VCV000208981.1 - ClinVar

GRCh38/hg38 12q13.2(chr12:55845043-55851177)

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

GRCh38/hg38 12q13.2(chr12:55845043-55851177)

Variation ID: 208981 Accession: VCV000208981.1

Type and length

Duplication, 6,135 bp

Location

Cytogenetic: 12q13.2 12: 55845042-55845043 (GRCh38) [ NCBI UCSC ] 12: 56238826-56238827 (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	Aug 22, 2016	Aug 22, 2016	Jan 12, 2015

HGVS

Nucleotide	Protein	Molecular consequence
NC_000012.12:g.55845043_55851177dup
NC_000012.11:g.56238827_56244961dup

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

OMIM: 601807.0001 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 25581579 to determine the location of this allele on the current reference sequence.

Triplication of a 6-kb genomic regulatory region upstream of gene MMP19.

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.
MMP19		-	-	GRCh38 GRCh37	50	58

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.
Familial cavitary optic disk anomaly	Pathogenic (1)	no assertion criteria provided	Jan 12, 2015	RCV000190900.4

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 12, 2015)	no assertion criteria provided Method: literature only	CAVITARY OPTIC DISC ANOMALIES Affected status: not provided Allele origin: germline	OMIM Accession: SCV000245774.3 First in ClinVar: Sep 20, 2015 Last updated: Aug 22, 2016	Publications: PubMed (2) PubMed: 10764862‚ 25581579 Comment on evidence: In affected members of 2 unrelated families with cavitary optic disc anomalies (CODA; 611543), 1 of which was originally described by Moore et al. (2000), … (more) In affected members of 2 unrelated families with cavitary optic disc anomalies (CODA; 611543), 1 of which was originally described by Moore et al. (2000), Hazlewood et al. (2015) identified a heterozygous triplication of a 6-kb DNA segment (chr2:56,238,827_56,244,961) 2.1-kb upstream of the MMP19 gene. The mutation segregated fully with disease in both families and was not found in 78 controls or in the Database of Genomic Variants. Analysis of transcriptional activity in transfected HEK293 cells showed increased luciferase activity with the 6-kb sequence, and a 773-bp fragment of the 6-kb DNA segment increased downstream gene expression 8-fold. Hazlewood et al. (2015) noted that the CNV is surrounded by repetitive DNA sequences (Alu elements), suggesting that the triplication was likely generated by nonallelic homologous recombination. (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
Heterozygous triplication of upstream regulatory sequences leads to dysregulation of matrix metalloproteinase 19 in patients with cavitary optic disc anomaly.	Hazlewood RJ	Human mutation	2015	PMID: 25581579
Progressive optic nerve cupping and neural rim decrease in a patient with bilateral autosomal dominant optic nerve colobomas.	Moore M	American journal of ophthalmology	2000	PMID: 10764862

Text-mined citations for this variant ...

Record last updated Oct 15, 2023

ClinVar Genomic variation as it relates to human health

GRCh38/hg38 12q13.2(chr12:55845043-55851177)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...