The c.104T>C variant in PALB2 is a missense variant predicted to cause substitution of leucine by proline at amino acid 35 (p.Leu35Pro). This variant is absent in gnomAD v2.1.1. The variant has been reported to segregate with breast cancer in 3 affected family members from one family (PMID: 28319063). This variant is non-functional in multiple protein assays (PMID: 31586400; 31636395; 31757951); however, due to a lack of positive missense controls with known clinical impact, these assays do not meet the requirements for use by the HBOP VCEP. PALB2, in which the variant was identified, is defined by the HBOP VCEP as a gene for which primarily truncating variants are known to cause disease. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for a autosomal dominant hereditary breast and pancreatic cancer and autosomal recessive FANCN based on the ACMG/AMP criteria applied as specified by the HBOP VCEP. (PM2_Supporting, PP1, BP1)