11-19713779-C-A

Variant names:

• chr11-19713779-C-A
• rs11828836
• NM_145117.5:c.84C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_145117.5(NAV2):​c.84C>A​(p.Pro28Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00365 in 1,612,914 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.020 (105 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (97 hom.)
• Consequence: NAV2 NM_145117.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.496
• 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=-0.3).
• BP6: Variant 11-19713779-C-A is Benign according to our data. Variant chr11-19713779-C-A is described in ClinVar as [Benign]. Clinvar id is 3039323.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.496 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5	c.84C>A	p.Pro28Pro	synonymous_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.84C>A	p.Pro28Pro	synonymous_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6
NAV2	ENST00000360655.8	c.76-118705C>A		intron_variant	Intron 1 of 37	1		ENSP00000353871.4
NAV2	ENST00000396087.7	c.84C>A	p.Pro28Pro	synonymous_variant	Exon 1 of 41	5		ENSP00000379396.3
NAV2	ENST00000396085.6	c.84C>A	p.Pro28Pro	synonymous_variant	Exon 1 of 39	5		ENSP00000379394.1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3019 AN: 152226 Hom.: 105 Cov.: 33

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00513 AC: 1252 AN: 243876 AF XY: 0.00375

Gnomad AFR exome AF: 0.0725

Gnomad AMR exome AF: 0.00294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000166

Gnomad OTH exome AF: 0.00151

GnomAD4 exome AF: 0.00196 AC: 2863 AN: 1460570 Hom.: 97 Cov.: 31 AF XY: 0.00167 AC XY: 1211 AN XY: 726570

African (AFR) AF: 0.0709 AC: 2373 AN: 33470

American (AMR) AF: 0.00331 AC: 148 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52748

Middle Eastern (MID) AF: 0.00157 AC: 9 AN: 5750

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1111684

Other (OTH) AF: 0.00418 AC: 252 AN: 60338

GnomAD4 genome AF: 0.0198 AC: 3022 AN: 152344 Hom.: 105 Cov.: 33 AF XY: 0.0195 AC XY: 1449 AN XY: 74486

African (AFR) AF: 0.0692 AC: 2876 AN: 41570

American (AMR) AF: 0.00581 AC: 89 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68036

Other (OTH) AF: 0.0175 AC: 37 AN: 2116

Alfa AF: 0.00641 Hom.: 5

Bravo AF: 0.0222

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NAV2-related disorder Benign:1

Jan 03, 2020

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
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.86
PhyloP100		0.50
PromoterAI		-0.025	Neutral
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: rs11828836; hg19: chr11-19735325;