Genetic Variant ATP13A2:c.289-109T>C (chr1-17005181-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_022089.4(ATP13A2):c.289-109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,514,810 control chromosomes in the GnomAD database, including 166,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21091 hom., cov: 32)

Exomes 𝑓: 0.46 ( 145383 hom. )

Consequence

ATP13A2
NM_022089.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0320

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:

ENSG00000288636 (HGNC:):

ENSG00000288636 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-17005181-A-G is Benign according to our data. Variant chr1-17005181-A-G is described in ClinVar as [Benign]. Clinvar id is 1270274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-17005181-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP13A2	NM_022089.4 link	c.289-109T>C		intron_variant	Intron 3 of 28	ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13 link	c.289-109T>C		intron_variant	Intron 3 of 28	1	NM_022089.4	ENSP00000327214.8		Q9NQ11-1
ENSG00000288636	ENST00000617114.5 link	c.308-109T>C		intron_variant	Intron 3 of 3	5		ENSP00000478781.2		A0A087WUM9

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78651

AN:

151868

Hom.:

21041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.714

Gnomad SAS

AF:

0.579

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.500

GnomAD4 exome

AF:

0.457

AC:

622609

AN:

1362826

Hom.:

145383

Cov.:

AF XY:

0.459

AC XY:

313272

AN XY:

681916

show subpopulations

Gnomad4 AFR exome

AF:

0.653

Gnomad4 AMR exome

AF:

0.497

Gnomad4 ASJ exome

AF:

0.467

Gnomad4 EAS exome

AF:

0.682

Gnomad4 SAS exome

AF:

0.557

Gnomad4 FIN exome

AF:

0.492

Gnomad4 NFE exome

AF:

0.429

Gnomad4 OTH exome

AF:

0.485

GnomAD4 genome

AF:

0.518

AC:

78756

AN:

151984

Hom.:

21091

Cov.:

AF XY:

0.525

AC XY:

39035

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.646

Gnomad4 AMR

AF:

0.512

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.715

Gnomad4 SAS

AF:

0.579

Gnomad4 FIN

AF:

0.501

Gnomad4 NFE

AF:

0.428

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.456

Hom.:

36854

Bravo

AF:

0.523

Asia WGS

AF:

0.658

AC:

2286

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

DANN

Benign

0.43

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.

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