GTS5:BRCA-related cancer predisposition syndrome (BRCA1, BRCA2): Difference between revisions
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|''BRCA2'' | |''BRCA2'' | ||
| | |'''SNVs''' (frameshift, nonsense, pathogenic missense, canonical splice-site, synonymous splice-altering variants); '''CNVs''' (inactivating multi-exon deletions or duplications) | ||
|Multiple variant types leading to '''loss of BRCA2 function''', resulting in defective '''homologous recombination–mediated DNA double-strand break repair''', genomic instability, and cancer susceptibility | |||
| | |'''Autosomal dominant''' cancer predisposition with '''incomplete penetrance''' and variable expressivity; '''autosomal recessive''' when biallelic, causing '''Fanconi anemia subtype D1 (FA-D1)''' | ||
| | |Heterozygous pathogenic variants confer increased lifetime risk of '''female and male breast, ovarian, pancreatic, prostate, and melanoma''' cancers. Estimated female breast cancer risk ~'''45–70%''', ovarian cancer ~'''10–30%''' . Founder mutations include '''c.5946delT (6174delT)''' in Ashkenazi Jewish populations . '''Large genomic rearrangements''' represent a clinically significant subset of pathogenic variants and may be missed by sequencing-only assays . Biallelic pathogenic variants result in '''FA-D1''', characterized by congenital anomalies, bone marrow failure, and early-onset malignancies | ||
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==Genetic Abnormalities: Somatic== | ==Genetic Abnormalities: Somatic== | ||