NM_001844.5(COL2A1):c.1222-2A>G AND Stickler syndrome type 1

Clinical significance:Pathogenic (Last evaluated: Jun 14, 1996)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000018917.28

Allele description [Variation Report for NM_001844.5(COL2A1):c.1222-2A>G]

NM_001844.5(COL2A1):c.1222-2A>G

Gene:
COL2A1:collagen type II alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.11
Genomic location:
Preferred name:
NM_001844.5(COL2A1):c.1222-2A>G
HGVS:
  • NC_000012.12:g.47987315T>C
  • NG_008072.1:g.22188A>G
  • NM_001844.5:c.1222-2A>GMANE SELECT
  • NM_033150.3:c.1015-2A>G
  • NC_000012.11:g.48381098T>C
Nucleotide change:
IVS17, A-G, -2
Links:
OMIM: 120140.0024
Molecular consequence:
  • NM_001844.5:c.1222-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_033150.3:c.1015-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
Functional consequence:
effect on RNA splicing [Variation Ontology: 0362]

Condition(s)

Name:
Stickler syndrome type 1 (STL1)
Synonyms:
Stickler syndrome, vitreous type 1; Stickler syndrome, membranous vitreous type; Arthroophthalmopathy, hereditary progressive
Identifiers:
MONDO: MONDO:0007160; MedGen: C2020284; Orphanet: 828; OMIM: 108300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000039202OMIMno assertion criteria providedPathogenic
(Jun 14, 1996)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

HEREDITARY PROGRESSIVE ARTHRO-OPHTHALMOPATHY.

STICKLER GB, BELAU PG, FARRELL FJ, JONES JD, PUGH DG, STEINBERG AG, WARD LE.

Mayo Clin Proc. 1965 Jun;40:433-55. No abstract available.

PubMed [citation]
PMID:
14299791

A-2-->G transition at the 3' acceptor splice site of IVS17 characterizes the COL2A1 gene mutation in the original Stickler syndrome kindred.

Williams CJ, Ganguly A, Considine E, McCarron S, Prockop DJ, Walsh-Vockley C, Michels VV.

Am J Med Genet. 1996 Jun 14;63(3):461-7.

PubMed [citation]
PMID:
8737653

Details of each submission

From OMIM, SCV000039202.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In the original Minnesota kindred on the basis of which Stickler et al. (1965) defined the Stickler syndrome (STL1; 108300), Williams et al. (1996) identified a splice site mutation in the COL2A1 gene. They used conformational sensitive gel electrophoresis (SSGE) to screen for mutations in the entire gene. They noted a prominent heteroduplex in the PCR product from a region of the gene including exons 17 to 20. Direct sequencing of PCR-amplified genomic DNA identified an A-to-G transition at the -2 position at the 3-prime acceptor splice site of IVS17. Sequencing of DNA from affected and unaffected family members confirmed that the mutation segregated with the disease phenotype. RT-PCR analysis of poly(A)+ RNA demonstrated that the mutant allele utilized a cryptic splice site in exon 18 of the gene, eliminating 16 bp at the start of exon 18. This frameshift eventually resulted in a premature termination codon. Williams et al. (1996) stated that this was the first report of a splice site mutation in classical Stickler syndrome. They provided a satisfying historical context in which to view COL2A1 mutations in this disorder.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 12, 2022

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