NM_012476.3:c.70C>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012476.3(VAX2):c.70C>G(p.Arg24Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00184 in 1,326,858 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0098 ( 32 hom., cov: 34)

Exomes 𝑓: 0.00081 ( 9 hom. )

Consequence

VAX2
NM_012476.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.167

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019215941).

BP6

Variant 2-70900691-C-G is Benign according to our data. Variant chr2-70900691-C-G is described in ClinVar as [Benign]. Clinvar id is 783331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00982 (1494/152166) while in subpopulation AFR AF= 0.034 (1414/41530). AF 95% confidence interval is 0.0326. There are 32 homozygotes in gnomad4. There are 725 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAX2	NM_012476.3 link	c.70C>G	p.Arg24Gly	missense_variant	Exon 1 of 3	ENST00000234392.3	NP_036608.1	Q9UIW0F1T0K5
VAX2	XM_011532750.4 link	c.70C>G	p.Arg24Gly	missense_variant	Exon 1 of 4		XP_011531052.1
VAX2	XM_011532751.4 link	c.70C>G	p.Arg24Gly	missense_variant	Exon 1 of 4		XP_011531053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAX2	ENST00000234392.3 link	c.70C>G	p.Arg24Gly	missense_variant	Exon 1 of 3	1	NM_012476.3	ENSP00000234392.2		Q9UIW0
VAX2	ENST00000432367.6 link	n.-108C>G		upstream_gene_variant		5		ENSP00000405114.2		C9J5E3

Frequencies

GnomAD3 genomes

AF:

0.00979

AC:

1489

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00136

AC:

AN:

11756

Hom.:

AF XY:

0.000849

AC XY:

AN XY:

7068

show subpopulations

Gnomad AFR exome

AF:

0.0586

Gnomad AMR exome

AF:

0.000618

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000511

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000235

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000811

AC:

953

AN:

1174692

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

376

AN XY:

567034

show subpopulations

Gnomad4 AFR exome

AF:

0.0336

Gnomad4 AMR exome

AF:

0.00245

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000258

Gnomad4 OTH exome

AF:

0.00208

GnomAD4 genome

AF:

0.00982

AC:

1494

AN:

152166

Hom.:

Cov.:

AF XY:

0.00975

AC XY:

725

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0340

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.0117

ExAC

AF:

0.000433

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.061

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.14

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.41

REVEL

Benign

0.15

Sift

Benign

0.087

Sift4G

Benign

0.45

Polyphen

0.017

Vest4

0.16

MVP

0.85

MPC

0.049

ClinPred

0.057

GERP RS

1.8

Varity_R

0.087

gMVP

0.25

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