11-19713746-C-G

Variant names:

• chr11-19713746-C-G
• rs184978478
• NM_145117.5:c.51C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_145117.5(NAV2):​c.51C>G​(p.Pro17Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000645 in 1,611,144 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00082 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (16 hom.)
• Consequence: NAV2 NM_145117.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0100
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 11-19713746-C-G is Benign according to our data. Variant chr11-19713746-C-G is described in ClinVar as Benign. ClinVar VariationId is 3051618.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.01 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00082 (125/152360) while in subpopulation EAS AF = 0.0222 (115/5180). AF 95% confidence interval is 0.0189. There are 2 homozygotes in GnomAd4. There are 71 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• 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.51C>G	p.Pro17Pro	synonymous	Exon 1 of 38	NP_660093.2
	NAV2	NM_001244963.2		c.51C>G	p.Pro17Pro	synonymous	Exon 1 of 41	NP_001231892.1	Q8IVL1-1
	NAV2	NM_182964.6		c.51C>G	p.Pro17Pro	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.51C>G	p.Pro17Pro	synonymous	Exon 1 of 38	ENSP00000309577.6	Q8IVL1-3
	NAV2	ENST00000360655.8	TSL:1	c.76-118738C>G		intron	N/A	ENSP00000353871.4	Q8IVL1-4
	NAV2	ENST00000396087.7	TSL:5	c.51C>G	p.Pro17Pro	synonymous	Exon 1 of 41	ENSP00000379396.3	Q8IVL1-1

Frequencies

GnomAD3 genomes AF: 0.000821 AC: 125 AN: 152242 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00199 AC: 487 AN: 244800 AF XY: 0.00197

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0247

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000734

Gnomad OTH exome AF: 0.000835

GnomAD4 exome AF: 0.000627 AC: 914 AN: 1458784 Hom.: 16 Cov.: 31 AF XY: 0.000662 AC XY: 480 AN XY: 725424

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.0000674 AC: 3 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.0190 AC: 754 AN: 39634

South Asian (SAS) AF: 0.000744 AC: 64 AN: 86000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52682

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5616

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1110670

Other (OTH) AF: 0.00108 AC: 65 AN: 60240

GnomAD4 genome AF: 0.000820 AC: 125 AN: 152360 Hom.: 2 Cov.: 32 AF XY: 0.000953 AC XY: 71 AN XY: 74514

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15314

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

East Asian (EAS) AF: 0.0222 AC: 115 AN: 5180

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000157 Hom.: 0

Bravo AF: 0.00123

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

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
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.010
PromoterAI		-0.020	Neutral
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs184978478; hg19: chr11-19735292;