ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.4961G>A (p.Arg1654Gln) (rs150868941)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227048 SCV000287082 uncertain significance Primary ciliary dyskinesia 2019-05-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1654 of the DNAH5 protein (p.Arg1654Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs150868941, ExAC 0.05%). This variant has not been reported in the literature in individuals with DNAH5-related conditions. ClinVar contains an entry for this variant (Variation ID: 238977). 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: "Possibly Damaging"; 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.
GeneDx RCV000519727 SCV000617019 uncertain significance not provided 2016-04-27 criteria provided, single submitter clinical testing The R1654Q variant in the DNAH5 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1654Q variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. The R1654Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R1654Q as a variant of uncertain significance.
Counsyl RCV000673861 SCV000799111 uncertain significance Ciliary dyskinesia, primary, 3 2018-04-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000673861 SCV001317702 uncertain significance Ciliary dyskinesia, primary, 3 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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