rs15786

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001141974.3(ATP13A2):c.3365C>T(p.Pro1122Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,559,316 control chromosomes in the GnomAD database, including 2,562 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 197 hom., cov: 31)

Exomes 𝑓: 0.053 ( 2365 hom. )

Consequence

ATP13A2
NM_001141974.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.380

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

Kufor-Rakeb syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Genomics England PanelApp, G2P, ClinGen
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

ATP13A2 links:

ENSG00000226526 (HGNC:):

ENSG00000226526 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023908615).

BP6

Variant 1-16986097-G-A is Benign according to our data. Variant chr1-16986097-G-A is described in ClinVar as Benign. ClinVar VariationId is 293763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141974.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATP13A2	NM_022089.4	MANE Select	c.*124C>T		3_prime_UTR	Exon 29 of 29	NP_071372.1
ATP13A2	NM_001141974.3		c.3365C>T	p.Pro1122Leu	missense	Exon 27 of 27	NP_001135446.1
ATP13A2	NM_001141973.3		c.*124C>T		3_prime_UTR	Exon 29 of 29	NP_001135445.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATP13A2	ENST00000341676.9	TSL:1	c.3365C>T	p.Pro1122Leu	missense	Exon 27 of 27	ENSP00000341115.5
ATP13A2	ENST00000326735.13	TSL:1 MANE Select	c.*124C>T		3_prime_UTR	Exon 29 of 29	ENSP00000327214.8
ATP13A2	ENST00000452699.5	TSL:1	c.*124C>T		3_prime_UTR	Exon 29 of 29	ENSP00000413307.1

Frequencies

GnomAD3 genomes

AF:

0.0394

AC:

5997

AN:

152062

Hom.:

197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00961

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0229

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00748

Gnomad FIN

AF:

0.0880

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0608

Gnomad OTH

AF:

0.0253

GnomAD2 exomes

AF:

0.0397

AC:

6881

AN:

173142

AF XY:

0.0392

show subpopulations

Gnomad AFR exome

AF:

0.00917

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.0209

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0911

Gnomad NFE exome

AF:

0.0598

Gnomad OTH exome

AF:

0.0397

GnomAD4 exome

AF:

0.0534

AC:

75085

AN:

1407136

Hom.:

2365

Cov.:

AF XY:

0.0522

AC XY:

36274

AN XY:

694332

show subpopulations

African (AFR)

AF:

0.00874

AC:

281

AN:

32146

American (AMR)

AF:

0.0138

AC:

471

AN:

34128

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

548

AN:

24708

East Asian (EAS)

AF:

0.0000265

AC:

AN:

37756

South Asian (SAS)

AF:

0.0106

AC:

845

AN:

80048

European-Finnish (FIN)

AF:

0.0926

AC:

4664

AN:

50348

Middle Eastern (MID)

AF:

0.00833

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.0605

AC:

65571

AN:

1084084

Other (OTH)

AF:

0.0456

AC:

2657

AN:

58278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

4505

9009

13514

18018

22523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2402

4804

7206

9608

12010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0394

AC:

5996

AN:

152180

Hom.:

197

Cov.:

AF XY:

0.0387

AC XY:

2877

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00958

AC:

398

AN:

41534

American (AMR)

AF:

0.0229

AC:

350

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3472

East Asian (EAS)

AF:

0.000580

AC:

AN:

5170

South Asian (SAS)

AF:

0.00728

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0880

AC:

933

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0609

AC:

4136

AN:

67966

Other (OTH)

AF:

0.0251

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

274

548

821

1095

1369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0508

Hom.:

807

Bravo

AF:

0.0339

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.0569

AC:

181

ExAC

AF:

0.0323

AC:

3786

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Kufor-Rakeb syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.20

CADD

Benign

2.5

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.48

PhyloP100

0.38

PROVEAN

Benign

0.38

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Vest4

0.13

ClinPred

0.0069

GERP RS

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=87/13

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over