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.1499A>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA1244011

1168919 (ClinVar)

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 62b36d6a-2aef-4aef-8115-eec1878f22bd

Approved on: 2023-07-05

Published on: 2023-07-05

HGVS expressions

NM_000261.2:c.1499A>G

NC_000001.11:g.171635941T>C

CM000663.2:g.171635941T>C

NC_000001.10:g.171605081T>C

CM000663.1:g.171605081T>C

NC_000001.9:g.169871704T>C

NG_008859.1:g.21693A>G

ENST00000037502.11:c.1499A>G

ENST00000637303.1:c.235-2689T>C

ENST00000638471.1:c.*837A>G

ENST00000037502.10:c.1499A>G

ENST00000614688.1:c.*463A>G

NM_000261.1:c.1499A>G

NM_000261.2(MYOC):c.1499A>G (p.Lys500Arg)

Likely Benign

BS1

BS3 BP7 BP4 PS2 PS1 PS3 PS4 PP1 PP3 BA1 PM6 PM2 PM5 PM4

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.1499A>G variant in MYOC is a missense variant predicted to cause substitution of Lysine by Arginine at amino acid 500 (p.Lys500Arg). The highest minor allele frequency of this variant was in the African/African American population of gnomAD (v2.1.1) = 0.006331, which meets the ≥0.001 threshold set for this criterion (158 alleles out of 24,958, meeting the threshold of ≥ 5 of at least 2,000 observed alleles). The REVEL score = 0.502, 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. 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 -4 and to be classified as likely benign (likely benign classification range -2 to -6) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BS1

BS1

The highest minor allele frequency of this variant was in the African/African American population of gnomAD (v2.1.1) = 0.006331, which meets the ≥0.001 threshold set for this criterion (158 alleles out of 24,958, meeting the threshold of ≥ 5 of at least 2,000 observed alleles).

BS3

No functional evidence has been found for this variant.

BP7

This is not a synonymous or non-coding variant.

BP4

The REVEL score = 0.502, which did not meet the ≤ 0.15 threshold required for BP4.

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.

PP1

As BS1 was met, PP1 did not apply and segregations were not counted.

PP3

The REVEL score = 0.502, which did not meet the ≥ 0.7 threshold for PP3.

BA1

This criterion was not met as BS1 has been met.

PM6

This variant has not been identified de novo.

PM2

This criterion was not met as BS1 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.

Curation History

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