Variant chr2-70932881-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012476.3(VAX2):c.550C>T(p.Arg184Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,613,542 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R184Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

VAX2
NM_012476.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAX2	NM_012476.3 linkuse as main transcript	c.550C>T	p.Arg184Trp	missense_variant	3/3	ENST00000234392.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
VAX2	ENST00000234392.3 linkuse as main transcript	c.550C>T	p.Arg184Trp	missense_variant	3/3	1	NM_012476.3	P1
VAX2	ENST00000432367.6 linkuse as main transcript	c.*45+8543C>T		intron_variant, NMD_transcript_variant		5
VAX2	ENST00000646783.1 linkuse as main transcript	c.80-6537C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000112

AC:

AN:

250450

Hom.:

AF XY:

0.0000812

AC XY:

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1461364

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000302

Gnomad4 NFE exome

AF:

0.0000683

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000151

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000150

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Aug 15, 2023

The c.550C>T (p.R184W) alteration is located in exon 3 (coding exon 3) of the VAX2 gene. This alteration results from a C to T substitution at nucleotide position 550, causing the arginine (R) at amino acid position 184 to be replaced by a tryptophan (W). 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

0.10

BayesDel_addAF

Benign

-0.0037

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.48

MetaRNN

Uncertain

0.65

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.8

REVEL

Pathogenic

0.73

Sift

Uncertain

0.022

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.69

MVP

1.0

MPC

0.28

ClinPred

0.48

GERP RS

4.2

Varity_R

0.32

gMVP

0.50

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