The BRCA1 c.615_622dup (p.Thr208AsnfsTer29; p.T208Nfs*29) variant has not been observed in COSMIC and has been reported in ClinVar, where the ClinGen ENIGMA expert panel classified it as uncertain significance.
clinvar ↗This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting rarity, although the available documentation was insufficient to assign BRCA1 ENIGMA PM2_Supporting under the full dataset and coverage requirements.
gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗Under the ENIGMA BRCA1 specification, this frameshift lies in exon 9(10), an exon designated PVS1_N/A and PM5_N/A for protein-truncating variants because rescue of an in-frame transcript is expected, so truncating status alone does not support PVS1 or PM5.
cspec ↗SpliceAI shows a maximum delta score of 0.11, which is below the BRCA1 splice PP3 threshold of 0.20 and above the BP4 no-impact threshold of 0.10; however, the BRCA1 computational rules are not designed to add PP3 or BP4 evidence for this frameshift variant.
spliceai ↗ cspec ↗
