NM_000169.3(GLA):c.484T>C (p.Trp162Arg) AND Angiokeratoma corporis diffusum

Clinical significance:Likely pathogenic (Last evaluated: Jul 2, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000011475.3

Allele description [Variation Report for NM_000169.3(GLA):c.484T>C (p.Trp162Arg)]

NM_000169.3(GLA):c.484T>C (p.Trp162Arg)

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.484T>C (p.Trp162Arg)
HGVS:
  • NC_000023.11:g.101401695A>G
  • NG_007119.1:g.11269T>C
  • NM_000169.2:c.484T>C
  • NM_000169.3:c.484T>CMANE SELECT
  • NM_001199973.2:c.300+6238A>G
  • NM_001199974.2:c.177+9873A>G
  • NP_000160.1:p.Trp162Arg
  • NP_000160.1:p.Trp162Arg
  • LRG_672t1:c.484T>C
  • LRG_672:g.11269T>C
  • LRG_672p1:p.Trp162Arg
  • NC_000023.10:g.100656683A>G
  • NR_164783.1:n.506T>C
  • P06280:p.Trp162Arg
Protein change:
W162R; TRP162ARG
Links:
UniProtKB: P06280#VAR_000458; OMIM: 300644.0016; dbSNP: rs28935196
NCBI 1000 Genomes Browser:
rs28935196
Molecular consequence:
  • NM_001199973.2:c.300+6238A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001199974.2:c.177+9873A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000169.2:c.484T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000169.3:c.484T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_164783.1:n.506T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Angiokeratoma corporis diffusum
Synonyms:
Fabry disease; Angiokeratoma, diffuse; Anderson-Fabry disease; 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
SCV000031707OMIMno assertion criteria providedPathogenic
(Dec 1, 1993)
germlineliterature only

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

SCV000828383Invitaecriteria provided, single submitter
Likely pathogenic
(Jul 2, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Results of a nationwide screening for Anderson-Fabry disease among dialysis patients.

Kotanko P, Kramar R, Devrnja D, Paschke E, Voigtländer T, Auinger M, Pagliardini S, Spada M, Demmelbauer K, Lorenz M, Hauser AC, Kofler HJ, Lhotta K, Neyer U, Pronai W, Wallner M, Wieser C, Wiesholzer M, Zodl H, Födinger M, Sunder-Plassmann G.

J Am Soc Nephrol. 2004 May;15(5):1323-9. Erratum in: J Am Soc Nephrol. 2004 Aug;15(8):1a. J Am Soc Nephrol. 2004 Sep;15(9):A4.

PubMed [citation]
PMID:
15100373

A pharmacogenetic approach to identify mutant forms of α-galactosidase A that respond to a pharmacological chaperone for Fabry disease.

Wu X, Katz E, Della Valle MC, Mascioli K, Flanagan JJ, Castelli JP, Schiffmann R, Boudes P, Lockhart DJ, Valenzano KJ, Benjamin ER.

Hum Mutat. 2011 Aug;32(8):965-77. doi: 10.1002/humu.21530. Epub 2011 Jul 12.

PubMed [citation]
PMID:
21598360
PMCID:
PMC3170878
See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000031707.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In an Italian patient with classic Fabry disease (301500), Eng et al. (1993) found a T-to-C transition in exon 3 of the GLA gene, resulting in a trp162-to-arg (W162R) substitution.

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

From Invitae, SCV000828383.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces tryptophan with arginine at codon 162 of the GLA protein (p.Trp162Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported as hemizygous in individuals affected with Fabry disease (PMID: 15100373, 12778775, 7504405). ClinVar contains an entry for this variant (Variation ID: 10728). Experimental studies have shown that this missense change results in a GLA protein with no alpha-galactosidase A enzyme activity (PMID: 21598360). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 20, 2021

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