Submissions for variant NM_001854.4(COL11A1):c.2808+1G>A

dbSNP: rs1553223152

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000598697	SCV000710657	pathogenic	not provided	2022-12-12	criteria provided, single submitter	clinical testing	Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed at significant frequency in large population cohorts (gnomAD); Deletions involving coding exons of this gene are a known mechanism of disease (HGMD); Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV000598697	SCV002163771	pathogenic	not provided	2022-02-06	criteria provided, single submitter	clinical testing	Disruption of this splice site has been observed in individual(s) with clinical features of autosomal dominant Stickler syndrome (PMID: 28983407). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 504339). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 36 of the COL11A1 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 COL11A1 are known to be pathogenic (PMID: 20513134, 21035103, 23922384, 25240749, 32427345, 32756486).