2-70905884-G-A

Variant names:

• chr2-70905884-G-A
• rs3771395
• NM_012476.3:c.247+5016G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012476.3(VAX2):​c.247+5016G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,210 control chromosomes in the GnomAD database, including 1,658 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1658 hom., cov: 32)
• Consequence: VAX2 NM_012476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAX2	NM_012476.3	c.247+5016G>A		intron_variant	Intron 1 of 2	ENST00000234392.3	NP_036608.1
VAX2	XM_011532750.4	c.247+5016G>A		intron_variant	Intron 1 of 3		XP_011531052.1
VAX2	XM_011532751.4	c.247+5016G>A		intron_variant	Intron 1 of 3		XP_011531053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAX2	ENST00000234392.3	c.247+5016G>A		intron_variant	Intron 1 of 2	1	NM_012476.3	ENSP00000234392.2
VAX2	ENST00000432367.6	n.70+5016G>A		intron_variant	Intron 1 of 14	5		ENSP00000405114.2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20798 AN: 152092 Hom.: 1653 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.0514

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20822 AN: 152210 Hom.: 1658 Cov.: 32 AF XY: 0.137 AC XY: 10169 AN XY: 74414

African (AFR) AF: 0.161 AC: 6666 AN: 41514

American (AMR) AF: 0.107 AC: 1638 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1327 AN: 5174

South Asian (SAS) AF: 0.278 AC: 1338 AN: 4812

European-Finnish (FIN) AF: 0.0514 AC: 546 AN: 10620

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8230 AN: 68008

Other (OTH) AF: 0.142 AC: 301 AN: 2116

Alfa AF: 0.130 Hom.: 5806

Bravo AF: 0.137

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.61
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3771395; hg19: chr2-71133014;