rs7304

Variant names:

• chr10-75231207-A-G
• rs7304
• NM_001391963.1:c.*218A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VDAC2	NM_001391963.1	MANE Select	c.*218A>G		3_prime_UTR	Exon 10 of 10	NP_001378892.1	A0A024QZT0
	VDAC2	NM_001184783.3		c.*218A>G		3_prime_UTR	Exon 12 of 12	NP_001171712.1	P45880-1
	VDAC2	NM_001184823.2		c.*218A>G		3_prime_UTR	Exon 10 of 10	NP_001171752.1	A0A024QZT0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VDAC2	ENST00000332211.11	TSL:1 MANE Select	c.*218A>G		3_prime_UTR	Exon 10 of 10	ENSP00000361686.3	P45880-3
	VDAC2	ENST00000313132.8	TSL:1	c.*218A>G		3_prime_UTR	Exon 11 of 11	ENSP00000361635.1	P45880-1
	VDAC2	ENST00000958959.1		c.*218A>G		3_prime_UTR	Exon 12 of 12	ENSP00000629018.1

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

African (AFR) AF: 0.116 AC: 938 AN: 8120

American (AMR) AF: 0.0352 AC: 312 AN: 8870

Ashkenazi Jewish (ASJ) AF: 0.0679 AC: 659 AN: 9708

East Asian (EAS) AF: 0.0143 AC: 296 AN: 20672

South Asian (SAS) AF: 0.0554 AC: 1392 AN: 25132

European-Finnish (FIN) AF: 0.0175 AC: 550 AN: 31484

Middle Eastern (MID) AF: 0.0669 AC: 95 AN: 1420

European-Non Finnish (NFE) AF: 0.0274 AC: 4901 AN: 178726

Other (OTH) AF: 0.0358 AC: 635 AN: 17728

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

African (AFR) AF: 0.118 AC: 4892 AN: 41538

American (AMR) AF: 0.0344 AC: 526 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 238 AN: 3468

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5188

South Asian (SAS) AF: 0.0584 AC: 282 AN: 4826

European-Finnish (FIN) AF: 0.0127 AC: 135 AN: 10614

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0271 AC: 1844 AN: 68024

Other (OTH) AF: 0.0512 AC: 108 AN: 2110

Alfa AF: 0.0383 Hom.: 61

Bravo AF: 0.0578

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.90
PhyloP100		5.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7304; hg19: chr10-76990965;