Variant 1-16986788-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000326735.13(ATP13A2):c.3235+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 1,609,774 control chromosomes in the GnomAD database, including 598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 48 hom., cov: 33)

Exomes 𝑓: 0.025 ( 550 hom. )

Consequence

ATP13A2
ENST00000326735.13 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.45

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=-0.8).

BP6

Variant 1-16986788-C-T is Benign according to our data. Variant chr1-16986788-C-T is described in ClinVar as [Benign]. Clinvar id is 261542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16986788-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0239 (3637/152272) while in subpopulation NFE AF= 0.0263 (1789/68014). AF 95% confidence interval is 0.0253. There are 48 homozygotes in gnomad4. There are 1781 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A2	NM_022089.4 linkuse as main transcript	c.3235+17G>A		intron_variant		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.3235+17G>A		intron_variant		1	NM_022089.4	ENSP00000327214	A1	Q9NQ11-1
	ENST00000446261.1 linkuse as main transcript	n.187+7676C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3638

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0221

AC:

5304

AN:

240380

Hom.:

AF XY:

0.0225

AC XY:

2943

AN XY:

130936

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.0224

Gnomad ASJ exome

AF:

0.0285

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0165

Gnomad FIN exome

AF:

0.0235

Gnomad NFE exome

AF:

0.0258

Gnomad OTH exome

AF:

0.0309

GnomAD4 exome

AF:

0.0253

AC:

36917

AN:

1457502

Hom.:

550

Cov.:

AF XY:

0.0251

AC XY:

18220

AN XY:

724960

show subpopulations

Gnomad4 AFR exome

AF:

0.0240

Gnomad4 AMR exome

AF:

0.0229

Gnomad4 ASJ exome

AF:

0.0275

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0175

Gnomad4 FIN exome

AF:

0.0220

Gnomad4 NFE exome

AF:

0.0269

Gnomad4 OTH exome

AF:

0.0270

GnomAD4 genome

AF:

0.0239

AC:

3637

AN:

152272

Hom.:

Cov.:

AF XY:

0.0239

AC XY:

1781

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.0258

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.0225

Gnomad4 NFE

AF:

0.0263

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0262

Hom.:

Bravo

AF:

0.0240

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	May 01, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.1

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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