ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.13458dup (p.Asn4487Ter) (rs775696136)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000377034 SCV000452932 likely pathogenic Primary ciliary dyskinesia 2016-06-14 criteria provided, single submitter clinical testing The c.13458dupT (p.Asn4487Ter) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Asn4487Ter variant has been reported in one patient with primary ciliary dyskinesia in a homozygous state, and three patients in a compound heterozygous state with a second missense or frameshift variant (Hornef et al. 2006). Control data are unavailable for this variant, which is reported at a frequency of 0.00070 in the African American population of the Exome Sequencing Project. Based on the evidence and the potential impact of frameshift variants, the p.Asn4487Ter variant is classified as likely pathogenic for primary ciliary dyskinesia.
Invitae RCV000377034 SCV000624219 pathogenic Primary ciliary dyskinesia 2020-10-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn4487*) in the DNAH5 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs775696136, ExAC 0.02%). This variant has been observed in several individuals and families affected with primary ciliary dyskinesia (PMID: 16627867, 21270641). Loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867). For these reasons, this variant has been classified as Pathogenic.
Centre for Genomic and Experimental Medicine,University of Edinburgh RCV000377034 SCV001334259 pathogenic Primary ciliary dyskinesia 2020-04-01 criteria provided, single submitter research
UNC Molecular Genetics Laboratory,University of North Carolina at Chapel Hill RCV000377034 SCV001431583 likely pathogenic Primary ciliary dyskinesia 2018-11-08 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV001257126 SCV001433658 pathogenic Ciliary dyskinesia, primary, 3 2019-12-18 criteria provided, single submitter clinical testing This DNAH5 variant (rs775696136) has been identified in the homozgyous or compound heterozgygous state in multiple patients with primary ciliary dyskinesia. It is rare in population datasets (gnomAD: 16/251312 total alleles; 0.006367%; no homozygotes). Two submitters to ClinVar have classified DNAH5 c.13458dupT as either likely pathogenic or pathogenic. This frameshift variant results in a premature stop codon in exon 77 of 79 likely leading to nonsense-mediated decay and lack of protein production. We consider this variant to be pathogenic.
Natera, Inc. RCV000377034 SCV001462278 pathogenic Primary ciliary dyskinesia 2020-09-16 no assertion criteria provided clinical testing
Genomics England Pilot Project,Genomics England RCV001257126 SCV001760149 pathogenic Ciliary dyskinesia, primary, 3 no assertion criteria provided clinical testing
GeneDx RCV001565222 SCV001788529 pathogenic not provided 2020-06-19 no assertion criteria provided clinical testing 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; This variant is associated with the following publications: (PMID: 31589614, 31980526, 31879361, 16627867, 24498942, 30293990, 21270641, 31638833)

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