NM_000153.4(GALC):c.972del (p.Leu324_Met325insTer) AND Galactosylceramide beta-galactosidase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 30, 2018
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000410081.7

Allele description [Variation Report for NM_000153.4(GALC):c.972del (p.Leu324_Met325insTer)]

NM_000153.4(GALC):c.972del (p.Leu324_Met325insTer)

Gene:

GALC:galactosylceramidase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

14q31.3

Genomic location:

Preferred name:

NM_000153.4(GALC):c.972del (p.Leu324_Met325insTer)

HGVS:

NC_000014.9:g.87965566del
NG_011853.3:g.32998del
NM_000153.4:c.972delMANE SELECT
NM_001201401.2:c.903del
NM_001201402.2:c.894del
NP_000144.2:p.Leu324_Met325insTer
NP_001188330.1:p.Leu301_Met302insTer
NP_001188331.1:p.Leu298_Met299insTer
NC_000014.8:g.88431910del
NC_000014.8:g.88431910delC
NG_011853.2:g.32998del
NM_000153.3:c.972delG

Links:

dbSNP: rs1057516808

NCBI 1000 Genomes Browser:

rs1057516808

Molecular consequence:

NM_000153.4:c.972del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001201401.2:c.903del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001201402.2:c.894del - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000486256	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Apr 25, 2016)	unknown	clinical testing	mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV000944425	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 30, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 7437911, 9272171, 16607461, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000486256

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Apr 25, 2016)

unknown

clinical testing

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000944425

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 30, 2018)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients.

Furuya H, Kukita Y, Nagano S, Sakai Y, Yamashita Y, Fukuyama H, Inatomi Y, Saito Y, Koike R, Tsuji S, Fukumaki Y, Hayashi K, Kobayashi T.

Hum Genet. 1997 Sep;100(3-4):450-6.

PubMed [citation]

PMID:: 9272171

See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000486256.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000944425.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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. This variant has not been reported in the literature in individuals with GALC-related conditions. ClinVar contains an entry for this variant (Variation ID: 370842). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Met325*) in the GALC gene. It is expected to result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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