Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001046053 | SCV001209938 | uncertain significance | Primary ciliary dyskinesia | 2022-02-05 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs762902639, gnomAD 0.007%). This sequence change affects codon 967 of the DNAH8 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DNAH8 protein. This variant also falls at the last nucleotide of exon 21, which is part of the consensus splice site for this exon. This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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: 843429). |