NM_000153.4(GALC):c.1335_1336del (p.Trp446fs) AND Galactosylceramide beta-galactosidase deficiency

Clinical significance:Pathogenic (Last evaluated: Oct 7, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001231281.2

Allele description [Variation Report for NM_000153.4(GALC):c.1335_1336del (p.Trp446fs)]

NM_000153.4(GALC):c.1335_1336del (p.Trp446fs)

Gene:
GALC:galactosylceramidase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
14q31.3
Genomic location:
Preferred name:
NM_000153.4(GALC):c.1335_1336del (p.Trp446fs)
HGVS:
  • NC_000014.9:g.87949848_87949849del
  • NG_011853.2:g.48716_48717del
  • NG_011853.3:g.48716_48717del
  • NM_000153.4:c.1335_1336delMANE SELECT
  • NM_001201401.1:c.1266_1267del
  • NM_001201402.1:c.1257_1258del
  • NP_000144.2:p.Trp446fs
  • NP_001188330.1:p.Trp423fs
  • NP_001188331.1:p.Trp420fs
  • NC_000014.8:g.88416191_88416192del
  • NC_000014.8:g.88416192_88416193del
  • NM_000153.3:c.1335_1336del
Protein change:
W420fs
Links:
Molecular consequence:
  • NM_000153.4:c.1335_1336del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001201401.1:c.1266_1267del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001201402.1:c.1257_1258del - 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
SCV001403797Invitaecriteria provided, single submitter
Pathogenic
(Oct 7, 2019)
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

Early infantile Krabbe disease: results of the World-Wide Krabbe Registry.

Duffner PK, Barczykowski A, Jalal K, Yan L, Kay DM, Carter RL.

Pediatr Neurol. 2011 Sep;45(3):141-8. doi: 10.1016/j.pediatrneurol.2011.05.007.

PubMed [citation]
PMID:
21824559

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, SCV001403797.2

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

Description

This sequence change creates a premature translational stop signal (p.Trp446Alafs*3) 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 affected with Krabbe Disease (PMID: 21824559). This variant is also known as p.W430AfsX3 in the literature. 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 10, 2021

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