Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000228661 | SCV000286347 | likely pathogenic | Primary ciliary dyskinesia | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 62 of the DNAH8 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 DNAH8 are known to be pathogenic (PMID: 24307375, 32619401, 32681648). This variant is present in population databases (rs144711161, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 238657). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Preventiongenetics, |
RCV003417812 | SCV004106300 | likely pathogenic | DNAH8-related condition | 2023-06-10 | criteria provided, single submitter | clinical testing | The DNAH8 c.9194+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in literature. This variant is reported in 0.015% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-38867683-G-A). However, loss-of-function variants have been reported to be causative for DNAH8-related disorders (for example, Watson et al. 2014. PubMed ID: 24307375; Liu et al. 2020. PubMed ID: 32619401; Yang et al. 2020. PubMed ID: 32681648; Zhou et al. 2021. PubMed ID: 33611675). In ClinVar, the c.9194+1G>A variant is interpreted as likely pathogenic (ClinVar ID: 239924). Based on these observations, this variant is classified as likely pathogenic. |