Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000578504 | SCV000680816 | likely pathogenic | not provided | 2017-06-16 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the KMT2C gene. The R1481X variant has been reported previously as apparently de novo in an individual with intellectual disability, hypotonia, behavioral problems, and additional features resembling Kleefstra syndrome (Kleefstra et al., 2012). This variant is a nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease. It is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Therefore, the R1481X variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| SIB Swiss Institute of Bioinformatics | RCV000074464 | SCV000787474 | likely pathogenic | Kleefstra syndrome 2 | 2018-04-16 | criteria provided, single submitter | curation | This variant is interpreted as a Likely Pathogenic, for Kleefstra syndrome 2, Autosomal Dominant inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PVS1-Moderate => PVS1 downgraded in strength to Moderate. PM6 => Assumed de novo, but without confirmation of paternity and maternity. |
| OMIM | RCV000074464 | SCV000108480 | pathogenic | Kleefstra syndrome 2 | 2012-07-13 | no assertion criteria provided | literature only |