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

CA1244068

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: cbe941bd-b404-4446-9f8e-867b1bb71721

HGVS expressions

NM_000261.2:c.1185T>G

NC_000001.11:g.171636255A>C

CM000663.2:g.171636255A>C

NC_000001.10:g.171605395A>C

CM000663.1:g.171605395A>C

NC_000001.9:g.169872018A>C

NG_008859.1:g.21379T>G

ENST00000037502.11:c.1185T>G

ENST00000637303.1:c.235-2375A>C

ENST00000638471.1:c.*523T>G

ENST00000037502.10:c.1185T>G

ENST00000614688.1:c.*149T>G

NM_000261.1:c.1185T>G

Uncertain Significance

BP4

BS3 BS1 BP7 BA1 PS2 PS3 PS1 PS4 PP1 PP3 PM4 PM5 PM6 PM2

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specification: ClinGen Glaucoma Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.1185T>G variant in MYOC is a missense variant predicted to cause substitution of Aspartate by Glutamate at amino acid 395 (p.Asp395Glu). The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.0001633 (5 alleles out of 30,616), which did not meet the PM2_Supporting allele frequency threshold (≤ 0.0001) or the BS1 allele frequency threshold (≥ 0.001). The REVEL score = 0.131, 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. Although probands with primary open angle glaucoma have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. 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.

BP4

The REVEL score = 0.131, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function.

BS3

No functional evidence has been found for this variant.

BS1

The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.0001633 (5 alleles out of 30,616), which did not meet the ≥ 0.001 threshold set for BS1.

BP7

This is not a synonymous or non-coding variant.

BA1

This variant did not meet the ≥ 0.01 minor allele frequency threshold in gnomAD (v2.1.1).

PS2

This variant has not been identified de novo.

PS3

No functional evidence has been found for this variant.

PS1

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

PS4

Although probands with POAG have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply.

PP1

No segregations have been reported for this variant.

PP3

This criterion was not met as BP4 has been met.

PM4

This variant does not cause a protein length change.

PM5

PM5_Supporting could not be applied to this variant as the other missense variants at the same amino acid residue (c.1183G>A, p.Asp395Asn, E Souzeau pers. comm.) was not classified as likely pathogenic or pathogenic.

PM6

This variant has not been identified de novo.

PM2

The highest minor allele frequency of this variant was in the South Asian population of gnomAD (v2.1.1) = 0.0001633 (5 alleles out of 30,616), which did not meet the ≤ 0.0001 threshold set for PM2_Supporting.

Approved on: 2023-07-05

Published on: 2023-07-05

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.