Submissions for variant NM_000261.2(MYOC):c.780A>G (p.Ala260=)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV003148616	SCV003836530	likely benign	Open-angle glaucoma	2023-02-15	reviewed by expert panel	curation	The c.780A>G variant in MYOC is a synonymous variant (p.Ala260=). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0002182 (4 alleles out of 18,334), which did not meet the PM2_Supporting allele frequency threshold (<=0.0001) or the BS1 allele frequency threshold (>=0.001). This variant was not predicted to affect splicing, as assessed with SpliceAI (<=0.2), with a CADD score (v1.6) = 0.319 which met the <=10 threshold for BP4, and the GERP score = -11.5 (threshold < 0), indicating a lack of conservation at this site (BP7). This evidence suggests that the variant does not impact 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 met the criteria to receive a score of -2 and to be classified as likely benign (likely benign classification range -2 to -6) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BP4, BP7