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(MYOC):c.864C>T (p.Ile288=)

CA1244136

874154 (ClinVar)

Gene: MYOC
Condition: juvenile open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: 61aa02eb-f312-4cfd-9268-ac6b223edaed

HGVS expressions

NM_000261.2:c.864C>T
NM_000261.2(MYOC):c.864C>T (p.Ile288=)
NC_000001.11:g.171636576G>A
CM000663.2:g.171636576G>A
NC_000001.10:g.171605716G>A
CM000663.1:g.171605716G>A
NC_000001.9:g.169872339G>A
NG_008859.1:g.21058C>T
ENST00000037502.11:c.864C>T
ENST00000637303.1:c.235-2054G>A
ENST00000638471.1:c.*202C>T
ENST00000037502.10:c.864C>T
ENST00000614688.1:c.864C>T
NM_000261.1:c.864C>T

Likely Benign

Met criteria codes 3
BS1 BP7 BP4
Not Met criteria codes 12
PM6 PM2 PM5 PM4 BS3 PS2 PS1 PS3 PS4 PP3 PP1 BA1

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.864C>T variant in MYOC is a synonymous variant (p.Ile288=). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.003060, which met the ≥ 0.001 threshold set for BS1 (61 alleles out of 19 934, meeting the threshold of ≥ 5 of at least 2,000 observed alleles). This variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), with a CADD score (v1.6) = 0.181 which met the ≤ 10 threshold for BP4, and the GERP score = -6.07 (threshold < 0), indicating a lack of conservation at this site (BP7). This evidence suggests that the variant does not impact MYOC function. Although probands with juvenile or 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 -6 and to be classified as likely benign (likely benign classification range -2 to -6) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BS1, BP4, BP7.
Met criteria codes
BS1
The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.003060, which met the ≥ 0.001 threshold set for BS1 (61 alleles out of 19 934, meeting the threshold of ≥ 5 of at least 2,000 observed alleles).
BP7
This synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2) and had a GERP score = -6.07 (threshold <0), indicating a lack of conservation at this site.
BP4
The CADD score (v1.6) = 0.181 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.
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
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.
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 JOAG or POAG have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply.
PP3
This is not a missense variant.
PP1
As BS1 was met, PP1 did not apply and segregations were not counted.
BA1
This criterion was not met as BS1 has been met.
Approved on: 2022-02-21
Published on: 2022-07-11
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.