The c.1515A>G variant in MYOC is a single nucleotide change, predicted to substitute the terminating codon by Tryptophan and extending the protein by an additional 42 amino acids (p.Ter505TrpextTer42). This variant is predicted to involve < 10% of the protein within the conserved olfactomedin domain, meeting PM4_Supporting. This variant was not found in any population of gnomAD (v2.1.1), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. There was no computational or functional evidence predicting a damaging or benign impact of this variant on MYOC function. 20 segregations in 1 family, with juvenile or primary open angle glaucoma (JOAG or POAG), have been reported (PMID: 34923728), which fulfilled PP1_Moderate (≥ 5 meioses in ≥ 1 family, but not the ≥ 7 meioses in > 1 family for the strong criterion). Only 1 proband with JOAG had been reported (PMID: 34923728), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 4 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PP1_Moderate, PM2_Supporting, PM4_Supporting.