NM_022089.4(ATP13A2):c.217del (p.Val73fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 9, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003782265.2

Allele description [Variation Report for NM_022089.4(ATP13A2):c.217del (p.Val73fs)]

NM_022089.4(ATP13A2):c.217del (p.Val73fs)

Gene:

ATP13A2:ATPase cation transporting 13A2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_022089.4(ATP13A2):c.217del (p.Val73fs)

HGVS:

NC_000001.11:g.17005450del
NG_009054.1:g.11484del
NM_001141973.3:c.217del
NM_001141974.3:c.217del
NM_022089.4:c.217delMANE SELECT
NP_001135445.1:p.Val73fs
NP_001135446.1:p.Val73fs
NP_071372.1:p.Val73fs
LRG_834t1:c.217del
LRG_834:g.11484del
LRG_834p1:p.Val73fs
NC_000001.10:g.17331940del
NC_000001.10:g.17331945del

Protein change:

V73fs

Molecular consequence:

NM_001141973.3:c.217del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001141974.3:c.217del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_022089.4:c.217del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Kufor-Rakeb syndrome (KRS)
Synonyms:: Park 9; Pallidopyramidal degeneration with supranuclear upgaze paresis, and dementia; PARKINSON DISEASE 9, AUTOSOMAL RECESSIVE, JUVENILE-ONSET
Identifiers:: MONDO: MONDO:0011706; MedGen: C1847640; Orphanet: 306674; Orphanet: 314632; OMIM: 606693

Name:: Autosomal recessive spastic paraplegia type 78
Identifiers:: MONDO: MONDO:0014975; MedGen: C5567893; OMIM: 617225

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004577715	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 9, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16964263, 21696388, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004577715

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 9, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase.

Ramirez A, Heimbach A, Gründemann J, Stiller B, Hampshire D, Cid LP, Goebel I, Mubaidin AF, Wriekat AL, Roeper J, Al-Din A, Hillmer AM, Karsak M, Liss B, Woods CG, Behrens MI, Kubisch C.

Nat Genet. 2006 Oct;38(10):1184-91. Epub 2006 Sep 10.

PubMed [citation]

PMID:: 16964263

Novel mutation in ATP13A2 widens the spectrum of Kufor-Rakeb syndrome (PARK9).

Eiberg H, Hansen L, Korbo L, Nielsen IM, Svenstrup K, Bech S, Pinborg LH, Friberg L, Hjermind LE, Olsen OR, Nielsen JE.

Clin Genet. 2012 Sep;82(3):256-63. doi: 10.1111/j.1399-0004.2011.01745.x. Epub 2011 Jul 18.

PubMed [citation]

PMID:: 21696388

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004577715.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ATP13A2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Val73Cysfs*20) in the ATP13A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP13A2 are known to be pathogenic (PMID: 16964263, 21696388).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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