NM_000059.3:c.5218_5223del (p.Leu1740_Ser1741del) is an in-frame deletion of 6 nucleotides in BRCA2 exon 11, removing two amino acids (Leu1740 and Ser1741) from a region between BRC repeats 5 and 6, outside the ENIGMA-defined clinically important functional domains.¹ The variant is present in gnomAD population databases at a grpmax filter allele frequency of 0.0106% (FAF = 0.000106) in gnomAD v2.1 exomes, exceeding the ENIGMA BS1 Strong threshold of > 0.01% (FAF > 0.0001). Highest subpopulation frequency is in East Asians (AF = 0.030%, 6/19,916 alleles). No homozygotes observed.² As an in-frame deletion located outside the ENIGMA-defined clinically important functional domains (PALB2 binding aa 10–40; DNA binding aa 2481–3186) with no splicing impact predicted (SpliceAI max delta = 0.00), ENIGMA BP1_Strong is met: in-frame deletion outside a clinically important domain without splicing prediction.³ Clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is 0.77 (8 probands), falling in the neutral zone. Neither PP4 nor BP5 is applicable.⁴ This variant has been reported in ClinVar as Uncertain significance by 9 clinical laboratories and Likely benign by 1 clinical laboratory (ClinVar Variation ID: 51824; review status: criteria provided, single submitter). No expert panel classification exists.⁵ No functional studies, case-control data, segregation data, or variant-specific publications were identified for this variant. Five publications were reviewed in full text; none mention NM_000059.3:c.5218_5223del. Applying the ENIGMA Table 3 combining rules: two Strong Benign criteria (BS1 + BP1) satisfy the Benign classification threshold (Strong Benign ≥ 2). This variant is classified as BENIGN.⁶