ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.7531C>T (p.Arg2511Trp) (rs564040169)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724052 SCV000230679 uncertain significance not provided 2014-07-29 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000214734 SCV000271690 uncertain significance not specified 2016-01-14 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Arg2511Trp va riant in DNAH5 has not been previously reported in individuals with pulmonary di sease and has been identified in 1/4612 European chromosomes by the Exome Aggreg ation Consortium (ExAC,; dbSNP rs564040169). Comp utational prediction tools and conservation analysis suggest that the p.Arg2511T rp variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance o f the p.Arg2511Trp variant is uncertain, these data suggest that it is more like ly to be benign.
Counsyl RCV000672878 SCV000798027 uncertain significance Ciliary dyskinesia, primary, 3 2018-02-20 criteria provided, single submitter clinical testing
Invitae RCV001037117 SCV001200515 uncertain significance Primary ciliary dyskinesia 2019-09-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 2511 of the DNAH5 protein (p.Arg2511Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. While this variant is present in population databases (rs564040169), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with DNAH5-related conditions. ClinVar contains an entry for this variant (Variation ID: 197517). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Natera, Inc. RCV001037117 SCV001457550 uncertain significance Primary ciliary dyskinesia 2020-01-24 no assertion criteria provided clinical testing

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