GRCh38/hg38 12q13.2(chr12:55845043-55851177) AND Familial cavitary optic disk anomaly

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 12, 2015
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000190900.4

Allele description [Variation Report for GRCh38/hg38 12q13.2(chr12:55845043-55851177)]

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

Gene:

MMP19:matrix metallopeptidase 19 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

12q13.2

Genomic location:

Preferred name:

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

HGVS:

NC_000012.12:g.55845043_55851177dup
NC_000012.11:g.56238827_56244961dup

Note:

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

Links:

OMIM: 601807.0001

Condition(s)

Name:: Familial cavitary optic disk anomaly
Synonyms:: Cavitary optic disc anomalies; Cavitary optic disc anomaly; Familial cavitary optic disc anomaly
Identifiers:: MONDO: MONDO:0012687; MedGen: C1969063; OMIM: 611543

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000245774	OMIM	no assertion criteria provided	Pathogenic (Jan 12, 2015)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10764862, 25581579

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000245774

OMIM

no assertion criteria provided

Pathogenic
(Jan 12, 2015)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Progressive optic nerve cupping and neural rim decrease in a patient with bilateral autosomal dominant optic nerve colobomas.

Moore M, Salles D, Jampol LM.

Am J Ophthalmol. 2000 Apr;129(4):517-20.

PubMed [citation]

PMID:: 10764862

Heterozygous triplication of upstream regulatory sequences leads to dysregulation of matrix metalloproteinase 19 in patients with cavitary optic disc anomaly.

Hazlewood RJ, Roos BR, Solivan-Timpe F, Honkanen RA, Jampol LM, Gieser SC, Meyer KJ, Mullins RF, Kuehn MH, Scheetz TE, Kwon YH, Alward WL, Stone EM, Fingert JH.

Hum Mutat. 2015 Mar;36(3):369-78. doi: 10.1002/humu.22754.

PubMed [citation]

PMID:: 25581579
PMCID:: PMC4591753

Details of each submission

From OMIM, SCV000245774.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 14, 2023

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