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.484_486dup

CA1139770939

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5c0d3f69-a585-4691-a31b-8a6f204f1c40

HGVS expressions

NM_000261.2:c.484_486dup

NC_000001.11:g.171652128_171652130dup

CM000663.2:g.171652128_171652130dup

NC_000001.10:g.171621268_171621270dup

CM000663.1:g.171621268_171621270dup

NC_000001.9:g.169887891_169887893dup

NG_008859.1:g.5506_5508dup

ENST00000037502.11:c.484_486dup

ENST00000638471.1:c.130+354_130+356dup

ENST00000037502.10:c.484_486dup

ENST00000614688.1:c.484_486dup

NM_000261.1:c.484_486dup

Uncertain Significance

PM2_Supporting

BA1 BS3 BS1 BP7 BP4 PS2 PS1 PS3 PS4 PP1 PP3 PM5 PM4 PM6

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.484_486dup variant in MYOC is predicted to cause a change in the length of the protein due to an in-frame insertion of 1 amino acid (p.Glu162dup). This in-frame insertion variant is predicted to involve ≤ 10% of the protein and is not within the conserved olfactomedin domain, thus PM4 did not apply. 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 functional evidence predicting a damaging or benign impact of this variant on MYOC function. Only 1 proband with OHT had been reported (PMID: 12215093), 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) 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.

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 OHT had been reported (PMID: 12215093), 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.

PM5

This is not a missense variant.

PM4

This in-frame insertion variant is predicted to involve ≤ 10% of the protein and is not within the conserved olfactomedin domain, thus PM4 did not apply.

PM6

This variant has not been identified de novo.

Approved on: 2022-11-10

Published on: 2022-11-10

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