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.11T>C

CA343720226

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ebb20c76-41a8-4819-8df4-fcf9d17e3b22

HGVS expressions

NM_000261.2:c.11T>C

NC_000001.11:g.171652601A>G

CM000663.2:g.171652601A>G

NC_000001.10:g.171621741A>G

CM000663.1:g.171621741A>G

NC_000001.9:g.169888364A>G

NG_008859.1:g.5033T>C

ENST00000037502.11:c.11T>C

ENST00000638471.1:c.11T>C

ENST00000037502.10:c.11T>C

ENST00000614688.1:c.11T>C

NM_000261.1:c.11T>C

Uncertain Significance

PM2_Supporting BP4 PS4_Supporting

BA1 BS3 BS1 BP7 PS2 PS1 PS3 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.11T>C variant in MYOC is a missense variant predicted to cause substitution of Phenylalanine by Serine at amino acid 4 (p.Phe4Ser). 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. The REVEL score = 0.068, which met the ≤ 0.15 threshold for BP4, 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 segregation had been reported for primary open angle glaucoma (POAG) (Charlesworth, J. 2006 PhD Thesis), not meeting the ≥ 3 segregations required for PP1. 2 probands with POAG have been reported carrying this variant (PMID: 10196380), which met PS4_Supporting (≥ 2 probands). 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): BP4, PS4_Supporting, 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.

BP4

The REVEL score = 0.068, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function.

PS4_Supporting

2 probands with POAG have been reported carrying this variant (PMID: 10196380), which met PS4_Supporting (≥ 2 probands).

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.

PS2

This variant has not been identified de novo.

PS1

An established pathogenic variant causing this same amino acid change has not been identified.

PS3

No functional evidence has been found for this variant.

PP1

Only 1 segregation had been reported for primary open angle glaucoma (Charlesworth, J. 2006 PhD Thesis), not meeting the ≥ 3 segregations required for PP1.

PP3

This criterion was not met as BP4 has been met.

PM5

No other missense variants at this amino acid residue have been identified.

PM4

This variant does not cause a protein length change.

PM6

This variant has not been identified de novo.

Approved on: 2022-08-28

Published on: 2022-08-28

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