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NM_000157.4(GBA1):c.970C>T (p.Arg324Cys) AND Gaucher disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 12, 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:
RCV001797810.1

Allele description [Variation Report for NM_000157.4(GBA1):c.970C>T (p.Arg324Cys)]

NM_000157.4(GBA1):c.970C>T (p.Arg324Cys)

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.970C>T (p.Arg324Cys)
HGVS:
  • NC_000001.11:g.155237370G>A
  • NG_009783.1:g.12328C>T
  • NG_042867.1:g.3832G>A
  • NM_000157.4:c.970C>TMANE SELECT
  • NM_001005741.3:c.970C>T
  • NM_001005742.3:c.970C>T
  • NM_001171811.2:c.709C>T
  • NM_001171812.2:c.823C>T
  • NP_000148.2:p.Arg324Cys
  • NP_001005741.1:p.Arg324Cys
  • NP_001005742.1:p.Arg324Cys
  • NP_001165282.1:p.Arg237Cys
  • NP_001165283.1:p.Arg275Cys
  • NC_000001.10:g.155207161G>A
  • NM_001005741.2:c.970C>T
Protein change:
R237C
Links:
dbSNP: rs765633380
NCBI 1000 Genomes Browser:
rs765633380
Molecular consequence:
  • NM_000157.4:c.970C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005741.3:c.970C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005742.3:c.970C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171811.2:c.709C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171812.2:c.823C>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002041600Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Nov 12, 2021) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification and functional characterization of five novel mutant alleles in 58 Italian patients with Gaucher disease type 1.

Miocić S, Filocamo M, Dominissini S, Montalvo AL, Vlahovicek K, Deganuto M, Mazzotti R, Cariati R, Bembi B, Pittis MG.

Hum Mutat. 2005 Jan;25(1):100.

PubMed [citation]
PMID:
15605411

Glucocerebrosidase mutations in Gaucher disease.

Beutler E, Demina A, Gelbart T.

Mol Med. 1994 Nov;1(1):82-92.

PubMed [citation]
PMID:
8790604
PMCID:
PMC2229932
See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002041600.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: GBA c.970C>T (p.Arg324Cys) results in a non-conservative amino acid change located in the Glycosyl hydrolase family 30, TIM-barrel domain (IPR033453) of 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 2e-05 in 251034 control chromosomes. c.970C>T has been reported in the literature as a compound heterozygous genotype in multiple individuals predominantly affected with Type I Gaucher Disease (example, Beutler_1994, Cormand_1998, Filocamo_2002, Miocic_2005, Baris_2016, Verma_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no variant specific experimental evidence demonstrating an impact on protein function has been reported. Although compound heterozygous individuals with this variant demonsrated decreased residual beta glucosidase enzyme activity, elevated Lyso GL-1 biomarker levels and elevated Chitotriosidase biomarker levels (example, Verma_2021). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 16, 2024