NM_004562.3(PRKN):c.98G>A (p.Arg33Gln) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 17, 2024
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:: RCV001090784.34

Allele description [Variation Report for NM_004562.3(PRKN):c.98G>A (p.Arg33Gln)]

NM_004562.3(PRKN):c.98G>A (p.Arg33Gln)

Gene:

PRKN:parkin RBR E3 ubiquitin protein ligase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q26

Genomic location:

Preferred name:

NM_004562.3(PRKN):c.98G>A (p.Arg33Gln)

HGVS:

NC_000006.12:g.162443383C>T
NG_008289.2:g.289420G>A
NM_004562.3:c.98G>AMANE SELECT
NM_013987.3:c.98G>A
NM_013988.3:c.98G>A
NP_004553.2:p.Arg33Gln
NP_054642.2:p.Arg33Gln
NP_054643.2:p.Arg33Gln
NC_000006.11:g.162864415C>T
NM_004562.2:c.98G>A

Protein change:

R33Q

Links:

dbSNP: rs147757966

NCBI 1000 Genomes Browser:

rs147757966

Molecular consequence:

NM_004562.3:c.98G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_013987.3:c.98G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_013988.3:c.98G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001246506	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (May 1, 2019)	germline	clinical testing	Citation Link,
SCV001584588	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 17, 2024)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 12730996, 16643317, 19636047, 15606901, 21348451, 21694720, 23770917, 24647965, 26631732, 27534820, 28492532
SCV002502335	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 10, 2021)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 12730996, 29530980, 21694720, 25939424, 15606901, 21348451, 18485927, 30994895, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001246506

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(May 1, 2019)

germline

clinical testing

Citation Link,

SCV001584588

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 17, 2024)

germline

clinical testing

PubMed (11)
[See all records that cite these PMIDs]

SCV002502335

AiLife Diagnostics, AiLife Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 10, 2021)

germline

clinical testing

PubMed (9)
[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	yes	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Low frequency of Parkin, Tyrosine Hydroxylase, and GTP Cyclohydrolase I gene mutations in a Danish population of early-onset Parkinson's Disease.

Hertz JM, Ostergaard K, Juncker I, Pedersen S, Romstad A, Møller LB, Güttler F, Dupont E.

Eur J Neurol. 2006 Apr;13(4):385-90.

PubMed [citation]

PMID:: 16643317

Parkin dosage mutations have greater pathogenicity in familial PD than simple sequence mutations.

Pankratz N, Kissell DK, Pauciulo MW, Halter CA, Rudolph A, Pfeiffer RF, Marder KS, Foroud T, Nichols WC; Parkinson Study Group-PROGENI Investigators..

Neurology. 2009 Jul 28;73(4):279-86. doi: 10.1212/WNL.0b013e3181af7a33.

PubMed [citation]

PMID:: 19636047
PMCID:: PMC2715211

See all PubMed Citations (16)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001246506.26

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001584588.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 33 of the PRKN protein (p.Arg33Gln). This variant is present in population databases (rs147757966, gnomAD 0.02%). This missense change has been observed in individuals with early-onset Parkinson disease (PMID: 12730996, 16643317, 19636047). It has also been observed to segregate with disease in related individuals. This variant is also known as 199G>A. ClinVar contains an entry for this variant (Variation ID: 578186). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects PRKN function (PMID: 15606901, 21348451, 21694720, 23770917, 24647965, 26631732, 27534820). For these reasons, this variant has been classified as Pathogenic.

#	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 AiLife Diagnostics, AiLife Diagnostics, SCV002502335.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (9)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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