rs11543

Positions:

• chr10-75210855-G-C
• chr10-75210855-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

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=-0.76).
• 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/exons	MANE	Protein	UniProt
VDAC2	NM_001391963.1	c.-109G>C		5_prime_UTR_variant	1/10	ENST00000332211.11	NP_001378892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VDAC2	ENST00000332211.11	c.-109G>C		5_prime_UTR_variant	1/10	1	NM_001391963.1	ENSP00000361686	P1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104877 AN: 151946 Hom.: 38567 Cov.: 33

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.: 2 AF XY: 0.603 AC XY: 54768 AN XY: 90876

Gnomad4 AFR exome AF: 0.908

Gnomad4 AMR exome AF: 0.769

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.964

Gnomad4 SAS exome AF: 0.782

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.630

GnomAD4 genome AF: 0.690 AC: 104996 AN: 152064 Hom.: 38630 Cov.: 33 AF XY: 0.695 AC XY: 51651 AN XY: 74338

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.962

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.702

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	12
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs11543; hg19: chr10-76970613;