Classification rationale
PM2
BP4BP7
Likely Benign
PALB2 c.1578T>C
The PALB2 c.1578T>C (p.His526=) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar with benign or likely benign single-submitter classifications.1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, placing its observed population frequency at 0%, below the PALB2 PM2_Supporting threshold of 0.000333%.2 In silico splice prediction shows no evidence of splice disruption, with a SpliceAI maximum delta score of 0.00; this is below the PALB2 BP4 threshold of 0.1 and well below the PP3 threshold of 0.2, supporting BP4 and BP7 rather than PP3.3
PM2 + BP4 + BP7
→
Likely Benign
