chr2-70900694-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_012476.3(VAX2):​c.73T>G​(p.Cys25Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

VAX2
NM_012476.3 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.513
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16893387).
BP6
Variant 2-70900694-T-G is Benign according to our data. Variant chr2-70900694-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2231484.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VAX2NM_012476.3 linkuse as main transcriptc.73T>G p.Cys25Gly missense_variant 1/3 ENST00000234392.3
VAX2XM_011532750.4 linkuse as main transcriptc.73T>G p.Cys25Gly missense_variant 1/4
VAX2XM_011532751.4 linkuse as main transcriptc.73T>G p.Cys25Gly missense_variant 1/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VAX2ENST00000234392.3 linkuse as main transcriptc.73T>G p.Cys25Gly missense_variant 1/31 NM_012476.3 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJan 18, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.036
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
5.8
DANN
Benign
0.55
DEOGEN2
Benign
0.049
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0020
N
LIST_S2
Benign
0.18
T
M_CAP
Pathogenic
0.82
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
-0.55
N
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.34
N
REVEL
Benign
0.22
Sift
Benign
0.68
T
Sift4G
Benign
0.47
T
Polyphen
0.0
B
Vest4
0.076
MutPred
0.25
Gain of relative solvent accessibility (P = 0.0082);
MVP
0.54
MPC
0.047
ClinPred
0.050
T
GERP RS
-2.3
Varity_R
0.059
gMVP
0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-71127824; API