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.239C>A (p.Thr80Asn)

CA10608383

293721 (ClinVar)

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
UUID: a7e827a3-b8b9-45fc-b2ee-a9d8437cb214

HGVS expressions

NM_000261.2:c.239C>A
NM_000261.2(MYOC):c.239C>A (p.Thr80Asn)
NC_000001.11:g.171652373G>T
CM000663.2:g.171652373G>T
NC_000001.10:g.171621513G>T
CM000663.1:g.171621513G>T
NC_000001.9:g.169888136G>T
NG_008859.1:g.5261C>A
ENST00000037502.11:c.239C>A
ENST00000638471.1:c.130+109C>A
ENST00000037502.10:c.239C>A
ENST00000614688.1:c.239C>A
NM_000261.1:c.239C>A

Uncertain Significance

Met criteria codes 2
BP4 PM2_Supporting
Not Met criteria codes 13
BP7 BA1 PM6 PM5 PM4 PS4 PS2 PS1 PS3 PP1 PP3 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.239C>A variant in MYOC is a missense variant predicted to cause substitution of Threonine by Asparagine at amino acid 80 (p.Thr80Asn). The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v2.1.1) = 0.000008827 (1 allele out of 113,284), which met the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. The REVEL score = 0.083, which met the ≤ 0.15 threshold for BP4, suggesting 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. This variant was identified in laboratory based testing, but has not yet been found in a proband with juvenile or primary open angle glaucoma, thus PS4 did not apply. 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 primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BP4, PM2
Met criteria codes
BP4
The REVEL score = 0.083, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function.
PM2_Supporting
The highest minor allele frequency of this variant was in the European (non-Finnish) population of gnomAD (v2.1.1) = 0.000008827 (1 allele out of 113,284), which met the ≤ 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles.
Not Met criteria codes
BP7
This is not a synonymous or non-coding variant.
BA1
This criterion was not met as PM2_Supporting has been met.
PM6
This variant has not been identified de novo.
PM5
No other missense variants at this amino acid residue have been identified.
PM4
This variant does not cause a protein length change.
PS4
This variant was identified in laboratory based testing, but has not yet been found in a proband with juvenile or primary open angle glaucoma.
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.
PP1
No segregations have been reported for this variant.
PP3
This criterion was not met as BP4 has been met.
BS3
No functional evidence has been found for this variant.
BS1
This criterion was not met as PM2_Supporting has been met.
Approved on: 2023-08-08
Published on: 2023-08-08
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