Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001030317 | SCV001576118 | likely pathogenic | Familial cancer of breast | 2023-08-10 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 5 of the PALB2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. 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: 19264984, 21285249). ClinVar contains an entry for this variant (Variation ID: 126657). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of this splice site affects PALB2 function (PMID: 30890586). Studies have shown that disruption of this splice site results in skipping of 6, but is expected to preserve the integrity of the reading-frame (PMID: 21285249, 26990772, 30890586; Invitae). 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 | RCV002426654 | SCV002744293 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-27 | criteria provided, single submitter | clinical testing | The c.2515-1G>T intronic variant results from a G to T substitution one nucleotide upstream from coding exon 6 of the PALB2 gene. This alteration has been detected in patients with familial pancreatic cancer and familial breast cancer (Jones S et al. Science, 2009 Apr;324:217; Casadei S et al. Cancer Res., 2011 Mar;71:2222-9; Antoniou AC et al. N. Engl. J. Med., 2014 Aug;371:497-506). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). 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. |
| Baylor Genetics | RCV001030317 | SCV004202707 | pathogenic | Familial cancer of breast | 2022-10-26 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000001312 | SCV000021462 | risk factor | Pancreatic cancer, susceptibility to, 3 | 2009-04-10 | no assertion criteria provided | literature only | |
| SNPedia | RCV000133479 | SCV000188553 | pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Pathogenic. | |
| Leiden Open Variation Database | RCV001030317 | SCV001193244 | likely pathogenic | Familial cancer of breast | 2019-05-13 | no assertion criteria provided | curation | Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz. |
| King Laboratory, |
RCV001171466 | SCV001251377 | pathogenic | Familial cancer of breast; Hereditary cancer-predisposing syndrome | 2019-09-01 | no assertion criteria provided | research |