NM_000153.4(GALC):c.688_694del (p.Trp230fs) AND Galactosylceramide beta-galactosidase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 2, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001775350.1

Allele description [Variation Report for NM_000153.4(GALC):c.688_694del (p.Trp230fs)]

NM_000153.4(GALC):c.688_694del (p.Trp230fs)

Gene:

GALC:galactosylceramidase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

14q31.3

Genomic location:

Preferred name:

NM_000153.4(GALC):c.688_694del (p.Trp230fs)

HGVS:

NC_000014.9:g.87976416_87976422del
NG_011853.3:g.22142_22148del
NM_000153.4:c.688_694delMANE SELECT
NM_001201401.2:c.619_625del
NM_001201402.2:c.610_616del
NP_000144.2:p.Trp230fs
NP_001188330.1:p.Trp207fs
NP_001188331.1:p.Trp204fs
NC_000014.8:g.88442760_88442766del
NG_011853.2:g.22142_22148del
NM_000153.3:c.688_694del

Protein change:

W204fs

Links:

dbSNP: rs780376041

NCBI 1000 Genomes Browser:

rs780376041

Molecular consequence:

NM_000153.4:c.688_694del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001201401.2:c.619_625del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001201402.2:c.610_616del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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
SCV002012170	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 2, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002012170

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 2, 2021)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV002012170.1

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

Description

Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2). Patient's phenotype is considered compatible with Krabbe disease (3billion dataset, PP4). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Dec 24, 2023

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