ClinVar

Description

This variant is a gross deletion of the genomic region encompassing the last exon of the PALB2 gene. The 5' boundary is likely confined to intron 12. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated PALB2 protein. Loss-of-function variants and gross deletions in PALB2 are known to be pathogenic. A deletion of exon 13 has been reported in the literature in an individual with breast cancer (PMID: 25099575). Exon 13 encodes two WD40-like repeat motifs in the PALB2 gene. WD40 motifs are required for interaction with the BRCA2 protein (PMID: 16793542, 19609323). In vitro experiments have shown that loss of either of the two WD40 repeats encoded by exon 13 affects PALB2-BRCA2 interaction (PMID: 19423707). This exonic deletion is likely to truncate the PALB2 protein and abolish its DNA repair function. For these reasons, this variant has been classified as Pathogenic.