Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000433468 | SCV000520910 | likely pathogenic | not provided | 2017-02-02 | criteria provided, single submitter | clinical testing | The c.226-2A>G pathogenic variant in the COL1A2 gene has been reported in multiple affected individuals from a family segregating an autosomal dominant form of Ehlers-Danlos syndrome characterized by marked joint laxity and multiple dislocations, with no reported skin fragility or fractures (Byers et al., 1997). This splice site variant destroys the canonical splice acceptor site in intron 5. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.226-2A>G variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.226-2A>G as a likely pathogenic variant |
Invitae | RCV002228040 | SCV000931982 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2018-12-03 | 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 COL1A2 are known to be pathogenic (PMID: 2993307, 3372533, 6092353, 11288717, 15077201, 16816023, 27510842). This variant has been observed to segregate with Ehlers-Danlos syndrome in a family (PMID: 9295084) and has been observed in an unrelated individual with arthrochalasia type Ehlers-Danlos syndrome (PMID: 21801164). This variant is also known as Intron 5 A-2>G in the literature. ClinVar contains an entry for this variant (Variation ID: 17270). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 5 of the COL1A2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Genome Diagnostics Laboratory, |
RCV002276561 | SCV002565566 | pathogenic | Ehlers-Danlos syndrome | 2020-01-01 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000018811 | SCV000039094 | pathogenic | Ehlers-danlos syndrome, arthrochalasia type, 2 | 2017-12-21 | no assertion criteria provided | literature only |