Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000454187 | SCV000538162 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | The c.2850delC pathogenic mutation, located in coding exon 9 of the PALB2 gene, results from a deletion of one nucleotide at nucleotide position 2850, causing a translational frameshift with a predicted alternate stop codon (p.S951Lfs*11). This alteration was detected in multiple breast cancer and familial breast cancer cohorts (Damiola F et al. Breast Cancer Res. Treat., 2015 Dec;154:463-71; Sun J et al. Clin. Cancer Res., 2017 Oct;23:6113-6119; Wu Y et al. Breast Cancer Res. Treat., 2020 Feb;179:605-614). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284198 | SCV001469849 | pathogenic | not provided | 2020-08-04 | criteria provided, single submitter | clinical testing | The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data. |
Invitae | RCV001383427 | SCV001582568 | pathogenic | Familial cancer of breast | 2022-10-07 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser951Leufs*11) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 28724667, 30303537). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 402303). |
Myriad Genetics, |
RCV001383427 | SCV004189406 | pathogenic | Familial cancer of breast | 2023-09-14 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |