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


Variant: NM_000261.2(MYOC):c.136C>T (p.Arg46Ter)

CA119179

7955 (ClinVar)

Gene: MYOC
Condition: juvenile open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: c3c20a7a-2e05-45a0-96c4-be750b6f69f7

HGVS expressions

NM_000261.2:c.136C>T
NM_000261.2(MYOC):c.136C>T (p.Arg46Ter)
NC_000001.11:g.171652476G>A
CM000663.2:g.171652476G>A
NC_000001.10:g.171621616G>A
CM000663.1:g.171621616G>A
NC_000001.9:g.169888239G>A
NG_008859.1:g.5158C>T
ENST00000037502.11:c.136C>T
ENST00000638471.1:c.130+6C>T
ENST00000037502.10:c.136C>T
ENST00000614688.1:c.136C>T
NM_000261.1:c.136C>T

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 1
BS1
Not Met criteria codes 14
BA1 BS3 BP4 BP7 PS2 PS1 PS3 PS4 PP3 PP1 PM6 PM2 PM5 PM4

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.136C>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 Arginine at amino acid 46. 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 East Asian population of gnomAD (v2.1.1) = 0.009224, which met the ≥ 0.001 threshold set for BS1 (184 alleles out of 19 948, meeting the threshold of ≥ 5 of at least 2,000 observed alleles). There was no computational or functional evidence predicting a damaging or benign impact of this variant on MYOC function. As BS1 was met, PP1 did not apply and segregations were not counted. Although probands with juvenile or primary open angle glaucoma have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant met the criteria to receive a score of -4 and to be classified as likely benign (likely benign classification range -2 to -6) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BS1
Met criteria codes
BS1
The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.009224, which met the ≥ 0.001 threshold set for BS1 (184 alleles out of 19 948, meeting the threshold of ≥ 5 of at least 2,000 observed alleles).
Not Met criteria codes
BA1
This criterion was not met as BS1 has been met.
BS3
No functional evidence has been found for this variant.
BP4
This is not a missense, synonymous or non-coding variant.
BP7
This is not a 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
Although probands with POAG or JOAG have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply.
PP3
This is not a missense variant.
PP1
As BS1 was met, PP1 did not apply and segregations were not counted.
PM6
This variant has not been identified de novo.
PM2
This criterion was not met as BS1 has been met.
PM5
This is not a missense variant.
PM4
Truncation of this protein occurs outside of the conserved olfactomedin domain, which did not meet this criterion.
Approved on: 2022-02-07
Published on: 2022-07-11
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