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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CA1244330

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: b2497530-9cc8-4ba3-a92f-f06d7aa386cf

HGVS expressions

NM_000261.2:c.98G>A
NC_000001.11:g.171652514C>T
CM000663.2:g.171652514C>T
NC_000001.10:g.171621654C>T
CM000663.1:g.171621654C>T
NC_000001.9:g.169888277C>T
NG_008859.1:g.5120G>A
ENST00000037502.11:c.98G>A
ENST00000638471.1:c.98G>A
ENST00000037502.10:c.98G>A
ENST00000614688.1:c.98G>A
NM_000261.1:c.98G>A

Likely Benign

Met criteria codes 2
BP4 BS1
Not Met criteria codes 13
PS2 PS1 PS3 PS4 BP7 BA1 PP3 PP1 PM5 PM4 PM6 PM2 BS3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.98G>A variant in MYOC is a missense variant predicted to cause substitution of Arginine by Lysine at amino acid 33 (p.Arg33Lys). The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.001241, which met the ≥ 0.001 threshold set for BS1 (38 alleles out of 30 610, meeting the threshold of ≥ 5 of at least 2,000 observed alleles). The REVEL score = 0.055, 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. Although a proband with primary open angle glaucoma had 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 -5 and to be classified as likely benign (likely benign classification range -2 to -6) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BS1, BP4
Met criteria codes
BP4
The REVEL score = 0.055, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function.
BS1
The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.001241, which met the ≥ 0.001 threshold set for BS1 (38 alleles out of 30 610, meeting the threshold of ≥ 5 of at least 2,000 observed alleles).
Not Met criteria codes
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.
PS4
Although a proband with POAG had been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply.
BP7
This is not a synonymous or non-coding variant.
BA1
This criterion was not met as BS1 has been met.
PP3
This criterion was not met as BP4 has been met.
PP1
As BA1/BS1 was met, PP1 did not apply and segregations were not counted.
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.
PM2
This criterion was not met as BS1 has been met.
BS3
No functional evidence has been found for this variant.
Approved on: 2022-08-28
Published on: 2022-08-28
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