ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.8449G>T (p.Asp2817Tyr) (rs745885469)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000693465 SCV000821336 likely pathogenic Primary ciliary dyskinesia 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 2817 of the DNAH5 protein (p.Asp2817Tyr). The aspartic acid residue is weakly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another DNAH5 variant in individuals affected with primary ciliary dyskinesia (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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