Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000705308 | SCV000834298 | pathogenic | Primary ciliary dyskinesia | 2022-08-10 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs764011276, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Ile473Phefs*2) in the CCDC40 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CCDC40 are known to be pathogenic (PMID: 21131974, 22693285, 23255504). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 581475). This variant is also known as c.1415delG. This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 23255504). It has also been observed to segregate with disease in related individuals. |
| Ambry Genetics | RCV000705308 | SCV002702975 | pathogenic | Primary ciliary dyskinesia | 2018-09-10 | criteria provided, single submitter | clinical testing | The c.1416delG pathogenic mutation, located in coding exon 9 of the CCDC40 gene, results from a deletion of one nucleotide at nucleotide position 1416, causing a translational frameshift with a predicted alternate stop codon (p.I473Ffs*2). This variant, designated as c.1415delG, was identified in the homozygous state in two siblings with primary ciliary dyskinesia (Antony D et al. Hum. Mutat., 2013 Mar;34:462-72). 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. |