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.1025G>A

CA343725043

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 22a04642-b6ed-4075-a354-6ee7267ef79a

HGVS expressions

NM_000261.2:c.1025G>A

NC_000001.11:g.171636415C>T

CM000663.2:g.171636415C>T

NC_000001.10:g.171605555C>T

CM000663.1:g.171605555C>T

NC_000001.9:g.169872178C>T

NG_008859.1:g.21219G>A

ENST00000037502.11:c.1025G>A

ENST00000637303.1:c.235-2215C>T

ENST00000638471.1:c.*363G>A

ENST00000037502.10:c.1025G>A

ENST00000614688.1:c.1024G>A

NM_000261.1:c.1025G>A

Uncertain Significance

PS4_Supporting PM2_Supporting

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

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.1025G>A variant in MYOC is a missense variant predicted to cause substitution of Arginine by Lysine at amino acid 342 (p.Arg342Lys). 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 = 0.649, which was neither above nor below the thresholds for PP3 (≥ 0.7) or BP4 (≤ 0.15), predicting a damaging or benign impact on MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. 2 probands with primary open angle glaucoma have been reported carrying this variant (PMID: 12362081), which met PS4_Supporting (≥ 2 probands). In summary, this variant met the criteria to receive a score of 2 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): PS4_Supporting, PM2_Supporting

PS4_Supporting

2 probands with POAG have been reported carrying this variant (PMID: 12362081), which met PS4_Supporting (≥ 2 probands).

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.

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.

BP4

The REVEL score = 0.649, which did not meet the ≤ 0.15 threshold required for BP4.

BP7

This is not a synonymous or non-coding variant.

BA1

This criterion was not met as PM2_Supporting has been met.

PP1

No segregations have been reported for this variant.

PP3

The REVEL score = 0.649, which did not meet the ≥ 0.7 threshold for PP3.

PM5

PM5_Supporting could not be applied to this variant as the other missense variant at the same amino acid residue (c.1024A>G, p.Arg342Gly) was not classified as likely pathogenic or pathogenic.

PM4

This variant does not cause a protein length change.

PM6

This variant has not been identified de novo.

BS3

No functional evidence has been found for this variant.

BS1

This criterion was not met as PM2_Supporting has been met.

Approved on: 2022-11-10

Published on: 2022-11-10

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