chr11-19713774-G-C

Variant names:

• chr11-19713774-G-C
• rs373558916
• NM_145117.5:c.79G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145117.5(NAV2):​c.79G>C​(p.Val27Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,612,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104164034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5	c.79G>C	p.Val27Leu	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.79G>C	p.Val27Leu	missense_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6
NAV2	ENST00000360655.8	c.76-118710G>C		intron_variant	Intron 1 of 37	1		ENSP00000353871.4
NAV2	ENST00000396087.7	c.79G>C	p.Val27Leu	missense_variant	Exon 1 of 41	5		ENSP00000379396.3
NAV2	ENST00000396085.6	c.79G>C	p.Val27Leu	missense_variant	Exon 1 of 39	5		ENSP00000379394.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460554 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726576

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44674

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111692

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.0038	.;.;T;.;T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	N;.;.;N;N
PhyloP100		3.7
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.040	N;.;.;N;N
REVEL	Benign	0.069
Sift	Benign	0.93	T;.;.;T;T
Sift4G	Benign	0.65	T;T;T;T;T
Polyphen		0.051	.;.;.;B;.
Vest4		0.31
MutPred		0.15		Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MVP		0.14
MPC		0.21
ClinPred		0.89	D
GERP RS		5.4
PromoterAI		0.073	Neutral
Varity_R		0.14
gMVP		0.18
Mutation Taster		=93/7	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: rs373558916; hg19: chr11-19735320;