NM_032409.3(PINK1):c.853G>A (p.Val285Met) AND Autosomal recessive early-onset Parkinson disease 6

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 22, 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:: RCV002785720.3

Allele description [Variation Report for NM_032409.3(PINK1):c.853G>A (p.Val285Met)]

NM_032409.3(PINK1):c.853G>A (p.Val285Met)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.12

Genomic location:

Preferred name:

NM_032409.3(PINK1):c.853G>A (p.Val285Met)

HGVS:

NC_000001.11:g.20644566G>A
NG_008164.1:g.16112G>A
NM_032409.3:c.853G>AMANE SELECT
NP_115785.1:p.Val285Met
NC_000001.10:g.20971059G>A

Protein change:

V285M

Molecular consequence:

NM_032409.3:c.853G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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PREDICTED: Homo sapiens dedicator of cytokinesis 8 (DOCK8), transcript variant X...
PREDICTED: Homo sapiens dedicator of cytokinesis 8 (DOCK8), transcript variant X7, mRNA
gi|2217381042|ref|XM_047423931.1|

Nucleotide
G500 actinobacteria
G500 actinobacteria

biosample
Homo sapiens interleukin 2 receptor subunit gamma (IL2RG), mRNA
Homo sapiens interleukin 2 receptor subunit gamma (IL2RG), mRNA
gi|1780222514|ref|NM_000206.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003021544	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32713623, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003021544

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 22, 2022)

germline

clinical testing

PubMed (2)
[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

The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1.

Hayashida A, Li Y, Yoshino H, Daida K, Ikeda A, Ogaki K, Fuse A, Mori A, Takanashi M, Nakahara T, Yoritaka A, Tomizawa Y, Furukawa Y, Kanai K, Nakayama Y, Ito H, Ogino M, Hattori Y, Hattori T, Ichinose Y, Takiyama Y, Saito T, et al.

Neurobiol Aging. 2021 Jan;97:146.e1-146.e13. doi: 10.1016/j.neurobiolaging.2020.06.017. Epub 2020 Jul 2.

PubMed [citation]

PMID:: 32713623

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003021544.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with Parkinson disease (PMID: 32713623). This variant is present in population databases (rs557503577, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 285 of the PINK1 protein (p.Val285Met).

#	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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