ClinVar Miner

Submissions for variant NM_000261.2(MYOC):c.1278C>T (p.Val426=)

dbSNP: rs1183498744
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Glaucoma Variant Curation Expert Panel RCV003226023 SCV003922091 uncertain significance Open-angle glaucoma 2023-05-02 reviewed by expert panel curation The c.1278C>T variant in MYOC is a synonymous variant (p.Val426=). 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. This variant was not predicted to affect splicing, as assessed with SpliceAI (<=0.2), with a CADD score (v1.6) = 0.173 which met the <=10 threshold for BP4, and the GERP score = -10.1 (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. Only 1 segregation had been reported for primary open angle glaucoma (personal communication from authors of PMID: 23922489), not meeting the >=3 segregations required for PP1. 2 probands with primary open angle glaucoma have been reported carrying this variant (PMID: 22736945 and personal communication with authors of PMID: 23922489), which met PS4_Supporting (>=2 probands). In summary, this variant met the criteria to receive a score of 0 and to be classified 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): BP4, BP7, PS4_Supporting, PM2_Supporting

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