rs1686482

Variant names:

• chr2-10782390-A-C
• rs1686482
• NM_001039362.2:c.1194+15A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039362.2(ATP6V1C2):​c.1194+15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,612,082 control chromosomes in the GnomAD database, including 176,728 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 0.40 (13467 hom., cov: 32)
  • Exomes 𝑓: 0.47 (163261 hom.)
• Consequence: ATP6V1C2 NM_001039362.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 14 publications found

Genes affected

ATP6V1C2 (HGNC:18264): (ATPase H+ transporting V1 subunit C2) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle 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,three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site. This gene encodes alternate transcriptional splice variants, encoding different V1 domain C subunit isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039362.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1C2	NM_001039362.2	MANE Select	c.1194+15A>C		intron	N/A	NP_001034451.1
	ATP6V1C2	NM_001410707.1		c.1224+15A>C		intron	N/A	NP_001397636.1
	ATP6V1C2	NM_144583.4		c.1056+15A>C		intron	N/A	NP_653184.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1C2	ENST00000272238.9	TSL:5 MANE Select	c.1194+15A>C		intron	N/A	ENSP00000272238.4
	ATP6V1C2	ENST00000635370.1	TSL:5	c.1224+15A>C		intron	N/A	ENSP00000489280.1
	ATP6V1C2	ENST00000381661.3	TSL:2	c.1056+15A>C		intron	N/A	ENSP00000371077.3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60586 AN: 151988 Hom.: 13471 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.452

GnomAD2 exomes AF: 0.467 AC: 116537 AN: 249648 AF XY: 0.468

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.541

Gnomad ASJ exome AF: 0.591

Gnomad EAS exome AF: 0.451

Gnomad FIN exome AF: 0.437

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.499

GnomAD4 exome AF: 0.469 AC: 684597 AN: 1459976 Hom.: 163261 Cov.: 35 AF XY: 0.469 AC XY: 340263 AN XY: 726220

African (AFR) AF: 0.178 AC: 5967 AN: 33434

American (AMR) AF: 0.531 AC: 23605 AN: 44436

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 15314 AN: 26072

East Asian (EAS) AF: 0.390 AC: 15454 AN: 39672

South Asian (SAS) AF: 0.422 AC: 36249 AN: 85914

European-Finnish (FIN) AF: 0.436 AC: 23253 AN: 53354

Middle Eastern (MID) AF: 0.547 AC: 3151 AN: 5756

European-Non Finnish (NFE) AF: 0.480 AC: 533224 AN: 1111016

Other (OTH) AF: 0.470 AC: 28380 AN: 60322

GnomAD4 genome AF: 0.398 AC: 60597 AN: 152106 Hom.: 13467 Cov.: 32 AF XY: 0.400 AC XY: 29745 AN XY: 74340

African (AFR) AF: 0.192 AC: 7973 AN: 41510

American (AMR) AF: 0.480 AC: 7327 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3472

East Asian (EAS) AF: 0.458 AC: 2374 AN: 5178

South Asian (SAS) AF: 0.426 AC: 2057 AN: 4826

European-Finnish (FIN) AF: 0.422 AC: 4454 AN: 10566

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32774 AN: 67958

Other (OTH) AF: 0.454 AC: 959 AN: 2114

Alfa AF: 0.470 Hom.: 24178

Bravo AF: 0.398

Asia WGS AF: 0.435 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.78
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1686482; hg19: chr2-10922516; COSMIC: COSV55349176; COSMIC: COSV55349176;