ClinVar Miner

Submissions for variant NM_001206927.2(DNAH8):c.11468C>T (p.Ala3823Val) (rs185283741)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000690315 SCV000817997 uncertain significance Primary ciliary dyskinesia 2018-12-15 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 3823 of the DNAH8 protein (p.Ala3823Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs185283741, ExAC 0.2%). This variant has not been reported in the literature in individuals with DNAH8-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, Align-GVGD) 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.
Johns Hopkins Genomics, Johns Hopkins University RCV001290377 SCV001478431 uncertain significance Spermatogenic failure 46 2021-01-19 criteria provided, single submitter clinical testing This DNAH8 variant (rs185283741) is present in a large population dataset (gnomAD: 102/280708 total alleles; 0.036%; no homozygotes) and has been reported in ClinVar. It has not been reported in the literature, to our knowledge. One bioinformatic tool queried predicts that this substitution would be tolerated, and the alanine residue at this position is poorly evolutionarily conserved across the species assessed. We consider the clinical significance of c.11432C>T to be uncertain at this time.

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