Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
MGZ Medical Genetics Center | RCV000030724 | SCV002580058 | pathogenic | Wiedemann-Steiner syndrome | 2022-05-31 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000030724 | SCV000053385 | pathogenic | Wiedemann-Steiner syndrome | 2012-08-10 | no assertion criteria provided | literature only | |
Clinical Genomics Laboratory, |
RCV000030724 | SCV004101780 | pathogenic | Wiedemann-Steiner syndrome | 2021-03-16 | no assertion criteria provided | clinical testing | The p.Arg2382* variant in the KMT2A gene has been previously reported de novo in 1 individual with Wiedemann-Steiner syndrome (Jones et al., 2012). This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The p.Arg2382* variant leads to a premature stop codon in exon 27 of 36 coding exons, and is therefore predicted to undergo nonsense-mediated decay resulting in a truncated or absent protein. Heterozygous loss of function is an established mechanism of disease for the KMT2A gene. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Arg2382* variant as pathogenic for autosomal dominant Wiedemann-Steiner syndrome based on the information above. [ACMG evidence codes used: PVS1; PS2; PM2] |