Variant: NM_000261.2:c.164G>C

CA343719476

1723160 (ClinVar)

Gene: MYOC

Condition: open-angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

UUID: fe222f3a-c8e2-46d5-bba2-1a2def1ab2da

Approved on: 2025-11-13

Published on: 2025-11-13

HGVS expressions

NM_000261.2:c.164G>C
NC_000001.11:g.171652448C>G
CM000663.2:g.171652448C>G
NC_000001.10:g.171621588C>G
CM000663.1:g.171621588C>G
NC_000001.9:g.169888211C>G
NG_008859.1:g.5186G>C
ENST00000037502.11:c.164G>C
ENST00000638471.1:c.130+34G>C
ENST00000037502.10:c.164G>C
ENST00000614688.1:c.164G>C
NM_000261.1:c.164G>C

Uncertain Significance

• Met criteria codes: PM2_Supporting BP4

• Not Met criteria codes: PM5 PM4 BA1 BS3 BS1 BP7 PS2 PS1 PS3 PS4 PP1 PP3

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.164G>C variant in MYOC is a missense variant predicted to cause substitution of Serine by Threonine at amino acid 55 (p.Ser55Thr). This variant was not found in any genetic ancestry group of gnomAD (v4.1.0), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles. The REVEL score = 0.16, which was within the 0.017-0.183 range for BP4_Moderate, 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. Only 1 proband with primary open angle glaucoma had been reported (PMID: 14642164), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of -1 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5, 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_Moderate, PM2_Supporting.

Met criteria codes

• PM2_Supporting: This variant was not found in any genetic ancestry group of gnomAD (v4.1.0), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles.
• BP4: at moderate level: The REVEL score = 0.16, which was within the 0.017-0.183 range for BP4_Moderate, suggesting that the variant does not impact MYOC function.

Not Met criteria codes

• PM5: No other missense variants at this amino acid residue have been identified.
• PM4: This variant does not cause a protein length change.
• BA1: This criterion was not met as PM2_Supporting has been met.
• 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.
• PS2: This variant has not been identified de novo.
• PS1: An established likely pathogenic or pathogenic variant causing this same amino acid change has not been identified.
• PS3: No functional evidence has been found for this variant.
• PS4: Only 1 proband with POAG had been reported (PMID: 14642164), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting.
• PP1: No segregations have been reported for this variant.
• PP3: This criterion was not met as BP4 has been met.