Variant chr10-75220903-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001391963.1(VDAC2):c.517T>G(p.Ser173Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000533 in 1,613,770 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: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

VDAC2
NM_001391963.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12484446).

BS2

High AC in GnomAd4 at 56 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VDAC2	NM_001391963.1 linkuse as main transcript	c.517T>G	p.Ser173Ala	missense_variant	7/10	ENST00000332211.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VDAC2	ENST00000332211.11 linkuse as main transcript	c.517T>G	p.Ser173Ala	missense_variant	7/10	1	NM_001391963.1	P1	P45880-3

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000322

AC:

AN:

251290

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000660

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000550

AC:

804

AN:

1461580

Hom.:

Cov.:

AF XY:

0.000530

AC XY:

385

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000707

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000368

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000458

Hom.:

Bravo

AF:

0.000359

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000329

AC:

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 16, 2024

The c.562T>G (p.S188A) alteration is located in exon 8 (coding exon 6) of the VDAC2 gene. This alteration results from a T to G substitution at nucleotide position 562, causing the serine (S) at amino acid position 188 to be replaced by an alanine (A). 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

0.20

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

.;T;.;T;.;.

Eigen

Benign

0.098

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D;.;D;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

.;L;.;L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.6

D;D;D;D;D;D

REVEL

Benign

0.15

Sift

Benign

0.13

T;T;T;T;T;T

Sift4G

Benign

0.093

T;T;D;T;T;D

Polyphen

0.0030, 0.011

.;B;.;B;B;.

Vest4

0.70, 0.70, 0.70

MVP

0.22

MPC

0.49

ClinPred

0.15

GERP RS

5.5

Varity_R

0.40

gMVP

0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over