The NM_177438.2:c.5276A>G variant in DICER1 is a missense variant predicted to cause substitution of Lysine by Arginine at amino acid 1759 (p.Lys1759Arg). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001071 in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2; Internal lab contributors: 61756, 500031). The computational predictor REVEL gives a score of 0.444, which is below the threshold of 0.5, and the splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4). This variant resides within the RNase IIIb domain of DICER1, that is defined as a mutational hotspot and critical functional domain by the ClinGen DICER1 VCEP (PMID: 31342592)(PM1_Supporting). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1 syndrome. Although there are both pathogenic and benign types of evidence for this variant, the pathogenic evidence is not considered inconsistent with the final classification. ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: (BS2, BP4, PM1_Supporting). (Bayesian Points: -4; VCEP specifications version 1; 02/11/2022).