NM_000169.3(GLA):c.620_630delinsCACT (p.Tyr207fs) AND Fabry disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 6, 2019
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:: RCV001193071.2

Allele description [Variation Report for NM_000169.3(GLA):c.620_630delinsCACT (p.Tyr207fs)]

NM_000169.3(GLA):c.620_630delinsCACT (p.Tyr207fs)

Genes:

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

Variant type:

Indel

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_000169.3(GLA):c.620_630delinsCACT (p.Tyr207fs)

HGVS:

NC_000023.11:g.101400675_101400685delinsAGTG
NG_007119.1:g.12279_12289delinsCACT
NM_000169.3:c.620_630delinsCACTMANE SELECT
NM_001199973.2:c.300+5218_300+5228delinsAGTG
NM_001199974.2:c.177+8853_177+8863delinsAGTG
NM_001406747.1:c.743_753delinsCACT
NM_001406748.1:c.620_630delinsCACT
NP_000160.1:p.Tyr207Serfs
NP_000160.1:p.Tyr207fs
NP_001393676.1:p.Tyr248fs
NP_001393677.1:p.Tyr207fs
LRG_672t1:c.620_630delinsCACT
LRG_672:g.12279_12289delinsCACT
NC_000023.10:g.100655663_100655673delinsAGTG
NM_000169.2:c.620_630delATATGTGGCCCinsCACT
NM_000169.2:c.620_630delinsCACT
NR_164783.1:n.642_652delinsCACT
NR_176253.1:n.757_767delinsCACT

Protein change:

Y207fs

Links:

dbSNP: rs1928279286

NCBI 1000 Genomes Browser:

rs1928279286

Molecular consequence:

NM_000169.3:c.620_630delinsCACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406747.1:c.743_753delinsCACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406748.1:c.620_630delinsCACT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001199973.2:c.300+5218_300+5228delinsAGTG - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.177+8853_177+8863delinsAGTG - intron variant - [Sequence Ontology: SO:0001627]
NR_164783.1:n.642_652delinsCACT - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176253.1:n.757_767delinsCACT - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV001361653	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Aug 6, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001361653

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Aug 6, 2019)

germline

clinical testing

Citation Link

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361653.1

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

Description

Variant summary: GLA c.620_630delinsCACT (p.Tyr207SerfsX31) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 179766 control chromosomes (gnomAD). To our knowledge, no occurrence of c.620_630delinsCACT in individuals affected with Fabry Disease and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as 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: Sep 16, 2024

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