NM_145117.5:c.326G>A

Variant names:

• chr11-19832542-G-A
• rs6483617
• NM_145117.5:c.326G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_145117.5(NAV2):​c.326G>A​(p.Arg109Lys) variant causes a missense change. The variant allele was found at a frequency of 0.33 in 1,613,540 control chromosomes in the GnomAD database, including 93,706 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.42 (14997 hom., cov: 32)
  • Exomes 𝑓: 0.32 (78709 hom.)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.38
• Publications: 29 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.98042E-5).
• BP6: Variant 11-19832542-G-A is Benign according to our data. Variant chr11-19832542-G-A is described in ClinVar as Benign. ClinVar VariationId is 3058864.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

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.326G>A	p.Arg109Lys	missense	Exon 2 of 38	NP_660093.2
	NAV2	NM_001244963.2		c.326G>A	p.Arg109Lys	missense	Exon 2 of 41	NP_001231892.1	Q8IVL1-1
	NAV2	NM_182964.6		c.326G>A	p.Arg109Lys	missense	Exon 2 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.326G>A	p.Arg109Lys	missense	Exon 2 of 38	ENSP00000309577.6	Q8IVL1-3
	NAV2	ENST00000360655.8	TSL:1	c.134G>A	p.Arg45Lys	missense	Exon 2 of 38	ENSP00000353871.4	Q8IVL1-4
	NAV2	ENST00000396087.7	TSL:5	c.326G>A	p.Arg109Lys	missense	Exon 2 of 41	ENSP00000379396.3	Q8IVL1-1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63495 AN: 151806 Hom.: 14962 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.448

GnomAD2 exomes AF: 0.347 AC: 87291 AN: 251430 AF XY: 0.334

Gnomad AFR exome AF: 0.651

Gnomad AMR exome AF: 0.386

Gnomad ASJ exome AF: 0.377

Gnomad EAS exome AF: 0.411

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.325

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.321 AC: 469123 AN: 1461614 Hom.: 78709 Cov.: 37 AF XY: 0.318 AC XY: 230912 AN XY: 727120

African (AFR) AF: 0.664 AC: 22235 AN: 33476

American (AMR) AF: 0.390 AC: 17450 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 9875 AN: 26132

East Asian (EAS) AF: 0.366 AC: 14517 AN: 39696

South Asian (SAS) AF: 0.213 AC: 18398 AN: 86248

European-Finnish (FIN) AF: 0.298 AC: 15925 AN: 53406

Middle Eastern (MID) AF: 0.404 AC: 2329 AN: 5768

European-Non Finnish (NFE) AF: 0.313 AC: 347953 AN: 1111776

Other (OTH) AF: 0.338 AC: 20441 AN: 60394

GnomAD4 genome AF: 0.418 AC: 63573 AN: 151926 Hom.: 14997 Cov.: 32 AF XY: 0.413 AC XY: 30681 AN XY: 74250

African (AFR) AF: 0.648 AC: 26839 AN: 41428

American (AMR) AF: 0.400 AC: 6117 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2005 AN: 5136

South Asian (SAS) AF: 0.206 AC: 993 AN: 4810

European-Finnish (FIN) AF: 0.307 AC: 3246 AN: 10564

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21682 AN: 67926

Other (OTH) AF: 0.441 AC: 931 AN: 2110

Alfa AF: 0.360 Hom.: 41858

Bravo AF: 0.445

TwinsUK AF: 0.311 AC: 1152

ALSPAC AF: 0.307 AC: 1183

ESP6500AA AF: 0.656 AC: 2886

ESP6500EA AF: 0.318 AC: 2734

ExAC AF: 0.348 AC: 42201

Asia WGS AF: 0.273 AC: 951 AN: 3478

EpiCase AF: 0.342

EpiControl AF: 0.339

ClinVar

ClinVar submissions

Significance: 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	0.051
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.72
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.000020	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.5	N
PhyloP100		6.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MPC		0.16
ClinPred		0.020	T
GERP RS		5.8
Varity_R		0.064
gMVP		0.45
Mutation Taster		=100/0	polymorphism (auto)

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: rs6483617; hg19: chr11-19854088; COSMIC: COSV62315614;