10-75212086-C-T

Position:

• chr10-75212086-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VDAC2	NM_001391963.1	c.32-144C>T		intron_variant		ENST00000332211.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VDAC2	ENST00000332211.11	c.32-144C>T		intron_variant		1	NM_001391963.1	P1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86138 AN: 151996 Hom.: 25992 Cov.: 33

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

Gnomad4 AFR exome AF: 0.733

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.486

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.445

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.567 AC: 86233 AN: 152114 Hom.: 26038 Cov.: 33 AF XY: 0.571 AC XY: 42452 AN XY: 74362

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.579

Alfa AF: 0.536 Hom.: 4034

Bravo AF: 0.594

Asia WGS AF: 0.734 AC: 2552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs2804535; hg19: chr10-76971844;