NM_000157.4(GBA):c.1060G>C (p.Asp354His) AND Gaucher disease

Clinical significance:Uncertain significance (Last evaluated: Sep 16, 2020)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001248921.2

Allele description [Variation Report for NM_000157.4(GBA):c.1060G>C (p.Asp354His)]

NM_000157.4(GBA):c.1060G>C (p.Asp354His)

Genes:
LOC106627981:GBA recombination region [Gene]
GBA:glucosylceramidase beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q22
Genomic location:
Preferred name:
NM_000157.4(GBA):c.1060G>C (p.Asp354His)
HGVS:
  • NC_000001.11:g.155236409C>G
  • NG_009783.1:g.13289G>C
  • NG_042867.1:g.2871C>G
  • NM_000157.4:c.1060G>CMANE SELECT
  • NM_001005741.2(GBA):c.1060G>C
  • NM_001005741.3:c.1060G>C
  • NM_001005742.3:c.1060G>C
  • NM_001171811.2:c.799G>C
  • NM_001171812.2:c.913G>C
  • NP_000148.2:p.Asp354His
  • NP_001005741.1:p.Asp354His
  • NP_001005741.1:p.Asp354His
  • NP_001005742.1:p.Asp354His
  • NP_001165282.1:p.Asp267His
  • NP_001165283.1:p.Asp305His
  • NC_000001.10:g.155206200C>G
  • NM_001005741.2(GBA):c.1060G>C
  • NM_001005741.2:c.1060G>C
  • P04062:p.Asp354His
Protein change:
D267H
Links:
UniProtKB: P04062#VAR_003292; dbSNP: rs398123526
NCBI 1000 Genomes Browser:
rs398123526
Molecular consequence:
  • NM_000157.4:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005741.3:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005742.3:c.1060G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171811.2:c.799G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171812.2:c.913G>C - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001422686Broad Institute Rare Disease Group, Broad Instituteno assertion criteria providedUncertain significance
(Jan 15, 2020)
germlinecuration

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

Citation Link,

SCV001461742Natera, Inc.no assertion criteria providedUncertain significance
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

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

Citations

PubMed

Three unrelated Gaucher's disease patients with three novel point mutations in the glucocerebrosidase gene (P266R, D315H and A318D).

Walley AJ, Ellis I, Harris A.

Br J Haematol. 1995 Oct;91(2):330-2.

PubMed [citation]
PMID:
8547070

Details of each submission

From Broad Institute Rare Disease Group, Broad Institute, SCV001422686.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The p.Asp354His variant in GBA has been reported in one Ashkenazi Jewish individual with Gaucher disease (PMID: 8547070) and has been identified in 0.003% (3/113764) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs398123526). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (VariationID: 93444) as pathogenic by EGL Genetic Diagnostics. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. The presence of this variant in combination with a reported pathogenic variant and in an individual with Gaucher disease increases the likelihood that the p.Asp354His variant is pathogenic (VariationID: 4290; PMID: 8547070). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PM3_supporting (Richards 2015).

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

From Natera, Inc., SCV001461742.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 18, 2021

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