Genetic Variant VAX2:p.Arg10Trp (chr2-70900649-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_012476.3(VAX2):c.28C>T(p.Arg10Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000888 in 1,125,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R10L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

VAX2
NM_012476.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.876

Publications

0 publications found

Variant links:

Genes affected

VAX2 (HGNC:12661): (ventral anterior homeobox 2) This gene encodes a homeobox protein and is almost exclusively expressed in the ventral portion of the retina during development. In mouse studies, this gene was found to be required for the correct formation of the optic fissure and other aspects of retinal development. [provided by RefSeq, Sep 2008]

VAX2 links:

ENSG00000296671 (HGNC:):

ENSG00000296671 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30494252).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012476.3. 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
	VAX2	NM_012476.3	MANE Select	c.28C>T	p.Arg10Trp	missense	Exon 1 of 3	NP_036608.1	F1T0K5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VAX2	ENST00000234392.3	TSL:1 MANE Select	c.28C>T	p.Arg10Trp	missense	Exon 1 of 3	ENSP00000234392.2	Q9UIW0
VAX2	ENST00000432367.6	TSL:5	n.-150C>T		upstream_gene	N/A	ENSP00000405114.2	C9J5E3
ENSG00000296671	ENST00000741093.1		n.-244G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

874

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.88e-7

AC:

AN:

1125960

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

538128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23112

American (AMR)

AF:

0.00

AC:

AN:

8528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15174

East Asian (EAS)

AF:

0.00

AC:

AN:

26702

South Asian (SAS)

AF:

0.00

AC:

AN:

33962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3044

European-Non Finnish (NFE)

AF:

0.00000106

AC:

AN:

944376

Other (OTH)

AF:

0.00

AC:

AN:

45596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

0.14

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.30

MetaSVM

Uncertain

0.21

MutationAssessor

Benign

1.5

PhyloP100

0.88

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.019

Polyphen

0.93

Vest4

0.20

MutPred

0.31

Loss of solvent accessibility (P = 6e-04)

MVP

0.99

MPC

0.075

ClinPred

0.96

GERP RS

3.9

PromoterAI

-0.0058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.26

gMVP

0.21

Mutation Taster

=72/28

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over