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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000261.2:c.1466_1467insC

CA1139771053

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5dacda88-7003-4057-bb38-044014a96dbe

HGVS expressions

NM_000261.2:c.1466_1467insC

NC_000001.11:g.171635973_171635974insG

CM000663.2:g.171635973_171635974insG

NC_000001.10:g.171605113_171605114insG

CM000663.1:g.171605113_171605114insG

NC_000001.9:g.169871736_169871737insG

NG_008859.1:g.21660_21661insC

ENST00000037502.11:c.1466_1467insC

ENST00000637303.1:c.235-2657_235-2656insG

ENST00000638471.1:c.*804_*805insC

ENST00000037502.10:c.1466_1467insC

ENST00000614688.1:c.*430_*431insC

NM_000261.1:c.1466_1467insC

Uncertain Significance

PM4_Supporting PM2_Supporting

BA1 BS3 BS1 BP7 BP4 PS2 PS1 PS3 PS4 PP1 PP3 PM6 PM5

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.1466_1467insC variant in MYOC is an insertion of a single nucleotide, predicted to encode a frameshift with consequent premature termination of the protein at codon 10 of the frameshift, or amino acid 499 (p.Trp489CysfsTer10). This variant is predicted to involve < 10% of the protein within the conserved olfactomedin domain, meeting PM4_Supporting. This variant was not found in any population of gnomAD (v2.1.1), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. There was no computational or 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: 10916185), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 2 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PM2_Supporting, PM4_Supporting

PM4_Supporting

This truncating variant is predicted to involve ≤ 10% of the protein and is within the conserved olfactomedin domain.

PM2_Supporting

This variant was not found in any population of gnomAD (v2.1.1), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles.

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 a synonymous or non-coding variant.

BP4

This is not a missense, synonymous or non-coding variant.

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

Only 1 proband with POAG had been reported (PMID: 10916185), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting.

PP1

No segregations have been reported for this variant.

PP3

This is not a missense variant.

PM6

This variant has not been identified de novo.

PM5

This is not a missense variant.

Approved on: 2023-06-01

Published on: 2023-06-01

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