11-19713777-C-T

Variant names:

• chr11-19713777-C-T
• rs1292653194
• NM_145117.5:c.82C>T

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.82C>T​(p.Pro28Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,572 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P28T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.51
• Publications: 2 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=0.17020175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5	c.82C>T	p.Pro28Ser	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.82C>T	p.Pro28Ser	missense_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6
NAV2	ENST00000360655.8	c.76-118707C>T		intron_variant	Intron 1 of 37	1		ENSP00000353871.4
NAV2	ENST00000396087.7	c.82C>T	p.Pro28Ser	missense_variant	Exon 1 of 41	5		ENSP00000379396.3
NAV2	ENST00000396085.6	c.82C>T	p.Pro28Ser	missense_variant	Exon 1 of 39	5		ENSP00000379394.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 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

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 243680 AF XY: 0.00000753

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: 0.00000923

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460352 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726472

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52684

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111592

Other (OTH) AF: 0.0000166 AC: 1 AN: 60338

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68046

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.015	.;.;T;.;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T;T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;.;.;N;N
PhyloP100		6.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.19	N;.;.;N;N
REVEL	Benign	0.086
Sift	Benign	0.076	T;.;.;T;T
Sift4G	Benign	0.18	T;T;T;T;T
Polyphen		0.34	.;.;.;B;.
Vest4		0.39
MutPred		0.23		Loss of catalytic residue at P28 (P = 0.004);Loss of catalytic residue at P28 (P = 0.004);Loss of catalytic residue at P28 (P = 0.004);Loss of catalytic residue at P28 (P = 0.004);Loss of catalytic residue at P28 (P = 0.004);
MVP		0.068
MPC		0.66
ClinPred		0.80	D
GERP RS		5.4
PromoterAI		-0.0088	Neutral
Varity_R		0.098
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: rs1292653194; hg19: chr11-19735323; COSMIC: COSV100585086; COSMIC: COSV100585086;