11-19713951-T-G

Variant names:

• chr11-19713951-T-G
• rs927556176
• NM_145117.5:c.256T>G

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>G​(p.Phe86Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. F86L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.15424138).

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>G	p.Phe86Val	missense	Exon 1 of 38	NP_660093.2
	NAV2	NM_001244963.2		c.256T>G	p.Phe86Val	missense	Exon 1 of 41	NP_001231892.1	Q8IVL1-1
	NAV2	NM_182964.6		c.256T>G	p.Phe86Val	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>G	p.Phe86Val	missense	Exon 1 of 38	ENSP00000309577.6	Q8IVL1-3
	NAV2	ENST00000360655.8	TSL:1	c.76-118533T>G		intron	N/A	ENSP00000353871.4	Q8IVL1-4
	NAV2	ENST00000396087.7	TSL:5	c.256T>G	p.Phe86Val	missense	Exon 1 of 41	ENSP00000379396.3	Q8IVL1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N
PhyloP100		4.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.18
Sift	Benign	0.37	T
Sift4G	Benign	0.090	T
Polyphen		0.039	B
Vest4		0.51
MutPred		0.53		Loss of stability (P = 0.0642)
MVP		0.19
MPC		0.22
ClinPred		0.61	D
GERP RS		5.1
PromoterAI		0.032	Neutral
Varity_R		0.24
gMVP		0.60
Mutation Taster		=78/22	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: rs927556176; hg19: chr11-19735497;