2-46512690-C-T

Variant names:

• chr2-46512690-C-T
• NM_001318063.2:c.22G>A

Variant summary

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

The NM_001318063.2(ATP6V1E2):​c.22G>A​(p.Val8Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP6V1E2 NM_001318063.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

Genes affected

ATP6V1E2 (HGNC:18125): (ATPase H+ transporting V1 subunit E2) Predicted to enable P-type proton-exporting transporter activity. Predicted to act upstream of or within proton transmembrane transport. Predicted to be located in cytosol. Predicted to be part of proton-transporting two-sector ATPase complex, catalytic domain. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
ATP6V1E2	NM_001318063.2	c.22G>A	p.Val8Met	missense_variant	Exon 5 of 5	ENST00000522587.6	NP_001304992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1E2	ENST00000522587.6	c.22G>A	p.Val8Met	missense_variant	Exon 5 of 5	3	NM_001318063.2	ENSP00000428141.1
ATP6V1E2	ENST00000306448.4	c.22G>A	p.Val8Met	missense_variant	Exon 2 of 2	1		ENSP00000304891.4
ATP6V1E2	ENST00000524249.5	n.776-21859G>A		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.22G>A (p.V8M) alteration is located in exon 2 (coding exon 1) of the ATP6V1E2 gene. This alteration results from a G to A substitution at nucleotide position 22, causing the valine (V) at amino acid position 8 to be replaced by a methionine (M). 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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	3.5	M;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;D
Vest4		0.56
MutPred		0.58		Loss of methylation at K9 (P = 0.0253);Loss of methylation at K9 (P = 0.0253);
MVP		0.33
MPC		0.068
ClinPred		0.97	D
GERP RS		3.2
Varity_R		0.78
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-46739829;