Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000702057 | SCV000830887 | pathogenic | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2024-11-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg3490Glnfs*4) in the DNAH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH1 are known to be pathogenic (PMID: 27573432, 27798045). This variant is present in population databases (rs759646845, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 578911). For these reasons, this variant has been classified as Pathogenic. |
| Foundation for Research in Genetics and Endocrinology, |
RCV004698428 | SCV005199850 | pathogenic | Spermatogenic failure 18 | 2024-08-20 | criteria provided, single submitter | clinical testing | A homozygous deletion variant in exon 65 of the DNAH1 gene (chr3: 52427030-CAGAG-C) that results in frameshift and premature translational stop signal (p.Arg3490Glnfs*4) in the DNAH1 gene was detected. Loss of function variants in the DNAH1 gene are known to be pathogenic (PMID: 27573432, 27798045). The p.Arg3490Glnfs*4 variant has population database with a frequency of 0.02% in the gnomAD exomes (rs759646845) and 0.0468% in 1000Genomes. In silico prediction suggest the variants to be damaging by PolyPhen2, MutationTaster, SIFT, REVEL and CADD. The gene is predominantly expressed in trachea and testis, 2 tissues containing axonemal structures and also expressed in brain, according to the Human Protein Atlas database. Based on the above evidence, the variant is classified as pathogenic according to the ACMG-AMP classification system and ClinGen framework. |