Submissions for variant NM_000261.2(MYOC):c.366C>T (p.Gly122=)

gnomAD frequency: 0.00244  dbSNP: rs145354114

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV001824125	SCV002073862	likely benign	Glaucoma of childhood	2022-02-07	reviewed by expert panel	curation	The c.366C>T variant in MYOC is a synonymous variant (p.Gly122=). The highest allele frequency of this variant was in the Ashkenazi Jewish population of gnomAD (v2.1.1) = 0.005694 , which met the >= 0.001 threshold set for BS1 (59 alleles out of 10,362, meeting the threshold of >= 5 of at least 2,000 observed alleles). This variant was not predicted to affect splicing, as assessed with SpliceAI (<= 0.2), with a CADD score (v1.6) = 0.347 which met the <= 10 threshold for BP4, and the GERP score = -3.49 (threshold < 0), indicating a lack of conservation at this site (BP7). This evidence suggests that the variant does not impact 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 -6 and to be classified as likely benign (likely benign classification range -2 to -6) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BS1, BP4, BP7.
Eurofins Ntd Llc (ga)	RCV000173090	SCV000224174	uncertain significance	not provided	2014-10-03	criteria provided, single submitter	clinical testing
Invitae	RCV000173090	SCV001106949	benign	not provided	2024-01-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001096966	SCV001253217	benign	Glaucoma 1, open angle, A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
PreventionGenetics, part of Exact Sciences	RCV003895175	SCV004711112	benign	MYOC-related condition	2019-06-10	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).