ACMG Criterion Value Set

TODO

SEPIO:0000395

Summary

IRI
SEPIO:0000395
Name
ACMG Criterion Value Set
Description
TODO

Included Codes

This value set includes codes from the following identifier systems:

  • Include any concept from http://purl.obolibrary.org/obo/sepio-clingen# ( ClinGen extensions to SEPIO )

Expansion

This value set is extensible and therefore can be extended to include concepts from the listed identifier systems by adding on the fly concepts defined by a sending system if no viable option from any of the identifier systems is acceptable.

This value set contains 28 concepts.

IRI Label Description
SEPIO-CG:99022 PVS1 null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease
SEPIO-CG:99023 PS1 Same amino acid change as a previously established pathogenic variant regardless of nucleotide change
SEPIO-CG:99024 PS2 De novo (both maternity and paternity confirmed) in a patient with the disease and no family history
SEPIO-CG:99025 PS3 Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product
SEPIO-CG:99026 PS4 The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls
SEPIO-CG:99027 PM1 Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation
SEPIO-CG:99028 PM2 Absent from controls (or at extremely low frequency if recessive) (Table 6) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
SEPIO-CG:99029 PM3 For recessive disorders, detected in trans with a pathogenic variant
SEPIO-CG:99030 PM4 Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants
SEPIO-CG:99031 PM5 Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before
SEPIO-CG:99032 PM6 Assumed de novo, but without confirmation of paternity and maternity
SEPIO-CG:99033 PP1 Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease
SEPIO-CG:99034 PP2 Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease
SEPIO-CG:99035 PP3 Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)
SEPIO-CG:99036 PP4 Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology
SEPIO-CG:99037 PP5 Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
SEPIO-CG:99038 BA1 Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
SEPIO-CG:99039 BS1 Allele frequency is greater than expected for disorder
SEPIO-CG:99040 BS2 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
SEPIO-CG:99041 BS3 Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing
SEPIO-CG:99042 BS4 Lack of segregation in affected members of a family
SEPIO-CG:99043 BP1 Missense variant in a gene for which primarily truncating variants are known to cause disease
SEPIO-CG:99044 BP2 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
SEPIO-CG:99045 BP3 In-frame deletions/insertions in a repetitive region without a known function
SEPIO-CG:99046 BP4 Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
SEPIO-CG:99047 BP5 Variant found in a case with an alternate molecular basis for disease
SEPIO-CG:99048 BP6 Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
SEPIO-CG:99049 BP7 A synonymous (silent) 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