NM_000157.4(GBA1):c.1504C>T (p.Arg502Cys) AND not specified

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 2, 2015
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:: RCV004018558.1

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)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002754629	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 2, 2015)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10796875, 16293621, 19286695, 1972019 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002754629

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 2, 2015)

germline

clinical testing

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

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

Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease.

Koprivica V, Stone DL, Park JK, Callahan M, Frisch A, Cohen IJ, Tayebi N, Sidransky E.

Am J Hum Genet. 2000 Jun;66(6):1777-86. Epub 2000 May 4.

PubMed [citation]

PMID:: 10796875
PMCID:: PMC1378059

Analyses of variant acid beta-glucosidases: effects of Gaucher disease mutations.

Liou B, Kazimierczuk A, Zhang M, Scott CR, Hegde RS, Grabowski GA.

J Biol Chem. 2006 Feb 17;281(7):4242-53. Epub 2005 Nov 17.

PubMed [citation]

PMID:: 16293621

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002754629.2

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

Description

The p.R502C pathogenic mutation (also known as c.1504C>T and p.R463C in the literature), located in coding exon 10 of the GBA gene, results from a C to T substitution at nucleotide position 1504. The arginine at codon 502 is replaced by cysteine, an amino acid with highly dissimilar properties. This mutation was originally identified in combination with p.L444P in a non-Jewish patient with Gaucher disease type 1 and results in a significant reduction of normal enzyme activity (Hong CM et al. DNA Cell Biol. 1990;9(4):233-241) This mutation was also observed in 10 patients, 9 of whom were non-Ashkenazi Jewish, and affected with either Gaucher disease type 1 or type 3 (subacute nueronopathic type) (Koprivica V, Am. J. Hum. Genet. 2000 Jun; 66(6):1777-86). Another functional study found this mutation inactivated the enzyme function completely by rapid degredation (Liou B, J. Biol. Chem. 2006 Feb; 281(7):4242-53). Based on the supporting evidence, p.R502C is interpreted as a disease-causing mutation.

#	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: Oct 8, 2024

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