Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001058221 | SCV001222778 | pathogenic | Primary ciliary dyskinesia | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 17 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 (rs774855011, gnomAD 0.06%). Disruption of this splice site has been observed in individuals with DNAH11-related conditions (PMID: 28976722; Invitae). ClinVar contains an entry for this variant (Variation ID: 853420). 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. |
Molecular Genetics Department, |
RCV003985835 | SCV004801781 | likely pathogenic | Primary ciliary dyskinesia 7 | criteria provided, single submitter | clinical testing | A previously undescribed nucleotide variant creates an alteration of the canonical splice site c.3426-1G>A in the DNAH11 gene. The variant was observed in compound heterozygous state with another LoF variant in an individual affected with Situs inversus. Homozygous and compound heterozygous variants are reported in patients with Ciliary dyskinesia, primary, 7, with or without situs inversus, 611884 (3). The variant is present in gnomAD population database at low frequency (12/247726 chromosomes, no homozygotes). 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. |