Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001218361 | SCV001390241 | likely pathogenic | Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome | 2019-06-16 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID:9475094). Disruption of this splice site has been observed in individuals affected with clinical features of WT1-related disorders (PMID: 9475094, 16717397, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in the last intron (intron 9) of the WT1 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. |