2-70900767-C-T

Variant names:

• chr2-70900767-C-T
• rs1032294407
• NM_012476.3:c.146C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012476.3(VAX2):​c.146C>T​(p.Thr49Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T49S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: VAX2 NM_012476.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4162042).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012476.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAX2	NM_012476.3	MANE Select	c.146C>T	p.Thr49Ile	missense	Exon 1 of 3	NP_036608.1	F1T0K5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAX2	ENST00000234392.3	TSL:1 MANE Select	c.146C>T	p.Thr49Ile	missense	Exon 1 of 3	ENSP00000234392.2	Q9UIW0
	VAX2	ENST00000432367.6	TSL:5	n.-32C>T		upstream_gene	N/A	ENSP00000405114.2	C9J5E3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 99708 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.86	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.4
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.91	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.059	T
Polyphen		0.97	D
Vest4		0.25
MutPred		0.14		Loss of glycosylation at T49 (P = 0.0153)
MVP		0.99
MPC		0.16
ClinPred		0.93	D
GERP RS		3.6
PromoterAI		0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.41
Mutation Taster		=76/24	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: rs1032294407; hg19: chr2-71127897;