The c.721A>G variant in PALB2 is a missense variant predicted to predicted to cause substitution of asparagine by aspartic acid at amino acid 241 (p.Asn241Asp). This variant has been observed in three homozygous individuals with no features of FANCN, a condition with full penetrance at an early age (Ambry Genetics). The highest population minor filtering allele frequency in gnomAD v2.1.1 is 0.005509 in the African population, which is higher than the HBOP VCEP threshold (>0.001) for BA1, and therefore meets this criterion. 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 benign for autosomal dominant hereditary breast and pancreatic cancer and autosomal recessive FANCN based on the ACMG/AMP criteria applied, as specified by the HBOP VCEP (BA1, BS2, BP1)