Evidence Repository
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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Variant: NM_000261.2:c.1447G>T

CA343723116

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0add327e-fa1d-4577-8fcf-edcb4817a061
Approved on: 2023-04-04
Published on: 2023-04-04

HGVS expressions

NM_000261.2:c.1447G>T
NC_000001.11:g.171635993C>A
CM000663.2:g.171635993C>A
NC_000001.10:g.171605133C>A
CM000663.1:g.171605133C>A
NC_000001.9:g.169871756C>A
NG_008859.1:g.21641G>T
ENST00000037502.11:c.1447G>T
ENST00000637303.1:c.235-2637C>A
ENST00000638471.1:c.*785G>T
ENST00000037502.10:c.1447G>T
ENST00000614688.1:c.*411G>T
NM_000261.1:c.1447G>T

Uncertain Significance

Met criteria codes 2
PM4_Supporting PM2_Supporting
Not Met criteria codes 13
BS3 BS1 BP7 BP4 PS2 PS1 PS3 PS4 BA1 PP1 PP3 PM5 PM6

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.1447G>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 Methionine at amino acid 483. This variant is predicted to cause a deletion of < 10% of the protein within the conserved olfactomedin domain, meeting PM4_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. There was no computational or 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: 10196380), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 2 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, PM4_Supporting.
Met criteria codes
PM4_Supporting
This truncating variant is predicted to cause a deletion of ≤ 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
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.
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: 10196380), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting.
BA1
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.
PM5
This is not a missense variant.
PM6
This variant has not been identified de novo.
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