Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV003476607 | SCV004202709 | likely pathogenic | Familial cancer of breast | 2022-09-29 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003476607 | SCV004504967 | uncertain significance | Familial cancer of breast | 2023-02-23 | criteria provided, single submitter | clinical testing | Experimental studies have shown that sequence changes at this splice site disrupt the consensus splice site and strengthen a cryptic acceptor site in exon 2, located 6 nucleotides downstream of the natural splice site. This results in an alternative transcript with an in-frame deletion of 2 amino acids, which do not affect known functional domains and/or critical residues (PMID: 30890586). Also, this alternative transcript has been shown to occur naturally in healthy individuals (PMID: 30890586). These studies suggest that the clinical significance of this splice variant may be uncertain. Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in exon 2 (PMID: 34846068). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Disruption of this splice site has been observed in individual(s) with breast cancer and/or colorectal cancer (PMID: 25452441, 29478780). This sequence change affects an acceptor splice site in intron 1 of the PALB2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the loss of 2 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). |