rs772414750

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022089.4(ATP13A2):c.878T>C(p.Met293Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,434,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ATP13A2
NM_022089.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.05

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0683935).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATP13A2	NM_022089.4	MANE Select	c.878T>C	p.Met293Thr	missense	Exon 10 of 29	NP_071372.1
ATP13A2	NM_001141973.3		c.863T>C	p.Met288Thr	missense	Exon 10 of 29	NP_001135445.1
ATP13A2	NM_001141974.3		c.863T>C	p.Met288Thr	missense	Exon 10 of 27	NP_001135446.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATP13A2	ENST00000326735.13	TSL:1 MANE Select	c.878T>C	p.Met293Thr	missense	Exon 10 of 29	ENSP00000327214.8
ATP13A2	ENST00000452699.5	TSL:1	c.863T>C	p.Met288Thr	missense	Exon 10 of 29	ENSP00000413307.1
ATP13A2	ENST00000341676.9	TSL:1	c.863T>C	p.Met288Thr	missense	Exon 10 of 27	ENSP00000341115.5

Frequencies

GnomAD3 genomes

AF:

0.0000289

AC:

AN:

138258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000614

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

197236

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000108

AC:

AN:

1295934

Hom.:

Cov.:

AF XY:

0.00000781

AC XY:

AN XY:

640430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28932

American (AMR)

AF:

0.00

AC:

AN:

35336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20494

East Asian (EAS)

AF:

0.00

AC:

AN:

25494

South Asian (SAS)

AF:

0.00

AC:

AN:

80636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5006

European-Non Finnish (NFE)

AF:

0.0000139

AC:

AN:

1009090

Other (OTH)

AF:

0.00

AC:

AN:

50320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000289

AC:

AN:

138258

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

66270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37586

American (AMR)

AF:

0.00

AC:

AN:

12808

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3352

East Asian (EAS)

AF:

0.00

AC:

AN:

4158

South Asian (SAS)

AF:

0.00

AC:

AN:

3984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.0000614

AC:

AN:

65116

Other (OTH)

AF:

0.00

AC:

AN:

1932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000726

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Kufor-Rakeb syndrome;C5567893:Autosomal recessive spastic paraplegia type 78 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.23

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.60

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.068

MetaSVM

Benign

-0.65

MutationAssessor

Benign

-0.97

PhyloP100

2.1

PrimateAI

Benign

0.37

PROVEAN

Benign

0.43

REVEL

Benign

0.28

Sift

Benign

0.20

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.18

MutPred

0.55

Gain of phosphorylation at M293 (P = 0.0241)

MVP

0.71

MPC

0.37

ClinPred

0.044

GERP RS

3.7

PromoterAI

-0.0052

Neutral

(source)

Varity_R

0.037

gMVP

0.42

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over