Variant 2-70921239-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012476.3(VAX2):c.389G>A(p.Arg130His) variant causes a missense change. The variant allele was found at a frequency of 0.0000502 in 1,613,226 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 (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

VAX2
NM_012476.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.45

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14165527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VAX2	NM_012476.3 linkuse as main transcript	c.389G>A	p.Arg130His	missense_variant	2/3	ENST00000234392.3	NP_036608.1
VAX2	XM_011532750.4 linkuse as main transcript	c.389G>A	p.Arg130His	missense_variant	2/4		XP_011531052.1
VAX2	XM_011532751.4 linkuse as main transcript	c.389G>A	p.Arg130His	missense_variant	2/4		XP_011531053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
VAX2	ENST00000234392.3 linkuse as main transcript	c.389G>A	p.Arg130His	missense_variant	2/3	1	NM_012476.3	ENSP00000234392	P1
VAX2	ENST00000432367.6 linkuse as main transcript	c.215G>A	p.Arg72His	missense_variant, NMD_transcript_variant	2/15	5		ENSP00000405114
VAX2	ENST00000646783.1 linkuse as main transcript	c.35G>A	p.Arg12His	missense_variant, NMD_transcript_variant	1/13			ENSP00000495231

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000964

AC:

AN:

249022

Hom.:

AF XY:

0.0000741

AC XY:

AN XY:

134862

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000219

AC:

AN:

1460956

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726740

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000322

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000296

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.389G>A (p.R130H) alteration is located in exon 2 (coding exon 2) of the VAX2 gene. This alteration results from a G to A substitution at nucleotide position 389, causing the arginine (R) at amino acid position 130 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.0082

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.70

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.14

MetaSVM

Uncertain

0.41

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.58

Sift

Uncertain

0.017

Sift4G

Benign

0.16

Polyphen

0.43

Vest4

0.45

MVP

1.0

MPC

0.061

ClinPred

0.14

GERP RS

5.4

Varity_R

0.35

gMVP

0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over