rs41273157

chr1-17004983-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_022089.4(ATP13A2):c.347+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 1,613,288 control chromosomes in the GnomAD database, including 373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (22 hom., cov: 32)
  • Exomes 𝑓: 0.020 (351 hom.)
• Consequence: ATP13A2 NM_022089.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-17004983-C-T is Benign according to our data. Variant chr1-17004983-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1212215.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0127 (1926/152228) while in subpopulation NFE AF= 0.0208 (1411/67982). AF 95% confidence interval is 0.0199. There are 22 homozygotes in gnomad4. There are 915 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP13A2	NM_022089.4	c.347+31G>A		intron_variant		ENST00000326735.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP13A2	ENST00000326735.13	c.347+31G>A		intron_variant		1	NM_022089.4	A1
	ENST00000446261.1	n.528C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1927 AN: 152110 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0101

GnomAD3 exomes AF: 0.0149 AC: 3729 AN: 250342 Hom.: 48 AF XY: 0.0162 AC XY: 2199 AN XY: 135524

Gnomad AFR exome AF: 0.00328

Gnomad AMR exome AF: 0.00617

Gnomad ASJ exome AF: 0.00269

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0243

Gnomad FIN exome AF: 0.0100

Gnomad NFE exome AF: 0.0211

Gnomad OTH exome AF: 0.0152

GnomAD4 exome AF: 0.0198 AC: 28868 AN: 1461060 Hom.: 351 Cov.: 33 AF XY: 0.0199 AC XY: 14497 AN XY: 726798

Gnomad4 AFR exome AF: 0.00284

Gnomad4 AMR exome AF: 0.00640

Gnomad4 ASJ exome AF: 0.00264

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0231

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.0222

Gnomad4 OTH exome AF: 0.0172

GnomAD4 genome AF: 0.0127 AC: 1926 AN: 152228 Hom.: 22 Cov.: 32 AF XY: 0.0123 AC XY: 915 AN XY: 74430

Gnomad4 AFR AF: 0.00318

Gnomad4 AMR AF: 0.00870

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.0109

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.00997

Alfa AF: 0.0155 Hom.: 2

Bravo AF: 0.0120

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	12
Dann	Benign	0.86

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: rs41273157; hg19: chr1-17331478;