ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.2431+5G>A (rs369244905)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489824 SCV000576553 uncertain significance not provided 2017-04-28 criteria provided, single submitter clinical testing The c.2431+5G>A variant in the DNAH5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant reduces the quality of the splice acceptor site in intron 16, and is expected to cause abnormal gene splicing. The c.2431+5G>A variant is observed in 11/10390 (0.11%) alleles from individuals of African background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.2431+5G>A as a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000311206 SCV000453254 uncertain significance Primary ciliary dyskinesia 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000311206 SCV000817546 uncertain significance Primary ciliary dyskinesia 2018-01-08 criteria provided, single submitter clinical testing This sequence change falls in intron 16 of the DNAH5 gene. It does not directly change the encoded amino acid sequence of the DNAH5 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs369244905, ExAC 0.1%). This variant has not been reported in the literature in individuals with DNAH5-related disease. ClinVar contains an entry for this variant (Variation ID: 351201). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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