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]

Variant: NM_000261.2:c.365G>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA343718550

Gene: MYOC

Condition: juvenile open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: dd7f31b8-6ec5-4fd1-b0b0-3bf4a22c9f9f

Approved on: 2023-04-04

Published on: 2023-04-04

HGVS expressions

NM_000261.2:c.365G>C

NC_000001.11:g.171652247C>G

CM000663.2:g.171652247C>G

NC_000001.10:g.171621387C>G

CM000663.1:g.171621387C>G

NC_000001.9:g.169888010C>G

NG_008859.1:g.5387G>C

ENST00000037502.11:c.365G>C

ENST00000638471.1:c.130+235G>C

ENST00000037502.10:c.365G>C

ENST00000614688.1:c.365G>C

NM_000261.1:c.365G>C

Uncertain Significance

BP4 PM2_Supporting

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

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.365G>C variant in MYOC is a missense variant predicted to cause substitution of Glycine by Alanine at amino acid 122 (p.Gly122Ala). 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 = 0.064, 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 proband with juvenile open angle glaucoma had been reported (PMID: Yadav et al, 2022, Pre-print), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 0 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BP4, PM2_Supporting.

BP4

The REVEL score = 0.064, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function.

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.

PS4

Only 1 proband with JOAG had been reported (PMID: Yadav et al, 2022, Pre-print), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting.

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.

BA1

This criterion was not met as PM2_Supporting has been met.

PP1

No segregations have been reported for this variant.

PP3

This criterion was not met as BP4 has been met.

PM6

This variant has not been identified de novo.

PM5

PM5_Supporting could not be applied to this variant as the other missense variants at the same amino acid residue (c.365G>A, p.Gly122Asp, ClinVarID: 1048923 and c.365G>T, p.Gly122Val, ClinVarID: 1302992) were not classified as likely pathogenic or pathogenic.

PM4

This variant does not cause a protein length change.

Curation History

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