Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000507280 | SCV000601794 | pathogenic | not provided | 2020-03-15 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, 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 found in general population data at a frequency that is consistent with pathogenicity. |
Invitae | RCV000535566 | SCV000633465 | pathogenic | Familial cancer of breast | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu21*) 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 variant is present in population databases (rs769240800, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 439237). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV000575810 | SCV000666926 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-03-08 | criteria provided, single submitter | clinical testing | The p.L21* pathogenic mutation (also known as c.62T>G), located in coding exon 2 of the PALB2 gene, results from a T to G substitution at nucleotide position 62. This changes the amino acid from a leucine to a stop codon within coding exon 2. 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. |
Gene |
RCV000507280 | SCV000680908 | pathogenic | not provided | 2023-04-21 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32581362, 30799775, 17200668, 17200671, 17200672, 24136930, 25099575, 29922827, 29909963) |
Academic Department of Medical Genetics, |
RCV000575810 | SCV000992221 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-01-26 | criteria provided, single submitter | research | Application of AMCG guidelines 2015. Used other ClinVar submission evidence where relevant. Loss of heterozygosity in tumours or immunohistochemistry abnormalities considered functional evidence of pathogenicity. |
Color Diagnostics, |
RCV000575810 | SCV001354811 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-10-12 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 2 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 been reported in one individual affected with breast cancer in the literature (PMID: 29909963). This variant has been identified in 2/251470 chromosomes 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. |
Sema4, |
RCV000575810 | SCV002531207 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-08-10 | criteria provided, single submitter | curation | |
Myriad Genetics, |
RCV000535566 | SCV004189378 | pathogenic | Familial cancer of breast | 2023-09-05 | 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 | RCV000535566 | SCV004202629 | pathogenic | Familial cancer of breast | 2023-05-22 | criteria provided, single submitter | clinical testing |