ClinVar

Description

The c.865G>A variant in MYOC is a missense variant predicted to cause substitution of Aspartic Acid by Asparagine at amino acid 289 (p.Asp289Asn). The highest minor allele frequency of this variant , in a population of at least 10,000 alleles, was in the South Asian population of gnomAD (v2.1.1) = 0.00003296 (1 allele out of 30,342), which met the <= 0.0001 threshold set for PM2_Supporting. The REVEL score = 0.428, which was neither above nor below the thresholds for PP3 (>= 0.7) or BP4 (<= 0.15), predicting a damaging or benign impact on MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. This variant was identified in laboratory based testing, but has not yet been found in a proband with juvenile or primary open angle glaucoma, thus PS4 did not apply. 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): PM2_Supporting