rs7304

Positions:

• chr10-75231207-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001391963.1(VDAC2):​c.*218A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0395 in 454,128 control chromosomes in the GnomAD database, including 585 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 0.054 (350 hom., cov: 33)
  • Exomes 𝑓: 0.032 (235 hom.)
• Consequence: VDAC2 NM_001391963.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VDAC2	NM_001391963.1	c.*218A>G		3_prime_UTR_variant	10/10	ENST00000332211.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VDAC2	ENST00000332211.11	c.*218A>G		3_prime_UTR_variant	10/10	1	NM_001391963.1	P1
VDAC2	ENST00000313132.8	c.*218A>G		3_prime_UTR_variant	11/11	1
VDAC2	ENST00000543351.5	c.*218A>G		3_prime_UTR_variant	10/10	5		P1
VDAC2	ENST00000460044.1	n.702A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8155 AN: 152150 Hom.: 352 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0522

GnomAD4 exome AF: 0.0324 AC: 9778 AN: 301860 Hom.: 235 Cov.: 3 AF XY: 0.0341 AC XY: 5354 AN XY: 157210

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0352

Gnomad4 ASJ exome AF: 0.0679

Gnomad4 EAS exome AF: 0.0143

Gnomad4 SAS exome AF: 0.0554

Gnomad4 FIN exome AF: 0.0175

Gnomad4 NFE exome AF: 0.0274

Gnomad4 OTH exome AF: 0.0358

GnomAD4 genome AF: 0.0536 AC: 8155 AN: 152268 Hom.: 350 Cov.: 33 AF XY: 0.0524 AC XY: 3905 AN XY: 74460

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0344

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.0584

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0271

Gnomad4 OTH AF: 0.0512

Alfa AF: 0.0373 Hom.: 32

Bravo AF: 0.0578

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.90

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: rs7304; hg19: chr10-76990965;