ClinVar

Description

The c.1041T>C variant in MYOC is a synonymous variant (p.Tyr347=). The highest minor allele frequency of this variant was in the Ashkenazi Jewish population of gnomAD (v2.1.1) = 0.08597, which met the >= 0.01 threshold set for BA1 (891 alleles out of 10,364, meeting the threshold of >= 5 of at least 2,000 observed alleles). This variant was not predicted to affect splicing, as assessed with SpliceAI (<= 0.2), with a CADD score (v1.6) = 0.087 which met the <= 10 threshold for BP4, and the GERP score = -6 (threshold < 0), indicating a lack of conservation at this site (BP7). This evidence suggests that the variant does not impact 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 (v1, 12 Oct 2021): BA1, BP4, BP7.