The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document


CA32686049

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: e051c567-315e-4453-b53d-b15598584fe9

HGVS expressions

NM_000261.2:c.879G>A
NC_000001.11:g.171636561C>T
CM000663.2:g.171636561C>T
NC_000001.10:g.171605701C>T
CM000663.1:g.171605701C>T
NC_000001.9:g.169872324C>T
NG_008859.1:g.21073G>A
ENST00000037502.11:c.879G>A
ENST00000637303.1:c.235-2069C>T
ENST00000638471.1:c.*217G>A
ENST00000037502.10:c.879G>A
ENST00000614688.1:c.879G>A
NM_000261.1:c.879G>A

Uncertain Significance

Met criteria codes 3
BP7 PM2_Supporting BP4
Not Met criteria codes 12
PM5 PM4 PS2 PS1 PS3 PS4 PM6 BA1 BS3 BS1 PP1 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Glaucoma Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.879G>A variant in MYOC is a synonymous variant (p.Thr293=). The highest minor allele frequency of this variant was in the African/African American population of gnomAD (v3.1.2) = 0.00009656 (4 alleles out of 41,426), which met 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) = 0.036 which met the ≤ 10 threshold for BP4, and the GERP score = -11.3 (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 proband with primary open angle glaucoma had been reported (PMID: 22933836), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of -1 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, PM2_Supporting.
Met criteria codes
BP7
This synonymous/non-coding variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2) and had a GERP score = -11.3 (threshold < 0), indicating a lack of conservation at this site.
PM2_Supporting
The highest minor allele frequency of this variant was in the African/African American population of gnomAD (v3.1.2) = 0.00009656 (4 alleles out of 41,426), which met the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles.
BP4
The CADD score (v1.6) = 0.036, which met the ≤ 10 threshold for BP4 and this variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), suggesting that the variant does not impact MYOC function.
Not Met criteria codes
PM5
This is not a missense variant.
PM4
This variant does not cause a protein length change.
PS2
This variant has not been identified de novo.
PS1
This variant does not involve an amino acid change.
PS3
No functional evidence has been found for this variant.
PS4
Only 1 proband with POAG had been reported (PMID: 22933836), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting.
PM6
This variant has not been identified de novo.
BA1
This criterion was not met as PM2_Supporting has been met.
BS3
No functional evidence has been found for this variant.
BS1
This criterion was not met as PM2_Supporting has been met.
PP1
No segregations have been reported for this variant.
PP3
This is not a missense variant.
Approved on: 2023-06-01
Published on: 2023-06-01
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