NM_001844.5(COL2A1):c.625C>T (p.Arg209Ter) AND not provided

Clinical significance:Pathogenic (Last evaluated: Feb 15, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000579130.3

Allele description [Variation Report for NM_001844.5(COL2A1):c.625C>T (p.Arg209Ter)]

NM_001844.5(COL2A1):c.625C>T (p.Arg209Ter)

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.625C>T (p.Arg209Ter)
Other names:
R9*
HGVS:
  • NC_000012.12:g.47995904G>A
  • NG_008072.1:g.13599C>T
  • NM_001844.5:c.625C>TMANE SELECT
  • NM_033150.3:c.418C>T
  • NP_001835.3:p.Arg209Ter
  • NP_149162.2:p.Arg140Ter
  • NC_000012.11:g.48389687G>A
  • NM_001844.4:c.625C>T
Protein change:
R140*; ARG9TER
Links:
OMIM: 120140.0010; dbSNP: rs121912869
NCBI 1000 Genomes Browser:
rs121912869
Molecular consequence:
  • NM_001844.5:c.625C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_033150.3:c.418C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000680706GeneDxcriteria provided, single submitter
Pathogenic
(May 20, 2019)
germlineclinical testing

Citation Link,

SCV001585159Invitaecriteria provided, single submitter
Pathogenic
(Feb 15, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A second mutation in the type II procollagen gene (COL2AI) causing stickler syndrome (arthro-ophthalmopathy) is also a premature termination codon.

Ahmad NN, McDonald-McGinn DM, Zackai EH, Knowlton RG, LaRossa D, DiMascio J, Prockop DJ.

Am J Hum Genet. 1993 Jan;52(1):39-45. Review.

PubMed [citation]
PMID:
8434604
PMCID:
PMC1682101

Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients.

Hoornaert KP, Vereecke I, Dewinter C, Rosenberg T, Beemer FA, Leroy JG, Bendix L, Björck E, Bonduelle M, Boute O, Cormier-Daire V, De Die-Smulders C, Dieux-Coeslier A, Dollfus H, Elting M, Green A, Guerci VI, Hennekam RC, Hilhorts-Hofstee Y, Holder M, Hoyng C, Jones KJ, et al.

Eur J Hum Genet. 2010 Aug;18(8):872-80. doi: 10.1038/ejhg.2010.23. Epub 2010 Feb 24. Erratum in: Eur J Hum Genet. 2010 Aug;18(8):881.

PubMed [citation]
PMID:
20179744
PMCID:
PMC2987380
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000680706.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25525159, 20179744, 8434604, 15895462, 26443184)

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

From Invitae, SCV001585159.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg209*) in the COL2A1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Stickler syndrome (PMID: 8434604). This amino acid change is also known as p.Arg9X in the literature. ClinVar contains an entry for this variant (Variation ID: 17360). Loss-of-function variants in COL2A1 are known to be pathogenic (PMID: 20179744). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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