Submissions for variant NM_000261.2(MYOC):c.1009del (p.Gln337fs)

dbSNP: rs2102944704

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV001838866	SCV002098425	uncertain significance	Glaucoma of childhood	2022-02-20	reviewed by expert panel	curation	The c.1009delC variant in MYOC is a deletion of a single nucleotide, predicted to encode a frameshift with consequent premature termination of the protein at codon 9 of the frameshift, or amino acid 346 (p.Gln337ArgfsTer9). This variant is predicted to cause a deletion of >= 10% of the protein within the conserved olfactomedin domain (PM4). This variant was not found in any population of gnomAD (v2.1.1), meeting the <= 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. There was no computational or functional evidence predicting a damaging or benign impact of this variant on MYOC function. 14 segregations in 1 family, with juvenile or primary open angle glaucoma (JOAG or POAG), have been reported (PMID: 18776955), which fulfilled PP1_Moderate (>=5 meioses in >=1 family, but not the >=7 meioses in >1 family for the strong criterion). Only 1 proband with JOAG had been reported (PMID: 18776955), not meeting the >= 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 5 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PM4, PP1_Moderate, PM2_Supporting