VCV001076887.2 - ClinVar

NC_000023.10:g.(?_37545215)_(38280335_?)del

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.

(2)

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_000023.10:g.(?_37545215)_(38280335_?)del

Variation ID: 1076887 Accession: VCV001076887.2

Type and length

Deletion, 735,121 bp

Location

Cytogenetic: Xp21.1-11.4 X: 37545215-38280335 (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	May 10, 2021	Jun 29, 2024	Aug 23, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NC_000023.10:g.(?_37545215)_(38280335_?)del

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

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.
CYBB		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	692	874
OTC		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	915	1070
DYNLT3		-	-	GRCh38 GRCh37	8	164
H2AP	-	-	-	GRCh38 GRCh37	-	164
RPGR		-	-	GRCh38 GRCh37	1601	1777
SRPX		-	-	GRCh38 GRCh37	48	204
SYTL5		-	-	GRCh38 GRCh37	57	223
XK		-	-	GRCh38 GRCh37	79	242

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.
Ornithine carbamoyltransferase deficiency	Pathogenic (1)	criteria provided, single submitter	Oct 27, 2020	RCV001390917.2
Primary ciliary dyskinesia	Pathogenic (1)	criteria provided, single submitter	Aug 23, 2023	RCV004579576.2

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 27, 2020)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Ornithine carbamoyltransferase deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001592790.1 First in ClinVar: May 10, 2021 Last updated: May 10, 2021	Publications: PubMed (9) PubMed: 22494545‚ 11793468‚ 19475717‚ 22382802‚ 18487280‚ 19138872‚ 19783189‚ 10946359‚ 16786505 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the OTC gene has been identified. The boundaries of this event are … (more) A gross deletion of the genomic region encompassing the full coding sequence of the OTC gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has been observed in individuals affected with OTC deficiency (PMID: 22494545, 11793468, 19475717, 22382802, 18487280, 19138872, 19783189). Loss-of-function variants in OTC are known to be pathogenic (PMID: 10946359, 16786505). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Aug 23, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Primary ciliary dyskinesia Affected status: unknown Allele origin: unknown	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV005064396.1 First in ClinVar: Jun 29, 2024 Last updated: Jun 29, 2024	Publications: PubMed (2) PubMed: 16055928‚ 16969763 Comment: For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RPGR-related conditions. … (more) For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RPGR-related conditions. A gross deletion of the genomic region encompassing the full coding sequence of the RPGR gene has been identified. Loss-of-function variants in RPGR are known to be pathogenic (PMID: 16055928, 16969763). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. (less)

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the OTC gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has been observed in individuals affected with OTC deficiency (PMID: 22494545, 11793468, 19475717, 22382802, 18487280, 19138872, 19783189). Loss-of-function variants in OTC are known to be pathogenic (PMID: 10946359, 16786505). For these reasons, this variant has been classified as Pathogenic.

Comment:

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RPGR-related conditions. A gross deletion of the genomic region encompassing the full coding sequence of the RPGR gene has been identified. Loss-of-function variants in RPGR are known to be pathogenic (PMID: 16055928, 16969763). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes.

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
Targeted array CGH as a valuable molecular diagnostic approach: experience in the diagnosis of mitochondrial and metabolic disorders.	Wang J	Molecular genetics and metabolism	2012	PMID: 22494545
Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders.	Aradhya S	Genetics in medicine : official journal of the American College of Medical Genetics	2012	PMID: 22382802
Contiguous gene deletion syndrome in a female with ornithine transcarbamylase deficiency.	Balasubramaniam S	Molecular genetics and metabolism	2010	PMID: 19783189
Molecular mechanisms underlying large genomic deletions in ornithine transcarbamylase (OTC) gene.	Quental R	Clinical genetics	2009	PMID: 19475717
High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH.	Shchelochkov OA	Molecular genetics and metabolism	2009	PMID: 19138872
Utility of oligonucleotide array-based comparative genomic hybridization for detection of target gene deletions.	Wong LJ	Clinical chemistry	2008	PMID: 18487280
Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype-phenotype correlations and impact on genetic counseling.	Pelletier V	Human mutation	2007	PMID: 16969763
Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene.	Yamaguchi S	Human mutation	2006	PMID: 16786505
RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa.	Moore A	Journal of medical genetics	2006	PMID: 16055928
Mutations and polymorphisms in the human ornithine transcarbamylase gene.	Tuchman M	Human mutation	2002	PMID: 11793468
Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype.	McCullough BA	American journal of medical genetics	2000	PMID: 10946359
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Text-mined citations for this variant ...

Record last updated Jan 13, 2025

ClinVar Genomic variation as it relates to human health

NC_000023.10:g.(?_37545215)_(38280335_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...