Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000220957 | SCV000270136 | likely benign | not specified | 2016-02-15 | criteria provided, single submitter | clinical testing | p.Pro663Leu in exon 11 of DNAAF1: This variant has been identified in 0.17% (17/ 10216) of African chromosomes by the Exome Aggregation Consortium (ExAC, http:// exac.broadinstitute.org; dbSNP rs147393144). This frequency in addition to the p oor evolutionary conservation of the affected amino acid (including two mammalia n species who carry the variant amino acid) make a primary disease causing role unlikely although a modifying role cannot be ruled out. |
| Invitae | RCV000813165 | SCV000953510 | uncertain significance | Primary ciliary dyskinesia | 2022-03-16 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 663 of the DNAAF1 protein (p.Pro663Leu). This variant is present in population databases (rs147393144, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with DNAAF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 227313). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV000813165 | SCV002718534 | uncertain significance | Primary ciliary dyskinesia | 2018-07-23 | criteria provided, single submitter | clinical testing | The p.P663L variant (also known as c.1988C>T), located in coding exon 11 of the DNAAF1 gene, results from a C to T substitution at nucleotide position 1988. The proline at codon 663 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |