rs1486035052

Variant names:

• chr2-70900835-G-A
• rs1486035052
• NM_012476.3:c.214G>A

Variant summary

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

The NM_012476.3(VAX2):​c.214G>A​(p.Glu72Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000229 in 1,310,406 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: VAX2 NM_012476.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03
• 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=0.32581466).

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.214G>A	p.Glu72Lys	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.214G>A	p.Glu72Lys	missense	Exon 1 of 3	ENSP00000234392.2	Q9UIW0
	VAX2	ENST00000432367.6	TSL:5	n.37G>A		non_coding_transcript_exon	Exon 1 of 15	ENSP00000405114.2	C9J5E3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1310406 Hom.: 0 Cov.: 33 AF XY: 0.00000155 AC XY: 1 AN XY: 644200

African (AFR) AF: 0.00 AC: 0 AN: 27066

American (AMR) AF: 0.00 AC: 0 AN: 26254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22348

East Asian (EAS) AF: 0.00 AC: 0 AN: 29814

South Asian (SAS) AF: 0.0000144 AC: 1 AN: 69326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3846

European-Non Finnish (NFE) AF: 0.00000192 AC: 2 AN: 1039088

Other (OTH) AF: 0.00 AC: 0 AN: 54052

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.0
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.74	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.65	T
Polyphen		0.96	D
Vest4		0.23
MutPred		0.30		Gain of ubiquitination at E72 (P = 0.0048)
MVP		0.92
MPC		0.095
ClinPred		0.85	D
GERP RS		4.0
PromoterAI		-0.00060	Neutral
Varity_R		0.26
gMVP		0.26
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1486035052; hg19: chr2-71127965;