ClinVar Miner

Submissions for variant NM_000261.2(MYOC):c.244C>T (p.Arg82Cys)

gnomAD frequency: 0.00008  dbSNP: rs764005392
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Glaucoma Variant Curation Expert Panel RCV001843367 SCV002102559 likely benign Glaucoma of childhood 2022-03-05 reviewed by expert panel curation The c.244C>T variant in MYOC is a missense variant predicted to cause substitution of Arginine by Cysteine at amino acid 82 (p.Arg82Cys). The highest minor allele frequency of this variant was in the Latino/Admixed American population of gnomAD (v2.1.1) = 0.0001695 (6 alleles out of 35 404), which did not meet the PM2_Supporting allele frequency threshold (<= 0.0001) or the BS1 allele frequency threshold (>= 0.001). The REVEL score = 0.268, which was neither above nor below the thresholds for PP3 (>= 0.7) or BP4 (<= 0.15), predicting a damaging or benign impact on MYOC function. A previous study (PMID: 16466712) demonstrated that the Arg82Cys protein had similar secretion levels to wild type myocilin protein and met the OddsPath threshold for BS3_Moderate (< 0.23), indicating that this variant did not impact protein function. Only 2 segregations had been reported in a family with mild glaucomatous disc changes (PMID: 11133859), not meeting the >= 3 segregations required for PP1. 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 -2 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): BS3_Moderate
PreventionGenetics, part of Exact Sciences RCV004733104 SCV005348777 likely benign MYOC-related disorder 2024-03-14 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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