2-46512063-C-T

Variant names:

• chr2-46512063-C-T
• rs1687480739
• NM_001318063.2:c.649G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001318063.2(ATP6V1E2):​c.649G>A​(p.Gly217Ser) 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: 3.31
• Publications: 0 publications found

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]

LINC02583 (HGNC:53812): (long intergenic non-protein coding RNA 2583)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318063.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1E2	NM_001318063.2	MANE Select	c.649G>A	p.Gly217Ser	missense	Exon 5 of 5	NP_001304992.1	A0A140VKA8
	ATP6V1E2	NM_001371281.1		c.649G>A	p.Gly217Ser	missense	Exon 5 of 5	NP_001358210.1	Q96A05
	ATP6V1E2	NM_001371282.1		c.649G>A	p.Gly217Ser	missense	Exon 5 of 5	NP_001358211.1	A0A140VKA8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1E2	ENST00000522587.6	TSL:3 MANE Select	c.649G>A	p.Gly217Ser	missense	Exon 5 of 5	ENSP00000428141.1	Q96A05
	ATP6V1E2	ENST00000306448.4	TSL:1	c.649G>A	p.Gly217Ser	missense	Exon 2 of 2	ENSP00000304891.4	Q96A05
	ATP6V1E2	ENST00000890126.1		c.649G>A	p.Gly217Ser	missense	Exon 6 of 6	ENSP00000560185.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.3
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.013	D
Sift4G	Benign	0.068	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.66		Gain of disorder (P = 0.0382)
MVP		0.30
MPC		0.086
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.67
gMVP		0.70
Mutation Taster		=18/82	disease causing

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

Other links and lift over

dbSNP: rs1687480739; hg19: chr2-46739202;