NM_007262.5(PARK7):c.535G>A (p.Ala179Thr) AND Autosomal recessive early-onset Parkinson disease 7

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 13, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001059800.6

Allele description [Variation Report for NM_007262.5(PARK7):c.535G>A (p.Ala179Thr)]

NM_007262.5(PARK7):c.535G>A (p.Ala179Thr)

Gene:

PARK7:Parkinsonism associated deglycase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.23

Genomic location:

Preferred name:

NM_007262.5(PARK7):c.535G>A (p.Ala179Thr)

HGVS:

NC_000001.11:g.7985019G>A
NG_008271.1:g.28366G>A
NM_001123377.2:c.535G>A
NM_007262.5:c.535G>AMANE SELECT
NP_001116849.1:p.Ala179Thr
NP_009193.2:p.Ala179Thr
NC_000001.10:g.8045079G>A
NC_000001.10:g.8045079G>A
NM_007262.4:c.535G>A

Protein change:

A179T

Links:

dbSNP: rs71653622

NCBI 1000 Genomes Browser:

rs71653622

Molecular consequence:

NM_001123377.2:c.535G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007262.5:c.535G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive early-onset Parkinson disease 7
Synonyms:: Parkinson disease 7
Identifiers:: MONDO: MONDO:0011658; MedGen: C1853445; Orphanet: 2828; OMIM: 606324

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001224448	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 13, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18973254, 23241025, 28993701, 28492532
SCV001255804	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001224448

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 13, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001255804

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease.

Macedo MG, Verbaan D, Fang Y, van Rooden SM, Visser M, Anar B, Uras A, Groen JL, Rizzu P, van Hilten JJ, Heutink P.

Mov Disord. 2009 Jan 30;24(2):196-203. doi: 10.1002/mds.22287.

PubMed [citation]

PMID:: 18973254

Loss of DJ-1 protein stability and cytoprotective function by Parkinson's disease-associated proline-158 deletion.

Rannikko EH, Vesterager LB, Shaik JH, Weber SS, Cornejo Castro EM, Fog K, Jensen PH, Kahle PJ.

J Neurochem. 2013 Apr;125(2):314-27. doi: 10.1111/jnc.12126. Epub 2013 Jan 15.

PubMed [citation]

PMID:: 23241025

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001224448.2

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 179 of the PARK7 protein (p.Ala179Thr). This variant is present in population databases (rs71653622, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with Parkinson disease (PMID: 18973254). ClinVar contains an entry for this variant (Variation ID: 854701). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Experimental studies have shown that this missense change does not substantially affect PARK7 function (PMID: 23241025, 28993701). 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.

#	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

From Illumina Laboratory Services, Illumina, SCV001255804.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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: Jan 6, 2024

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