Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001224395 | SCV001396587 | pathogenic | Primary ciliary dyskinesia | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 3422 of the DNAH11 protein (p.Gly3422Arg). This variant is present in population databases (rs764509824, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of primary ciliary dyskinesia (PMID: 20513915; Invitae). ClinVar contains an entry for this variant (Variation ID: 952311). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DNAH11 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Genetics and Molecular Pathology, |
RCV003447580 | SCV004175485 | likely pathogenic | Primary ciliary dyskinesia 7 | 2023-05-02 | criteria provided, single submitter | clinical testing | The DNAH11 c.10264G>A variant is classified a likely pathogenic (PM2, PS4_supporting, PM3, PP3_Supporting). The DNAH11 c.10264G>A variant is a single nucleotide change in exon 63/82 of the DNAH11 gene, which is predicted to change the amino acid glycine at position 3422 in the protein to arginine. This variant is absent from population databases (PM2). This variant has been detected in trans with a second pathogenic variant in three patients from two unrelated families affected with primary ciliary dyskinesia (PMID: 20513915, 36003331) (PM3, PS4_supporting). It has also been reported as homozygous in a patient with PCD, classified as a VUS (PMID: 33447612). Computational predictions support a deleterious effect on the gene or gene (PP3_Supporting). The variant has been reported in dbSNP (rs764509824) and in the HGMD database (CM105718). It has been reported as likely pathogenic by other diagnostic laboratory (ClinVar Variation ID: 952311). |