rs3738814

Positions:

• chr1-17005181-A-G
• chr1-17005181-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0320

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]

(HGNC:):

ACMG classification

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/exons	MANE	UniProt
ATP13A2	NM_022089.4	c.289-109T>C		intron_variant		ENST00000326735.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP13A2	ENST00000326735.13	c.289-109T>C		intron_variant		1	NM_022089.4	A1
	ENST00000617114.5	c.308-109T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78651 AN: 151868 Hom.: 21041 Cov.: 32

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.: 22 AF XY: 0.459 AC XY: 313272 AN XY: 681916

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.: 32 AF XY: 0.525 AC XY: 39035 AN XY: 74282

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

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 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:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

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

Other links and lift over

dbSNP: rs3738814; hg19: chr1-17331676; COSMIC: COSV58699306; COSMIC: COSV58699306;