Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Breda Genetics srl | RCV001353094 | SCV001548212 | likely pathogenic | Kabuki syndrome 1 | 2019-01-17 | criteria provided, single submitter | clinical testing | The variant c.12039_12046del (p.Ala4014Serfs*23) creates a shift in the reading frame which is predicted to result in a premature stop codon 23 amino acids downstream. This variant is likely to result in a truncated protein or protein loss due to nonsense-mediated messenger decay (NMD). This variant has not been reported in dbSNP, gnomAD, 1000 Genomes, NHLI Exome Sequencing Project (ESP) or ClinVar. The majority of pathogenic variants are nonsense and frameshift (72%), followed by missense variants (16%), splice-site variants (9%), and in-frame deletions/insertions (3%). The proportion of KMT2D-related Kabuki syndrome caused by de novo variants is likely high (Adam et al., 2013; PMID: 21882399). |