VCV001070140.2 - ClinVar

NC_000014.8:g.(?_88391504)_88423173del

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000014.8:g.(?_88391504)_88423173del

Variation ID: 1070140 Accession: VCV001070140.2

Type and length

Deletion, -

Location

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 2, 2021	Dec 2, 2021	Mar 29, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NC_000014.8:g.(?_88391504)_88423173del
NC_000014.8:g.(?_88391504_88423173del

Protein change

Other names

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GALC		-	-	GRCh38 GRCh37	1333	1446

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Galactosylceramide beta-galactosidase deficiency	Pathogenic (1)	criteria provided, single submitter	Mar 29, 2020	RCV001382170.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Mar 29, 2020)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Galactosylceramide beta-galactosidase deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001580802.2 First in ClinVar: May 10, 2021 Last updated: Dec 02, 2021	Publications: PubMed (3) PubMed: 7581365‚ 22073273‚ 26795590 Comment: This variant is a gross deletion of the genomic region encompassing exons 11-17 of the GALC gene. While it is not anticipated to result in … (more) This variant is a gross deletion of the genomic region encompassing exons 11-17 of the GALC gene. While it is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. Loss-of-function variants in GALC are known to be pathogenic. This particular variant is consistent with the well known 30kb deletion, which is the most common cause of Krabbe disease in the European population, found in more than 30% of affected individuals investigated and at a frequency of 0.2% in a sample of 2,330 control European individuals (PMID: 7581365, 22073273, 26795590). This variant has been associated with an increased risk for primary open-angle glaucoma, but the clinical relevance of this finding is unclear (PMID: 22073273). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

This variant is a gross deletion of the genomic region encompassing exons 11-17 of the GALC gene. While it is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. Loss-of-function variants in GALC are known to be pathogenic. This particular variant is consistent with the well known 30kb deletion, which is the most common cause of Krabbe disease in the European population, found in more than 30% of affected individuals investigated and at a frequency of 0.2% in a sample of 2,330 control European individuals (PMID: 7581365, 22073273, 26795590). This variant has been associated with an increased risk for primary open-angle glaucoma, but the clinical relevance of this finding is unclear (PMID: 22073273). For these reasons, this variant has been classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Newborn screening for Krabbe disease in New York State: the first eight years' experience.	Orsini JJ	Genetics in medicine : official journal of the American College of Medical Genetics	2016	PMID: 26795590
GALC deletions increase the risk of primary open-angle glaucoma: the role of Mendelian variants in complex disease.	Liu Y	PloS one	2011	PMID: 22073273
A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease.	Rafi MA	Human molecular genetics	1995	PMID: 7581365

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000014.8:g.(?_88391504)_88423173del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...