ClinVar

Description

The c.624C>G variant in MYOC is a missense variant predicted to cause substitution of Aspartic acid by Glutamic acid at amino acid 208 (p.Asp208Glu). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.007468, which met the >= 0.001 threshold set for BS1 (149 alleles out of 19,952, meeting the threshold of >= 5 of at least 2,000 observed alleles). The REVEL score = 0.126, which met the <= 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function. The studies reporting functional evidence (PMIDs: 27092720, 14688426) demonstrated that the Asp208Glu protein had similar secretion levels compared to wild type myocilin protein, but did not meet the OddsPath threshold (< 0.48) for BS3_Supporting to be applied. As BS1 was met, PP1 did not apply and segregations were not counted. Although probands with primary open angle glaucoma have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant met the criteria to receive a score of -5 and to be classified as likely benign (likely benign classification range -2 to -6) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BS1, BP4.