2-10771871-T-C

Position:

chr2-10771871-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_001039362.2(ATP6V1C2):c.503T>C(p.Ile168Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,614,116 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

ATP6V1C2
NM_001039362.2 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-10771871-T-C is Pathogenic according to our data. Variant chr2-10771871-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1344706.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.016740263). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1C2	NM_001039362.2 linkuse as main transcript	c.503T>C	p.Ile168Thr	missense_variant	7/14	ENST00000272238.9	NP_001034451.1
LOC105373428	XR_922797.4 linkuse as main transcript	n.963+570A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1C2	ENST00000272238.9 linkuse as main transcript	c.503T>C	p.Ile168Thr	missense_variant	7/14	5	NM_001039362.2	ENSP00000272238		Q8NEY4-1
ATP6V1C2	ENST00000635370.1 linkuse as main transcript	c.533T>C	p.Ile178Thr	missense_variant	7/14	5		ENSP00000489280
ATP6V1C2	ENST00000381661.3 linkuse as main transcript	c.503T>C	p.Ile168Thr	missense_variant	7/13	2		ENSP00000371077	P1	Q8NEY4-2
ATP6V1C2	ENST00000648362.1 linkuse as main transcript	c.503T>C	p.Ile168Thr	missense_variant	7/12			ENSP00000497038

Frequencies

GnomAD3 genomes

AF:

0.00242

AC:

369

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00854

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000612

AC:

154

AN:

251482

Hom.:

AF XY:

0.000434

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00794

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000279

AC:

408

AN:

1461826

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

179

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00822

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000594

Gnomad4 OTH exome

AF:

0.000695

GnomAD4 genome

AF:

0.00245

AC:

373

AN:

152290

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00862

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000362

Hom.:

Bravo

AF:

0.00277

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000692

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Distal renal tubular acidosis

Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Yale Center for Mendelian Genomics, Yale University

Oct 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;T;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.061

MetaRNN

Benign

0.017

T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Pathogenic

3.2

.;M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.8

.;D;D;.

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

.;D;D;.

Sift4G

Uncertain

0.0030

.;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.97, 0.93, 0.96

MVP

0.57

MPC

0.81

ClinPred

0.056

GERP RS

2.7

Varity_R

0.56

gMVP

0.58

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

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