2-46512582-G-T

Variant names:

• chr2-46512582-G-T
• rs150480219
• NM_001318063.2:c.130C>A

Variant summary

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

The NM_001318063.2(ATP6V1E2):​c.130C>A​(p.Arg44Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R44C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATP6V1E2 NM_001318063.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• 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.130C>A	p.Arg44Ser	missense	Exon 5 of 5	NP_001304992.1	A0A140VKA8
	ATP6V1E2	NM_001371281.1		c.130C>A	p.Arg44Ser	missense	Exon 5 of 5	NP_001358210.1	Q96A05
	ATP6V1E2	NM_001371282.1		c.130C>A	p.Arg44Ser	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.130C>A	p.Arg44Ser	missense	Exon 5 of 5	ENSP00000428141.1	Q96A05
	ATP6V1E2	ENST00000306448.4	TSL:1	c.130C>A	p.Arg44Ser	missense	Exon 2 of 2	ENSP00000304891.4	Q96A05
	ATP6V1E2	ENST00000890126.1		c.130C>A	p.Arg44Ser	missense	Exon 6 of 6	ENSP00000560185.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.082	T
Polyphen		0.71	P
Vest4		0.70
MutPred		0.58		Loss of MoRF binding (P = 0.0303)
MVP		0.28
MPC		0.057
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.92
gMVP		0.39
Mutation Taster		=20/80	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: rs150480219; hg19: chr2-46739721;