NM_000153.4(GALC):c.411_413del (p.Lys139del) AND Galactosylceramide beta-galactosidase deficiency

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Sep 21, 2023
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:: RCV000671072.6

Allele description [Variation Report for NM_000153.4(GALC):c.411_413del (p.Lys139del)]

NM_000153.4(GALC):c.411_413del (p.Lys139del)

Gene:

GALC:galactosylceramidase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

14q31.3

Genomic location:

Preferred name:

NM_000153.4(GALC):c.411_413del (p.Lys139del)

HGVS:

NC_000014.9:g.87986518_87986520del
NG_011853.3:g.12044_12046del
NM_000153.4:c.411_413delMANE SELECT
NM_001201401.2:c.342_344del
NM_001201402.2:c.333_335del
NP_000144.2:p.Lys139del
NP_001188330.1:p.Lys116del
NP_001188331.1:p.Lys113del
NC_000014.8:g.88452862_88452864del
NG_011853.2:g.12044_12046del
NM_000153.3:c.411_413delTAA

Protein change:

K113del

Links:

dbSNP: rs1555383687

NCBI 1000 Genomes Browser:

rs1555383687

Molecular consequence:

NM_000153.4:c.411_413del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001201401.2:c.342_344del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001201402.2:c.333_335del - inframe_deletion - [Sequence Ontology: SO:0001822]

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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protein MAL2 [Homo sapiens]
protein MAL2 [Homo sapiens]
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000796013	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Nov 30, 2017)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23197103, 27785412, 26108647 Citation Link,
SCV004297153	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 21, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23197103, 26108647, 35286032, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000796013

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Nov 30, 2017)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV004297153

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 21, 2023)

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	germline	yes	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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Neuroradiological, neurophysiological and molecular findings in infantile Krabbe disease: two case reports.

Vargiami E, Papathanasiou E, Batzios S, Kyriazi M, Dimitriou E, Anastasiou A, Michelakakis H, Giese AK, Zafeiriou DI.

Balkan J Med Genet. 2016 Jul 1;19(1):85-90.

PubMed [citation]

PMID:: 27785412
PMCID:: PMC5026284

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

See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000796013.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	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 Ege University Pediatric Genetics, Ege University, SCV000925626.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297153.1

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

Description

This variant, c.411_413del, results in the deletion of 1 amino acid(s) of the GALC protein (p.Lys139del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Krabbe disease (PMID: 23197103, 26108647, 35286032). This variant is also known as K123del. ClinVar contains an entry for this variant (Variation ID: 555281). For these reasons, this variant has been classified as Pathogenic.

#	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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000925626	Ege University Pediatric Genetics, Ege University	flagged submission Reason: Claim with insufficient supporting evidence Notes: Does not cite a number of articles with case-level data supporting pathogenicity. (ACMG Guidelines, 2015)	Uncertain significance (May 15, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 31319225

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000925626

Ege University Pediatric Genetics, Ege University

flagged submission

Reason: Claim with insufficient supporting evidence

Notes: Does not cite a number of articles with case-level data supporting pathogenicity.

(ACMG Guidelines, 2015)

Uncertain significance
(May 15, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine