NM_000169.2(GLA):c.239G>A (p.Gly80Asp) AND Fabry disease

Clinical significance:Uncertain significance (Last evaluated: Oct 9, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000209421.8

Allele description [Variation Report for NM_000169.2(GLA):c.239G>A (p.Gly80Asp)]

NM_000169.2(GLA):c.239G>A (p.Gly80Asp)

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_000169.2(GLA):c.239G>A (p.Gly80Asp)
HGVS:
  • NC_000023.11:g.101403941C>T
  • NG_007119.1:g.9023G>A
  • NG_016327.1:g.739C>T
  • NM_000169.2:c.239G>A
  • NM_001199973.2:c.301-7995C>T
  • NM_001199974.2:c.178-7995C>T
  • NP_000160.1:p.Gly80Asp
  • LRG_672t1:c.239G>A
  • LRG_672:g.9023G>A
  • LRG_672p1:p.Gly80Asp
  • NC_000023.10:g.100658929C>T
  • P06280:p.Gly80Asp
  • p.G80D
Protein change:
G80D
Links:
UniProtKB: P06280#VAR_077378; dbSNP: rs781838005
NCBI 1000 Genomes Browser:
rs781838005
Molecular consequence:
  • NM_001199973.2:c.301-7995C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001199974.2:c.178-7995C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000169.2:c.239G>A - missense variant - [Sequence Ontology: SO:0001583]
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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000246033Albrecht-Kossel-Institute,Medical University Rostockno assertion criteria providedLikely pathogenic
(Jan 1, 2014)
inheritedresearch

PubMed (1)
[See all records that cite this PMID]

SCV000748699Invitaecriteria provided, single submitter
Uncertain significance
(Oct 9, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001458762Natera, Inc.no assertion criteria providedUncertain significance
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Citations

PubMed

Functional and Clinical Consequences of Novel α-Galactosidase A Mutations in Fabry Disease.

Lukas J, Scalia S, Eichler S, Pockrandt AM, Dehn N, Cozma C, Giese AK, Rolfs A.

Hum Mutat. 2016 Jan;37(1):43-51. doi: 10.1002/humu.22910. Epub 2015 Oct 27.

PubMed [citation]
PMID:
26415523

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Albrecht-Kossel-Institute,Medical University Rostock, SCV000246033.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000748699.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces glycine with aspartic acid at codon 80 of the GLA protein (p.Gly80Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Fabry disease (PMID: 26415523). ClinVar contains an entry for this variant (Variation ID: 217380). Experimental studies have shown that this missense change decreases GLA enzyme activity in vitro (PMID: 26415523). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Natera, Inc., SCV001458762.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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