A synonymous germline variant PALB2 c.18G>T (p.Gly6=) disrupts normal splicing in a family with pancreatic and breast cancers
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Mutations in PALB2 have been associated with a predisposition to breast and pancreatic cancers. This study aims to characterize a novel PALB2 synonymous variant c.18G>T (p.Gly6=) identified in a family with pancreatic and breast cancers.
The PALB2 c.18G>T (p.Gly6=) variant in this family was identified using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT™). RT-PCR and subsequent cloning were performed to investigate whether this variant affects normal splicing.
This variant completely disrupts normal splicing and leads to several abnormal transcripts, which presumably leads to premature protein truncation. The major abnormal transcript resulted in a deletion of 32 base pairs in exon 1 and frameshift.
Our results indicate that the PALB2 c.18G>T (p.Gly6=) variant is likely pathogenic. This study provided important laboratory evidence for classification of this variant and guided improved patient management.
KeywordsSynonymous germline variant PALB2 Splicing
This study was funded by Department of Pathology, Memorial Sloan Kettering Cancer Center.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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