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
  • ClinVar Id was derived from the Allele Registry.
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Variant: NM_000261.2:c.1464C>T

CA1244015

1013537 (ClinVar)

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 4ad91f7a-4e5a-4d60-b8d6-805bd9cc1134

HGVS expressions

NM_000261.2:c.1464C>T
NC_000001.11:g.171635976G>A
CM000663.2:g.171635976G>A
NC_000001.10:g.171605116G>A
CM000663.1:g.171605116G>A
NC_000001.9:g.169871739G>A
NG_008859.1:g.21658C>T
ENST00000037502.11:c.1464C>T
ENST00000637303.1:c.235-2654G>A
ENST00000638471.1:c.*802C>T
ENST00000037502.10:c.1464C>T
ENST00000614688.1:c.*428C>T
NM_000261.1:c.1464C>T

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

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.1464C>T variant in MYOC is a synonymous variant (p.Ala488=). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.001253, which met the ≥ 0.001 threshold set for BS1 (25 alleles out of 19,950), meeting the threshold of ≥ 5 of at least 2,000 observed alleles). Although this synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), it had a CADD score (v1.6) = 10.96, which did not meet the ≤ 10 threshold for BP4 and a GERP score = 2.87 (threshold < 0), not meeting BP7 and indicating conservation at this site. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. As BS1 was met, PP1 did not apply and segregations were not counted. 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) = 0.001253, which met the ≥ 0.001 threshold set for BS1 (25 alleles out of 19,950), meeting the threshold of ≥ 5 of at least 2,000 observed alleles).
Not Met criteria codes
PM5
This is not a missense variant.
PM4
This variant does not cause a protein length change.
PM6
This variant has not been identified de novo.
PM2
This criterion was not met as BS1 has been met.
BA1
This criterion was not met as BS1 has been met.
BS3
No functional evidence has been found for this variant.
BP7
Although this synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), it had a GERP score = 2.87 (threshold < 0), indicating conservation at this site.
BP4
Although this synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), it had a CADD score (v1.6) = 10.96, which does not meet the ≤ 10 threshold for BP4.
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.
PP1
As BS1 was met, PP1 did not apply and segregations were not counted.
PP3
This is not a missense variant.
Approved on: 2023-05-03
Published on: 2023-05-03
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