chr12-123756823-G-A

Position:

• chr12-123756823-G-A

Variant summary

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

The ENST00000330342.8(ATP6V0A2):​c.2302G>A​(p.Asp768Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATP6V0A2 ENST00000330342.8 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 8.14

Genes affected

ATP6V0A2 (HGNC:18481): (ATPase H+ transporting V0 subunit a2) The protein encoded by this gene is a subunit of the vacuolar ATPase (v-ATPase), an heteromultimeric enzyme that is present in intracellular vesicles and in the plasma membrane of specialized cells, and which is essential for the acidification of diverse cellular components. V-ATPase is comprised of a membrane peripheral V(1) domain for ATP hydrolysis, and an integral membrane V(0) domain for proton translocation. The subunit encoded by this gene is a component of the V(0) domain. Mutations in this gene are a cause of both cutis laxa type II and wrinkly skin syndrome. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V0A2	NM_012463.4	c.2302G>A	p.Asp768Asn	missense_variant	19/20	ENST00000330342.8	NP_036595.2
ATP6V0A2	XM_024448910.2	c.2182G>A	p.Asp728Asn	missense_variant	18/19		XP_024304678.1
ATP6V0A2	XM_024448911.2	c.1789G>A	p.Asp597Asn	missense_variant	15/16		XP_024304679.1
ATP6V0A2	XM_024448912.2	c.1480G>A	p.Asp494Asn	missense_variant	12/13		XP_024304680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V0A2	ENST00000330342.8	c.2302G>A	p.Asp768Asn	missense_variant	19/20	1	NM_012463.4	ENSP00000332247	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Cutis laxa with osteodystrophy Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;.;T
Eigen	Benign	-0.036
Eigen_PC	Benign	0.050
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	0.73	N;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.043	B;.;.
Vest4		0.55
MutPred		0.60		Gain of catalytic residue at V769 (P = 6e-04);.;.;
MVP		0.64
MPC		0.24
ClinPred		0.75	D
GERP RS		5.7
Varity_R		0.47
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs367543008; hg19: chr12-124241370;