NM_000169.3(GLA):c.707G>A (p.Trp236Ter) AND Fabry disease

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 20, 2021
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:: RCV000692369.10

Allele description [Variation Report for NM_000169.3(GLA):c.707G>A (p.Trp236Ter)]

NM_000169.3(GLA):c.707G>A (p.Trp236Ter)

Genes:

RPL36A-HNRNPH2:RPL36A-HNRNPH2 readthrough [Gene - HGNC]
GLA:galactosidase alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_000169.3(GLA):c.707G>A (p.Trp236Ter)

HGVS:

NC_000023.11:g.101398879C>T
NG_007119.1:g.14085G>A
NM_000169.3:c.707G>AMANE SELECT
NM_001199973.2:c.300+3422C>T
NM_001199974.2:c.177+7057C>T
NP_000160.1:p.Trp236Ter
NP_000160.1:p.Trp236Ter
LRG_672t1:c.707G>A
LRG_672:g.14085G>A
LRG_672p1:p.Trp236Ter
NC_000023.10:g.100653867C>T
NM_000169.2:c.707G>A
NR_164783.1:n.786G>A

Protein change:

W236*

Links:

dbSNP: rs879254022

NCBI 1000 Genomes Browser:

rs879254022

Molecular consequence:

NM_001199973.2:c.300+3422C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.177+7057C>T - intron variant - [Sequence Ontology: SO:0001627]
NR_164783.1:n.786G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000169.3:c.707G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Fabry disease
Synonyms:: Angiokeratoma, diffuse; Anderson-Fabry disease; Hereditary dystopic lipidosis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010526; MedGen: C0002986; Orphanet: 324; OMIM: 301500; Human Phenotype Ontology: HP:0001071

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000820189	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 20, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10666480, 12175777, 12428061, 27560961, 28492532
SCV002054417	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000820189

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 20, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002054417

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 15, 2021)

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Twenty novel mutations in the alpha-galactosidase A gene causing Fabry disease.

Topaloglu AK, Ashley GA, Tong B, Shabbeer J, Astrin KH, Eng CM, Desnick RJ.

Mol Med. 1999 Dec;5(12):806-11.

PubMed [citation]

PMID:: 10666480
PMCID:: PMC2230489

Fabry disease: 45 novel mutations in the alpha-galactosidase A gene causing the classical phenotype.

Shabbeer J, Yasuda M, Luca E, Desnick RJ.

Mol Genet Metab. 2002 May;76(1):23-30.

PubMed [citation]

PMID:: 12175777

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000820189.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Trp236*) in the GLA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 245967). This premature translational stop signal has been observed in individuals with classic Fabry disease (PMID: 12428061, 27560961). This variant is not present in population databases (ExAC no frequency).

#	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 Genome-Nilou Lab, SCV002054417.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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