ClinVar

Description

The c.1463C>T variant in MYOC is a missense variant predicted to cause substitution of Alanine by Valine at amino acid 488 (p.Ala488Val). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0002719 (5 alleles out of 18,386), which did not meet the PM2_Supporting allele frequency threshold (<= 0.0001) or the BS1 allele frequency threshold (>= 0.001). The REVEL score = 0.715, which met the >= 0.7 threshold for PP3, predicting a damaging effect on MYOC function. 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 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): PP3.