The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • cspecId property did not resolve into a valid CSPEC request: https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/635003681!
  • No CSPEC computed assertion could be determined for this classification!

  • See Evidence submitted by expert panel for details.

Variant: NM_000261.2:c.1058C>T

CA1244086

1013538 (ClinVar)

Gene: MYOC
Condition: juvenile open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: d41b1c25-85d2-44e3-b208-881563323147
Approved on: 2022-02-21
Published on: 2022-02-21

HGVS expressions

NM_000261.2:c.1058C>T
NC_000001.11:g.171636382G>A
CM000663.2:g.171636382G>A
NC_000001.10:g.171605522G>A
CM000663.1:g.171605522G>A
NC_000001.9:g.169872145G>A
NG_008859.1:g.21252C>T
ENST00000037502.11:c.1058C>T
ENST00000637303.1:c.235-2248G>A
ENST00000638471.1:c.*396C>T
ENST00000037502.10:c.1058C>T
ENST00000614688.1:c.*22C>T
NM_000261.1:c.1058C>T
More

Likely Benign

Met criteria codes 2
BS3_Supporting BS1
Not Met criteria codes 13
PS1 PS2 PS3 PS4 PP1 PP3 PM6 PM2 PM5 PM4 BA1 BP7 BP4

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.1058C>T variant in MYOC is a missense variant predicted to cause substitution of Threonine by Isoleucine at amino acid 353 (p.Thr353Ile). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.009122, which met the ≥ 0.001 threshold set for BS1 (182 alleles out of 19,952, meeting the threshold of ≥ 5 of at least 2,000 observed alleles). The REVEL score = 0.316, 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. A previous study (PMID: 16466712) demonstrated that the Thr353Ile protein had similar secretion levels to wild type myocilin protein and met the OddsPath threshold for BS3_Moderate (< 0.23), indicating that this variant did not impact protein 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 -6 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, BS3_Moderate.
Met criteria codes
BS3_Supporting
Applied at the BS3_Moderate level. A previous study (PMID: 16466712) demonstrated that the Thr353Ile protein had similar secretion levels to wild type myocilin protein and met the OddsPath threshold for BS3_Moderate (< 0.23), indicating that this variant did not impact protein function.

BS1
The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.009122, which met the ≥ 0.001 threshold set for BS1 (182 alleles out of 19,952, meeting the threshold of ≥ 5 of at least 2,000 observed alleles).
Not Met criteria codes
PS1
An established pathogenic variant causing this same amino acid change has not been identified.
PS2
This variant has not been identified de novo.
PS3
This criterion was not met as BS3_Moderate has been met.
PS4
Although probands with JOAG or POAG have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply.
PP1
As BS1 was met, PP1 did not apply and segregations were not counted.
PP3
The REVEL score = 0.316, which did not meet the ≥ 0.7 threshold for PP3.
PM6
This variant has not been identified de novo.
PM2
This criterion was not met as BS1 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.
BA1
This criterion was not met as BS1 has been met.
BP7
This is not a synonymous or non-coding variant.
BP4
The REVEL score = 0.316, which did not meet the ≤ 0.15 threshold required for BP4.
Curation History
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.