Variant: NM_000261.2(MYOC):c.343G>T (p.Glu115Ter)

CA343718634

631579 (ClinVar)

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

UUID: 07bc3f4b-ace5-479d-b58e-d87184f9a968

Approved on: 2023-08-08

Published on: 2023-08-08

HGVS expressions

NM_000261.2:c.343G>T
NM_000261.2(MYOC):c.343G>T (p.Glu115Ter)
NC_000001.11:g.171652269C>A
CM000663.2:g.171652269C>A
NC_000001.10:g.171621409C>A
CM000663.1:g.171621409C>A
NC_000001.9:g.169888032C>A
NG_008859.1:g.5365G>T
ENST00000037502.11:c.343G>T
ENST00000638471.1:c.130+213G>T
ENST00000037502.10:c.343G>T
ENST00000614688.1:c.343G>T
NM_000261.1:c.343G>T

Uncertain Significance

• Met criteria codes: PM2_Supporting

• Not Met criteria codes: BS3 BS1 BP7 BP4 BA1 PS4 PS2 PS1 PS3 PP1 PP3 PM5 PM4 PM6

Expert Panel

Glaucoma VCEP

Criteria Specification Information

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

Evidence submitted by expert panel

Glaucoma VCEP

The c.343G>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 115 (p.Glu115Ter). Truncation of this protein occurs outside of the conserved olfactomedin domain, which did not meet PM4. The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v3.1.2) = 0.00001470 (1 allele out of 68,036), which met 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 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): PM2_Supporting

Met criteria codes

• PM2_Supporting: The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v3.1.2) = 0.00001470 (1 allele out of 68,036), which met the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles.

Not Met criteria codes

• BS3: No functional evidence has been found for this variant.
• BS1: This criterion was not met as PM2_Supporting has been met.
• BP7: This is not a synonymous or non-coding variant.
• BP4: This is not a missense, synonymous or non-coding variant.
• BA1: This criterion was not met as PM2_Supporting has been met.
• 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.
• PM4: Truncation of this protein occurs outside of the conserved olfactomedin domain, which did not meet PM4.
• PM6: This variant has not been identified de novo.