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]
Link to SEPIO compliant JSON-LD document
  • No ClinVar Id was directly found from the curated document
  • See Evidence submitted by expert panel for details.

CA1244053

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7674d2bb-4cc5-4551-9b3b-5e3113199d38

HGVS expressions

NM_000261.2:c.1264C>T
NC_000001.11:g.171636176G>A
CM000663.2:g.171636176G>A
NC_000001.10:g.171605316G>A
CM000663.1:g.171605316G>A
NC_000001.9:g.169871939G>A
NG_008859.1:g.21458C>T
ENST00000037502.11:c.1264C>T
ENST00000637303.1:c.235-2454G>A
ENST00000638471.1:c.*602C>T
ENST00000037502.10:c.1264C>T
ENST00000614688.1:c.*228C>T
NM_000261.1:c.1264C>T

Uncertain Significance

Met criteria codes 1
PM2_Supporting
Not Met criteria codes 14
BA1 BP7 BP4 BS3 BS1 PP1 PP3 PS2 PS1 PS4 PS3 PM5 PM4 PM6

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.1264C>T variant in MYOC is a missense variant predicted to cause substitution of Arginine by Cysteine at amino acid 422 (p.Arg422Cys). The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v2.1.1) = 0.00004645 (6 alleles out of 129,180), which met the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. The REVEL score = 0.646, which was neither above nor below the thresholds for PP3 (≥ 0.7) or BP4 (≤ 0.15), predicting a damaging or benign impact on MYOC function. The study reporting functional evidence (PMID: 10545602) was inconclusive for the Arg422Cys protein, therefore, PS3 was not applied. 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. In summary, this variant met the criteria to receive a score of 1 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
Met criteria codes
PM2_Supporting
The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v2.1.1) = 0.00004645 (6 alleles out of 129,180), which met the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles.
Not Met criteria codes
BA1
This criterion was not met as PM2_Supporting has been met.
BP7
This is not a synonymous or non-coding variant.
BP4
The REVEL score = 0.646, which did not meet the ≤ 0.15 threshold required for BP4.
BS3
The study reporting functional evidence (PMID: 10545602) was inconclusive for the Arg422Cys protein, therefore, BS3 was not applied.
The R422C demonstrated partial solubility. This study meets the OddsPath threshold for PS3_Supporting (> 2.1) but not the threshold for PS3_Moderate (> 4.3). PubMed:10545602
BS1
This criterion was not met as PM2_Supporting has been met.
PP1
No segregations have been reported for this variant.
PP3
The REVEL score = 0.646 , which did not meet the ≥ 0.7 threshold for PP3.
PS2
This variant has not been identified de novo.
PS1
An established pathogenic variant causing this same amino acid change has not been identified.
PS4
This variant has not yet been identified in a proband with JOAG or POAG, only in a participant of the control cohort.
PS3
The study reporting functional evidence (PMID: 10545602) was inconclusive for the Arg422Cys protein, therefore, PS3 was not applied.
The R422C demonstrated partial solubility. This study meets the OddsPath threshold for PS3_Supporting (> 2.1) but not the threshold for PS3_Moderate (> 4.3). PubMed:10545602
PM5
PM5_Supporting could not be applied to this variant as the other missense variants at the same amino acid residue (c.1265G>A, p.Arg422His PMID: 9535666) was not classified as likely pathogenic or pathogenic.
PM4
This variant does not cause a protein length change.
PM6
This variant has not been identified de novo.
Approved on: 2022-05-10
Published on: 2022-05-25
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.