ClinVar

Description

The c.1302C>T variant in MYOC is a synonymous variant (p.Gly434=). The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.0001307 (4 alleles out of 30,616), which did not meet the PM2_Supporting allele frequency threshold (<= 0.0001) or the BS1 allele frequency threshold (>= 0.001). Although this synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (<= 0.2), it had a CADD score (v1.6) = 10.12, which did not meet the <= 10 threshold for BP4 and a GERP score = 4.26 (threshold <0), not meeting BP7 and indicating conservation at this site. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Although a proband with primary open angle glaucoma had been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant did not meet any criteria, receiving a score of 0 and a classification 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): none