ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.1653T>A (p.Tyr551Ter) (rs118203997)

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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 RCV000217204 SCV000273333 pathogenic Hereditary cancer-predisposing syndrome 2018-06-07 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
GeneDx RCV000235772 SCV000293130 pathogenic not provided 2018-11-05 criteria provided, single submitter clinical testing This variant is denoted PALB2 c.1653T>A at the cDNA level and p.Tyr551Ter (Y551X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAT>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 in the heterozygous state in individuals with a personal and family history of breast and/or pancreatic cancer as well as in trans with a partial PALB2 gene deletion in an individual with Fanconi Anemia (Xia 2007, Jones 2009, Casadei 2011, Blanco 2013). We consider this variant to be pathogenic.
Invitae RCV000476387 SCV000550804 pathogenic Familial cancer of breast 2019-09-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr551*) 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 affected with breast and/or ovarian cancer, and with Fanconi anemia (PMID: 17200672, 23935836, 21285249). ClinVar contains an entry for this variant (Variation ID: 1243). 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.
Color RCV000217204 SCV000685893 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000235772 SCV001150871 likely pathogenic not provided 2017-01-01 criteria provided, single submitter clinical testing
OMIM RCV000001302 SCV000021452 pathogenic Fanconi anemia, complementation group N 2007-02-01 no assertion criteria provided literature only
Leiden Open Variation Database RCV000235772 SCV001193131 pathogenic not provided 2019-05-13 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Johan de Winter, LOVD-team, but with Curator vacancy, Marc Tischkowitz.

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