Submissions for variant NM_001844.5(COL2A1):c.2094+1G>C

dbSNP: rs2136552560

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001385790	SCV001585753	pathogenic	not provided	2021-04-08	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL2A1 are known to be pathogenic (PMID: 20179744). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individual(s) with Stickler syndrome (PMID: 20179744, 31625567). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 32 of the COL2A1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Institute of Human Genetics, University of Leipzig Medical Center	RCV003493854	SCV004242484	pathogenic	Stickler syndrome type 1	2024-01-17	criteria provided, single submitter	clinical testing	Criteria applied: PVS1,PS2,PS1_SUP,PS4_SUP,PM2_SUP,PP4