NM_000153.4(GALC):c.560A>T (p.Asp187Val) AND Galactosylceramide beta-galactosidase deficiency

Clinical significance:Likely pathogenic (Last evaluated: Aug 16, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000796371.2

Allele description [Variation Report for NM_000153.4(GALC):c.560A>T (p.Asp187Val)]

NM_000153.4(GALC):c.560A>T (p.Asp187Val)

Gene:
GALC:galactosylceramidase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q31.3
Genomic location:
Preferred name:
NM_000153.4(GALC):c.560A>T (p.Asp187Val)
HGVS:
  • NC_000014.9:g.87984416T>A
  • NG_011853.2:g.14148A>T
  • NM_000153.4:c.560A>TMANE SELECT
  • NM_001201401.1:c.491A>T
  • NM_001201402.1:c.482A>T
  • NP_000144.2:p.Asp187Val
  • NP_001188330.1:p.Asp164Val
  • NP_001188331.1:p.Asp161Val
  • NC_000014.8:g.88450760T>A
  • NM_000153.3:c.560A>T
Protein change:
D161V
Links:
dbSNP: rs997021099
NCBI 1000 Genomes Browser:
rs997021099
Molecular consequence:
  • NM_000153.4:c.560A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001201401.1:c.491A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001201402.1:c.482A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Galactosylceramide beta-galactosidase deficiency
Synonyms:
Krabbe leukodystrophy; Globoid cell leukoencephalopathy; Galactocerebrosidase deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009499; MedGen: C0023521; Orphanet: 487; OMIM: 245200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000935881Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 16, 2018)
germlineclinical testing

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

SCV001454073Natera, Inc.no assertion criteria providedLikely pathogenic
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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 Invitae, SCV000935881.1

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

Description

This sequence change replaces aspartic acid with valine at codon 187 of the GALC protein (p.Asp187Val). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with significantly reduced GALC enzyme activity, findings that are highly specific for Krabbe disease (Pubmed: 20886637). This variant has also been observed in several individuals with GALC-related conditions (PMID: 8687180, 27442402). This variant is also known as Asp171Val in the literature. Experimental studies have shown that this missense change has a deleterious effect on protein function (PMID: 27638593). 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

From Natera, Inc., SCV001454073.1

#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: Aug 27, 2021

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