ClinVar Miner

Submissions for variant NM_001369.3(DNAH5):c.8998C>T (p.Arg3000Ter)

gnomAD frequency: 0.00001  dbSNP: rs769054713
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000168445 SCV000219142 pathogenic Primary ciliary dyskinesia 2024-10-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg3000*) in the DNAH5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867). This variant is present in population databases (rs769054713, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with clinical features of primary ciliary dyskinesia and/or primary ciliary dyskinesia (PMID: 22416021; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 188388). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003221832 SCV003918603 likely pathogenic not provided 2022-10-10 criteria provided, single submitter clinical testing Observed with another DNAH5 variant in a patient with PCD in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Djakow et al., 2012); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22416021)
Natera, Inc. RCV000168445 SCV001452274 pathogenic Primary ciliary dyskinesia 2020-09-16 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004742300 SCV005352566 pathogenic DNAH5-related disorder 2024-08-05 no assertion criteria provided clinical testing The DNAH5 c.8998C>T variant is predicted to result in premature protein termination (p.Arg3000*). This variant was reported in an individual with primary ciliary dyskinesia (Djakow et al. 2012. PubMed ID: 22416021). This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD and is interpreted as pathogenic/likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/188388/). Loss-of-function variants in DNAH5 are expected to be pathogenic (Olbrich et al. 2002. PubMed ID: 11788826; Hornef et al. 2006. PubMed ID: 16627867). This variant is interpreted as pathogenic.

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