NM_000157.4(GBA1):c.1504C>T (p.Arg502Cys) AND Parkinson disease, late-onset

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 3, 2021
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:: RCV000004531.16

Allele description [Variation Report for NM_000157.4(GBA1):c.1504C>T (p.Arg502Cys)]

NM_000157.4(GBA1):c.1504C>T (p.Arg502Cys)

Genes:

LOC106627981:GBA recombination region [Gene]
GBA1:glucosylceramidase beta 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_000157.4(GBA1):c.1504C>T (p.Arg502Cys)

Other names:

R463C; (p.Arg502Cys)

HGVS:

NC_000001.11:g.155235196G>A
NG_009783.1:g.14502C>T
NG_042867.1:g.1658G>A
NM_000157.4:c.1504C>TMANE SELECT
NM_001005741.3:c.1504C>T
NM_001005742.3:c.1504C>T
NM_001171811.2:c.1243C>T
NM_001171812.2:c.1357C>T
NP_000148.2:p.Arg502Cys
NP_001005741.1:p.Arg502Cys
NP_001005741.1:p.Arg502Cys
NP_001005742.1:p.Arg502Cys
NP_001165282.1:p.Arg415Cys
NP_001165283.1:p.Arg453Cys
NC_000001.10:g.155204987G>A
NM_000157.2:c.1504C>T
NM_000157.3:c.1504C>T
NM_000157.4:c.1504C>T
NM_001005741.2(GBA):c.1504C>T
NM_001005741.2:c.1504C>T
NM_001005742.2:c.1504C>T
NM_001005742.3:c.1504C>T
P04062:p.Arg502Cys
c.1504C>T (p.Arg502Cys)

Protein change:

R415C; ARG463CYS

Links:

UniProtKB: P04062#VAR_003324; OMIM: 606463.0008; dbSNP: rs80356771

NCBI 1000 Genomes Browser:

rs80356771

Molecular consequence:

NM_000157.4:c.1504C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005741.3:c.1504C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005742.3:c.1504C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171811.2:c.1243C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171812.2:c.1357C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Unknown function

Condition(s)

Name:: Parkinson disease, late-onset (PD)
Synonyms:: Parkinson's disease; PARKINSON DISEASE, LATE-ONSET, SUSCEPTIBILITY TO; Susceptibility to Parkinson's Disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008199; MedGen: C3160718; OMIM: 168600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000024705	OMIM	no assertion criteria provided	risk factor (Jul 1, 2009)	germline	literature only	PubMed (4) [See all records that cite these PMIDs] 1972019, 1348297, 12595585, 19286695
SCV001652788	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 3, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000024705

OMIM

no assertion criteria provided

risk factor
(Jul 1, 2009)

germline

literature only

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

SCV001652788

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 3, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sequence of two alleles responsible for Gaucher disease.

Hong CM, Ohashi T, Yu XJ, Weiler S, Barranger JA.

DNA Cell Biol. 1990 May;9(4):233-41.

PubMed [citation]

PMID:: 1972019

Genetic diagnosis of Gaucher's disease.

Mistry PK, Smith SJ, Ali M, Hatton CS, McIntyre N, Cox TM.

Lancet. 1992 Apr 11;339(8798):889-92.

PubMed [citation]

PMID:: 1348297

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000024705.5

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

Description

Gaucher Disease

In a non-Jewish patient with type I Gaucher disease (230800), Hong et al. (1990) identified a 1504C-T transition in exon 10 of the GBA gene, resulting in an arg463-to-cys (R463C) substitution.

By the amplification refractory mutation system, Mistry et al. (1992) identified the R463C mutation and the L444P mutation (606463.0001) in association with rapidly progressive disease and neurologic involvement in non-Jewish patients (see 230900).

Park et al. (2003) identified the R463C mutation in patients with type III Gaucher disease (231000).

Parkinson Disease

Neumann et al. (2009) identified a heterozygous R463C mutation in 3 (0.38%) of 790 British patients with Parkinson disease (PD; 168600) that was not found in 257 controls, suggesting that heterozygosity for the mutation increases susceptibility for development of PD.

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

From Fulgent Genetics, Fulgent Genetics, SCV001652788.1

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

#	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		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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