NM_022089.4(ATP13A2):c.348-9_351del AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 3, 2023
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:: RCV001378978.4

Allele description [Variation Report for NM_022089.4(ATP13A2):c.348-9_351del]

NM_022089.4(ATP13A2):c.348-9_351del

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.348-9_351del

HGVS:

NC_000001.10:g.17331313_17331325del
NC_000001.11:g.17004822_17004834del
NG_009054.1:g.12099_12111del
NM_001141973.3:c.348-9_351del
NM_001141974.3:c.348-9_351del
NM_022089.4:c.348-9_351delMANE SELECT
LRG_834t1:c.348-9_351del
LRG_834:g.12099_12111del
NC_000001.10:g.17331313_17331325del
NC_000001.10:g.17331313_17331325delCAGGCTGGGGAAG
NC_000001.10:g.17331317_17331329del
NM_022089.2:c.348-9_351del13

Links:

dbSNP: rs749798211

NCBI 1000 Genomes Browser:

rs749798211

Molecular consequence:

NM_001141973.3:c.348-9_351del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001141974.3:c.348-9_351del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_022089.4:c.348-9_351del - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001576689	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 16964263, 21696388, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001576689

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 3, 2023)

germline

clinical testing

PubMed (4)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001576689.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 209135). This variant has not been reported in the literature in individuals affected with ATP13A2-related conditions. This variant is present in population databases (rs749798211, gnomAD 0.004%). This variant results in the deletion of part of exon 5 (c.348-9_351del) of the ATP13A2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and 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

ClinVar

Relating variation to medicine