rs2523503

Positions:

• chr6-31545782-C-A

Variant summary

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

The NM_130463.4(ATP6V1G2):​c.184-201G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 646,382 control chromosomes in the GnomAD database, including 8,942 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 0.15 (1770 hom., cov: 32)
  • Exomes 𝑓: 0.17 (7172 hom.)
• Consequence: ATP6V1G2 NM_130463.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.970

Genes affected

ATP6V1G2 (HGNC:862): (ATPase H+ transporting V1 subunit G2) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of three V1 domain G subunit proteins. This gene had previous gene symbols of ATP6G and ATP6G2. Alternatively spliced transcript variants encoding different isoforms have been described. Read-through transcription also exists between this gene and the downstream DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B (DDX39B) gene. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B (HGNC:41999): (ATP6V1G2-DDX39B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) and DDX39B (DEAD box polypeptide 39B) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript and is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ATP6V1G2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1G2	NM_130463.4	c.184-201G>T		intron_variant		ENST00000303892.10	NP_569730.1
ATP6V1G2	NM_001204078.2	c.106-243G>T		intron_variant			NP_001191007.1
ATP6V1G2	NM_138282.3	c.61-201G>T		intron_variant			NP_612139.1
ATP6V1G2-DDX39B	NR_037853.1	n.472+327G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2	ENST00000303892.10	c.184-201G>T		intron_variant		1	NM_130463.4	ENSP00000302194.5
ATP6V1G2-DDX39B	ENST00000376185.5	n.183+327G>T		intron_variant		2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22598 AN: 151994 Hom.: 1773 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.166 AC: 81943 AN: 494270 Hom.: 7172 Cov.: 6 AF XY: 0.170 AC XY: 44030 AN XY: 258744

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.149 AC: 22607 AN: 152112 Hom.: 1770 Cov.: 32 AF XY: 0.150 AC XY: 11178 AN XY: 74356

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.163

Alfa AF: 0.150 Hom.: 448

Bravo AF: 0.144

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.82

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: rs2523503; hg19: chr6-31513559;