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NM_000157.4(GBA1):c.1279G>T (p.Glu427Ter) AND Gaucher disease

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 21, 2016
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:
RCV000607009.4

Allele description [Variation Report for NM_000157.4(GBA1):c.1279G>T (p.Glu427Ter)]

NM_000157.4(GBA1):c.1279G>T (p.Glu427Ter)

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.1279G>T (p.Glu427Ter)
HGVS:
  • NC_000001.11:g.155235790C>A
  • NG_009783.1:g.13908G>T
  • NG_042867.1:g.2252C>A
  • NM_000157.4:c.1279G>TMANE SELECT
  • NM_001005741.3:c.1279G>T
  • NM_001005742.3:c.1279G>T
  • NM_001171811.2:c.1018G>T
  • NM_001171812.2:c.1132G>T
  • NP_000148.2:p.Glu427Ter
  • NP_001005741.1:p.Glu427Ter
  • NP_001005742.1:p.Glu427Ter
  • NP_001165282.1:p.Glu340Ter
  • NP_001165283.1:p.Glu378Ter
  • NC_000001.10:g.155205581C>A
  • NM_001005741.2:c.1279G>T
  • p.Glu427X
Protein change:
E340*
Links:
dbSNP: rs149171124
NCBI 1000 Genomes Browser:
rs149171124
Molecular consequence:
  • NM_000157.4:c.1279G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001005741.3:c.1279G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001005742.3:c.1279G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001171811.2:c.1018G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001171812.2:c.1132G>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

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
SCV000712549Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(Nov 21, 2016) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

Hematologically important mutations: Gaucher disease.

Beutler E, Gelbart T, Scott CR.

Blood Cells Mol Dis. 2005 Nov-Dec;35(3):355-64. Epub 2005 Sep 26. Review. No abstract available.

PubMed [citation]
PMID:
16185900

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000712549.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The p.Glu427X variant in GBA has not been previously reported in patients with G aucher disease and was absent from large population studies. This nonsense varia nt leads to a premature termination codon at position 427, which is predicted to lead to a truncated or absent protein. Biallelic mutations (including loss of f unction) in the GBA gene cause Gaucher disease. In summary, this variant meets c riteria to be classified as likely pathogenic for Gaucher disease in an autosoma l recessive manner based upon predicted null effect. Please note that, due to th e technical limitations of the next generation sequencing and Sanger confirmatio n assays, the GBA pseudogene cannot be reliably avoided. Therefore, before makin g clinical decisions regarding this variant, further testing via targeted assays that guarantee avoidance of GBA pseudogene would be required to confirm the pre sence of this variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Dec 24, 2022