Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002406075 | SCV002712538 | uncertain significance | Primary ciliary dyskinesia | 2014-05-23 | criteria provided, single submitter | clinical testing | The p.D562N variant (also known as c.1684G>A), located in coding exon 17 of the DNAI1 gene, results from a G to A substitution at nucleotide position 1684. The aspartic acid at codon 562 is replaced by asparagine, an amino acid with some highly similar properties. This variant has been detected in conjunction with a pathogenic mutation in DNAI1 by our laboratory. It is unknown if this variant is in cis or trans with this known pathogenic mutation. In addition, this variant co-occurred with a pathogenic mutation in the CFTR gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. This amino acid position is completely conserved on sequence alignment. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV002406075 | SCV003453856 | pathogenic | Primary ciliary dyskinesia | 2023-08-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 DNAI1 protein function. ClinVar contains an entry for this variant (Variation ID: 1777972). This missense change has been observed in individual(s) with primary ciliary dyskinesia (PMID: 30300419, 34445527; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.0008%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 562 of the DNAI1 protein (p.Asp562Asn). |