ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.4361G>A (p.Arg1454Gln) (rs542708170)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000266533 SCV000341564 uncertain significance not provided 2016-06-09 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000477841 SCV000453168 uncertain significance Ciliary dyskinesia, primary, 3 2016-07-11 criteria provided, single submitter clinical testing The DNAH5 c.4361G>A (p.Arg1454Gln) variant is a missense variant that has has been reported in four studies, all of which describe the same family of German origin (Olbrich et al. 2002; Olbrich et al. 2006; Loges et al. 2008; Raidt et al. 2014). The p.Arg1454Gln variant was found in a compound heterozygous state with a frameshift variant in two siblings with primary ciliary dyskinesia. The p.Arg1454Gln variant was absent from 200 control chromosomes (Olbrich et al. 2002) and is reported at a frequency of 0.00034 in the African population of the Exome Aggregation Consortium. Direct visualization of respiratory cells from the individuals carrying the variant showed an absence of cilia or membrane alterations. In the remaining ciliated cells, variant DNAH5 was absent from the ciliary axonemes and mislocalized to the basal body region (Olbrich et al. 2006; Loges et al. 2008). The evidence for this variant is limited. The p.Arg1454Gln variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for primary ciliary dyskinesia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV001247795 SCV001421238 uncertain significance Primary ciliary dyskinesia 2019-05-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1454 of the DNAH5 protein (p.Arg1454Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs542708170, ExAC 0.04%). This variant has been observed to segregate with primary ciliary dyskinesia in a family (PMID: 11788826). ClinVar contains an entry for this variant (Variation ID: 287698). This variant has been reported to affect DNAH5 protein function (PMID:16492982). 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.
Division of Human Genetics,Children's Hospital of Philadelphia RCV000477841 SCV000536778 likely pathogenic Ciliary dyskinesia, primary, 3 2016-02-10 no assertion criteria provided research

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