2-70900783-C-T

Variant names:

• chr2-70900783-C-T
• rs1553409632
• NM_012476.3:c.162C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_012476.3(VAX2):​c.162C>T​(p.Pro54Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,346,536 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: VAX2 NM_012476.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.58
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-70900783-C-T is Benign according to our data. Variant chr2-70900783-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3771688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.58 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAX2	NM_012476.3	c.162C>T	p.Pro54Pro	synonymous_variant	Exon 1 of 3	ENST00000234392.3	NP_036608.1
VAX2	XM_011532750.4	c.162C>T	p.Pro54Pro	synonymous_variant	Exon 1 of 4		XP_011531052.1
VAX2	XM_011532751.4	c.162C>T	p.Pro54Pro	synonymous_variant	Exon 1 of 4		XP_011531053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAX2	ENST00000234392.3	c.162C>T	p.Pro54Pro	synonymous_variant	Exon 1 of 3	1	NM_012476.3	ENSP00000234392.2
VAX2	ENST00000432367.6	n.-16C>T		upstream_gene_variant		5		ENSP00000405114.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1346536 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 663832

African (AFR) AF: 0.00 AC: 0 AN: 28290

American (AMR) AF: 0.00 AC: 0 AN: 31070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24036

East Asian (EAS) AF: 0.00 AC: 0 AN: 30860

South Asian (SAS) AF: 0.00 AC: 0 AN: 74312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3986

European-Non Finnish (NFE) AF: 9.46e-7 AC: 1 AN: 1056554

Other (OTH) AF: 0.00 AC: 0 AN: 55746

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

VAX2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.7
DANN	Benign	0.95
PhyloP100		-2.6
PromoterAI		0.0018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs1553409632; hg19: chr2-71127913;