ClinVar Genomic variation as it relates to human health

The c.384G>C variant in MYOC is a synonymous variant (p.Arg128=). 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. This variant was not predicted to affect splicing, as assessed with SpliceAI (<= 0.2), with a CADD score (v1.6) = 7.875 which met the <= 10 threshold for BP4, and the GERP score = -1.02 (threshold < 0), indicating a lack of conservation at this site (BP7). This evidence suggests that the variant does not impact MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Only 1 proband with primary open angle glaucoma had been reported (PMID: 16148883), not meeting the >= 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of -1 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BP4, BP7, PM2_Supporting.