rs3771395

Positions:

• chr2-70905884-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
VAX2	NM_012476.3	c.247+5016G>A		intron_variant		ENST00000234392.3	NP_036608.1
VAX2	XM_011532750.4	c.247+5016G>A		intron_variant			XP_011531052.1
VAX2	XM_011532751.4	c.247+5016G>A		intron_variant			XP_011531053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAX2	ENST00000234392.3	c.247+5016G>A		intron_variant		1	NM_012476.3	ENSP00000234392	P1
VAX2	ENST00000432367.6	c.71+5016G>A		intron_variant, NMD_transcript_variant		5		ENSP00000405114

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

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.0514

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.142

Alfa AF: 0.129 Hom.: 2520

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

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

Other links and lift over

dbSNP: rs3771395; hg19: chr2-71133014;