Variant 10-75214054-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001391963.1(VDAC2):c.134A>G(p.Lys45Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,942 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: 6.8e-7 ( 0 hom. )

Consequence

VDAC2
NM_001391963.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16

Variant links:

Genes affected

VDAC2 (HGNC:12672): (voltage dependent anion channel 2) This gene encodes a member of the voltage-dependent anion channel pore-forming family of proteins that are considered the main pathway for metabolite diffusion across the mitochondrial outer membrane. The encoded protein is also thought to be involved in the mitochondrial apoptotic pathway via regulation of BCL2-antagonist/killer 1 protein activity. Pseudogenes have been identified on chromosomes 1, 2, 12 and 21, and alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

VDAC2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34748885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VDAC2	NM_001391963.1 linkuse as main transcript	c.134A>G	p.Lys45Arg	missense_variant	4/10	ENST00000332211.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VDAC2	ENST00000332211.11 linkuse as main transcript	c.134A>G	p.Lys45Arg	missense_variant	4/10	1	NM_001391963.1	P1	P45880-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460942

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.179A>G (p.K60R) alteration is located in exon 5 (coding exon 3) of the VDAC2 gene. This alteration results from a A to G substitution at nucleotide position 179, causing the lysine (K) at amino acid position 60 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

.;T;.;T;.;.;T

Eigen

Benign

0.098

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D;.;D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.35

T;T;T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Pathogenic

3.1

.;M;.;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.4

N;N;D;N;N;D;D

REVEL

Benign

0.18

Sift

Benign

0.079

T;T;T;T;T;T;T

Sift4G

Benign

0.10

T;T;T;T;T;T;T

Polyphen

0.0080, 0.0040

.;B;.;B;B;.;.

Vest4

0.42, 0.42

MutPred

0.55

Loss of ubiquitination at K45 (P = 0.0127);Loss of ubiquitination at K45 (P = 0.0127);Loss of ubiquitination at K45 (P = 0.0127);Loss of ubiquitination at K45 (P = 0.0127);.;Loss of ubiquitination at K45 (P = 0.0127);.;

MVP

0.22

MPC

0.54

ClinPred

0.96

GERP RS

4.5

Varity_R

0.28

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over