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]

Variant: NM_000261.2:c.1452G>A

CA421938581

2429763 (ClinVar)

Gene: MYOC (HGNC:4653)

Condition: open-angle glaucoma (MONDO:0005338)

Inheritance Mode: Autosomal dominant inheritance

UUID: ca98206c-190d-4706-87c3-4473c409e130

Approved on: 2026-02-19

Published on: 2026-02-18

HGVS expressions

NM_000261.2:c.1452G>A

NC_000001.11:g.171635988C>T

CM000663.2:g.171635988C>T

NC_000001.10:g.171605128C>T

CM000663.1:g.171605128C>T

NC_000001.9:g.169871751C>T

NG_008859.1:g.21646G>A

ENST00000037502.11:c.1452G>A

ENST00000637303.1:c.235-2642C>T

ENST00000638471.1:c.*790G>A

ENST00000037502.10:c.1452G>A

ENST00000614688.1:c.*416G>A

NM_000261.1:c.1452G>A

Likely Benign

BP4 BP7

BS3 BS1 PM2 PM5 PM4 PS4 PS2 PS1 PS3 BA1 PP1 PP3

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specification: ClinGen Glaucoma Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MYOC Version 2.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.1452G>A variant in MYOC is a synonymous variant (p.Lys484=). This variant was identified in controls in a North Indian study (PMID: 39998747). The gnomAD (v4.1.0) database did not well represent the genetic ancestry group from which the variant has been reported (South Asian). Thus PM2_Supporting was not applied to this variant. The SpliceAI score = 0.01, which met the ≤ 0.1 threshold for BP4, suggesting that the variant does not impact MYOC function. This synonymous variant meets BP4, so BP7 is met. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Although probands with juvenile 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 -2 and to be classified as likely benign (likely benign classification range -2 to -6, adapted from PMID: 32720330) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v2.0.0, 5 Dec 2024): BP4, BP7

BP4

The SpliceAI score = 0.01, which met the ≤ 0.1 threshold for BP4, suggesting that the variant does not impact MYOC function.

BP7

This synonymous variant meets BP4, so BP7 is met.

BS3

No functional evidence has been found for this variant.

BS1

The highest minor allele frequency of this variant was in the African/African American genetic ancestry group of gnomAD (v4.1.0) = 0.00002669 (2 alleles out of 74,934), which did not meet the ≥ 0.001 threshold set for BS1.

PM2

This variant was identified in controls in a North Indian study (PMID: 39998747). The gnomAD (v4.1.0) database did not well represent the genetic ancestry group from which the variant has been reported (South Asian). Thus PM2_Supporting was not applied to this variant.

PM5

This is not a missense variant.

PM4

This variant does not cause a protein length change.

PS4

Although probands with juvenile open angle glaucoma have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply.

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.

BA1

This variant did not meet the ≥ 0.01 minor allele frequency threshold in gnomAD (v4.1.0).

PP1

No segregations have been reported for this variant.

PP3

This criterion did not apply to this variant.

Curation History

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