NM_001844.5(COL2A1):c.2678dup (p.Ala895fs) AND Stickler syndrome type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 3, 2020
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:: RCV001263467.1

Allele description [Variation Report for NM_001844.5(COL2A1):c.2678dup (p.Ala895fs)]

NM_001844.5(COL2A1):c.2678dup (p.Ala895fs)

Gene:

COL2A1:collagen type II alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

12q13.11

Genomic location:

Preferred name:

NM_001844.5(COL2A1):c.2678dup (p.Ala895fs)

HGVS:

NC_000012.12:g.47980015dup
NG_008072.1:g.29493dup
NM_001844.5:c.2678dupMANE SELECT
NM_033150.3:c.2471dup
NP_001835.3:p.Ala895fs
NP_149162.2:p.Ala826fs
NC_000012.11:g.48373792_48373793insG
NC_000012.11:g.48373798dup
NM_001844.4:c.2678dup
NM_001844.5:c.2678dupCMANE SELECT

Protein change:

A826fs

Links:

dbSNP: rs1938958532

NCBI 1000 Genomes Browser:

rs1938958532

Molecular consequence:

NM_001844.5:c.2678dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033150.3:c.2471dup - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001441541	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 3, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20179744, 22522174, 26626311, 26709265, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001441541

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 3, 2020)

germline

clinical testing

PubMed (5)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Mosaicism in Stickler syndrome.

Stevenson DA, Vanzo R, Damjanovich K, Hanson H, Muntz H, Hoffman RO, Bayrak-Toydemir P.

Eur J Med Genet. 2012 Jun;55(6-7):418-22. doi: 10.1016/j.ejmg.2012.03.006. Epub 2012 Mar 30.

PubMed [citation]

PMID:: 22522174
PMCID:: PMC3674818

See all PubMed Citations (5)

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV001441541.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This COL2A1 variant is absent from a large population database and has an entry in ClinVar. It has been reported in individuals affected with Stickler syndrome type I and Kniest dysplasia. This variant was detected in the paternal sample used for analysis. The reduced alternate allele fraction and suggestion of mild COL2A1-associated phenotypes suggest this variant is mosaic in the patient father. This frameshift variant occurs in exon 40 of 54 likely leading to nonsense-mediated decay and lack of protein production. We consider c.2678dupC to be pathogenic.

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

Last Updated: Feb 20, 2024

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