chr1-16986163-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000341676.9(ATP13A2):ā€‹c.3299A>Gā€‹(p.Asp1100Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,609,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00015 ( 0 hom., cov: 31)
Exomes š‘“: 0.00018 ( 0 hom. )

Consequence

ATP13A2
ENST00000341676.9 missense

Scores

2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.182
Variant links:
Genes affected
ATP13A2 (HGNC:30213): (ATPase cation transporting 13A2) This gene encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. Mutations in this gene are associated with Kufor-Rakeb syndrome (KRS), also referred to as Parkinson disease 9. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.013765067).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATP13A2NM_022089.4 linkuse as main transcriptc.*58A>G 3_prime_UTR_variant 29/29 ENST00000326735.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATP13A2ENST00000326735.13 linkuse as main transcriptc.*58A>G 3_prime_UTR_variant 29/291 NM_022089.4 A1Q9NQ11-1
ENST00000446261.1 linkuse as main transcriptn.187+7051T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000146
AC:
22
AN:
151062
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000488
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:
0.000855
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000341
AC:
81
AN:
237852
Hom.:
0
AF XY:
0.000286
AC XY:
37
AN XY:
129546
show subpopulations
Gnomad AFR exome
AF:
0.0000701
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000646
Gnomad NFE exome
AF:
0.000614
Gnomad OTH exome
AF:
0.000174
GnomAD4 exome
AF:
0.000182
AC:
265
AN:
1458066
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
117
AN XY:
724884
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000774
Gnomad4 NFE exome
AF:
0.000183
Gnomad4 OTH exome
AF:
0.000332
GnomAD4 genome
AF:
0.000146
AC:
22
AN:
151062
Hom.:
0
Cov.:
31
AF XY:
0.000190
AC XY:
14
AN XY:
73724
show subpopulations
Gnomad4 AFR
AF:
0.0000488
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000855
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000153
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000314
AC:
1
ExAC
AF:
0.000488
AC:
59

ClinVar

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

Submissions by phenotype

Kufor-Rakeb syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
8.6
DANN
Benign
0.96
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.49
T;T
M_CAP
Uncertain
0.090
D
MetaRNN
Benign
0.014
T;T
MetaSVM
Uncertain
-0.15
T
MutationTaster
Benign
1.0
N;N;N
PROVEAN
Benign
-0.37
N;N
REVEL
Benign
0.23
Sift
Benign
0.040
D;D
Sift4G
Benign
0.082
.;T
Vest4
0.21
MVP
0.24
ClinPred
0.013
T
GERP RS
-4.2

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: rs369126613; hg19: chr1-17312658; API