Classification rationale
1
The RECQL4 c.2296del (p.Arg766GlyfsTer77) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar as Benign by 3 single-submitter clinical laboratory submissions.
clinvar ↗2
This variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada, supporting rarity for a RECQL4 germline variant.
gnomad_v2 ↗ gnomad_v4 ↗ gnomad_canada ↗3
This deletion causes a frameshift with premature termination, and the generic PVS1 framework supports loss-of-function interpretation because RECQL4 loss of function is an established germline disease mechanism.
pvs1_generic_framework ↗4
SpliceAI predicts no significant splice impact for this variant with a maximum delta score of 0.15, and missense-oriented predictors such as REVEL and BayesDel are not applicable to this deletion.
spliceai ↗
