Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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  • No ClinVar Id was directly found from the curated document

CA1244115

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f00fce4a-51a0-425b-941c-2ef5f72cae33

HGVS expressions

NM_000261.2:c.938C>T
NC_000001.11:g.171636502G>A
CM000663.2:g.171636502G>A
NC_000001.10:g.171605642G>A
CM000663.1:g.171605642G>A
NC_000001.9:g.169872265G>A
NG_008859.1:g.21132C>T
ENST00000037502.11:c.938C>T
ENST00000637303.1:c.235-2128G>A
ENST00000638471.1:c.*276C>T
ENST00000037502.10:c.938C>T
ENST00000614688.1:c.938C>T
NM_000261.1:c.938C>T

Uncertain Significance

The Expert Panel has overridden the computationally generated classification - "[unknown]"
Not Met criteria codes 15
PS2 PS1 PS3 PS4 BP4 BP7 BA1 PP1 PP3 PM5 PM4 PM6 PM2 BS3 BS1

Evidence Links 0

Expert Panel

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.938C>T variant in MYOC is a missense variant predicted to cause substitution of Serine by Phenylalanine at amino acid 313 (p.Ser313Phe). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0008024 (16 alleles out of 19,940), which did not meet the PM2_Supporting allele frequency threshold (≤ 0.0001) or the BS1 allele frequency threshold (≥ 0.001). The REVEL score = 0.554, 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 did not meet any criteria, receiving a score of 0 and a classification 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): none.
Not Met criteria codes
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.
BP4
The REVEL score = 0.554, which did not meet the ≤ 0.15 threshold required for BP4.
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).
PP1
No segregations have been reported for this variant.
PP3
REVEL score = 0.554 which does not meet the ≥0.7 threshold required for this criterion.
PM5
No other missense variants at this amino acid residue have been identified.
PM4
This variant does not cause a protein length change.
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) = 0.0008024 (16 alleles out of 19,940), which did not meet the ≤ 0.0001 threshold set for PM2_Supporting.
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) = 0.0008024 (16 alleles out of 19,940), which did not meet the ≥ 0.001 threshold set for BS1.
Approved on: 2023-02-15
Published on: 2023-02-15
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