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Variant: NM_000261.2(MYOC):c.304T>A (p.Leu102Met)

CA10608379

293720 (ClinVar)

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: 084e62a6-3c84-4808-95c3-4847e6b20e7c

HGVS expressions

NM_000261.2:c.304T>A
NM_000261.2(MYOC):c.304T>A (p.Leu102Met)
NC_000001.11:g.171652308A>T
CM000663.2:g.171652308A>T
NC_000001.10:g.171621448A>T
CM000663.1:g.171621448A>T
NC_000001.9:g.169888071A>T
NG_008859.1:g.5326T>A
ENST00000037502.11:c.304T>A
ENST00000638471.1:c.130+174T>A
ENST00000037502.10:c.304T>A
ENST00000614688.1:c.304T>A
NM_000261.1:c.304T>A

Uncertain Significance

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.304T>A variant in MYOC is a missense variant predicted to cause substitution of Leucine by Methionine at amino acid 102 (p.Leu102Met). 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. The REVEL score = 0.071, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. This variant has not yet been identified in a proband with juvenile or primary open angle glaucoma, only in a participant of the control cohort, thus PS4 did not apply. In summary, this variant met the criteria to receive a score of 0 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): BP4, PM2_Supporting.
Met criteria codes
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.
BP4
The REVEL score = 0.071, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function.
Not Met criteria codes
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.
BP7
This is not a synonymous or non-coding variant.
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
An established pathogenic variant causing this same amino acid change has not been identified.
PS3
No functional evidence has been found for this variant.
PP1
No segregations have been reported for this variant.
PP3
This criterion was not met as BP4 has been met.
PM6
This variant has not been identified de novo.
PM5
No other missense variants at this amino acid residue have been identified.
PM4
This variant does not cause a protein length change.
Approved on: 2023-08-08
Published on: 2023-08-08
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