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]
Link to SEPIO compliant JSON-LD document
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.
  • 'cspec' property is found but contains no ID!
  • See Evidence submitted by expert panel for details.

Variant: NM_000261.2:c.57G>T

CA1244336

1684937 (ClinVar)

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 4595b4a3-b5fb-4f21-95d8-796203d9e5e1

HGVS expressions

NM_000261.2:c.57G>T
NC_000001.11:g.171652555C>A
CM000663.2:g.171652555C>A
NC_000001.10:g.171621695C>A
CM000663.1:g.171621695C>A
NC_000001.9:g.169888318C>A
NG_008859.1:g.5079G>T
ENST00000037502.11:c.57G>T
ENST00000638471.1:c.57G>T
ENST00000037502.10:c.57G>T
ENST00000614688.1:c.57G>T
NM_000261.1:c.57G>T
NM_000261.2(MYOC):c.57G>T (p.Gln19His)

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 1
BS1
Not Met criteria codes 14
PM6 PM2 PM5 PM4 BS3 BP7 BP4 PS2 PS1 PS3 PS4 BA1 PP1 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.57G>T variant in MYOC is a missense variant predicted to cause substitution of Glutamine by Histidine at amino acid 19 (p.Gln19His). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.003559, which met the ≥ 0.001 threshold set for BS1 (71 alleles out of 19 952, meeting the threshold of ≥ 5 of at least 2,000 observed alleles). The REVEL score = 0.256, 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
Met criteria codes
BS1
The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.003559, which met the ≥ 0.001 threshold set for BS1 (71 alleles out of 19 952, meeting the threshold of ≥ 5 of at least 2,000 observed alleles).
Not Met criteria codes
PM6
This variant has not been identified de novo.
PM2
This criterion was not met as BS1 has been met.
PM5
PM5_Supporting could not be applied to this variant as the other missense variant at the same amino acid residue (c.55C>A, p.Gln19Lys) was not classified as likely pathogenic or pathogenic.
PM4
This variant does not cause a protein length change.
BS3
No functional evidence has been found for this variant.
BP7
This is not a synonymous or non-coding variant.
BP4
The REVEL score = 0.256, 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.
BA1
This criterion was not met as BS1 has been met.
PP1
As BS1 was met, PP1 did not apply and segregations were not counted.
PP3
The REVEL score = 0.256, which did not meet the ≥ 0.7 threshold for PP3.
Approved on: 2023-02-15
Published on: 2023-02-15
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