owencqueen/cgbench_data huggingface dataset:
Gene: MYOC (HGNC:7610)
Evidence Code: PS2 — Strong
≥2 confirmed de novo in JOAG
Use the proposed SVI point recommendations for “phenotype consistent with gene but not highly specific” for JOAG




Both maternity and paternity need to be proven for confirmed de novo variants.


Parents need to be clinically assessed and not have a diagnosis of glaucoma.
Gene: MYOC (HGNC:7610)
Evidence Code: PS2 — Supporting
1 confirmed de novo in POAG
Use proposed SVI point recommendations for “phenotype consistent with the gene but not highly specific and with high genetic heterogeneity” for POAG. 




Both maternity and paternity need to be proven for confirmed de novo variants. 


Parents need to be clinically assessed and not have a diagnosis of glaucoma.
Gene: MYOC (HGNC:7610)
Evidence Code: PS3 — Strong
Assays with OddsPath >18.7 as per the SVI recommendations




Applies to the following functional studies: Solubility or secretion assays OR animal models that replicate the glaucoma phenotype.


PS3 should only be applied if the assay includes both negative and positive controls and includes technical and/or biological replicates.


If multiple results from functional assays are available for a single variant, then the evidence from the assay that is best validated should apply.


Controls from the same general class of assay can be combined to calculate the odds of pathogenicity (OddsPath) as per the published SVI recommendations.


If results from different assays are conflicting for a single variant, then the level of validation of each assay should be considered to decide whether the results from one assay can override the results from another.
Gene: MYOC (HGNC:7610)
Evidence Code: PS3 — Supporting
Assays with OddsPath >2.1 as per the SVI recommendations




Applies to the following functional studies: Solubility or secretion assays OR animal models that replicate the glaucoma phenotype.


PS3 should only be applied if the assay includes both negative and positive controls and includes technical and/or biological replicates.


If multiple results from functional assays are available for a single variant, then the evidence from the assay that is best validated should apply.


Controls from the same general class of assay can be combined to calculate the odds of pathogenicity (OddsPath) as per the published SVI recommendations.


If results from different assays are conflicting for a single variant, then the level of validation of each assay should be considered to decide whether the results from one assay can override the results from another.
Gene: MYOC (HGNC:7610)
Evidence Code: PS4 — Strong
≥ 15 probands from multiple independent studies




Probands counted should be clinically assessed and have a diagnosis of JOAG or POAG.


PM2_Supporting must be met.
Gene: MYOC (HGNC:7610)
Evidence Code: PS4 — Moderate
≥ 6 probands from multiple independent studies




Probands counted should be clinically assessed and have a diagnosis of JOAG or POAG.


PM2_Supporting must be met.
Gene: MYOC (HGNC:7610)
Evidence Code: PS4 — Supporting
≥ 2 probands from multiple independent studies




Probands counted should be clinically assessed and have a diagnosis of JOAG or POAG.


PM2_Supporting must be met.
Gene: MYOC (HGNC:7610)
Evidence Code: PM2 — Supporting
Allele frequency ≤ 0.0001 in population databases




The highest allele frequency in population databases should be used. 


Only applies to populations of ≥ 10,000 alleles.
Gene: MYOC (HGNC:7610)
Evidence Code: PM4 — Moderate
In-frame del/ins and truncating variants involving >10% of the protein and located within the conserved olfactomedin domain (AA 246-502)
Gene: MYOC (HGNC:7610)
Evidence Code: PM4 — Supporting
In-frame del/ins and truncating variants involving ≤10% of the protein and located within the conserved olfactomedin domain (AA 246-502)
Gene: MYOC (HGNC:7610)
Evidence Code: PM5 — Supporting
Same residue as a previously established likely pathogenic variant (assessed independently of PM5)




The novel change must not affect splicing (SpliceAI ≤ 0.2), must meet PP3 and have a Grantham score equal or greater than the previously established P/LP variants.
Gene: MYOC (HGNC:7610)
Evidence Code: PM6 — Moderate
≥2 assumed de novo in JOAG
Use proposed SVI point recommendations for “phenotype consistent with gene but not highly specific” for JOAG.




