.Tyr52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,613,580 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (1 hom.)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.20
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02209562).
• BP6: Variant 11-19713850-A-G is Benign according to our data. Variant chr11-19713850-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3042108.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145117.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV2	NM_145117.5	MANE Select	c.155A>G	p.Tyr52Cys	missense	Exon 1 of 38	NP_660093.2
	NAV2	NM_001244963.2		c.155A>G	p.Tyr52Cys	missense	Exon 1 of 41	NP_001231892.1	Q8IVL1-1
	NAV2	NM_182964.6		c.155A>G	p.Tyr52Cys	missense	Exon 1 of 39	NP_892009.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV2	ENST00000349880.9	TSL:1 MANE Select	c.155A>G	p.Tyr52Cys	missense	Exon 1 of 38	ENSP00000309577.6	Q8IVL1-3
	NAV2	ENST00000360655.8	TSL:1	c.76-118634A>G		intron	N/A	ENSP00000353871.4	Q8IVL1-4
	NAV2	ENST00000396087.7	TSL:5	c.155A>G	p.Tyr52Cys	missense	Exon 1 of 41	ENSP00000379396.3	Q8IVL1-1

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 229 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00127 AC: 315 AN: 247790 AF XY: 0.00135

Gnomad AFR exome AF: 0.000436

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00160

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000931

Gnomad NFE exome AF: 0.00210

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00193 AC: 2821 AN: 1461290 Hom.: 1 Cov.: 31 AF XY: 0.00185 AC XY: 1348 AN XY: 726940

African (AFR) AF: 0.000329 AC: 11 AN: 33478

American (AMR) AF: 0.00139 AC: 62 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.0000755 AC: 4 AN: 52990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00235 AC: 2611 AN: 1111888

Other (OTH) AF: 0.00142 AC: 86 AN: 60360

GnomAD4 genome AF: 0.00150 AC: 229 AN: 152290 Hom.: 0 Cov.: 33 AF XY: 0.00128 AC XY: 95 AN XY: 74474

African (AFR) AF: 0.000457 AC: 19 AN: 41564

American (AMR) AF: 0.00222 AC: 34 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00240 AC: 163 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00174 Hom.: 8

Bravo AF: 0.00170

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.00210 AC: 18

ExAC AF: 0.00148 AC: 180

EpiCase AF: 0.00196

EpiControl AF: 0.00261

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NAV2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.0079
Eigen_PC	Benign	0.033
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.2
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.28
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.069	T
Polyphen		0.99	D
Vest4		0.73
MVP		0.043
MPC		0.75
ClinPred		0.034	T
GERP RS		2.9
PromoterAI		-0.046	Neutral
Varity_R		0.10
gMVP		0.59
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs148165391; hg19: chr11-19735396; COSMIC: COSV62315837; COSMIC: COSV62315837;