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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  • See Evidence submitted by expert panel for details.

Variant: NM_000261.2:c.547G>A

CA1244260

1313921 (ClinVar)

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 18e110e1-dc37-4009-b344-a29138965fea

HGVS expressions

NM_000261.2:c.547G>A
NC_000001.11:g.171652065C>T
CM000663.2:g.171652065C>T
NC_000001.10:g.171621205C>T
CM000663.1:g.171621205C>T
NC_000001.9:g.169887828C>T
NG_008859.1:g.5569G>A
ENST00000037502.11:c.547G>A
ENST00000638471.1:c.130+417G>A
ENST00000037502.10:c.547G>A
ENST00000614688.1:c.547G>A
NM_000261.1:c.547G>A
NM_000261.2(MYOC):c.547G>A (p.Gly183Ser)

Uncertain Significance

Met criteria codes 1
BP4
Not Met criteria codes 14
PM6 PM2 PM5 PM4 BS3 BS1 BP7 PS2 PS1 PS3 PS4 BA1 PP1 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.547G>A variant in MYOC is a missense variant predicted to cause substitution of Glycine by Serine at amino acid 183 (p.Gly183Ser). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0006524 (12 alleles out of 18,394), which did not meet the PM2_Supporting allele frequency threshold (≤ 0.0001) or the BS1 allele frequency threshold (≥ 0.001). The REVEL score = 0.126, 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. 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 -1 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.
Met criteria codes
BP4
The REVEL score = 0.126, which met the ≤ 0.15 threshold for BP4, suggesting that the variant does not impact MYOC function.
Not Met criteria codes
PM6
This variant has not been identified de novo.
PM2
The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.0006524 (12 alleles out of 18,394), which did not meet the ≤ 0.0001 threshold set for PM2_Supporting.
PM5
No other missense variants at this amino acid residue have been identified.
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 East Asian population of gnomAD (v2.1.1) = 0.0006524 (12 alleles out of 18,394), which did not meet the ≥ 0.001 threshold set for BS1.
BP7
This is not a synonymous or non-coding variant.
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.
PS4
Although probands with POAG had 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 criterion was not met as BP4 has been met.
Approved on: 2023-02-15
Published on: 2023-02-15
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