Both maternity and paternity need to be proven for confirmed de novo variants.


Parents need to be clinically assessed and not have a diagnosis of glaucoma.
Gene: MYOC (HGNC:7610)
Evidence Code: PP1 — Strong
≥7 meioses in >1 family




BA1 and BS1 must not be met.


Only genotype positive/phenotype positive and obligate carriers/phenotype positive individuals should be counted as segregations.


Phenotype positive need to be clinically assessed and either have a diagnosis of glaucoma or suspicious signs of glaucoma.
Gene: MYOC (HGNC:7610)
Evidence Code: PP1 — Moderate
≥ 5 meioses




BA1 and BS1 must not be met.


Only genotype positive/phenotype positive and obligate carriers/phenotype positive individuals should be counted as segregations.


Phenotype positive need to be clinically assessed and either have a diagnosis of glaucoma or suspicious signs of glaucoma.
Gene: MYOC (HGNC:7610)
Evidence Code: PP1 — Supporting
≥ 3 meioses




BA1 and BS1 must not be met.


Only genotype positive/phenotype positive and obligate carriers/phenotype positive individuals should be counted as segregations.


Phenotype positive need to be clinically assessed and either have a diagnosis of glaucoma or suspicious signs of glaucoma.
Gene: MYOC (HGNC:7610)
Evidence Code: PP3 — Supporting
Applies to missense variants with a REVEL score of ≥ 0.7
Gene: MYOC (HGNC:7610)
Evidence Code: BA1 — Stand Alone
Allele frequency ≥ 0.01 in population databases




The highest allele frequency in population databases should be used.


Variant must be present in ≥ 5 alleles in any validated general continental population dataset of at least 2,000 observed alleles.
Gene: MYOC (HGNC:7610)
Evidence Code: BS1 — Strong
Allele frequency ≥ 0.001 in population databases




The highest allele frequency in population databases should be used. 


Variant must be present in ≥ 5 alleles in any validated general continental population dataset of at least 2,000 observed alleles. 


Does not apply to p.Gln368Ter.
Gene: MYOC (HGNC:7610)
Evidence Code: BS3 — Moderate
Applies to variants showing solubility or secretion in functional assays for studies with OddsPath <0.23 as per the SVI recommendations




Only apply if the assay includes both negative and positive controls and includes technical and/or biological replicates.


If multiple results from functional assays are available for a single variant, then the evidence from the assay that is best validated should apply.


Controls from the same general class of assay can be combined to calculate the odds of pathogenicity (OddsPath) as per the published SVI recommendations.


If results from different assays are conflicting for a single variant, then the level of validation of each assay should be considered to decide whether the results from one assay can override the results from another.
Gene: MYOC (HGNC:7610)
Evidence Code: BS3 — Supporting
Applies to variants showing solubility or secretion in functional assays for studies with OddsPath <0.48 as per the SVI recommendations




Only apply if the assay includes both negative and positive controls and includes technical and/or biological replicates.


If multiple results from functional assays are available for a single variant, then the evidence from the assay that is best validated should apply.


Controls from the same general class of assay can be combined to calculate the odds of pathogenicity (OddsPath) as per the published SVI recommendations.


If results from different assays are conflicting for a single variant, then the level of validation of each assay should be considered to decide whether the results from one assay can override the results from another.
Gene: MYOC (HGNC:7610)
Evidence Code: BP4 — Supporting
Applies to:




Missense variants with a REVEL score of ≤ 0.15


Synonymous variants or noncoding variants with a CADD score of ≤ 10 AND SpliceAI ≤ 0.2
Gene: MYOC (HGNC:7610)
Evidence Code: BP7 — Supporting
Applies to synonymous variants or noncoding variants with no impact on splicing (SpliceAI ≤ 0.2) and GERP <0 for conservation