ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.2323C>T (p.Gln775Ter) (rs180177111)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164897 SCV000215584 pathogenic Hereditary cancer-predisposing syndrome 2017-03-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000164897 SCV000905027 pathogenic Hereditary cancer-predisposing syndrome 2018-04-25 criteria provided, single submitter clinical testing
Counsyl RCV000114521 SCV000677768 pathogenic Familial cancer of breast 2015-05-01 criteria provided, single submitter clinical testing
GeneDx RCV000413982 SCV000490685 pathogenic not provided 2015-08-12 criteria provided, single submitter clinical testing This pathogenic variant is denoted PALB2 c.2323C>T at the cDNA level and p.Gln775Ter (Q775X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported as a French Canadian founder pathogenic variant and has been observed in multiple women with a personal and/or family history of hereditary breast and ovarian cancer (Catucci 2014, Tischkowitz 2013, Ghadirian 2009, Foulkes 2007) and is considered pathogenic.
Invitae RCV000114521 SCV000218806 pathogenic Familial cancer of breast 2018-12-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln775*) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals with breast cancer (PMID: 23302520, 23341105, 19863560, 18053174). ClinVar contains an entry for this variant (Variation ID: 126646). Experimental in vitro studies have shown that this nonsense variant results in defective DNA repair (PMID: 24485656). Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 24136930, 25099575). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000144702 SCV000190686 risk factor Breast cancer, susceptibility to 2007-01-01 no assertion criteria provided literature only
PALB2 database RCV000114521 SCV000148467 pathogenic Familial cancer of breast 2012-07-16 no assertion criteria provided literature only

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