Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000368003 | SCV000453238 | uncertain significance | Primary ciliary dyskinesia 3 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Genetics and Molecular Pathology, |
RCV000368003 | SCV002556892 | uncertain significance | Primary ciliary dyskinesia 3 | 2020-06-15 | criteria provided, single submitter | clinical testing | PM2, PP3 |
| Ambry Genetics | RCV002323556 | SCV002605791 | uncertain significance | Primary ciliary dyskinesia | 2015-08-03 | criteria provided, single submitter | clinical testing | The p.N1105K variant (also known as c.3315C>A), located in coding exon 22 of the DNAH5 gene, results from a C to A substitution at nucleotide position 3315. The asparagine at codon 1105 is replaced by lysine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs144053917. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.02% (2/13006) total alleles studied, having been observed in 0.02% (2/8600) European American alleles. This amino acid position is 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 variant remains unclear. |
| Labcorp Genetics |
RCV002323556 | SCV003291069 | uncertain significance | Primary ciliary dyskinesia | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1105 of the DNAH5 protein (p.Asn1105Lys). This variant is present in population databases (rs144053917, gnomAD 0.06%). This missense change has been observed in individual(s) with clinical features of DNAH5-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 351192). 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 not expected to disrupt DNAH5 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. |
| Mayo Clinic Laboratories, |
RCV004791424 | SCV005411773 | uncertain significance | not provided | 2024-01-09 | criteria provided, single submitter | clinical testing | BP4 |