Genetic Variant NM_001391963.1:c.-109G>C (chr10-75210855-G-C) – 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.-109G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 328,884 control chromosomes in the GnomAD database, including 72,903 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 0.69 ( 38630 hom., cov: 33)

Exomes 𝑓: 0.60 ( 34273 hom. )

Consequence

VDAC2
NM_001391963.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.529

Publications

12 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:

ENSG00000296693 (HGNC:):

ENSG00000296693 links:

Genome browser will be placed here

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=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VDAC2	NM_001391963.1 link	c.-109G>C		5_prime_UTR_variant	Exon 1 of 10	ENST00000332211.11	NP_001378892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VDAC2	ENST00000332211.11 link	c.-109G>C		5_prime_UTR_variant	Exon 1 of 10	1	NM_001391963.1	ENSP00000361686.3		P45880-3

Frequencies

GnomAD3 genomes

AF:

0.690

AC:

104877

AN:

151946

Hom.:

38567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.920

Gnomad AMI

AF:

0.529

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.503

Gnomad EAS

AF:

0.962

Gnomad SAS

AF:

0.815

Gnomad FIN

AF:

0.517

Gnomad MID

AF:

0.702

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.699

GnomAD4 exome

AF:

0.604

AC:

106780

AN:

176820

Hom.:

34273

Cov.:

AF XY:

0.603

AC XY:

54768

AN XY:

90876

show subpopulations

African (AFR)

AF:

0.908

AC:

4480

AN:

4934

American (AMR)

AF:

0.769

AC:

3668

AN:

4770

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

3365

AN:

6642

East Asian (EAS)

AF:

0.964

AC:

14898

AN:

15454

South Asian (SAS)

AF:

0.782

AC:

4107

AN:

5250

European-Finnish (FIN)

AF:

0.515

AC:

7431

AN:

14428

Middle Eastern (MID)

AF:

0.696

AC:

656

AN:

942

European-Non Finnish (NFE)

AF:

0.540

AC:

60904

AN:

112850

Other (OTH)

AF:

0.630

AC:

7271

AN:

11550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1808

3615

5423

7230

9038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.690

AC:

104996

AN:

152064

Hom.:

38630

Cov.:

AF XY:

0.695

AC XY:

51651

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.920

AC:

38237

AN:

41544

American (AMR)

AF:

0.749

AC:

11446

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.503

AC:

1747

AN:

3472

East Asian (EAS)

AF:

0.962

AC:

4948

AN:

5144

South Asian (SAS)

AF:

0.815

AC:

3933

AN:

4828

European-Finnish (FIN)

AF:

0.517

AC:

5468

AN:

10576

Middle Eastern (MID)

AF:

0.700

AC:

203

AN:

290

European-Non Finnish (NFE)

AF:

0.546

AC:

37053

AN:

67908

Other (OTH)

AF:

0.702

AC:

1481

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1501

3003

4504

6006

7507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.447

Hom.:

1098

Bravo

AF:

0.715

Asia WGS

AF:

0.902

AC:

3129

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

-0.53

PromoterAI

-0.048

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over