NM_000157.4(GBA1):c.476G>A (p.Arg159Gln) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 6, 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:: RCV001250522.1

Allele description [Variation Report for NM_000157.4(GBA1):c.476G>A (p.Arg159Gln)]

NM_000157.4(GBA1):c.476G>A (p.Arg159Gln)

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.476G>A (p.Arg159Gln)

Other names:

R119Q

HGVS:

NC_000001.11:g.155238629C>T
NG_009783.1:g.11069G>A
NG_042867.1:g.5091C>T
NM_000157.4:c.476G>AMANE SELECT
NM_001005741.3:c.476G>A
NM_001005742.3:c.476G>A
NM_001171811.2:c.215G>A
NM_001171812.2:c.329G>A
NP_000148.2:p.Arg159Gln
NP_001005741.1:p.Arg159Gln
NP_001005742.1:p.Arg159Gln
NP_001165282.1:p.Arg72Gln
NP_001165283.1:p.Arg110Gln
NC_000001.10:g.155208420C>T
NM_000157.2:c.476G>A
NM_000157.3(GBA):c.476G>A
NM_000157.3:c.476G>A
NM_001005741.2:c.476G>A
NM_001005741.3:c.476G>A
NM_001005742.2:c.476G>A
P04062:p.Arg159Gln

Protein change:

R110Q; ARG119GLN

Links:

UniProtKB: P04062#VAR_003263; OMIM: 606463.0004; dbSNP: rs79653797

NCBI 1000 Genomes Browser:

rs79653797

Molecular consequence:

NM_000157.4:c.476G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005741.3:c.476G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005742.3:c.476G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171811.2:c.215G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171812.2:c.329G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Gaucher disease type I (GD1)
Synonyms:: GBA DEFICIENCY; GD I; Gaucher's disease, type 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009265; MedGen: C1961835; Orphanet: 355; Orphanet: 77259; OMIM: 230800

Name:: Gaucher disease type II (GD2)
Synonyms:: GD II; Gaucher disease type 2; GD 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009266; MedGen: C0268250; OMIM: 230900

Name:: Gaucher disease type III
Synonyms:: GD III; GD 3; Gaucher disease, juvenile and adult, cerebral; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009267; MedGen: C0268251; Orphanet: 355; Orphanet: 77261; OMIM: 231000

Name:: Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome
Synonyms:: GAUCHER DISEASE, TYPE IIIC; Gaucher disease type 3C
Identifiers:: MONDO: MONDO:0009268; MedGen: C1856476; OMIM: 231005

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001425323	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 6, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15214004, 16546416, 17059888, 1899336, 3180993, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001425323

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 6, 2020)

germline

clinical testing

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

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

Intrauterine onset of acute neuropathic type 2 Gaucher disease: identification of a novel insertion sequence.

Felderhoff-Mueser U, Uhl J, Penzel R, Van Landeghem F, Vogel M, Obladen M, Kopitz J.

Am J Med Genet A. 2004 Jul 15;128A(2):138-43.

PubMed [citation]

PMID:: 15214004

Mutation analysis of Gaucher disease patients in Taiwan: high prevalence of the RecNciI and L444P mutations.

Wan L, Hsu CM, Tsai CH, Lee CC, Hwu WL, Tsai FJ.

Blood Cells Mol Dis. 2006 May-Jun;36(3):422-5. Epub 2006 Mar 20.

PubMed [citation]

PMID:: 16546416

See all PubMed Citations (6)

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV001425323.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

GBA c.476G>A has been reported in multiple individuals presenting with Gaucher disease. This GBA variant (rs79653797) is rare (<0.1%) in a large population dataset (gnomAD: 2/251180 total alleles; 0.0008%; no homozygotes). This variant is located within a mutational hotpspot, which is in proximity to glucocerebrosidase catalytic sites. An alternate pathogenic missense change (p.Arg159Trp) has been reported at the same amino acid residue. This variant has been reported in ClinVar. Three bioinformatic tools queried predict that this substitution would be damaging, and the arginine residue at this position is highly evolutionarily conserved across most species assessed. We consider this variant to be likely 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

Last Updated: Mar 30, 2024

ClinVar

Relating variation to medicine