ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.7502G>C (p.Arg2501Pro) (rs78853309)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000156495 SCV000206214 uncertain significance not specified 2019-05-22 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Invitae RCV000556129 SCV000624290 uncertain significance Primary ciliary dyskinesia 2018-02-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 2501 of the DNAH5 protein (p.Arg2501Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. While this variant is present in population databases (rs78853309), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in several individuals affected with primary ciliary dyskinesia (PMID: 16627867, 19357118, 25802884) and is found at relatively high frequency in individuals of Ashkenazi Jewish descent (PMID: 25802884). ClinVar contains an entry for this variant (Variation ID: 179699). 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 disruptive, 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.
Illumina Clinical Services Laboratory,Illumina RCV000778752 SCV000915116 uncertain significance Ciliary dyskinesia, primary, 3 2016-09-21 criteria provided, single submitter clinical testing The DNAH5 c.7502G>C (p.Arg2501Pro) variant is a missense variant that has been reported in a total of three individuals with primary ciliary dyskinesia, two of whom were sibling. In the siblings, the variant was found in trans with consensus splice-site variant, while in the third individual, it was in a compound heterozygous state with a missense variant (Hornef et al. 2006; Fedick et al. 2015). In addition, Failly et al. (2009) reported the p.Arg2501Pro variant in a patient who also carried two other missense variants, with phase unknown. The p.Arg2501Pro variant was absent from 70 controls but is reported at a frequency of 0.00128 in the European (non-Finnish) population of the Exome Aggregation Consortium. The evidence for this variant is limited. The p.Arg2501Pro 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.
Natera, Inc. RCV000556129 SCV001452283 uncertain significance Primary ciliary dyskinesia 2020-09-16 no assertion criteria provided clinical testing

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