Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000223514 | SCV000271354 | pathogenic | Primary ciliary dyskinesia | 2016-01-07 | criteria provided, single submitter | clinical testing | The p.Arg2082X variant in DNAH11 has been reported in 1 individual with PCD who carried a second, pathogenic variant on the other allele (Knowles 2012). This va riant has also been identified in 2/10842 Latino chromosomes by the Exome Aggreg ation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs200693106). Alth ough this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsense varian t leads to a premature termination codon at position 2082, which is predicted to lead to a truncated or absent protein. In summary, the p.Arg2082X variant meets our criteria to be classified as pathogenic for PCD in an autosomal recessive m anner. |
Invitae | RCV000223514 | SCV000750404 | pathogenic | Primary ciliary dyskinesia | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg2082*) in the DNAH11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH11 are known to be pathogenic (PMID: 18022865, 20513915, 22184204). This variant is present in population databases (rs200693106, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 22184204, 31879361). ClinVar contains an entry for this variant (Variation ID: 228333). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001554971 | SCV001776313 | pathogenic | not provided | 2020-11-27 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31589614, 31879361, 22184204, 25802884) |
Revvity Omics, |
RCV001782703 | SCV002021708 | pathogenic | Primary ciliary dyskinesia 7 | 2019-02-06 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000223514 | SCV002656410 | pathogenic | Primary ciliary dyskinesia | 2020-01-17 | criteria provided, single submitter | clinical testing | The p.R2082* pathogenic mutation (also known as c.6244C>T), located in coding exon 37 of the DNAH11 gene, results from a C to T substitution at nucleotide position 6244. This changes the amino acid from an arginine to a stop codon within coding exon 37. This mutation was identified in one individual with a second nonsense variant confirmed in trans; clinical symptoms included situs inversus, neonatal respiratory distress, otitis media, bonchiectasis, sinusitis, and dyskinetic/hyperkinetic cilia on ciliary videomicroscopy (Knowles MR et al. Thorax, 2012 May;67:433-41). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Baylor Genetics | RCV001782703 | SCV004041507 | pathogenic | Primary ciliary dyskinesia 7 | 2023-03-26 | criteria provided, single submitter | clinical testing | |
Yale Center for Mendelian Genomics, |
RCV000223514 | SCV002106488 | likely pathogenic | Primary ciliary dyskinesia | 2018-08-01 | no assertion criteria provided | literature only |