VCV000587360.1 - ClinVar

NC_000008.10:g.11667760_11787743del

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000008.10:g.11667760_11787743del

Variation ID: 587360 Accession: VCV000587360.1

Type and length

Deletion, 119,984 bp

Location

Cytogenetic: 8p23.1 8: 11667760-11787743 (GRCh37) [ NCBI UCSC ]

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	Oct 29, 2018	Oct 29, 2018	Oct 25, 2018

HGVS

Nucleotide	Protein	Molecular consequence
NC_000008.10:g.11667760_11787743del

Protein change

Other names

120-KB DEL

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

OMIM: 184420.0001 VarSome

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.
CTSB		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	116	254
FDFT1		-	-	GRCh38 GRCh38 GRCh37	88	223

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.
Squalene synthase deficiency	Pathogenic (1)	no assertion criteria provided	Oct 25, 2018	RCV000714473.1

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 (Oct 25, 2018)	no assertion criteria provided Method: literature only	SQUALENE SYNTHASE DEFICIENCY Affected status: not provided Allele origin: germline	OMIM Accession: SCV000845170.1 First in ClinVar: Oct 29, 2018 Last updated: Oct 29, 2018	Publications: PubMed (1) PubMed: 29909962 Comment on evidence: In 2 sibs with squalene synthase deficiency (SQSD; 618156), Coman et al. (2018) identified compound heterozygosity for mutations in the FDFT1 gene. The maternal allele … (more) In 2 sibs with squalene synthase deficiency (SQSD; 618156), Coman et al. (2018) identified compound heterozygosity for mutations in the FDFT1 gene. The maternal allele carried a 120-kb deletion (chr8.11667760-11787743, GRCh37) encompassing exons 6 through 10 of the FDFT1 gene and all of the cathepsin B gene (CTSB; 116810). The paternal allele carried a TC deletion/AG insertion in intron 8 (184420.0002) that created a novel splice acceptor site and resulted in the retention of 22 bp of intron 8 sequence. Western blot analysis showed marked reduction in FDFT1 protein in patient-derived lymphoblasts and fibroblasts; there was even more dramatic reduction in fibroblasts grown in lipid-free media. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Squalene Synthase Deficiency: Clinical, Biochemical, and Molecular Characterization of a Defect in Cholesterol Biosynthesis.	Coman D	American journal of human genetics	2018	PMID: 29909962

Text-mined citations for this variant ...

Record last updated Sep 01, 2024

ClinVar Genomic variation as it relates to human health

NC_000008.10:g.11667760_11787743del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...