11-19713865-C-G

Variant names:

• chr11-19713865-C-G
• rs141966195
• NM_145117.5:c.170C>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_145117.5(NAV2):​c.170C>G​(p.Pro57Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000967 in 1,613,716 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0053 (11 hom., cov: 33)
  • Exomes 𝑓: 0.00051 (11 hom.)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.90

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0059349537).
• BP6: Variant 11-19713865-C-G is Benign according to our data. Variant chr11-19713865-C-G is described in ClinVar as [Benign]. Clinvar id is 3040987.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00531 (809/152344) while in subpopulation AFR AF= 0.0185 (771/41580). AF 95% confidence interval is 0.0175. There are 11 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5	c.170C>G	p.Pro57Arg	missense_variant	Exon 1 of 38	ENST00000349880.9	NP_660093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV2	ENST00000349880.9	c.170C>G	p.Pro57Arg	missense_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6
NAV2	ENST00000360655.8	c.76-118619C>G		intron_variant	Intron 1 of 37	1		ENSP00000353871.4
NAV2	ENST00000396087.7	c.170C>G	p.Pro57Arg	missense_variant	Exon 1 of 41	5		ENSP00000379396.3
NAV2	ENST00000396085.6	c.170C>G	p.Pro57Arg	missense_variant	Exon 1 of 39	5		ENSP00000379394.1

Frequencies

GnomAD3 genomes AF: 0.00533 AC: 811 AN: 152226 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00143 AC: 356 AN: 248544 Hom.: 4 AF XY: 0.00101 AC XY: 136 AN XY: 134830

Gnomad AFR exome AF: 0.0199

Gnomad AMR exome AF: 0.000810

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000270

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000514 AC: 751 AN: 1461372 Hom.: 11 Cov.: 31 AF XY: 0.000411 AC XY: 299 AN XY: 727002

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.000939

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00531 AC: 809 AN: 152344 Hom.: 11 Cov.: 33 AF XY: 0.00540 AC XY: 402 AN XY: 74494

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00145 Hom.: 1

Bravo AF: 0.00605

ESP6500AA AF: 0.0216 AC: 95

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00178 AC: 216

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NAV2-related disorder Benign:1

Nov 25, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	.;.;T;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T;T;T;T;T
MetaRNN	Benign	0.0059	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N;.;.;N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.0	N;.;.;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D;.;.;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D
Polyphen		0.94	.;.;.;P;.
Vest4		0.55
MVP		0.068
MPC		0.31
ClinPred		0.030	T
GERP RS		5.3
Varity_R		0.29
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141966195; hg19: chr11-19735411;