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.740del

CA1139770963

Gene: N/A

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b058e60f-4b68-4544-8f38-0286cc905c2d

Approved on: 2023-08-08

Published on: 2023-08-08

HGVS expressions

NM_000261.2:c.740del

NC_000001.11:g.171636700del

CM000663.2:g.171636700del

NC_000001.10:g.171605840del

CM000663.1:g.171605840del

NC_000001.9:g.169872463del

NG_008859.1:g.20935del

ENST00000037502.11:c.741del

ENST00000637303.1:c.235-1930del

ENST00000638471.1:c.*79del

ENST00000037502.10:c.741del

ENST00000614688.1:c.741del

NM_000261.1:c.741del

NM_000261.2:c.741del

Uncertain Significance

PM4 PM2_Supporting

BS3 BS1 BP7 BP4 PS2 PS1 PS3 PS4 BA1 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.741del variant in MYOC is a deletion of a single nucleotide, predicted to encode a frameshift with consequent premature termination of the protein at codon 2 of the frameshift, or amino acid 248 (p.Glu247AspfsTer2). This variant is predicted to cause a deletion of ≥ 10% of the protein within the conserved olfactomedin domain, meeting PM4. 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: 14642164), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 3 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): PM4, PM2_Supporting

PM4

This truncating variant is predicted to cause a deletion of ≥ 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.

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: 14642164), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting.

BA1

This criterion was not met as PM2_Supporting has been met.

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.

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