The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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CA1244287

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: d6ea3e7b-6f2e-46d5-aec4-74afad983465
Approved on: 2023-02-15
Published on: 2023-02-15

HGVS expressions

NM_000261.2:c.382C>T
NC_000001.11:g.171652230G>A
CM000663.2:g.171652230G>A
NC_000001.10:g.171621370G>A
CM000663.1:g.171621370G>A
NC_000001.9:g.169887993G>A
NG_008859.1:g.5404C>T
ENST00000037502.11:c.382C>T
ENST00000638471.1:c.130+252C>T
ENST00000037502.10:c.382C>T
ENST00000614688.1:c.382C>T
NM_000261.1:c.382C>T

Uncertain Significance

The Expert Panel has overridden the computationally generated classification - "[unknown]"
Not Met criteria codes 15
BS3 BS1 BP7 BP4 PS3 PS2 PS1 PS4 PM5 PM4 BA1 PM6 PM2 PP1 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.382C>T variant in MYOC is a missense variant predicted to cause substitution of Arginine by Tryptophan at amino acid 128 (p.Arg128Trp). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0005437 (10 alleles out of 18,394), which did not meet the PM2_Supporting allele frequency threshold (≤ 0.0001) or the BS1 allele frequency threshold (≥ 0.001). The REVEL score = 0.207, 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. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Although probands 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.
Not Met criteria codes
BS3
No functional evidence has been found for this variant.
BS1
The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0005437 (10 alleles out of 18,394), which did not meet the ≥ 0.001 threshold set for BS1.
BP7
This is not a synonymous or non-coding variant.
BP4
The REVEL score = 0.207, which did not meet the ≤ 0.15 threshold required for BP4.
PS3
No functional evidence has been found for this variant.
PS2
This variant has not been identified de novo.
PS1
An established pathogenic variant causing this same amino acid change has not been identified.
PS4
Although probands with JOAG/POAG had been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply.
PM5
No other missense variants at this amino acid residue have been identified.
PM4
This variant does not cause a protein length change.
BA1
This variant did not meet the ≥ 0.01 minor allele frequency threshold in gnomAD (v2.1.1).
PM6
This variant has not been identified de novo.
PM2
The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0005437 (10 alleles out of 18,394), which did not meet the ≤ 0.0001 threshold set for PM2_Supporting.
PP1
No segregations have been reported for this variant.
PP3
The REVEL score = 0.207, which did not meet the ≥ 0.7 threshold for PP3.
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