Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000635924 | SCV000757351 | pathogenic | Familial cancer of breast | 2022-03-14 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the PALB2 protein in which other variant(s) (p.Tyr1183*) have been determined to be pathogenic (PMID: 17200668, 17200671, 19609323, 21365267, 22241545, 26315354). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 530199). This sequence change creates a premature translational stop signal (p.Ser1165*) in the PALB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 22 amino acid(s) of the PALB2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. |
| Ambry Genetics | RCV003303005 | SCV004007936 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-06 | criteria provided, single submitter | clinical testing | The p.S1165* variant (also known as c.3494C>A), located in coding exon 13 of the PALB2 gene, results from a C to A substitution at nucleotide position 3494. This changes the amino acid from a serine to a stop codon within coding exon 13. This alteration occurs at the 3' terminus of thePALB2 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 22 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Myriad Genetics, |
RCV000635924 | SCV004189396 | pathogenic | Familial cancer of breast | 2023-09-15 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| Baylor Genetics | RCV000635924 | SCV004202748 | likely pathogenic | Familial cancer of breast | 2022-04-13 | criteria provided, single submitter | clinical testing | |
| CZECANCA consortium | RCV001270994 | SCV001451806 | pathogenic | Breast and/or ovarian cancer | 2019-06-11 | no assertion criteria provided | case-control |