dbSNP rs761421: ATP13A2:p.Val990Val (chr1-16987159-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022089.4(ATP13A2):c.2970G>A(p.Val990Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,612,896 control chromosomes in the GnomAD database, including 203,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14650 hom., cov: 33)

Exomes 𝑓: 0.50 ( 188913 hom. )

Consequence

ATP13A2
NM_022089.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -0.854

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=-0.61).

BP6

Variant 1-16987159-C-T is Benign according to our data. Variant chr1-16987159-C-T is described in ClinVar as [Benign]. Clinvar id is 128470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16987159-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.854 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP13A2	NM_022089.4 link	c.2970G>A	p.Val990Val	synonymous_variant	Exon 26 of 29	ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13 link	c.2970G>A	p.Val990Val	synonymous_variant	Exon 26 of 29	1	NM_022089.4	ENSP00000327214.8		Q9NQ11-1

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63475

AN:

151926

Hom.:

14645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.472

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.527

Gnomad OTH

AF:

0.431

GnomAD3 exomes

AF:

0.465

AC:

115513

AN:

248224

Hom.:

27876

AF XY:

0.471

AC XY:

63408

AN XY:

134658

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.479

Gnomad ASJ exome

AF:

0.483

Gnomad EAS exome

AF:

0.283

Gnomad SAS exome

AF:

0.473

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.520

Gnomad OTH exome

AF:

0.470

GnomAD4 exome

AF:

0.504

AC:

735772

AN:

1460852

Hom.:

188913

Cov.:

AF XY:

0.504

AC XY:

365963

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.475

Gnomad4 ASJ exome

AF:

0.485

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.472

Gnomad4 FIN exome

AF:

0.485

Gnomad4 NFE exome

AF:

0.526

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.418

AC:

63492

AN:

152044

Hom.:

14650

Cov.:

AF XY:

0.413

AC XY:

30710

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.447

Gnomad4 ASJ

AF:

0.473

Gnomad4 EAS

AF:

0.274

Gnomad4 SAS

AF:

0.453

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.527

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.497

Hom.:

10301

Bravo

AF:

0.407

Asia WGS

AF:

0.339

AC:

1178

AN:

3478

EpiCase

AF:

0.516

EpiControl

AF:

0.518

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 71% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 66. Only high quality variants are reported. -

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Kufor-Rakeb syndrome

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive spastic paraplegia type 78

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as 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

-0.61

CADD

Benign

0.12

DANN

Benign

0.90

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