NM_004562.3(PRKN):c.633A>T (p.Lys211Asn) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 9, 2023
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:: RCV001851722.5

Allele description [Variation Report for NM_004562.3(PRKN):c.633A>T (p.Lys211Asn)]

NM_004562.3(PRKN):c.633A>T (p.Lys211Asn)

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.633A>T (p.Lys211Asn)

HGVS:

NC_000006.12:g.161973403T>A
NG_008289.2:g.759400A>T
NM_004562.3:c.633A>TMANE SELECT
NM_013987.3:c.549A>T
NM_013988.3:c.186A>T
NP_004553.2:p.Lys211Asn
NP_054642.2:p.Lys183Asn
NP_054643.2:p.Lys62Asn
NC_000006.11:g.162394435T>A
O60260:p.Lys211Asn

Protein change:

K183N; LYS211ASN

Links:

UniProtKB: O60260#VAR_019744; OMIM: 602544.0018; dbSNP: rs137853060

NCBI 1000 Genomes Browser:

rs137853060

Molecular consequence:

NM_004562.3:c.633A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_013987.3:c.549A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_013988.3:c.186A>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002177079	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 14, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25591737, 11222808, 15970950, 25833766, 28492532
SCV005413767	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 9, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 10824074, 16714300, 25833766, 25939424, 30994895, 33045815, 33845304, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002177079

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 14, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV005413767

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 9, 2023)

germline

clinical testing

PubMed (8)
[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	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Parkin maintains mitochondrial levels of the protective Parkinson's disease-related enzyme 17-β hydroxysteroid dehydrogenase type 10.

Bertolin G, Jacoupy M, Traver S, Ferrando-Miguel R, Saint Georges T, Grenier K, Ardila-Osorio H, Muriel MP, Takahashi H, Lees AJ, Gautier C, Guedin D, Coge F, Fon EA, Brice A, Corti O.

Cell Death Differ. 2015 Oct;22(10):1563-76. doi: 10.1038/cdd.2014.224. Epub 2015 Jan 16.

PubMed [citation]

PMID:: 25591737
PMCID:: PMC4563777

Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations.

van de Warrenburg BP, Lammens M, Lücking CB, Denèfle P, Wesseling P, Booij J, Praamstra P, Quinn N, Brice A, Horstink MW.

Neurology. 2001 Feb 27;56(4):555-7.

PubMed [citation]

PMID:: 11222808

See all PubMed Citations (12)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002177079.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PRKN function (PMID: 25591737). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 7051). This missense change has been observed in individual(s) with early-onset Parkinson disease (PMID: 11222808, 15970950, 25833766). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs137853060, gnomAD 0.004%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 211 of the PRKN protein (p.Lys211Asn).

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV005413767.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (8)

Description

PM2_moderate, PM3_strong, PS3_moderate, PS4_moderate

#	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		1	not provided	not provided	not provided

Last Updated: Feb 8, 2025

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