chr11-19713951-T-C

Variant names:

• chr11-19713951-T-C
• rs927556176
• NM_145117.5:c.256T>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.256T>C​(p.Phe86Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29
• 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=0.092084974).

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.256T>C	p.Phe86Leu	missense	Exon 1 of 38	NP_660093.2
	NAV2	NM_001244963.2		c.256T>C	p.Phe86Leu	missense	Exon 1 of 41	NP_001231892.1	Q8IVL1-1
	NAV2	NM_182964.6		c.256T>C	p.Phe86Leu	missense	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.256T>C	p.Phe86Leu	missense	Exon 1 of 38	ENSP00000309577.6	Q8IVL1-3
	NAV2	ENST00000360655.8	TSL:1	c.76-118533T>C		intron	N/A	ENSP00000353871.4	Q8IVL1-4
	NAV2	ENST00000396087.7	TSL:5	c.256T>C	p.Phe86Leu	missense	Exon 1 of 41	ENSP00000379396.3	Q8IVL1-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151252 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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000809 AC: 2 AN: 247146 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460732 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726676

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

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111844

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151252 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73844

African (AFR) AF: 0.00 AC: 0 AN: 41064

American (AMR) AF: 0.00 AC: 0 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67774

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.3
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.11
Sift	Benign	0.93	T
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.50		Gain of catalytic residue at F86 (P = 0.0091)
MVP		0.093
MPC		0.18
ClinPred		0.30	T
GERP RS		5.1
PromoterAI		0.0028	Neutral
Varity_R		0.23
gMVP		0.49
Mutation Taster		=78/22	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: rs927556176; hg19: chr11-19735497;