This variant is a missense substitution in BARD1 (NM_000465.4:c.928T>G, p.Ser310Ala) located in exon 4. BARD1 is a tumor suppressor gene involved in the DNA damage response, with germline loss-of-function variants associated with hereditary breast and ovarian cancer susceptibility.¹ This variant is absent from gnomAD v2.1 and is present at an extremely low frequency in gnomAD v4.1 (AF = 6.20e-6; 10/1,613,658 alleles, all in the European non-Finnish subpopulation; 0 homozygotes). This extremely low population frequency meets PM2 at supporting strength (well below the 0.1% threshold).² Multiple lines of computational evidence predict a benign effect. REVEL score is 0.086 (strongly benign-leaning). BayesDel score is -0.575 (benign-leaning). SpliceAI max delta score is 0.02, predicting no splicing impact. Multiple independent clinical laboratories concurred that in silico tools predict a benign effect, with Labcorp noting five of five tools predicted no impact. This meets BP4 at supporting strength.³ No variant-specific functional studies, case-control data, segregation data, or de novo reports were identified. The variant has been reported in ClinVar predominantly as a Variant of Uncertain Significance (5 clinical laboratories) with one Likely benign classification (Ambry Genetics). No expert panel review has been performed.⁴ Applying generic ACMG/AMP 2015 combination rules (PMIDs:25741868): PM2 (supporting) + BP4 (supporting) results in a final classification of Variant of Uncertain Significance, as the evidence supporting pathogenicity and benign impact are insufficient to reach a more definitive classification.⁵