rs7531163

Positions:

chr1-16986959-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022089.4(ATP13A2):c.3084-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,613,342 control chromosomes in the GnomAD database, including 53,206 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4955 hom., cov: 29)

Exomes 𝑓: 0.25 ( 48251 hom. )

Consequence

ATP13A2
NM_022089.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001061

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.747

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 1-16986959-G-A is Benign according to our data. Variant chr1-16986959-G-A is described in ClinVar as [Benign]. Clinvar id is 128471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16986959-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP13A2	NM_022089.4 linkuse as main transcript	c.3084-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000326735.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP13A2	ENST00000326735.13 linkuse as main transcript	c.3084-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_022089.4	A1	Q9NQ11-1
	ENST00000446261.1 linkuse as main transcript	n.187+7847G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36781

AN:

151530

Hom.:

4944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.282

AC:

70700

AN:

250814

Hom.:

11144

AF XY:

0.277

AC XY:

37663

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.551

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.317

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.250

AC:

365088

AN:

1461694

Hom.:

48251

Cov.:

AF XY:

0.249

AC XY:

181231

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.356

Gnomad4 ASJ exome

AF:

0.263

Gnomad4 EAS exome

AF:

0.534

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.243

AC:

36817

AN:

151648

Hom.:

4955

Cov.:

AF XY:

0.251

AC XY:

18579

AN XY:

74050

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.558

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.262

Alfa

AF:

0.235

Hom.:

2234

Bravo

AF:

0.244

Asia WGS

AF:

0.363

AC:

1262

AN:

3478

EpiCase

AF:

0.246

EpiControl

AF:

0.249

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 44. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Kufor-Rakeb syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
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	Jan 13, 2018	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 16, 2015	- -

Autosomal recessive spastic paraplegia type 78

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 24, 2016

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

-0.55

CADD

Benign

7.0

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0011

dbscSNV1_RF

Benign

0.10

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.

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