Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000255848 | SCV000322537 | likely pathogenic | not provided | 2023-07-28 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate that variants affecting this canonical SAS lead to the deletion of exon 11 (Lopez-Perolio et al., 2019); This variant is associated with the following publications: (PMID: 33193564, 34439348, 30720863, 32068069, 32339256, 30890586, 28825143) |
| Labcorp Genetics |
RCV000551424 | SCV000633403 | likely pathogenic | Familial cancer of breast | 2024-06-18 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 10 of the PALB2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast cancer and/or pancreatic cancer (PMID: 28825143, 32068069, 32339256, 33193564, 35171259). ClinVar contains an entry for this variant (Variation ID: 265552). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Ambry Genetics | RCV000569707 | SCV000666942 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-27 | criteria provided, single submitter | clinical testing | The c.3114-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 11 of the PALB2 gene. This alteration has been detected in multiple Chinese breast cancer patients (Zhang K et al. Breast Cancer Res Treat, 2017 Dec;166:865-873; Deng M et al. Int J Cancer, 2019 09;145:1517-1528; Zhou J et al. Cancer, 2020 07;126:3202-3208; Kwong A et al. J Mol Diagn, 2020 04;22:544-554; Hu ZY et al. Front Genet, 2020 Aug;11:829). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Myriad Genetics, |
RCV000551424 | SCV004188434 | likely pathogenic | Familial cancer of breast | 2023-09-14 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
| Baylor Genetics | RCV000551424 | SCV004202697 | pathogenic | Familial cancer of breast | 2022-11-22 | criteria provided, single submitter | clinical testing |