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.816A>T

CA1244148

2570629 (ClinVar)

Gene: MYOC (HGNC:4653)

Condition: open-angle glaucoma (MONDO:0005338)

Inheritance Mode: Autosomal dominant inheritance

UUID: dc4619f5-2785-45f7-8c0d-02455cf12ed5

Approved on: 2026-01-21

Published on: 2026-01-20

HGVS expressions

NM_000261.2:c.816A>T

NC_000001.11:g.171636624T>A

CM000663.2:g.171636624T>A

NC_000001.10:g.171605764T>A

CM000663.1:g.171605764T>A

NC_000001.9:g.169872387T>A

NG_008859.1:g.21010A>T

ENST00000037502.11:c.816A>T

ENST00000637303.1:c.235-2006T>A

ENST00000638471.1:c.*154A>T

ENST00000037502.10:c.816A>T

ENST00000614688.1:c.816A>T

NM_000261.1:c.816A>T

Likely Benign

BP7 BP4

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

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.816A>T variant in MYOC is a synonymous variant (p.Arg272=). The highest minor allele frequency of this variant was in the South Asian genetic ancestry group of gnomAD (v4.1.0) = 0.0002087 (19 alleles out of 91,040), which did not meet the PM2_Supporting allele frequency threshold (≤ 0.0001) or the BS1 allele frequency threshold (≥ 0.001). 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 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 -2 and to be classified as likely benign (likely benign classification range -2 to -6, adapted from PMID: 32720330) for primary 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.

BP7

This synonymous variant meets BP4, so BP7 is met.

BP4

The SpliceAI score = 0.01, which met the ≤ 0.1 threshold for BP4, 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.

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 is not a missense variant.

PM5

This is not a missense variant.

PM4

This variant does not cause a protein length change.

PM2

The highest minor allele frequency of this variant was in the South Asian genetic ancestry group of gnomAD (v4.1.0) = 0.0002087 (19 alleles out of 91,040), which did not meet the ≤ 0.0001 threshold set for PM2_Supporting.

BS3

No functional evidence has been found for this variant.

BS1

The highest minor allele frequency of this variant was in the South Asian genetic ancestry group of gnomAD (v4.1.0) = 0.0002087 (19 alleles out of 91,040), which did not meet the ≥ 0.001 threshold set for BS1.

Curation History

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