Submissions for variant NM_000261.2(MYOC):c.56_72dup (p.Cys25fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV002306269	SCV002600126	uncertain significance	Glaucoma 1, open angle, E	2022-11-09	reviewed by expert panel	curation	The c.56_72dup variant in MYOC is predicted to cause a change in the length of the protein due to a duplication of 17 nucleotides which leads to a frameshift and termination of the protein at amino acid 89 (p.Cys25SerfsTer65). Truncation of this protein occurs outside of the conserved olfactomedin domain, which did not meet PM4. The highest minor allele frequency of this variant was in the African/African-American population of gnomAD (v2.1.1) = 0.0001231 (2 alleles out of 16,244), which did not meet the PM2_Supporting allele frequency threshold (<= 0.0001) or the BS1 allele frequency threshold (>= 0.001). There was no computational or functional evidence predicting a damaging or benign impact of this variant on MYOC function. Although a proband with primary open angle glaucoma had 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.