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Variant: NM_000261.2(MYOC):c.898G>T (p.Glu300Ter)

CA343725609

1324771 (ClinVar)

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: f7946c80-7560-4c25-bb27-9540ec12a470

HGVS expressions

NM_000261.2:c.898G>T
NM_000261.2(MYOC):c.898G>T (p.Glu300Ter)
NC_000001.11:g.171636542C>A
CM000663.2:g.171636542C>A
NC_000001.10:g.171605682C>A
CM000663.1:g.171605682C>A
NC_000001.9:g.169872305C>A
NG_008859.1:g.21092G>T
ENST00000037502.11:c.898G>T
ENST00000637303.1:c.235-2088C>A
ENST00000638471.1:c.*236G>T
ENST00000037502.10:c.898G>T
ENST00000614688.1:c.898G>T
NM_000261.1:c.898G>T

Uncertain Significance

Met criteria codes 2
PM4 PM2_Supporting
Not Met criteria codes 13
PS4 PS2 PS1 PS3 PP1 PP3 PM5 PM6 BA1 BS3 BS1 BP4 BP7

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.898G>T variant in MYOC is predicted to cause a change in the length of the protein due to the insertion of a terminating codon instead of the usual Glutamic Acid at amino acid 300 (p.Glu300Ter). This variant is predicted to cause a deletion of ≥ 10% of the protein within the conserved olfactomedin domain, meeting 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. This variant was identified in laboratory based testing, but has not yet been found in a proband with juvenile or primary open angle glaucoma, thus PS4 did not apply. In summary, this variant met the criteria to receive a score of 3 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): PM4, PM2_Supporting
Met criteria codes
PM4
This truncating variant is predicted to cause a deletion ≥ 10% of the protein and is within the conserved olfactomedin domain.
PM2_Supporting
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.
Not Met criteria codes
PS4
This variant was identified in laboratory based testing, but has not yet been found in a proband with juvenile or primary open angle glaucoma.
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.
PP1
No segregations have been reported for this variant.
PP3
This is not a missense variant.
PM5
This is not a missense variant.
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.
BP4
This is not a missense, synonymous or non-coding variant.
BP7
This is not a synonymous or non-coding variant.
Approved on: 2023-06-01
Published on: 2023-06-01
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