Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001218361 | SCV001390241 | pathogenic | Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome | 2024-02-23 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 9 of the WT1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the loss of 3 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with WT1-related conditions (PMID: 9475094, 16717397, 33565430; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 947309). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in intron 9 (PMID: 9475094). For these reasons, this variant has been classified as Pathogenic. |