SEQ

Pathogenicity Calculator

Select evidence codes to see pathogenicity result for your variant. Based on ACMG Standards and Guidelines (2015).
Disclaimer: This feature is experimental and helps you to visualize ACMG standards. It should not be used to give medical reports alone.

Selected Evidence Codes:

None

Result:

Uncertain Significance

Edit Family Segregation (PP1):

PP1

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

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

PS1

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

PS2

De novo (both maternity and paternity confirmed) in a patient with the disease and no family history. (The gene must be associated with the phenotype.)

PS3

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

PS4

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

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

PM2

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

PM3

For recessive disorders, detected in trans with a pathogenic variant

PM4

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

PM5

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

PM6

Assumed de novo, but without confirmation of paternity and maternity

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

PP3

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

PP4

Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology

PP5

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

BA1

Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium

BS1

Allele frequency is greater than expected for disorder

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

BS3

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

BS4

Lack of segregation in affected members of a family

BP1

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

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

BP3

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

BP4

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

BP5

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

BP6

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

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