chr2-10722893-A-G

Position:

• chr2-10722893-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039362.2(ATP6V1C2):​c.44A>G​(p.Asn15Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATP6V1C2 NM_001039362.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.41

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119240195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1C2	NM_001039362.2	c.44A>G	p.Asn15Ser	missense_variant	2/14	ENST00000272238.9	NP_001034451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1C2	ENST00000272238.9	c.44A>G	p.Asn15Ser	missense_variant	2/14	5	NM_001039362.2	ENSP00000272238.4
ATP6V1C2	ENST00000635370.1	c.44A>G	p.Asn15Ser	missense_variant	1/14	5		ENSP00000489280.1
ATP6V1C2	ENST00000381661.3	c.44A>G	p.Asn15Ser	missense_variant	2/13	2		ENSP00000371077.3
ATP6V1C2	ENST00000648362.1	c.44A>G	p.Asn15Ser	missense_variant	2/12			ENSP00000497038.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.44A>G (p.N15S) alteration is located in exon 2 (coding exon 1) of the ATP6V1C2 gene. This alteration results from a A to G substitution at nucleotide position 44, causing the asparagine (N) at amino acid position 15 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.67
DEOGEN2	Benign	0.0030	.;T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.073
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	.;N;N;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.88	.;N;N;.
REVEL	Benign	0.094
Sift	Benign	1.0	.;T;T;.
Sift4G	Benign	1.0	.;T;T;T
Polyphen		0.0090, 0.0070	.;B;B;.
Vest4		0.62, 0.63, 0.64
MutPred		0.50		Gain of disorder (P = 0.0613);Gain of disorder (P = 0.0613);Gain of disorder (P = 0.0613);Gain of disorder (P = 0.0613);
MVP		0.34
MPC		0.14
ClinPred		0.52	D
GERP RS		5.6
Varity_R		0.12
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-10863019;