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]

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CA1244318

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 24f8edb3-707f-4bb0-a681-745355765035

HGVS expressions

NM_000261.2:c.154A>G

NC_000001.11:g.171652458T>C

CM000663.2:g.171652458T>C

NC_000001.10:g.171621598T>C

CM000663.1:g.171621598T>C

NC_000001.9:g.169888221T>C

NG_008859.1:g.5176A>G

ENST00000037502.11:c.154A>G

ENST00000638471.1:c.130+24A>G

ENST00000037502.10:c.154A>G

ENST00000614688.1:c.154A>G

NM_000261.1:c.154A>G

Likely Benign

BS1 BP4

PS2 PS1 PS3 PS4 BA1 PP1 PP3 PM6 PM2 PM5 PM4 BS3 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.154A>G variant in MYOC is a missense variant predicted to cause substitution of Serine by Glycine at amino acid 52 (p.Ser52Gly). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v3.1.2) = 0.001154, which met the ≥ 0.001 threshold set for BS1 (6 alleles out of 5,200), meeting the threshold of ≥ 5 of at least 2,000 observed alleles). The REVEL score = 0.036, 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.

BS1

The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v3.1.2) = 0.001154, which met the ≥ 0.001 threshold set for BS1 (6 alleles out of 5,200), meeting the threshold of ≥ 5 of at least 2,000 observed alleles).

BP4

The REVEL score = 0.036, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function.

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.

BA1

This criterion was not met as BS1 has been met.

PP1

No segregations have been reported for this variant.

PP3

This criterion was not met as BP4 has been met.

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.

BS3

No functional evidence has been found for this variant.

BP7

This is not a synonymous or non-coding variant.

Approved on: 2023-08-08

Published on: 2023-08-08

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