Submissions for variant NM_001206927.2(DNAH8):c.14059C>T (p.Arg4687Ter)

gnomAD frequency: 0.00058  dbSNP: rs146551804

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000232177	SCV000286328	uncertain significance	Primary ciliary dyskinesia	2022-10-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg4687*) in the DNAH8 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 21 amino acid(s) of the DNAH8 protein. This variant is present in population databases (rs146551804, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. 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: 238638). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill	RCV000232177	SCV001810026	uncertain significance	Primary ciliary dyskinesia	2021-03-02	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002487057	SCV002783400	uncertain significance	Spermatogenic failure 46	2022-03-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001729472	SCV003936645	uncertain significance	not provided	2022-12-28	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation as the last 21amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001729472	SCV001977720	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001729472	SCV001978702	uncertain significance	not provided		no assertion criteria provided	clinical testing