chr1-16993764-G-A

Position:

chr1-16993764-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_022089.4(ATP13A2):c.1614C>T(p.Pro538Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,589,758 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 19 hom. )

Consequence

ATP13A2
NM_022089.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.68

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]

ATP13A2 links:

ENSG00000226526 (HGNC:):

ENSG00000226526 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-16993764-G-A is Benign according to our data. Variant chr1-16993764-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16993764-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00343 (522/152326) while in subpopulation SAS AF= 0.0101 (49/4830). AF 95% confidence interval is 0.00788. There are 2 homozygotes in gnomad4. There are 262 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A2	NM_022089.4 linkuse as main transcript	c.1614C>T	p.Pro538Pro	synonymous_variant	16/29	ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13 linkuse as main transcript	c.1614C>T	p.Pro538Pro	synonymous_variant	16/29	1	NM_022089.4	ENSP00000327214.8		Q9NQ11-1

Frequencies

GnomAD3 genomes

AF:

0.00342

AC:

521

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00342

AC:

700

AN:

204484

Hom.:

AF XY:

0.00379

AC XY:

422

AN XY:

111320

show subpopulations

Gnomad AFR exome

AF:

0.00623

Gnomad AMR exome

AF:

0.00545

Gnomad ASJ exome

AF:

0.00489

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00946

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00160

Gnomad OTH exome

AF:

0.00464

GnomAD4 exome

AF:

0.00205

AC:

2947

AN:

1437432

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

1698

AN XY:

713006

show subpopulations

Gnomad4 AFR exome

AF:

0.00630

Gnomad4 AMR exome

AF:

0.00531

Gnomad4 ASJ exome

AF:

0.00505

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.0000198

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.00335

GnomAD4 genome

AF:

0.00343

AC:

522

AN:

152326

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00604

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00246

Hom.:

Bravo

AF:

0.00357

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 31, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	ATP13A2: BP4, BP7, BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Kufor-Rakeb syndrome

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Kufor-Rakeb syndrome;C5567893:Autosomal recessive spastic paraplegia type 78

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2016

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.96

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over