NM_001844.5(COL2A1):c.2862C>T (p.Gly954=) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Sep 11, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV001269946.4

Allele description [Variation Report for NM_001844.5(COL2A1):c.2862C>T (p.Gly954=)]

NM_001844.5(COL2A1):c.2862C>T (p.Gly954=)

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.2862C>T (p.Gly954=)
HGVS:
  • NC_000012.12:g.47978630G>A
  • NG_008072.1:g.30873C>T
  • NM_001844.5:c.2862C>TMANE SELECT
  • NM_033150.3:c.2655C>T
  • NP_001835.3:p.Gly954=
  • NP_149162.2:p.Gly885=
  • NC_000012.11:g.48372413G>A
  • NM_001844.4:c.2862C>T
Molecular consequence:
  • NM_001844.5:c.2862C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_033150.3:c.2655C>T - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
2

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001450321Clinical Genetics Karolinska University Hospital,Karolinska University Hospitalcriteria provided, single submitter
Pathogenic
(Oct 17, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001574302Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 11, 2020)
germlineclinical testing

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

SCV001808400Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensusno assertion criteria providedPathogenicgermlineclinical testing

SCV001811906GeneDxno assertion criteria provided
Pathogenic
(Feb 4, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1.

Richards AJ, McNinch A, Martin H, Oakhill K, Rai H, Waller S, Treacy B, Whittaker J, Meredith S, Poulson A, Snead MP.

Hum Mutat. 2010 Jun;31(6):E1461-71. doi: 10.1002/humu.21257.

PubMed [citation]
PMID:
20513134
See all PubMed Citations (4)

Details of each submission

From Clinical Genetics Karolinska University Hospital,Karolinska University Hospital, SCV001450321.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

From Invitae, SCV001574302.1

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

Description

This sequence change affects codon 954 of the COL2A1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL2A1 protein. 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: 20513134, 20179744). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: PMID: 20513134, 20179744). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001808400.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV001811906.1

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

Description

Non-canonical splice site variant demonstrated to result in loss-of-function (Richards et al., 2010); This variant is associated with the following publications: (PMID: 20513134, 26443184, 27193475, 31781920, 20179744)

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

Last Updated: Sep 7, 2021

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