Evidence Repository - Clinical Genome Resources

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

CA1244297

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ff03b7b2-0001-4b66-bef6-fa3af3ecc5a2

HGVS expressions

NM_000261.2:c.309C>T

NC_000001.11:g.171652303G>A

CM000663.2:g.171652303G>A

NC_000001.10:g.171621443G>A

CM000663.1:g.171621443G>A

NC_000001.9:g.169888066G>A

NG_008859.1:g.5331C>T

ENST00000037502.11:c.309C>T

ENST00000638471.1:c.130+179C>T

ENST00000037502.10:c.309C>T

ENST00000614688.1:c.309C>T

NM_000261.1:c.309C>T

Likely Benign

BS1 BP4

PS2 PS1 PS3 PS4 PP1 PP3 BA1 PM6 PM2 BS3 PM5 PM4 BP7

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.309C>T variant in MYOC is a synonymous variant (p.Thr103=). The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v3.1.2) = 0.001243, which met the ≥ 0.001 threshold set for BS1 (6 alleles out of 4,828), meeting the threshold of ≥ 5 of at least 2,000 observed alleles). The CADD score (v1.6) = 1.117, which met the ≤ 10 threshold for BP4 and this variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), suggesting that the variant does not impact MYOC function. However, BP7 was not met as this variant had a GERP score = 1.59 (threshold < 0), indicating conservation at this site. 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.

BS1

The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v3.1.2) = 0.001243, which met the ≥ 0.001 threshold set for BS1 (6 alleles out of 4,828), meeting the threshold of ≥ 5 of at least 2,000 observed alleles).

BP4

The CADD score (v1.6) = 1.117, which met the ≤ 10 threshold for BP4 and this variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), suggesting that the variant does not impact MYOC function.

PS2

This variant has not been identified de novo.

PS1

This variant does not involve an amino acid change.

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.

PP1

No segregations have been reported for this variant.

PP3

This is not a missense variant.

BA1

This criterion was not met as BS1 has been met.

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.

PM5

This is not a missense variant.

PM4

This variant does not cause a protein length change.

BP7

Although this synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), it had a GERP score = 1.59 (threshold <0), indicating conservation at this site.

Approved on: 2022-11-10

Published on: 2022-11-10

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.