ClinVar

Description

The c.402A>G variant in MYOC is a synonymous variant (p.Gln134=). 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. The CADD score (v1.6) = 6.819, which met the <= 10 threshold for BP4 and this variant was not predicted to affect splicing, as assessed with SpliceAI (<= 0.2), suggesting that the variant does not impact MYOC function. However, BP7 was not met as this variant had a GERP score = 1.1 (threshold <0), indicating conservation at this site. 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 0 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, PM2_Supporting