Submissions for variant NM_000261.2(MYOC):c.1024A>G (p.Arg342Gly)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV003148605	SCV003836519	uncertain significance	Open-angle glaucoma	2023-02-15	reviewed by expert panel	curation	The c.1024A>G variant in MYOC is a missense variant predicted to cause substitution of Arginine by Glycine at amino acid 342 (p.Arg342Gly). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0001631 (3 alleles out of 18,392), which did not meet the PM2_Supporting allele frequency threshold (<=0.0001) or the BS1 allele frequency threshold (>=0.001). The REVEL score = 0.59, 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. Although probands with primary open angle glaucoma have 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