Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
UNC Molecular Genetics Laboratory, |
RCV001095711 | SCV001251547 | likely pathogenic | Primary ciliary dyskinesia 7 | criteria provided, single submitter | research | The DNAH11 c.6983+1G>A (p.?) variant is predicted to alter a canonical mRNA splice donor site, which may result in an abnormal protein. To our knowledge, it has not been described in the literature. | |
Invitae | RCV003769038 | SCV004626587 | pathogenic | Primary ciliary dyskinesia | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 42 of the DNAH11 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 DNAH11 are known to be pathogenic (PMID: 18022865, 20513915, 22184204). This variant is present in population databases (rs771953930, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with primary ciliary dyskinesia (PMID: 31765523, 32253119). ClinVar contains an entry for this variant (Variation ID: 873476). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |