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Variant: NM_000261.2(MYOC):c.224A>G (p.Gln75Arg)

CA10608781

293722 (ClinVar)

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: dd2692fe-7418-4129-9345-cf4da7f689e8

HGVS expressions

NM_000261.2:c.224A>G
NM_000261.2(MYOC):c.224A>G (p.Gln75Arg)
NC_000001.11:g.171652388T>C
CM000663.2:g.171652388T>C
NC_000001.10:g.171621528T>C
CM000663.1:g.171621528T>C
NC_000001.9:g.169888151T>C
NG_008859.1:g.5246A>G
ENST00000037502.11:c.224A>G
ENST00000638471.1:c.130+94A>G
ENST00000037502.10:c.224A>G
ENST00000614688.1:c.224A>G
NM_000261.1:c.224A>G

Uncertain Significance

Met criteria codes 2
BP4 PM2_Supporting
Not Met criteria codes 13
BS3 BS1 BP7 PS4 PS2 PS1 PS3 BA1 PP1 PP3 PM5 PM4 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.224A>G variant in MYOC is a missense variant predicted to cause substitution of Glutamine by Arginine at amino acid 75 (p.Gln75Arg). 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 = 0.11, 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 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 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
BP4
The REVEL score = 0.11, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function.
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.
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.
BA1
This criterion was not met as PM2_Supporting has been met.
PP1
No segregations have been reported for this variant.
PP3
This criterion was not met as BP4 has been met.
PM5
No other missense variants at this amino acid residue have been identified.
PM4
This variant does not cause a protein length change.
PM6
This variant has not been identified de novo.
Approved on: 2023-08-08
Published on: 2023-08-08
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