11-19713734-A-C

Variant names:

• chr11-19713734-A-C
• rs146393896
• NM_145117.5:c.39A>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_145117.5(NAV2):​c.39A>C​(p.Gly13Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,595,400 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (18 hom.)
• Consequence: NAV2 NM_145117.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.53
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-19713734-A-C is Benign according to our data. Variant chr11-19713734-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2641676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.53 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.39A>C	p.Gly13Gly	synonymous	Exon 1 of 38	NP_660093.2
	NAV2	NM_001244963.2		c.39A>C	p.Gly13Gly	synonymous	Exon 1 of 41	NP_001231892.1	Q8IVL1-1
	NAV2	NM_182964.6		c.39A>C	p.Gly13Gly	synonymous	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.39A>C	p.Gly13Gly	synonymous	Exon 1 of 38	ENSP00000309577.6	Q8IVL1-3
	NAV2	ENST00000360655.8	TSL:1	c.76-118750A>C		intron	N/A	ENSP00000353871.4	Q8IVL1-4
	NAV2	ENST00000396087.7	TSL:5	c.39A>C	p.Gly13Gly	synonymous	Exon 1 of 41	ENSP00000379396.3	Q8IVL1-1

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 380 AN: 152156 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00451

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00224 AC: 541 AN: 241678 AF XY: 0.00225

Gnomad AFR exome AF: 0.000572

Gnomad AMR exome AF: 0.000687

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000376

Gnomad NFE exome AF: 0.00459

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.00430 AC: 6205 AN: 1443126 Hom.: 18 Cov.: 31 AF XY: 0.00403 AC XY: 2884 AN XY: 714836

African (AFR) AF: 0.000607 AC: 20 AN: 32938

American (AMR) AF: 0.000646 AC: 28 AN: 43318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25604

East Asian (EAS) AF: 0.00 AC: 0 AN: 39174

South Asian (SAS) AF: 0.00 AC: 0 AN: 85134

European-Finnish (FIN) AF: 0.000400 AC: 21 AN: 52440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5398

European-Non Finnish (NFE) AF: 0.00543 AC: 5975 AN: 1099732

Other (OTH) AF: 0.00271 AC: 161 AN: 59388

GnomAD4 genome AF: 0.00250 AC: 380 AN: 152274 Hom.: 2 Cov.: 33 AF XY: 0.00235 AC XY: 175 AN XY: 74470

African (AFR) AF: 0.000722 AC: 30 AN: 41548

American (AMR) AF: 0.00235 AC: 36 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00451 AC: 307 AN: 68030

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00263 Hom.: 1

Bravo AF: 0.00264

EpiCase AF: 0.00383

EpiControl AF: 0.00451

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	NAV2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		2.5
PromoterAI		0.13	Neutral
Mutation Taster		=100/0	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: rs146393896; hg19: chr11-19735280; COSMIC: COSV100587367; COSMIC: COSV100587367;