Variant: NM_000261.2:c.1160G>A

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CA1244072

2505287 (ClinVar)

Gene: MYOC (HGNC:4653)

Condition: open-angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

UUID: b9227514-de3a-44ac-8340-f2653214de03

Approved on: 2026-02-19

Published on: 2026-02-18

HGVS expressions

NM_000261.2:c.1160G>A
NC_000001.11:g.171636280C>T
CM000663.2:g.171636280C>T
NC_000001.10:g.171605420C>T
CM000663.1:g.171605420C>T
NC_000001.9:g.169872043C>T
NG_008859.1:g.21354G>A
ENST00000037502.11:c.1160G>A
ENST00000637303.1:c.235-2350C>T
ENST00000638471.1:c.*498G>A
ENST00000037502.10:c.1160G>A
ENST00000614688.1:c.*124G>A
NM_000261.1:c.1160G>A

Likely Pathogenic

• Met criteria codes: PS4_Supporting PM2_Supporting PP3_Strong

• Not Met criteria codes: PS2 PS1 PS3 BA1 PP1 PM5 PM4 BS3 BS1 BP7 BP4

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

Evidence submitted by expert panel

Glaucoma VCEP

The c.1160G>A variant in MYOC is a missense variant predicted to cause substitution of Glycine by Aspartic Acid at amino acid 387 (p.Gly387Asp). The highest minor allele frequency of this variant was in the East Asian genetic ancestry group of gnomAD (v4.1.0) = 0.00004455 (2 alleles out of 44,890), which met the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles. The REVEL score = 0.958, which met the ≥ 0.932 threshold for PP3_Strong, predicting a damaging effect on MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. 2 probands with primary open angle glaucoma have been reported carrying this variant (PMID: 24825108), which met PS4_Supporting (≥ 2 probands). In summary, this variant met the criteria to receive a score of 6 and to be classified as likely pathogenic (likely pathogenic classification range 6 to 9, 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): PP3_Strong, PS4_Supporting, PM2_Supporting

Met criteria codes

• PS4_Supporting: 2 probands with primary open angle glaucoma have been reported carrying this variant (PMID: 24825108), which met PS4_Supporting (≥ 2 probands).
• PM2_Supporting: The highest minor allele frequency of this variant was in the East Asian genetic ancestry group of gnomAD (v4.1.0) = 0.00004455 (2 alleles out of 44,890), which met the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles.
• PP3_Strong: The REVEL score = 0.958, which met the ≥ 0.932 threshold for PP3_Strong, predicting a damaging effect on MYOC function.

Not Met criteria codes

• PS2: This variant has not been identified de novo.
• PS1: An established LP or P variant causing this same amino acid change has not been identified.
• PS3: No functional evidence has been found for this variant.
• BA1: This criterion was not met as PM2_Supporting has been met.
• PP1: No segregations have been reported for this variant.
• PM5: No other LP or P 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.
• BS1: This criterion was not met as PM2_Supporting has been met.
• BP7: This is not an intronic, synonymous or non-coding variant.
• BP4: This criterion was not met as PP3 has been met.