Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000705308 | SCV000834298 | pathogenic | Primary ciliary dyskinesia | 2022-08-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 581475). For these reasons, this variant has been classified as Pathogenic. 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). This variant is present in population databases (rs764011276, gnomAD 0.02%). 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. This variant is also known as c.1415delG. |
| 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. |
| Victorian Clinical Genetics Services, |
RCV004788138 | SCV005400617 | pathogenic | Primary ciliary dyskinesia 15 | 2024-10-11 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with primary ciliary dyskinesia 15 MIM#613808. (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v4) <0.01 for a recessive condition (19 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many pathogenic NMD-predicted variants have been identified in ClinVar. (SP)) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |