rs9435662

Variant names:

• chr1-16988447-G-A
• rs9435662
• NM_022089.4:c.2637C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022089.4(ATP13A2):​c.2637C>T​(p.Gly879Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,613,584 control chromosomes in the GnomAD database, including 203,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14427 hom., cov: 33)
  • Exomes 𝑓: 0.50 (188830 hom.)
• Consequence: ATP13A2 NM_022089.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -5.03
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• Kufor-Rakeb syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Illumina
• autosomal recessive spastic paraplegia type 78

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• parkinsonism due to ATP13A2 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000226526 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 1-16988447-G-A is Benign according to our data. Variant chr1-16988447-G-A is described in ClinVar as Benign. ClinVar VariationId is 128466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022089.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A2	NM_022089.4	MANE Select	c.2637C>T	p.Gly879Gly	synonymous	Exon 24 of 29	NP_071372.1	Q9NQ11-1
	ATP13A2	NM_001141973.3		c.2622C>T	p.Gly874Gly	synonymous	Exon 24 of 29	NP_001135445.1	Q9NQ11-3
	ATP13A2	NM_001141974.3		c.2505C>T	p.Gly835Gly	synonymous	Exon 23 of 27	NP_001135446.1	Q9NQ11-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A2	ENST00000326735.13	TSL:1 MANE Select	c.2637C>T	p.Gly879Gly	synonymous	Exon 24 of 29	ENSP00000327214.8	Q9NQ11-1
	ATP13A2	ENST00000452699.5	TSL:1	c.2622C>T	p.Gly874Gly	synonymous	Exon 24 of 29	ENSP00000413307.1	Q9NQ11-3
	ATP13A2	ENST00000341676.9	TSL:1	c.2505C>T	p.Gly835Gly	synonymous	Exon 23 of 27	ENSP00000341115.5	Q9NQ11-2

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62417 AN: 151924 Hom.: 14422 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.427

GnomAD2 exomes AF: 0.463 AC: 116385 AN: 251228 AF XY: 0.469

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.482

Gnomad EAS exome AF: 0.289

Gnomad FIN exome AF: 0.479

Gnomad NFE exome AF: 0.519

Gnomad OTH exome AF: 0.469

GnomAD4 exome AF: 0.503 AC: 735242 AN: 1461540 Hom.: 188830 Cov.: 75 AF XY: 0.503 AC XY: 365778 AN XY: 727084

African (AFR) AF: 0.177 AC: 5939 AN: 33478

American (AMR) AF: 0.473 AC: 21171 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 12660 AN: 26136

East Asian (EAS) AF: 0.307 AC: 12197 AN: 39700

South Asian (SAS) AF: 0.472 AC: 40713 AN: 86254

European-Finnish (FIN) AF: 0.485 AC: 25759 AN: 53100

Middle Eastern (MID) AF: 0.472 AC: 2719 AN: 5766

European-Non Finnish (NFE) AF: 0.527 AC: 585562 AN: 1111986

Other (OTH) AF: 0.472 AC: 28522 AN: 60396

GnomAD4 genome AF: 0.411 AC: 62419 AN: 152044 Hom.: 14427 Cov.: 33 AF XY: 0.407 AC XY: 30248 AN XY: 74318

African (AFR) AF: 0.194 AC: 8047 AN: 41500

American (AMR) AF: 0.445 AC: 6808 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1642 AN: 3470

East Asian (EAS) AF: 0.282 AC: 1450 AN: 5144

South Asian (SAS) AF: 0.454 AC: 2192 AN: 4824

European-Finnish (FIN) AF: 0.474 AC: 5004 AN: 10568

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35833 AN: 67938

Other (OTH) AF: 0.421 AC: 889 AN: 2110

Alfa AF: 0.437 Hom.: 9670

Bravo AF: 0.399

Asia WGS AF: 0.339 AC: 1180 AN: 3478

EpiCase AF: 0.516

EpiControl AF: 0.517

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	4	not provided (4)
-	-	2	Kufor-Rakeb syndrome (2)
-	-	1	Autosomal recessive spastic paraplegia type 78 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	Kufor-Rakeb syndrome;C5567893:Autosomal recessive spastic paraplegia type 78 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.6
DANN	Benign	0.89
PhyloP100		-5.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9435662; hg19: chr1-17314942; COSMIC: COSV58700683; COSMIC: COSV58700683;