Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000825634 | SCV000966997 | likely pathogenic | Non-syndromic male infertility due to sperm motility disorder | 2018-10-02 | criteria provided, single submitter | clinical testing | The p.Lys984SerfsX3 variant in DNAH1 has not been previously reported in individ uals with spermatogenic failure but has been identified in 3/246070 of chromosom es by gnomAD (http://gnomad.broadinstitute.org). This variant is predicted to ca use a frameshift, which alters the protein?s amino acid sequence beginning at po sition 984 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Bial lelic loss of function variants have been reported in several infertile males wi th spermatogenic failure. In summary, although additional studies are required t o fully establish its clinical significance, the p.Lys984SerfsX3 variant is like ly pathogenic. ACMG/AMP criteria applied: PVS1, PM2. |