ClinVar Miner

Submissions for variant NM_001206927.2(DNAH8):c.665A>G (p.Tyr222Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Johns Hopkins Genomics, Johns Hopkins University RCV001290375 SCV001478429 uncertain significance Spermatogenic failure 46 2021-01-19 criteria provided, single submitter clinical testing This DNAH8 variant (rs753974456) is rare (<0.1%) in a large population dataset (gnomAD: 31/282634 total alleles; 0.01%; no homozygotes) and has not been reported in ClinVar nor the literature, to our knowledge. Of two bioinformatics tools queried, one predicts that the substitution would be damaging, while the other predicts that it would be tolerated. The tyrosine residue at this position is highly evolutionarily conserved across most species assessed. We consider the clinical significance of c.629A>G to be uncertain at this time.
Invitae RCV001363072 SCV001559161 uncertain significance Primary ciliary dyskinesia 2020-10-14 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 222 of the DNAH8 protein (p.Tyr222Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs753974456, ExAC 0.08%). This variant has not been reported in the literature in individuals with DNAH8-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Not Available; Align-GVGD: Class C0). 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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