Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000344104 | SCV000330117 | pathogenic | not provided | 2018-01-26 | criteria provided, single submitter | clinical testing | The c.1106+2T>A pathogenic variant in the BBS4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 13. 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.1106+2T>A variant was not observed in approximately 6,500 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.1106+2T>A as a pathogenic variant. |
Invitae | RCV000787534 | SCV000944498 | likely pathogenic | Bardet-Biedl syndrome | 2018-10-21 | criteria provided, single submitter | clinical testing | Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BBS4 are known to be pathogenic (PMID: 11381270). This variant has been observed in a deceased fetus with bilateral enlarged cystic kidneys (PMID: 28425981). ClinVar contains an entry for this variant (Variation ID: 280217). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 13 of the BBS4 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Department of Clinical Genetics, |
RCV000787534 | SCV000926506 | likely pathogenic | Bardet-Biedl syndrome | 2018-04-01 | no assertion criteria provided | research |