Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000584638 | SCV000690896 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 10 of the PALB2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Invitae | RCV000803999 | SCV000943889 | pathogenic | Familial cancer of breast | 2019-03-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 24136930, 25099575). This variant has not been reported in the literature in individuals with PALB2-related disease. ClinVar contains an entry for this variant (Variation ID: 492209). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln1023*) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001269180 | SCV001448464 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2020-11-19 | criteria provided, single submitter | clinical testing | Variant summary: PALB2 c.3067C>T (p.Gln1023X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251444 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3067C>T in individuals affected with Hereditary Breast and Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both of them classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |