PS1
No evidence was identified showing that another nucleotide change causing the same amino acid substitution, p.(Arg21Leu), has already been established as pathogenic or likely pathogenic.
PS2
No confirmed de novo observation with verified maternity and paternity was identified.
PS3
No well-established functional study showing a damaging effect of this specific variant was identified.
PS4
No case-control enrichment or multiple independent affected observations were identified to show that this variant is significantly increased in affected individuals over controls.
PM1
This variant has not been identified in a statistically significant hotspot, and available evidence does not show that codon 21 lies in a well-established critical region without benign variation.
PM5
No evidence was identified showing that a different missense change at the same amino acid residue has already been established as pathogenic or likely pathogenic.
PM6
No assumed de novo observation without confirmed parentage was identified.
PP1
No segregation data were identified to show that this variant tracks with disease in affected family members.
PP2
Available evidence does not establish that pathogenic missense variation is a common disease mechanism in BARD1 or that this gene has a low rate of benign missense variation sufficient for PP2.
PP3
Available computational evidence does not support a deleterious effect.
PP4
No phenotype or family history data were identified showing a highly specific clinical presentation attributable to a single genetic cause for this variant assessment.
PP5
ClinVar reports this variant as uncertain significance rather than pathogenic or likely pathogenic, so external classification evidence does not support PP5.
