NM_000157.4(GBA1):c.115+1G>A AND not provided

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Jul 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000790724.47

Allele description [Variation Report for NM_000157.4(GBA1):c.115+1G>A]

NM_000157.4(GBA1):c.115+1G>A

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.115+1G>A

Other names:

IVS2DS+1G-A

HGVS:

NC_000001.11:g.155240629C>T
NG_009783.1:g.9069G>A
NM_000157.4:c.115+1G>AMANE SELECT
NM_001005741.3:c.115+1G>A
NM_001005742.3:c.115+1G>A
NM_001171811.2:c.-146-552G>A
NM_001171812.2:c.115+1G>A
NC_000001.10:g.155210420C>T
NM_000157.3:c.115+1G>A
NM_001005741.2(GBA):c.115+1G>A
NM_001005741.2:c.115+1G>A
NM_001005741.3:c.115+1G>A
NM_001005742.2:c.115+1G>A
c.115+1G>A (p.?)

Nucleotide change:

IVS2DS, G-A, +1

Links:

OMIM: 606463.0015; dbSNP: rs104886460

NCBI 1000 Genomes Browser:

rs104886460

Molecular consequence:

NM_001171811.2:c.-146-552G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000157.4:c.115+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001005741.3:c.115+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001005742.3:c.115+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001171812.2:c.115+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

MULTISPECIES: universal stress protein [Sedimenticola]
MULTISPECIES: universal stress protein [Sedimenticola]
gi|2526762160|ref|WP_288107550.1|

Protein
endoplasmic reticulum magnesium-transporting P-type ATPase isoform X45 [Homo sap...
endoplasmic reticulum magnesium-transporting P-type ATPase isoform X45 [Homo sapiens]
gi|2462559237|ref|XP_054174000.1|

Protein
cytochrome oxidase subunit 1, partial (mitochondrion) [Eusterinx sp. BIOUG15137-...
cytochrome oxidase subunit 1, partial (mitochondrion) [Eusterinx sp. BIOUG15137-G08]
gi|1578793976|gb|QBF39478.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000228922	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Sep 3, 2015)	germline	clinical testing	Citation Link,
SCV000935506	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 28, 2022)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 16199547, 9153297, 10079102, 10796875, 11783951, 20816920, 23430873, 25653295, 26117366, 27682613, 28492532
SCV001247925	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jun 1, 2024)	germline	clinical testing	Citation Link,
SCV001763816	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 25, 2024)	germline	clinical testing	Citation Link,
SCV002503250	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 15, 2021)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 1558964, 26117366, 21228398, 20816920, 25653295, 22975760, 26689913, 21700325, 31561936, 25525159, 27682613, 25741868
SCV003825838	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 10, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005198013	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	7	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	5	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Identification and expression of acid beta-glucosidase mutations causing severe type 1 and neurologic type 2 Gaucher disease in non-Jewish patients.

Grace ME, Desnick RJ, Pastores GM.

J Clin Invest. 1997 May 15;99(10):2530-7.

PubMed [citation]

PMID:: 9153297
PMCID:: PMC508094

See all PubMed Citations (19)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000228922.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	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		7	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000935506.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

This sequence change affects a donor splice site in intron 3 of the GBA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GBA are known to be pathogenic (PMID: 9153297, 10079102, 10796875, 11783951). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. Disruption of this splice site has been observed in individuals with Gaucher disease and/or Parkinson disease (PMID: 20816920, 23430873, 25653295, 26117366, 27682613). This variant is also known as IVS2+1. ClinVar contains an entry for this variant (Variation ID: 93445). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been 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 CeGaT Center for Human Genetics Tuebingen, SCV001247925.26

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

Description

GBA1: PVS1, PS4:Moderate, PM2:Supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		4	not provided	not provided	not provided

From GeneDx, SCV001763816.4

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

Description

Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 22975760, 20816920, 25653295, 25525159, 21228398, 1558964, 23430873, 21700325, 35861108, 33473340, 26689913, 26117366, 27682613, 31561936, 33176831, 36637080, 32191290, 33402667, 33301762, 34867278, 34930372, 35747619, 34308104, 35242582, 35845720, 37198191, 35639160, 36879366, 33972609, 32613234)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From AiLife Diagnostics, AiLife Diagnostics, SCV002503250.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (12)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003825838.2

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

#	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 Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005198013.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

Relating variation to medicine