NM_000153.4(GALC):c.432_433dup (p.Thr145fs) AND Galactosylceramide beta-galactosidase deficiency

Clinical significance:Pathogenic (Last evaluated: Jun 22, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001383047.1

Allele description [Variation Report for NM_000153.4(GALC):c.432_433dup (p.Thr145fs)]

NM_000153.4(GALC):c.432_433dup (p.Thr145fs)

Gene:
GALC:galactosylceramidase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
14q31.3
Genomic location:
Preferred name:
NM_000153.4(GALC):c.432_433dup (p.Thr145fs)
HGVS:
  • NC_000014.9:g.87986498_87986499dup
  • NG_011853.2:g.12065_12066dup
  • NG_011853.3:g.12065_12066dup
  • NM_000153.4:c.432_433dupMANE SELECT
  • NM_001201401.2:c.363_364dup
  • NM_001201402.2:c.354_355dup
  • NP_000144.2:p.Thr145fs
  • NP_001188330.1:p.Thr122fs
  • NP_001188331.1:p.Thr119fs
  • NC_000014.8:g.88452841_88452842insTA
  • NC_000014.8:g.88452842_88452843dup
Protein change:
T119fs
Links:
Molecular consequence:
  • NM_000153.4:c.432_433dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001201401.2:c.363_364dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001201402.2:c.354_355dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001582064Invitaecriteria provided, single submitter
Pathogenic
(Jun 22, 2020)
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

Citations

PubMed

Newborn screening for Krabbe disease in New York State: the first eight years' experience.

Orsini JJ, Kay DM, Saavedra-Matiz CA, Wenger DA, Duffner PK, Erbe RW, Biski C, Martin M, Krein LM, Nichols M, Kurtzberg J, Escolar ML, Adams DJ, Arnold GL, Iglesias A, Galvin-Parton P, Kronn DF, Kwon JM, Levy PA, Pellegrino JE, Shur N, Wasserstein MP, et al.

Genet Med. 2016 Mar;18(3):239-48. doi: 10.1038/gim.2015.211. Epub 2016 Jan 21.

PubMed [citation]
PMID:
26795590

The Twitcher mouse: an enzymatically authentic model of human globoid cell leukodystrophy (Krabbe disease).

Kobayashi T, Yamanaka T, Jacobs JM, Teixeira F, Suzuki K.

Brain Res. 1980 Dec 8;202(2):479-83.

PubMed [citation]
PMID:
7437911
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001582064.1

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

Description

This sequence change creates a premature translational stop signal (p.Thr145Ilefs*27) in the GALC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with a positive newborn screening result for GALC-related disease (PMID: 26795590). Loss-of-function variants in GALC are known to be pathogenic (PMID: 7437911, 9272171, 16607461). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 14, 2021

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