rs1198872

Variant names:

• chr2-10763286-C-T
• rs1198872
• NM_001039362.2:c.284-1045C>T

Variant summary

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

The NM_001039362.2(ATP6V1C2):​c.284-1045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,904 control chromosomes in the GnomAD database, including 11,429 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 0.38 (11429 hom., cov: 31)
• Consequence: ATP6V1C2 NM_001039362.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1C2	NM_001039362.2	c.284-1045C>T		intron_variant	Intron 4 of 13	ENST00000272238.9	NP_001034451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1C2	ENST00000272238.9	c.284-1045C>T		intron_variant	Intron 4 of 13	5	NM_001039362.2	ENSP00000272238.4
ATP6V1C2	ENST00000635370.1	c.314-1045C>T		intron_variant	Intron 4 of 13	5		ENSP00000489280.1
ATP6V1C2	ENST00000381661.3	c.284-1045C>T		intron_variant	Intron 4 of 12	2		ENSP00000371077.3
ATP6V1C2	ENST00000648362.1	c.284-1045C>T		intron_variant	Intron 4 of 11			ENSP00000497038.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57990 AN: 151786 Hom.: 11430 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.386

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.382 AC: 58011 AN: 151904 Hom.: 11429 Cov.: 31 AF XY: 0.387 AC XY: 28714 AN XY: 74224

African (AFR) AF: 0.414 AC: 17131 AN: 41414

American (AMR) AF: 0.396 AC: 6041 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1387 AN: 3472

East Asian (EAS) AF: 0.524 AC: 2692 AN: 5136

South Asian (SAS) AF: 0.378 AC: 1822 AN: 4816

European-Finnish (FIN) AF: 0.382 AC: 4025 AN: 10536

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23822 AN: 67942

Other (OTH) AF: 0.383 AC: 810 AN: 2114

Alfa AF: 0.367 Hom.: 29227

Bravo AF: 0.387

Asia WGS AF: 0.453 AC: 1575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.68
PhyloP100		-1.3
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: rs1198872; hg19: chr2-10903412;