rs2239705

Positions:

• chr6-31545625-G-A
• chr6-31545625-G-T

Variant summary

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

The NM_130463.4(ATP6V1G2):​c.184-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,594,274 control chromosomes in the GnomAD database, including 24,083 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 0.16 (2263 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21820 hom.)
• Consequence: ATP6V1G2 NM_130463.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1G2	NM_130463.4	c.184-44C>T		intron_variant		ENST00000303892.10	NP_569730.1
ATP6V1G2-DDX39B	NR_037853.1	n.472+484C>T		intron_variant, non_coding_transcript_variant
ATP6V1G2	NM_001204078.2	c.106-86C>T		intron_variant			NP_001191007.1
ATP6V1G2	NM_138282.3	c.61-44C>T		intron_variant			NP_612139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2	ENST00000303892.10	c.184-44C>T		intron_variant		1	NM_130463.4	ENSP00000302194	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24659 AN: 152024 Hom.: 2265 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.176

GnomAD3 exomes AF: 0.184 AC: 41711 AN: 226950 Hom.: 4446 AF XY: 0.183 AC XY: 22579 AN XY: 123458

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.291

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.158

Gnomad SAS exome AF: 0.163

Gnomad FIN exome AF: 0.0932

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.168 AC: 242360 AN: 1442134 Hom.: 21820 Cov.: 30 AF XY: 0.169 AC XY: 121050 AN XY: 716760

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.0891

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.162 AC: 24673 AN: 152140 Hom.: 2263 Cov.: 32 AF XY: 0.161 AC XY: 11997 AN XY: 74386

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0885

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.179

Alfa AF: 0.186 Hom.: 6078

Bravo AF: 0.176

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2239705; hg19: chr6-31513402;