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]
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data

Variant: NM_000261.2:c.1008C>T

CA343725131

2575098 (ClinVar)

Gene: MYOC
Condition: juvenile open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 20a98120-57b2-4101-aa41-7e0d4cd2a1b7
Approved on: 2023-08-08
Published on: 2023-08-08

HGVS expressions

NM_000261.2:c.1008C>T
NC_000001.11:g.171636432G>A
CM000663.2:g.171636432G>A
NC_000001.10:g.171605572G>A
CM000663.1:g.171605572G>A
NC_000001.9:g.169872195G>A
NG_008859.1:g.21202C>T
ENST00000037502.11:c.1008C>T
ENST00000637303.1:c.235-2198G>A
ENST00000638471.1:c.*346C>T
ENST00000037502.10:c.1008C>T
ENST00000614688.1:c.1008C>T
NM_000261.1:c.1008C>T
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Uncertain Significance

Met criteria codes 2
PM2_Supporting BP4
Not Met criteria codes 13
PM6 PM5 PM4 BA1 BS1 BS3 BP7 PS1 PS2 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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.1008C>T variant in MYOC is a synonymous variant (p.Phe336=). This variant was not found in any population of gnomAD (v2.1.1), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. The CADD score (v1.6) = 7.603, 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. However, BP7 was not met as this variant had a GERP score = 3.56 (threshold < 0), indicating conservation at this site. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Only 1 segregation had been reported for juvenile open angle glaucoma (JOAG) (PMID: 19688280), not meeting the ≥ 3 segregations required for PP1. Only 1 proband with JOAG had been reported (PMID: 19688280), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 0 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BP4, PM2_Supporting.
Met criteria codes
PM2_Supporting
This variant was not found in any population of gnomAD (v2.1.1), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles.
BP4
The CADD score (v1.6) = 7.603, 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.
PM5
This is not a missense variant.
PM4
This variant does not cause a protein length change.
BA1
This criterion was not met as PM2_Supporting has been met.
BS1
This criterion was not met as PM2_Supporting has been met.
BS3
No functional evidence has been found for this variant.
BP7
Although this synonymous/non-coding variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2), it had a GERP score = 3.56 (threshold <0), indicating conservation at this site.
PS1
This variant does not involve an amino acid change.
PS2
This variant has not been identified de novo.
PS3
No functional evidence has been found for this variant.
PS4
Only 1 proband with JOAG had been reported (PMID: 19688280), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting.
PP1
Only 1 segregation had been reported for juvenile open angle glaucoma (PMID: 19688280), not meeting the ≥ 3 segregations required for PP1.
PP3
This is not a missense variant.
Curation History
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