Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001851925 | SCV002126903 | pathogenic | not provided | 2023-04-30 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individual(s) with autosomal dominant Stickler syndrome (PMID: 10706362). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 25 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 also known as intron 25+1G>A. For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 10706362). ClinVar contains an entry for this variant (Variation ID: 17382). |
OMIM | RCV000018925 | SCV000039210 | pathogenic | Stickler syndrome type 1 | 2000-02-28 | no assertion criteria provided | literature only |