Variant 2-10772538-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039362.2(ATP6V1C2):c.570-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,613,272 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 168 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 143 hom. )

Consequence

ATP6V1C2
NM_001039362.2 splice_region, intron

Scores

Splicing: ADA: 0.00007931

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.285

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:

LOC105373428 (HGNC:):

LOC105373428 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-10772538-G-A is Benign according to our data. Variant chr2-10772538-G-A is described in ClinVar as [Benign]. Clinvar id is 785958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1C2	NM_001039362.2 linkuse as main transcript	c.570-4G>A		splice_region_variant, intron_variant		ENST00000272238.9	NP_001034451.1	Q8NEY4-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ATP6V1C2	ENST00000272238.9 linkuse as main transcript	c.570-4G>A	splice_region_variant, intron_variant	5	NM_001039362.2	ENSP00000272238.4	Q8NEY4-1
ATP6V1C2	ENST00000635370.1 linkuse as main transcript	c.600-4G>A	splice_region_variant, intron_variant	5		ENSP00000489280.1	A0A0U1RR16
ATP6V1C2	ENST00000381661.3 linkuse as main transcript	c.570-4G>A	splice_region_variant, intron_variant	2		ENSP00000371077.3	Q8NEY4-2
ATP6V1C2	ENST00000648362.1 linkuse as main transcript	c.570-4G>A	splice_region_variant, intron_variant			ENSP00000497038.1	A0A3B3IRZ7

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3687

AN:

152160

Hom.:

168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0853

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00629

AC:

1581

AN:

251476

Hom.:

AF XY:

0.00451

AC XY:

613

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0857

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.00249

AC:

3640

AN:

1460994

Hom.:

143

Cov.:

AF XY:

0.00207

AC XY:

1506

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.0889

Gnomad4 AMR exome

AF:

0.00490

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.00580

GnomAD4 genome

AF:

0.0243

AC:

3694

AN:

152278

Hom.:

168

Cov.:

AF XY:

0.0230

AC XY:

1709

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0852

Gnomad4 AMR

AF:

0.00732

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00966

Hom.:

Bravo

AF:

0.0282

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.14

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000079

dbscSNV1_RF

Benign

0.0020

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over