Submissions for variant NM_000261.2(MYOC):c.1188G>A (p.Glu396=)

gnomAD frequency: 0.00852  dbSNP: rs61730975

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV002248513	SCV002520354	benign	Glaucoma 1, open angle, E	2022-05-09	reviewed by expert panel	curation	The c.1188G>A variant in MYOC is a synonymous variant (p.Glu396=). The highest minor allele frequency of this variant was in the African/African American population of gnomAD (v2.1.1) = 0.02893, which met the >= 0.01 threshold set for BA1 (722 alleles out of 24,958, 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) = 0.360 which met the <= 10 threshold for BP4, and the GERP score = -4.66 (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 POAG have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant was classified as benign (BA1 is a stand-alone criterion for a benign level of pathogenicity) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BA1, BP4, BP7
Illumina Laboratory Services, Illumina	RCV000337368	SCV000351276	likely benign	Glaucoma	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000397533	SCV000351277	benign	Glaucoma 1, open angle, A	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000972663	SCV001120386	benign	not provided	2024-05-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000972663	SCV001753203	likely benign	not provided	2021-03-17	criteria provided, single submitter	clinical testing