The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document


Variant: NM_000261.2:c.14G>A

CA343720209

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: 44e6d4ec-6733-4fe2-a78e-1ca1a3bf2a51

HGVS expressions

NM_000261.2:c.14G>A
NC_000001.11:g.171652598C>T
CM000663.2:g.171652598C>T
NC_000001.10:g.171621738C>T
CM000663.1:g.171621738C>T
NC_000001.9:g.169888361C>T
NG_008859.1:g.5036G>A
ENST00000037502.11:c.14G>A
ENST00000638471.1:c.14G>A
ENST00000037502.10:c.14G>A
ENST00000614688.1:c.14G>A
NM_000261.1:c.14G>A

Uncertain Significance

Met criteria codes 2
PM2_Supporting BP4
Not Met criteria codes 13
BA1 PP1 PP3 PM5 PM4 PM6 BS3 BS1 BP7 PS4 PS2 PS1 PS3

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.14G>A variant in MYOC is a missense variant predicted to cause substitution of Cysteine by Tyrosine at amino acid 5 (p.Cys5Tyr). 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 = 0.044, 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. Only 1 proband with primary open angle glaucoma had been reported (PMID: 32476818), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. 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 = 0.044, 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.
PP1
No segregations have been reported for this variant.
PP3
This criterion was not met as BP4 has been met.
PM5
No other pathogenic 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.
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
Only 1 proband with POAG had been reported (PMID: 32476818), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting.
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.
Approved on: 2023-07-05
Published on: 2023-07-05
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.