ACMG classification of variants frontend

[pontikos]

[pontikos]

ACMG guidelines: http://wintervar.wglab.org/evds2.php?&pvs1=0&ps1=0&ps2=0&ps3=0&ps4=0&pm1=1&pm2=1&pm3=0&pm4=0&pm5=0&pm6=0&pp1=0&pp2=0&pp3=1&pp4=0&pp5=1&ba1=0&bs1=0&bs2=0&bs3=0&bs4=0&bp1=0&bp2=0&bp3=0&bp4=0&bp5=0&bp6=0&bp7=0&chr=1&start=115828756&ref=G&alt=A&gene=NGF&clnsg=Likely%20pathogenic

Re-Interpret your variant with position: 1:115828756 Ref:G Alt:A Gene: NGF The automated clinical interpretation is : Likely pathogenic ,but you can manually adjust it by checking/unchecking the criteria below The blue color represents the criteria that need manual adjustment PVS1: null variant (nonsense, frameshift, canonical +- 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease

Strong PS1: Same amino acid change as a previously established pathogenic variant regardless of nucleotide change

Strong PS2: De novo (both maternity and paternity confirmed) in a patient with the disease and no family history

Strong PS3: Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product

Strong PS4: The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls

Strong PS5: The user has additional 1 strong pathogenic evidence

Moderate 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

Moderate PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium

Moderate PM3: For recessive disorders, detected in trans with a pathogenic variant

Moderate PM4: Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants

Moderate PM5: Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before

Moderate PM6: Assumed de novo, but without confirmation of paternity and maternity

Moderate PM7: The user has additional 1 moderate pathogenic evidence

Supporting PP1: Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease

Supporting 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

Supporting PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)

Supporting PP4: Patient's phenotype or family history is highly specific for a disease with a single genetic etiology

Supporting PP5: Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation

Supporting PP6: The user has additional 1 supporting pathogenic evidence BA1: Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium

Strong BS1: Allele frequency is greater than expected for disorder

Strong 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

Strong BS3: Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing

Strong BS4: Lack of segregation in affected members of a family

Strong BS5: The user has additional 1 strong benign evidence

Supporting BP1: Missense variant in a gene for which primarily truncating variants are known to cause disease

Supporting 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

Supporting BP3: In-frame deletions/insertions in a repetitive region without a known function

Supporting BP4: Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)

Supporting BP5: Variant found in a case with an alternate molecular basis for disease

Supporting BP6: Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation

Supporting 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

Supporting BP8: The user has additional 1 supporting benign evidence

[pontikos]

https://www.acmg.net/docs/Standards_Guidelines_for_the_Interpretation_of_Sequence_Variants.pdf