ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.697del (p.Val233fs)

dbSNP: rs180177090
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000114653 SCV000260556 pathogenic Familial cancer of breast 2023-09-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 126764). This premature translational stop signal has been observed in individual(s) with pancreatic cancer and breast cancer (PMID: 19333784, 27106063). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val233Leufs*5) 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).
GeneDx RCV000481242 SCV000567726 pathogenic not provided 2022-04-28 criteria provided, single submitter clinical testing Observed in individuals with PALB2-related cancers (Sluiter 2009, Borecka 2016); Frameshift 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: 23935381, 20122277, 21932393, 20346647, 21165770, 19763884, 21618343, 24136930, 25099575, 17200668, 19333784, 27106063, 32295079, 20858716, 30263132)
Color Diagnostics, LLC DBA Color Health RCV000771207 SCV000903222 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 4 of the PALB2 gene, creating a frameshift and 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.
Ambry Genetics RCV000771207 SCV001188147 pathogenic Hereditary cancer-predisposing syndrome 2023-03-09 criteria provided, single submitter clinical testing The c.697delG pathogenic mutation, located in coding exon 4 of the PALB2 gene, results from a deletion of one nucleotide at nucleotide position 697, causing a translational frameshift with a predicted alternate stop codon (p.V233Lfs*5). This alteration has been reported in a South African woman with early onset breast cancer and a family history of pancreatic, colon and prostate cancers (Sluiter M et al. Fam. Cancer, 2009 Mar;8:347-53). This alteration was also reported in a cohort of 152 unselected Czech patients with pancreatic ductal adenocarcinoma and not in 1226 healthy controls (Borecka M et al. Cancer Genet, 2016 May;209:199-204). 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.
Myriad Genetics, Inc. RCV000114653 SCV004189334 pathogenic Familial cancer of breast 2023-09-07 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics RCV000114653 SCV004202790 pathogenic Familial cancer of breast 2021-04-06 criteria provided, single submitter clinical testing
Leiden Open Variation Database RCV000114653 SCV001193004 pathogenic Familial cancer of breast 2019-05-13 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.
CZECANCA consortium RCV001270997 SCV001451809 pathogenic Breast and/or ovarian cancer 2019-06-11 no assertion criteria provided clinical testing

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