dbSNP rs1686482: ATP6V1C2:c.1194+15A>C (chr2-10782390-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

Variant links:

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]

ATP6V1C2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1C2	NM_001039362.2 link	c.1194+15A>C		intron_variant	Intron 13 of 13	ENST00000272238.9	NP_001034451.1	Q8NEY4-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATP6V1C2	ENST00000272238.9 link	c.1194+15A>C	intron_variant	Intron 13 of 13	5	NM_001039362.2	ENSP00000272238.4	Q8NEY4-1
ATP6V1C2	ENST00000635370.1 link	c.1224+15A>C	intron_variant	Intron 13 of 13	5		ENSP00000489280.1	A0A0U1RR16
ATP6V1C2	ENST00000381661.3 link	c.1056+15A>C	intron_variant	Intron 12 of 12	2		ENSP00000371077.3	Q8NEY4-2
ATP6V1C2	ENST00000480289.1 link	n.315+15A>C	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60586

AN:

151988

Hom.:

13471

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.467

AC:

116537

AN:

249648

Hom.:

28296

AF XY:

0.468

AC XY:

63149

AN XY:

134908

show subpopulations

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 SAS exome

AF:

0.425

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.:

AF XY:

0.469

AC XY:

340263

AN XY:

726220

show subpopulations

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.531

Gnomad4 ASJ exome

AF:

0.587

Gnomad4 EAS exome

AF:

0.390

Gnomad4 SAS exome

AF:

0.422

Gnomad4 FIN exome

AF:

0.436

Gnomad4 NFE exome

AF:

0.480

Gnomad4 OTH exome

AF:

0.470

GnomAD4 genome

AF:

0.398

AC:

60597

AN:

152106

Hom.:

13467

Cov.:

AF XY:

0.400

AC XY:

29745

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.480

Gnomad4 ASJ

AF:

0.596

Gnomad4 EAS

AF:

0.458

Gnomad4 SAS

AF:

0.426

Gnomad4 FIN

AF:

0.422

Gnomad4 NFE

AF:

0.482

Gnomad4 OTH

AF:

0.454

Alfa

AF:

0.481

Hom.:

19546

Bravo

AF:

0.398

Asia WGS

AF:

0.435

AC:

1511

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.3

DANN

Benign

0.78

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over