ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.13194_13197del (p.Asp4398fs) (rs727502971)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150465 SCV000197651 likely pathogenic Primary ciliary dyskinesia 2013-11-08 criteria provided, single submitter clinical testing The Asp4398fs variant in DNAH5 has been reported in one individual with PCD and outer dynein arm (ODA) defects who carried a missense variant identified on the other copy of this gene (Hornef 2006). The variant has not been identified in la rge population studies. This frameshift variant is predicted to alter the protei n's amino acid sequence beginning at position 4398 and lead to a premature termi nation codon 16 amino acids downstream. This alteration is then predicted to lea d to a truncated or absent protein. Frameshift and other truncating variants in DNAH5 are associated with autosomal recessive PCD (Hornef 2006). In summary, thi s variant is likely pathogenic, though additional studies are required to fully establish its clinical significance.
Invitae RCV000150465 SCV000624215 pathogenic Primary ciliary dyskinesia 2020-10-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp4398Glufs*16) in the DNAH5 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs727502971, ExAC 0.003%). This variant has been observed in individual(s) with primary ciliary dyskinesia (PMID: 16627867, 26373788). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 163134). Loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268785 SCV001447966 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.