ClinVar Miner

Submissions for variant NM_001206927.2(DNAH8):c.5210G>A (p.Arg1737His)

gnomAD frequency: 0.00004  dbSNP: rs568480936
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538535 SCV000624020 uncertain significance Primary ciliary dyskinesia 2022-07-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1737 of the DNAH8 protein (p.Arg1737His). This variant is present in population databases (rs568480936, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 454578). 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.
Johns Hopkins Genomics, Johns Hopkins University RCV002282202 SCV002570343 uncertain significance Spermatogenic failure 46 2022-08-31 criteria provided, single submitter clinical testing This DNAH8 missense variant (rs568480936) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 21/250132 total alleles; 0.0084%; no homozygotes). It has been reported in ClinVar (Variation ID 454578), but has not been reported in the literature, to our knowledge. Two bioinformatic tools queried predict that this substitution would be damaging, and the arginine residue at this position is evolutionarily conserved across many of the species assessed. The contribution of DNAH8 to primary ciliary dyskinesia has not been confirmed. We consider the clinical significance of c.5210G>A in DNAH8 to be uncertain at this time.
Ambry Genetics RCV004023707 SCV003941118 uncertain significance not specified 2023-06-12 criteria provided, single submitter clinical testing The c.5210G>A (p.R1737H) alteration is located in exon 38 (coding exon 37) of the DNAH8 gene. This alteration results from a G to A substitution at nucleotide position 5210, causing the arginine (R) at amino acid position 1737 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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