dbSNP rs1314127727: VAX2:p.Gly66Arg (chr2-70900817-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012476.3(VAX2):c.196G>C(p.Gly66Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 1,332,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

VAX2
NM_012476.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0600

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05795452).

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.196G>C	p.Gly66Arg	missense	Exon 1 of 3	NP_036608.1	F1T0K5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAX2	ENST00000234392.3	TSL:1 MANE Select	c.196G>C	p.Gly66Arg	missense	Exon 1 of 3	ENSP00000234392.2	Q9UIW0
	VAX2	ENST00000432367.6	TSL:5	n.19G>C		non_coding_transcript_exon	Exon 1 of 15	ENSP00000405114.2	C9J5E3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000225

AC:

AN:

1332494

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

656178

show subpopulations

African (AFR)

AF:

0.0000360

AC:

AN:

27780

American (AMR)

AF:

0.00

AC:

AN:

29306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23444

East Asian (EAS)

AF:

0.00

AC:

AN:

30412

South Asian (SAS)

AF:

0.00

AC:

AN:

72624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3924

European-Non Finnish (NFE)

AF:

0.00000191

AC:

AN:

1049812

Other (OTH)

AF:

0.00

AC:

AN:

55084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

0.095

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.056

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.4

PhyloP100

0.060

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.65

REVEL

Benign

0.12

Sift

Benign

0.62

Sift4G

Benign

0.47

Polyphen

0.0070

Vest4

0.054

MutPred

0.22

Loss of catalytic residue at G66 (P = 0.129)

MVP

0.92

MPC

0.046

ClinPred

0.16

GERP RS

0.96

PromoterAI

0.041

Neutral

(source)

Varity_R

0.086

gMVP

0.14

Mutation Taster

=96/4

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