Atypical cancer risk profile in carriers of Italian founder BRCA1 variant p.His1673del: Implications for classification and clinical management.

ABSTRACT:

Background

BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence.

Methods

Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1-ABRAXAS1 interaction was assessed using a GFP-fragment reassembly-based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2.

Results

Variant-carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0-155.0; c

SUBMITTER: Innella G 

PROVIDER: S-EPMC11350839 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature