owencqueen/cgbench_data huggingface dataset:
Gene: Unknown
Evidence Code: PVS1 — Original ACMG Summary
Null variant (nonsense, frameshift, canonical +/−1 or 2 splice sites, initiation codon, single or multi-exon deletion) in a gene where loss of function (LOF) is a known mechanism of disease.
Caveats:
 • Beware of genes where LOF is not a known disease mechanism (e.g. GFAP, MYH7).
 • Use caution interpreting LOF variants at the extreme 3’ end of a gene.
 • Use caution with splice variants that are predicted to lead to exon skipping but leave the remainder of the protein intact.
 • Use caution in the presence of multiple transcripts.
Gene: Unknown
Evidence Code: PVS1 — Very Strong
Large heteroplasmic mtDNA deletions, where at least one gene is completely deleted
Gene: Unknown
Evidence Code: PVS1 — Strong
Assessment of small deletions, nonsense, and frameshift variants in protein-coding genes should follow established guidelines (Abou Tayoun et al., 2018)
Gene: Unknown
Evidence Code: PVS1 — Moderate
Assessment of small deletions, nonsense, and frameshift variants in protein-coding genes should follow established guidelines (Abou Tayoun et al., 2018)
Gene: Unknown
Evidence Code: PVS1 — Supporting
Assessment of small deletions, nonsense, and frameshift variants in protein-coding genes should follow established guidelines (Abou Tayoun et al., 2018)
Gene: Unknown
Evidence Code: PS1 — Original ACMG Summary
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change.
Example: Val->Leu caused by either G>C or G>T in the same codon.
Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
Gene: Unknown
Evidence Code: PS1 — Strong
Applied per original ACMG/AMP guidelines
Gene: Unknown
Evidence Code: PS2 — Original ACMG Summary
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
Note: Confirmation of paternity only is insufficient. Egg donation, surrogate motherhood, errors in embryo transfer, etc. can contribute to non-maternity.
Gene: Unknown
Evidence Code: PS2 — Very Strong
De novo (maternity confirmed or identical full mtDNA sequence) in a patient with the disease and no family history; with weighting per ClinGen SVI guidance
Gene: Unknown
Evidence Code: PS2 — Strong
De novo (maternity confirmed or identical full mtDNA sequence) in a patient with the disease and no family history; with weighting per ClinGen SVI guidance
Gene: Unknown
Evidence Code: PS2 — Moderate
De novo (maternity confirmed or identical full mtDNA sequence) in a patient with the disease and no family history; with weighting per ClinGen SVI guidance
Gene: Unknown
Evidence Code: PS2 — Supporting
De novo (maternity confirmed or identical full mtDNA sequence) in a patient with the disease and no family history; with weighting per ClinGen SVI guidance
Gene: Unknown
Evidence Code: PS3 — Original ACMG Summary
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
Note: Functional studies that have been validated and shown to be reproducible and robust in a clinical diagnostic laboratory setting are considered the most well-established.
Gene: Unknown
Evidence Code: PS3 — Supporting
Functional validation is present in cybrid studies or single fiber analysis
Gene: Unknown
Evidence Code: PS4 — Original ACMG Summary
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls.
Note 1: Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0. See manuscript for detailed guidance.
Note 2: In instances of very rare variants where case-control studies may not reach statistical significance, the prior observation of the variant in multiple unrelated patients with the same phenotype, and its absence in controls, may be used as moderate level of evidence.
Gene: Unknown
Evidence Code: PS4 — Strong
Variant present in ≥16 unrelated probands
Gene: Unknown
Evidence Code: PS4 — Moderate
Variant present in ≥4 unrelated probands
Gene: Unknown
Evidence Code: PS4 — Supporting
Variant present in 2 unrelated probands in different top-level haplogroups
Gene: Unknown
Evidence Code: PM1 — Original ACMG Summary
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
Gene: Unknown
Evidence Code: PM2 — Original ACMG Summary
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
Caveat: Population data for indels may be poorly called by next generation sequencing.
Gene: Unknown
Evidence Code: PM2 — Supporting
Frequency <0.00002 (0.002%, 1/50,000) from controls
Gene: Unknown
Evidence Code: PM3 — Original ACMG Summary
For recessive disorders, detected in trans with a pathogenic variant
Note: This requires testing of parents (or offspring) to determine phase.
Gene: Unknown
Evidence Code: PM4 — Original ACMG Summary
Protein length changes due to in-frame deletions/insertions in a non-repeat region or stop-loss variants.
Gene: Unknown
Evidence Code: PM4 — Moderate
Applied per original ACMG/AMP guidelines
Gene: Unknown
Evidence Code: PM5 — Original ACMG Summary
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.
Example: Arg156His is pathogenic; now you observe Arg156Cys.
Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
Gene: Unknown
Evidence Code: PM5 — Moderate
Applied per original ACMG/AMP guidelines (protein-coding genes)
Gene: Unknown
Evidence Code: PM5 — Supporting
Same nucleotide position as previously established pathogenic variant in a rRNA/tRNA
Gene: Unknown
Evidence Code: PM6 — Original ACMG Summary
Assumed de novo, but without confirmation of paternity and maternity.
Gene: Unknown
Evidence Code: PM6 — Very Strong
Assumed de novo, but without confirmation of maternity (maternal testing done by targeted variant analysis and/or targeted gene sequencing)
Gene: Unknown
Evidence Code: PM6 — Strong
Assumed de novo, but without confirmation of maternity (maternal testing done by targeted variant analysis and/or targeted gene sequencing)
Gene: Unknown
Evidence Code: PM6 — Moderate
Assumed de novo, but without confirmation of maternity (maternal testing done by targeted variant analysis and/or targeted gene sequencing)
Gene: Unknown
Evidence Code: PM6 — Supporting
Assumed de novo, but without confirmation of maternity (maternal testing done by targeted variant analysis and/or targeted gene sequencing)
Gene: Unknown
Evidence Code: PP1 — Original ACMG Summary
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease.
Note: May be used as stronger evidence with increasing segregation data.
Gene: Unknown
Evidence Code: PP1 — Moderate
Co-segregation with disease in 5+ maternal family members and level of heteroplasmy segregating with disease manifestations
Gene: Unknown
Evidence Code: PP1 — Supporting
Co-segregation with disease in 2-4 maternal family members and level of heteroplasmy segregating with disease manifestations
Gene: Unknown
Evidence Code: PP2 — Original ACMG Summary
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
Gene: Unknown
Evidence Code: PP3 — Original ACMG Summary
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
Caveat: As many in silico algorithms use the same or very similar input for their predictions, each algorithm should not be counted as an independent criterion. PP3 can be used only once in any evaluation of a variant.
Gene: Unknown
Evidence Code: PP3 — Supporting
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, etc)
Gene: Unknown
Evidence Code: PP4 — Original ACMG Summary
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
Gene: Unknown
Evidence Code: PP4 — Supporting
Decreased ETC enzyme activity (<20%) performed in a CLIA-approved (or equivalently-certified) laboratory in muscle, liver, and/or fibroblasts (for fibroblasts, must be seen in multiple unrelated probands and/or assayed in different individuals).
Gene: Unknown
Evidence Code: PP5 — Original ACMG Summary
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
Gene: Unknown
Evidence Code: BA1 — Original ACMG Summary
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
Gene: Unknown
Evidence Code: BA1 — Stand Alone
Top-level haplogroup defining variants in individuals that are members of that same top-level haplogroup OR Allele frequency > 0.01 (1%)
Gene: Unknown
Evidence Code: BS1 — Original ACMG Summary
Allele frequency is greater than expected for disorder.
Gene: Unknown
Evidence Code: BS1 — Strong
Allele frequency 0.005 - 0.0099 (0.5% - 0.99%)
Gene: Unknown
Evidence Code: BS2 — Original ACMG Summary
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
Gene: Unknown
Evidence Code: BS2 — Strong
Observed at a higher heteroplasmy in a healthy adult individual, especially in healthy maternal family members, than in same tissue tested in an affected individual
Gene: Unknown
Evidence Code: BS2 — Supporting
Observed at a higher heteroplasmy in a healthy adult individual, especially in healthy maternal family members, than in different tissue(s) tested in an affected individual
Gene: Unknown
Evidence Code: BS3 — Original ACMG Summary
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
Gene: Unknown
Evidence Code: BS3 — Supporting
No evidence of functional effect in cybrid studies or single fiber analysis is present (no statistically significant difference from control; mean values of <2 SD from control mean, or 50% enzyme activity compared to controls).
Gene: Unknown
Evidence Code: BS4 — Original ACMG Summary
Lack of segregation in affected members of a family.
Caveat: The presence of phenocopies for common phenotypes (i.e. cancer, epilepsy) can mimic lack of segregation among affected individuals. Also, families may have more than one pathogenic variant contributing to an autosomal dominant disorder, further confounding an apparent lack of segregation.
Gene: Unknown
Evidence Code: BS4 — Strong
Lack of segregation in affected members of a family and/or segregation of disease in paternal family members
Gene: Unknown
Evidence Code: BP1 — Original ACMG Summary
Missense variant in a gene for which primarily truncating variants are known to cause disease.
Gene: Unknown
Evidence Code: BP2 — Original ACMG Summary
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
Gene: Unknown
Evidence Code: BP2 — Supporting
Other mtDNA variant is observed in individual’s mtDNA that has previously been confirmed to be pathogenic
Gene: Unknown
Evidence Code: BP3 — Original ACMG Summary
In frame-deletions/insertions in a repetitive region without a known function.
Gene: Unknown
Evidence Code: BP4 — Original ACMG Summary
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
Caveat: As many in silico algorithms use the same or very similar input for their predictions, each algorithm cannot be counted as an independent criterion. BP4 can be used only once in any evaluation of a variant.
Gene: Unknown
Evidence Code: BP4 — Supporting
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, etc)
Gene: Unknown
Evidence Code: BP5 — Original ACMG Summary
Variant found in a case with an alternate molecular basis for disease.
Gene: Unknown
Evidence Code: BP5 — Supporting
Mitochondrial DNA variant found in a case with a nuclear DNA-related disease
Gene: Unknown
Evidence Code: BP6 — Original ACMG Summary
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
Gene: Unknown
Evidence Code: BP7 — Original ACMG Summary
A synonymous variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved.
Gene: Unknown
Evidence Code: BP7 — Supporting
A synonymous (silent) variant.