This synonymous variant (NM_000051.3:c.8751C>T, p.Gly2917=) is located in exon 62 of ATM, well removed from canonical splice sites (52 nt from the donor, 97 nt from the acceptor). SpliceAI predicts no splice impact (max delta = 0.01), consistent with BP4_Supporting under the ATM HBOP VCEP v1.5.0.

As a synonymous variant not near splice consensus boundaries and with no predicted or observed splice defect, BP7_Supporting is met under ATM VCEP v1.5.0.

The variant is extremely rare in population databases: absent from gnomAD v2.1 and present at AF = 0.00019% (3/1,613,812 alleles, grpmax FAF = 6.8e-07) in gnomAD v4.1, meeting PM2_Supporting under ATM VCEP v1.5.0 (threshold ≤ 0.001%).

This variant has been classified as Likely Benign by the ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer VCEP (ClinVar Variation ID 453745, reviewed by expert panel). Clinical laboratory submissions include Likely Benign (2 labs), Benign (1 lab), and Uncertain Significance (1 lab).

PVS1, PS1, and PM5 are not applicable as the variant is synonymous and does not cause a null effect, amino acid change, or premature termination codon. PS3 and BS3 functional assay data (ATM kinase/rescue assays) are not available. PS4 case-control data and PP1 segregation data are absent. BA1 and BS1 population frequency thresholds are not met. PP3 computational evidence for pathogenicity is not met.

Under the ATM VCEP v1.5.0 combination rules (adapted from Richards et al. 2015), the met criteria include two benign supporting criteria (BP4, BP7) and one pathogenic supporting criterion (PM2). Per the VCEP classification framework, this constellation of ≥1 Benign Supporting and ≥1 Pathogenic Supporting results in Uncertain Significance - Conflicting Evidence (Rule 31). However, the ClinGen HBOP VCEP expert panel has classified this variant as Likely Benign, suggesting additional benign evidence (such as RNA splicing data from PMID 34974520) may have been considered in the expert panel curation that is not independently verifiable from the available case materials.