chr11-20044048-C-T

Variant names:

• chr11-20044048-C-T
• NM_145117.5:c.2975C>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.2975C>T​(p.Ser992Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69
• 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]

NAV2-AS2 (HGNC:40743): (NAV2 antisense RNA 2)

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=0.14126945).

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.2975C>T	p.Ser992Leu	missense	Exon 13 of 38	NP_660093.2
	NAV2	NM_001244963.2		c.3044C>T	p.Ser1015Leu	missense	Exon 14 of 41	NP_001231892.1	Q8IVL1-1
	NAV2	NM_182964.6		c.2975C>T	p.Ser992Leu	missense	Exon 13 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.2975C>T	p.Ser992Leu	missense	Exon 13 of 38	ENSP00000309577.6	Q8IVL1-3
	NAV2	ENST00000360655.8	TSL:1	c.2783C>T	p.Ser928Leu	missense	Exon 13 of 38	ENSP00000353871.4	Q8IVL1-4
	NAV2	ENST00000396087.7	TSL:5	c.3044C>T	p.Ser1015Leu	missense	Exon 14 of 41	ENSP00000379396.3	Q8IVL1-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	Benign	0.12
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.73	N
PhyloP100		4.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.13
Sift	Benign	0.16	T
Sift4G	Benign	0.12	T
Polyphen		0.028	B
Vest4		0.55
MutPred		0.18		Loss of phosphorylation at S78 (P = 0.0067)
MVP		0.068
MPC		0.62
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.10
gMVP		0.33
Mutation Taster		=69/31	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

hg19: chr11-20065594; COSMIC: COSV60657361;