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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CA1244123

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: ab562f1c-0583-4ffd-9e76-524167f636e9

HGVS expressions

NM_000261.2:c.906C>T
NC_000001.11:g.171636534G>A
CM000663.2:g.171636534G>A
NC_000001.10:g.171605674G>A
CM000663.1:g.171605674G>A
NC_000001.9:g.169872297G>A
NG_008859.1:g.21100C>T
ENST00000037502.11:c.906C>T
ENST00000637303.1:c.235-2096G>A
ENST00000638471.1:c.*244C>T
ENST00000037502.10:c.906C>T
ENST00000614688.1:c.906C>T
NM_000261.1:c.906C>T

Likely Benign

Met criteria codes 2
BP4 BP7
Not Met criteria codes 13
PS2 PS1 PS3 PS4 BA1 PP1 PP3 PM6 PM2 PM5 PM4 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.906C>T variant in MYOC is a synonymous variant (p.Asp302=). The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v2.1.1) = 0.0002977 (38 alleles out of 127,636), which did not meet the PM2_Supporting allele frequency threshold (≤ 0.0001) or the BS1 allele frequency threshold (≥ 0.001). This variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), with a CADD score (v1.6) = 0.289 which met the ≤ 10 threshold for BP4, and the GERP score = -2.74 (threshold < 0), indicating a lack of conservation at this site (BP7). This evidence suggests 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. 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 -2 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): BP4, BP7.
Met criteria codes
BP4
The CADD score (v1.6) = 0.289, which met the ≤ 10 threshold for BP4 and this variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), suggesting that the variant does not impact MYOC function.
BP7
This synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2) and had a GERP score = -2.74 (threshold <0), indicating a lack of conservation at this site.
Not Met criteria codes
PS2
This variant has not been identified de novo.
PS1
This variant does not involve an amino acid change.
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 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
This is not a missense variant.
PM6
This variant has not been identified de novo.
PM2
The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v2.1.1) = 0.0002977 (38 alleles out of 127,636), which did not meet the ≤ 0.0001 threshold set for PM2_Supporting.
PM5
This is not a missense variant.
PM4
This variant does not cause a protein length change.
BS3
No functional evidence has been found for this variant.
BS1
The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v2.1.1) = 0.0002977 (38 alleles out of 127,636), which did not meet the ≥ 0.001 threshold set for BS1.
Approved on: 2022-12-14
Published on: 2022-12-14
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