ClinVar Miner

Submissions for variant NM_033028.5(BBS4):c.1106+2T>A

dbSNP: rs886041464
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, Copenhagen University Hospital, Rigshospitalet RCV000787534 SCV000926506 likely pathogenic Bardet-Biedl syndrome 2018-04-01 no assertion criteria provided research

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