Submissions for variant NM_000090.4(COL3A1):c.2022+2T>C

dbSNP: rs587779429

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000087352	SCV000631638	pathogenic	Ehlers-Danlos syndrome, type 4	2017-07-15	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 COL3A1 are known to be pathogenic (PMID: 24922459). 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. This variant has been reported in individuals affected with Ehlers-Danlos syndrome IV (PMID: 24922459). ClinVar contains an entry for this variant (Variation ID: 101115). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 29 of the COL3A1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Collagen Diagnostic Laboratory, University of Washington	RCV000087352	SCV000120234	pathogenic	Ehlers-Danlos syndrome, type 4		no assertion criteria provided	clinical testing