Submissions for variant NM_000261.2(MYOC):c.644T>C (p.Leu215Pro)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV003148602	SCV003836516	likely benign	Open-angle glaucoma	2023-02-15	reviewed by expert panel	curation	The c.644T>C variant in MYOC is a missense variant predicted to cause substitution of Leucine by Proline at amino acid 215 (p.Leu215Pro). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.001002, which met the >=0.001 threshold set for BS1 (20 alleles out of 19,954), meeting the threshold of >=5 of at least 2,000 observed alleles). The REVEL score = 0.724, 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. As BS1 was met, PP1 did not apply and segregations were not counted. Although probands with juvenile or 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 -3 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): BS1, PP3.