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NM_001844.5(COL2A1):c.1681-2_1681-1del AND Stickler syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 12, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000826159.4

Allele description [Variation Report for NM_001844.5(COL2A1):c.1681-2_1681-1del]

NM_001844.5(COL2A1):c.1681-2_1681-1del

Gene:
COL2A1:collagen type II alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
12q13.11
Genomic location:
Preferred name:
NM_001844.5(COL2A1):c.1681-2_1681-1del
HGVS:
  • NC_000012.12:g.47985588_47985589del
  • NG_008072.1:g.23914_23915del
  • NM_001844.5:c.1681-2_1681-1delMANE SELECT
  • NM_033150.3:c.1474-2_1474-1del
  • NC_000012.11:g.48379371_48379372del
  • NC_000012.11:g.48379371_48379372delCT
  • NM_001844.4:c.1681-2_1681-1delAG
Links:
dbSNP: rs1592217071
NCBI 1000 Genomes Browser:
rs1592217071
Molecular consequence:
  • NM_001844.5:c.1681-2_1681-1del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_033150.3:c.1474-2_1474-1del - splice acceptor variant - [Sequence Ontology: SO:0001574]
Observations:
1

Condition(s)

Name:
Stickler syndrome
Identifiers:
MONDO: MONDO:0019354; MedGen: C0265253; OMIM: PS108300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000967695Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)
Likely pathogenic
(Nov 12, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967695.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The c.1681-2_1681-1delAG variant in COL2A1 has not been previously reported in a ffected individuals and was absent from large population databases. This variant is a deletion of two nucleotides within the canonical splice site (+/- 1,2). Al though additional studies are needed to definitively establish the impact of thi s deletion on splicing, computational tools predict that it shifts the location of the splice site by one base, causing a frameshift that leads to a premature t ermination codon 68 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the COL2A1 gene is a n established disease mechanism in autosomal dominant Stickler syndrome. In summ ary, although additional studies are required to fully establish its clinical si gnificance, the c.1681-2_1681-1delAG variant is likely pathogenic. ACMG/AMP Crit eria applied: PVS1_Strong, PM2.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Dec 24, 2022