Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000255847 | SCV000321558 | pathogenic | not provided | 2022-04-22 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30919572, 32367404) |
Invitae | RCV000629338 | SCV000750273 | pathogenic | Primary ciliary dyskinesia | 2022-09-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 265099). Disruption of this splice site has been observed in individuals with dextrocardia and/or primary ciliary dyskinesia (PMID: 30919572, 32367404; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 34 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). |
Prevention |
RCV003430812 | SCV004116492 | pathogenic | DNAH11-related condition | 2022-11-02 | criteria provided, single submitter | clinical testing | The DNAH11 c.5924+1G>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported to be causative for primary ciliary dyskinesia (Table S1, Al-Dewik et al. 2019. PubMed ID: 30919572; Shamseldin et al. 2020. PubMed ID: 32367404). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice donor site in DNAH11 are expected to be pathogenic. This variant is interpreted as pathogenic. |