NM_032409.3(PINK1):c.1252-2_1272del AND Autosomal recessive early-onset Parkinson disease 6

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 5, 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:: RCV003497597.2

Allele description [Variation Report for NM_032409.3(PINK1):c.1252-2_1272del]

NM_032409.3(PINK1):c.1252-2_1272del

Genes:

PINK1-AS:PINK1 antisense RNA [Gene - HGNC]
PINK1:PTEN induced kinase 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p36.12

Genomic location:

Preferred name:

NM_032409.3(PINK1):c.1252-2_1272del

HGVS:

NC_000001.11:g.20648993_20649015del
NG_008164.1:g.20539_20561del
NM_032409.3:c.1252-2_1272delMANE SELECT
NC_000001.10:g.20975484_20975506del
NC_000001.10:g.20975486_20975508del
NR_046507.1:n.3181_3203del

Molecular consequence:

NR_046507.1:n.3181_3203del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_032409.3:c.1252-2_1272del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Autosomal recessive early-onset Parkinson disease 6 (PARK6)
Synonyms:: PARKINSON DISEASE 6, EARLY-ONSET; PARKINSON DISEASE 6, MODIFIER OF; PINK1-Related Parkinson Disease
Identifiers:: MONDO: MONDO:0011613; MedGen: C1853833; Orphanet: 2828; OMIM: 605909

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004305063	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 5, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 15087508, 15349870, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004305063

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 5, 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 early-onset Parkinson's disease caused by mutations in PINK1.

Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, González-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW.

Science. 2004 May 21;304(5674):1158-60. Epub 2004 Apr 15.

PubMed [citation]

PMID:: 15087508

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004305063.1

#	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. This variant has not been reported in the literature in individuals affected with PINK1-related conditions. This variant is present in population databases (rs748860758, gnomAD 0.003%). This variant results in the deletion of part of exon 7 (c.1252-2_1272del) of the PINK1 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 PINK1 are known to be pathogenic (PMID: 15087508, 15349870).

#	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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