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]
  • See Evidence submitted by expert panel for details.

Variant: NM_000261.2(MYOC):c.1188G>A (p.Glu396=)

CA1244067

293708 (ClinVar)

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: d74b9dfa-bc9e-40bf-8ead-a22f57f27e68
Approved on: 2022-05-10
Published on: 2022-05-25

HGVS expressions

NM_000261.2:c.1188G>A
NM_000261.2(MYOC):c.1188G>A (p.Glu396=)
NC_000001.11:g.171636252C>T
CM000663.2:g.171636252C>T
NC_000001.10:g.171605392C>T
CM000663.1:g.171605392C>T
NC_000001.9:g.169872015C>T
NG_008859.1:g.21382G>A
ENST00000037502.11:c.1188G>A
ENST00000637303.1:c.235-2378C>T
ENST00000638471.1:c.*526G>A
ENST00000037502.10:c.1188G>A
ENST00000614688.1:c.*152G>A
NM_000261.1:c.1188G>A
More

Benign

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

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.1188G>A variant in MYOC is a synonymous variant (p.Glu396=). The highest minor allele frequency of this variant was in the African/African American population of gnomAD (v2.1.1) = 0.02893, which met the ≥ 0.01 threshold set for BA1 (722 alleles out of 24,958, 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) = 0.360 which met the ≤ 10 threshold for BP4, and the GERP score = -4.66 (threshold < 0), indicating a lack of conservation at this site (BP7). This evidence suggests 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 POAG have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant was classified as benign (BA1 is a stand-alone criterion for a benign level of pathogenicity) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BA1, BP4, BP7
Met criteria codes
BP7
This synonymous variant was not predicted to affect splicing, as assessed with SpliceAI (≤ 0.2) and had a GERP score = -4.66 (threshold <0), indicating a lack of conservation at this site.
BP4
The CADD score (v1.6) = 0.360, 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.
BA1
The highest minor allele frequency of this variant was in the African/African American population of gnomAD (v2.1.1) = 0.02893, which met the ≥ 0.01 threshold set for BA1 (722 alleles out of 24,958, meeting the threshold of ≥ 5 of at least 2,000 observed alleles).
Not Met criteria codes
BS3
No functional evidence has been found for this variant.
BS1
This criterion was not met as BA1 has been met.
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 have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply.
PP1
As BA1 was met, PP1 did not apply and segregations were not counted.
PP3
This is not a missense variant.
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 BA1 has been met.
Curation History
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