NM_000157.4(GBA1):c.1603C>T (p.Arg535Cys) AND Gaucher disease

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 1, 2020
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:: RCV001175549.4

Allele description [Variation Report for NM_000157.4(GBA1):c.1603C>T (p.Arg535Cys)]

NM_000157.4(GBA1):c.1603C>T (p.Arg535Cys)

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.1603C>T (p.Arg535Cys)

Other names:

R496C

HGVS:

NC_000001.11:g.155235003G>A
NG_009783.1:g.14695C>T
NG_042867.1:g.1465G>A
NM_000157.3(GBA):c.1603C>T
NM_000157.4:c.1603C>TMANE SELECT
NM_001005741.3:c.1603C>T
NM_001005742.3:c.1603C>T
NM_001171811.2:c.1342C>T
NM_001171812.2:c.1456C>T
NP_000148.2:p.Arg535Cys
NP_001005741.1:p.Arg535Cys
NP_001005742.1:p.Arg535Cys
NP_001165282.1:p.Arg448Cys
NP_001165283.1:p.Arg486Cys
NC_000001.10:g.155204794G>A
NC_000001.10:g.155204794G>A
NM_000157.3(GBA):c.1603C>T
NM_000157.3:c.1603C>T
NM_000157.4:c.1603C>T
NM_001005741.2:c.1603C>T
NM_001005741.3:c.1603C>T
P04062:p.Arg535Cys

Protein change:

R448C

Links:

UniProtKB: P04062#VAR_003327; dbSNP: rs747506979

NCBI 1000 Genomes Browser:

rs747506979

Molecular consequence:

NM_000157.4:c.1603C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005741.3:c.1603C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005742.3:c.1603C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171811.2:c.1342C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171812.2:c.1456C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Gaucher disease
Synonyms:: Acute cerebral Gaucher disease; Cerebroside lipidosis syndrome; Gaucher splenomegaly; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018150; MedGen: C0017205

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Taxonomy Links for Nucleotide (Select 2462527393) (1)
Taxonomy
Actinobacillus capsulatus DSM 19761 C228DRAFT_scaffold00033.33, whole genome sho...
Actinobacillus capsulatus DSM 19761 C228DRAFT_scaffold00033.33, whole genome shotgun sequence
gi|483999190|ref|NZ_KB893962.1||gnl NZ_ARFN01|C228DRAFT_scaffold00033.33

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001339173	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Mar 1, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23426826, 27865684, 24522292, 1487244 Citation Link,
SCV002086446	Natera, Inc.	no assertion criteria provided	Pathogenic (May 4, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001339173

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Mar 1, 2020)

germline

clinical testing

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

Citation Link,

SCV002086446

Natera, Inc.

no assertion criteria provided

Pathogenic
(May 4, 2020)

germline

clinical testing

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 of the β-glucocerebrosidase gene in Turkish Gaucher disease patients: mutation profile and description of a novel mutant allele.

Karaca E, Kalkan S, Onay H, Aykut A, Coker M, Ozkinay F.

J Pediatr Endocrinol Metab. 2012;25(9-10):957-62. doi: 10.1515/jpem-2012-0155.

PubMed [citation]

PMID:: 23426826

Clinical and molecular characteristics of patients with Gaucher disease in Southern China.

Feng Y, Huang Y, Tang C, Hu H, Zhao X, Sheng H, Zhang W, Tan M, Xie T, Zheng J, Liu Z, Su X, Shao Y, Li X, Cheng J, Mao X, Liu L.

Blood Cells Mol Dis. 2018 Feb;68:30-34. doi: 10.1016/j.bcmd.2016.10.026. Epub 2016 Nov 3.

PubMed [citation]

PMID:: 27865684

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001339173.1

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

Description

Variant summary: GBA c.1603C>T (p.Arg535Cys) also widely reported as p.Arg496Cys, results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 172274 control chromosomes. c.1603C>T has been well reported in the literature in multiple individuals from diverse ethnicities affected with Gaucher Disease (example, Kawame_1992, Karaca_2012, Ankleshwaria_2014 and Feng_2018). These data indicate that the variant is very likely to be associated with disease. No experimental evidence demonstrating an impact on protein function was ascertained. Although at-least one publication reported its identification in a enzymatically and clinically diagnosed Gaucher disease homozygous individual with no primary data provided (Kawame_1992). One researcher has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. This submitter cites an overlapping publication utilized in the context of this evaluation. Based on the evidence outlined above, the variant was 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 Natera, Inc., SCV002086446.1

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

Last Updated: Oct 8, 2024

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