NM_000169.3(GLA):c.32del (p.Gly11fs) AND Fabry disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 8, 2022
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:: RCV003041472.4

Allele description [Variation Report for NM_000169.3(GLA):c.32del (p.Gly11fs)]

NM_000169.3(GLA):c.32del (p.Gly11fs)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_000169.3(GLA):c.32del (p.Gly11fs)

HGVS:

NC_000023.11:g.101407874del
NG_007119.1:g.5092del
NG_016327.1:g.4672del
NM_000169.3:c.32delMANE SELECT
NM_001199973.2:c.301-4062del
NM_001199974.2:c.178-4062del
NM_001406747.1:c.32del
NM_001406748.1:c.32del
NM_001406749.1:c.32del
NP_000160.1:p.Gly11Alafs
NP_000160.1:p.Gly11fs
NP_001393676.1:p.Gly11fs
NP_001393677.1:p.Gly11fs
NP_001393678.1:p.Gly11fs
LRG_672t1:c.30del
LRG_672:g.5092del
LRG_672p1:p.Gly11Alafs
NC_000023.10:g.100662860del
NC_000023.10:g.100662862del
NM_000169.2:c.30delG
NR_164783.1:n.54del
NR_176252.1:n.54del
NR_176253.1:n.54del
p.G11Afs*110

Protein change:

G11fs

Links:

dbSNP: rs869312278

NCBI 1000 Genomes Browser:

rs869312278

Molecular consequence:

NM_000169.3:c.32del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406747.1:c.32del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406748.1:c.32del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406749.1:c.32del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001199973.2:c.301-4062del - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.178-4062del - intron variant - [Sequence Ontology: SO:0001627]
NR_164783.1:n.54del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176252.1:n.54del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176253.1:n.54del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Functional consequence:

effect on protein activity [Variation Ontology: 0053]

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
SCV003445178	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 8, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10360396, 10666480, 12175777, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003445178

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 8, 2022)

germline

clinical testing

PubMed (4)
[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

Fabry disease: comparison of enzymatic, linkage, and mutation analysis for carrier detection in a family with a novel mutation (30delG).

Ashton-Prolla P, Ashley GA, Giugliani R, Pires RF, Desnick RJ, Eng CM.

Am J Med Genet. 1999 Jun 11;84(5):420-4.

PubMed [citation]

PMID:: 10360396

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003445178.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.30delG. This premature translational stop signal has been observed in individual(s) with Fabry disease (PMID: 10360396). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly11Alafs*110) 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).

#	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: Sep 29, 2024

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