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

CA1244072

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b9227514-de3a-44ac-8340-f2653214de03

HGVS expressions

NM_000261.2:c.1160G>A

NC_000001.11:g.171636280C>T

CM000663.2:g.171636280C>T

NC_000001.10:g.171605420C>T

CM000663.1:g.171605420C>T

NC_000001.9:g.169872043C>T

NG_008859.1:g.21354G>A

ENST00000037502.11:c.1160G>A

ENST00000637303.1:c.235-2350C>T

ENST00000638471.1:c.*498G>A

ENST00000037502.10:c.1160G>A

ENST00000614688.1:c.*124G>A

NM_000261.1:c.1160G>A

Uncertain Significance

PP3

PS2 PS1 PS3 PS4 BA1 PP1 PM6 PM2 PM5 PM4 BS3 BS1 BP4 BP7

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.1160G>A variant in MYOC is a missense variant predicted to cause substitution of Glycine by Aspartic Acid at amino acid 387 (p.Gly387Asp). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0001631 (3 alleles out of 18,392), which did not meet the PM2_Supporting allele frequency threshold (≤ 0.0001) or the BS1 allele frequency threshold (≥ 0.001). The REVEL score = 0.958, which met the ≥ 0.7 threshold for PP3, predicting a damaging effect on 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): PP3

PP3

The REVEL score = 0.958, which met the ≥ 0.7 threshold for PP3, predicting a damaging effect on MYOC function.

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.

PS4

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

BA1

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

PP1

No segregations have been reported for this variant.

PM6

This variant has not been identified de novo.

PM2

The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0001631 (3 alleles out of 18,392), which did not meet the ≤ 0.0001 threshold set for PM2_Supporting.

PM5

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

PM4

This variant does not cause a protein length change.

BS3

No functional evidence has been found for this variant.

BS1

The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0001631 (3 alleles out of 18,392), which did not meet the ≥ 0.001 threshold set for BS1.

BP4

This criterion was not met as PP3 has been met.

BP7

This is not a synonymous or non-coding variant.

Approved on: 2023-06-01

Published on: 2023-06-01

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