ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.820dup (p.Thr274fs) (rs1555461611)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657281 SCV000779012 likely pathogenic not provided 2017-01-03 criteria provided, single submitter clinical testing This duplication of one nucleotide in PALB2 is denoted c.820dupA at the cDNA level and p.Thr274AsnfsX9 (T274NfsX9) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ACTT[dupA]CTAC. The duplication causes a frameshift which changes a Threonine to an Asparagine at codon 274, and creates a premature stop codon at position 9 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this duplication to be a likely pathogenic variant.
Ambry Genetics RCV001027286 SCV001189821 pathogenic Hereditary cancer-predisposing syndrome 2019-08-16 criteria provided, single submitter clinical testing The c.820dupA pathogenic mutation, located in coding exon 4 of the PALB2 gene, results from a duplication of A at nucleotide position 820, causing a translational frameshift with a predicted alternate stop codon (p.T274Nfs*9). This alteration has been reported with a carrier frequency of 0.00014 in 7051 unselected breast cancer patients and 0 in 11241 female controls of Japanese ancestry (Momozawa et al. Nat Commun 2018 10;9(1):4083). 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.
Cancer Genomics Group,Japanese Foundation For Cancer Research RCV001030717 SCV001193685 likely pathogenic Hereditary breast and ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
Leiden Open Variation Database RCV000657281 SCV001193024 pathogenic not provided 2018-10-10 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.

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