VCV000978826.1 - ClinVar

NC_000012.11:g.120940098_120949687dup

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_000012.11:g.120940098_120949687dup

Variation ID: 978826 Accession: VCV000978826.1

Type and length

Duplication, 9,590 bp

Location

Cytogenetic: 12q24.31 12: 120502294-120502295 (GRCh38) [ NCBI UCSC ] 12: 120940097-120940098 (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 3, 2020	Oct 3, 2020	Jan 25, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NC_000012.12:g.120502295_120511884dup
NC_000012.11:g.120940098_120949687dup

Protein change

Other names

9.6-KB DUP

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: 616359.0001 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.
COQ5		-	-	GRCh38 GRCh37	38	54

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.
Coenzyme q10 deficiency, primary, 9	Pathogenic (1)	no assertion criteria provided	Jan 25, 2021	RCV001257583.1

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 (Jan 25, 2021)	no assertion criteria provided Method: literature only	COENZYME Q10 DEFICIENCY, PRIMARY, 9 (1 family) Affected status: not provided Allele origin: germline	OMIM Accession: SCV001434392.1 First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020	Publications: PubMed (1) PubMed: 29044765 Comment on evidence: In 3 sisters, born of unrelated parents of Iraqi-Jewish descent, with coenzyme Q10 deficiency-9 (COQ10D9; 619028), Malicdan et al. (2018) identified a homozygous 9,590-bp duplication … (more) In 3 sisters, born of unrelated parents of Iraqi-Jewish descent, with coenzyme Q10 deficiency-9 (COQ10D9; 619028), Malicdan et al. (2018) identified a homozygous 9,590-bp duplication (chr12:120,940,098-120,949,687, GRCh37) in the COQ5 gene. The duplication, which was found by detailed genetic analysis and confirmed by Sanger sequencing, segregated with the disorder in the family. The duplication spanned the last 4 exons of the COQ5 gene, but did not alter the open reading frame: it was located about 1 kb beyond the DNA sequence that encodes the 3-prime untranslated region. Patient fibroblasts and leukocytes, and skeletal muscle tissue from 1 patient, had significantly decreased COQ5 mRNA and protein levels compared to controls. Cultured fibroblasts from 1 patient showed a defect in mitochondrial complex II+III activity and abnormal oxygen consumption, suggesting that the mutation had an adverse effect on mitochondrial respiration. Homozygosity for the variant was not found in 92 healthy individuals from the same ethnic background; however, there were 3 heterozygous carriers, yielding a minor allele frequency of about 1.5%. (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
A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency.	Malicdan MCV	Human mutation	2018	PMID: 29044765

Text-mined citations for this variant ...

Record last updated Apr 25, 2022

ClinVar Genomic variation as it relates to human health

NC_000012.11:g.120940098_120949687dup

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...