MYOC p.Pro13=

The c.39T>G variant in MYOC is a synonymous variant (p.Pro13=). The highest minor allele frequency of this variant was in the African/African-American genetic ancestry group of gnomAD (v4.1.0) = 0.07326, which met the ≥ 0.01 threshold set for BA1 (5,497 alleles out of 75032, meeting the threshold of ≥ 5 of at least 2,000 observed alleles). The SpliceAI score = 0, which met the ≤ 0.1 threshold for BP4, suggesting that the variant does not impact MYOC function. This synonymous variant meets BP4, so BP7 is met. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. As BA1 was met, PP1 did not apply and segregations were not counted. Although probands with juvenile or primary open angle glaucoma have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant was classified as benign (BA1 is a stand-alone criterion for a benign level of pathogenicity) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v2.0.0, 5 Dec 2024): BA1, BP4, BP7