NM_022089.4(ATP13A2):c.1306+5G>A AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 19, 2021
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:: RCV001851532.4

Allele description [Variation Report for NM_022089.4(ATP13A2):c.1306+5G>A]

NM_022089.4(ATP13A2):c.1306+5G>A

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_022089.4(ATP13A2):c.1306+5G>A

HGVS:

NC_000001.11:g.16996381C>T
NG_009054.1:g.20548G>A
NM_001141973.3:c.1291+5G>A
NM_001141974.3:c.1291+5G>A
NM_022089.4:c.1306+5G>AMANE SELECT
LRG_834t1:c.1306+5G>A
LRG_834:g.20548G>A
NC_000001.10:g.17322876C>T
NM_022089.3:c.1306+5G>A

Nucleotide change:

IVS13, G-A, +5

Links:

OMIM: 610513.0002; dbSNP: rs786205056

NCBI 1000 Genomes Browser:

rs786205056

Molecular consequence:

NM_001141973.3:c.1291+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001141974.3:c.1291+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_022089.4:c.1306+5G>A - intron variant - [Sequence Ontology: SO:0001627]

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
SCV002232548	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 19, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17576681, 9536098, 21724849, 23499937, 16964263, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002232548

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 19, 2021)

germline

clinical testing

PubMed (6)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002232548.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 13, but is expected to preserve the integrity of the reading-frame (PMID: 16964263). Experimental studies have shown that this variant affects ATP13A2 protein function (PMID: 21724849, 23499937). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 1219). This variant is also known as ATP13A2SKP13. This variant has been observed in individual(s) with clinical features of autosomal recessive Kufor-Rakeb syndrome (PMID: 16964263). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 13 of the ATP13A2 gene. It does not directly change the encoded amino acid sequence of the ATP13A2 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product.

#	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: Oct 8, 2024

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