2-46512563-C-T

Variant summary

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

The NM_001318063.2(ATP6V1E2):​c.149G>A​(p.Arg50Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ATP6V1E2
NM_001318063.2 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
ATP6V1E2NM_001318063.2 linkc.149G>A p.Arg50Gln missense_variant Exon 5 of 5 ENST00000522587.6 NP_001304992.1 Q96A05A0A140VKA8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATP6V1E2ENST00000522587.6 linkc.149G>A p.Arg50Gln missense_variant Exon 5 of 5 3 NM_001318063.2 ENSP00000428141.1 Q96A05
ATP6V1E2ENST00000306448.4 linkc.149G>A p.Arg50Gln missense_variant Exon 2 of 2 1 ENSP00000304891.4 Q96A05
ATP6V1E2ENST00000524249.5 linkn.776-21732G>A intron_variant Intron 4 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251426
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461880
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.149G>A (p.R50Q) 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 149, causing the arginine (R) at amino acid position 50 to be replaced by a glutamine (Q). 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
0.24
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.18
T;T
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.99
.;D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Uncertain
2.7
M;M
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.6
D;D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.012
D;D
Polyphen
0.98
D;D
Vest4
0.83
MutPred
0.57
Loss of MoRF binding (P = 0.0486);Loss of MoRF binding (P = 0.0486);
MVP
0.28
MPC
0.11
ClinPred
0.99
D
GERP RS
4.1
Varity_R
0.69
gMVP
0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs778583536; hg19: chr2-46739702; COSMIC: COSV60576132; API