NM_001844.5(COL2A1):c.3111+2T>A AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 13, 2022
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:: RCV002866207.3

Allele description [Variation Report for NM_001844.5(COL2A1):c.3111+2T>A]

NM_001844.5(COL2A1):c.3111+2T>A

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.3111+2T>A

HGVS:

NC_000012.12:g.47978008A>T
NG_008072.1:g.31495T>A
NM_001844.5:c.3111+2T>AMANE SELECT
NM_033150.3:c.2904+2T>A
NC_000012.11:g.48371791A>T

Molecular consequence:

NM_001844.5:c.3111+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_033150.3:c.2904+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003225859	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 13, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 20179744, 32896647, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003225859

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 13, 2022)

germline

clinical testing

PubMed (4)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003225859.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change affects a donor splice site in intron 44 of the COL2A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL2A1 are known to be pathogenic (PMID: 20179744). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with autosomal recessive spondyloepiphyseal dysplasia and/or Stickler syndrome (PMID: 20179744, 32896647; Invitae). It has also been observed to segregate with disease in related individuals. Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (PMID: 32896647). 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.

#	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: Sep 29, 2024

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