Genetic Variant VDAC2:c.32-144C>T (chr10-75212086-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001391963.1(VDAC2):c.32-144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 701,628 control chromosomes in the GnomAD database, including 99,154 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 26038 hom., cov: 33)

Exomes 𝑓: 0.50 ( 73116 hom. )

Consequence

VDAC2
NM_001391963.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.493

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391963.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VDAC2	NM_001391963.1	MANE Select	c.32-144C>T	intron	N/A	NP_001378892.1	A0A024QZT0
VDAC2	NM_001184783.3		c.77-144C>T	intron	N/A	NP_001171712.1	P45880-1
VDAC2	NM_001184823.2		c.32-144C>T	intron	N/A	NP_001171752.1	A0A024QZT0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VDAC2	ENST00000332211.11	TSL:1 MANE Select	c.32-144C>T	intron	N/A	ENSP00000361686.3	P45880-3
VDAC2	ENST00000313132.8	TSL:1	c.77-144C>T	intron	N/A	ENSP00000361635.1	P45880-1
VDAC2	ENST00000958959.1		c.32-144C>T	intron	N/A	ENSP00000629018.1

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86138

AN:

151996

Hom.:

25992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.731

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.922

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.574

GnomAD4 exome

AF:

0.499

AC:

273971

AN:

549514

Hom.:

73116

AF XY:

0.496

AC XY:

145405

AN XY:

293276

show subpopulations

African (AFR)

AF:

0.733

AC:

10106

AN:

13788

American (AMR)

AF:

0.691

AC:

14083

AN:

20372

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

7654

AN:

18016

East Asian (EAS)

AF:

0.920

AC:

28949

AN:

31470

South Asian (SAS)

AF:

0.486

AC:

26499

AN:

54522

European-Finnish (FIN)

AF:

0.473

AC:

17290

AN:

36540

Middle Eastern (MID)

AF:

0.557

AC:

1684

AN:

3026

European-Non Finnish (NFE)

AF:

0.445

AC:

152433

AN:

342238

Other (OTH)

AF:

0.517

AC:

15273

AN:

29542

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

6130

12261

18391

24522

30652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1596

3192

4788

6384

7980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.567

AC:

86233

AN:

152114

Hom.:

26038

Cov.:

AF XY:

0.571

AC XY:

42452

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.731

AC:

30343

AN:

41486

American (AMR)

AF:

0.657

AC:

10055

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

1457

AN:

3470

East Asian (EAS)

AF:

0.922

AC:

4783

AN:

5188

South Asian (SAS)

AF:

0.504

AC:

2431

AN:

4824

European-Finnish (FIN)

AF:

0.469

AC:

4955

AN:

10562

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.447

AC:

30365

AN:

67980

Other (OTH)

AF:

0.579

AC:

1220

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1799

3598

5397

7196

8995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.594

Hom.:

12176

Bravo

AF:

0.594

Asia WGS

AF:

0.734

AC:

2552

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.5

(source)

DANN

Benign

0.70

PhyloP100

0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over