Guidelines
The structuring guidelines in clinical genetics, grouped by domain then by theme. Each row links to the official source.
Constitutional genetics
Variant classification, gene-disease validity, secondary findings, sequencing indications, prenatal and ethical framework.
Variant classification
Reference framework classifying variants into 5 tiers (pathogenic to benign) from weighted criteria.
Forthcoming joint standard subdividing VUS by likelihood of pathogenicity (VUS-low / -mid / -high) via a Bayesian point-based system. In pilot phase, not yet finalised.
Calibrated thresholds for computational tools (REVEL ≥ 0.7 / ≤ 0.3…) to apply the PP3/BP4 criteria.
Points-based scoring system to classify copy-number variants and harmonise classification across laboratories.
Gene-disease validity
Secondary findings
Genes to report as secondary findings (actionable P/LP variants) in exome/genome sequencing; ABCD1, CYP27A1, PLN added.
Cautious European stance: proportionality, autonomy and the right not to know regarding secondary findings.
Indications & diagnostic strategy
Strong recommendation: exome/genome sequencing as first- or second-line test in children with congenital anomalies or intellectual disability.
Genome sequencing via the national platforms for HAS-validated rare-disease and cancer-predisposition pre-indications.
Prenatal & preconception
Carrier screening (113 genes, Tier 3) to offer at preconception or in pregnancy for autosomal-recessive and X-linked conditions.
Non-invasive prenatal screening for T21 from cell-free fetal DNA; opportunity to extend to other aneuploidies (Oct 2024).
Prenatal fetal exome: as a trio, after validation, with pre/post-test counselling — not routine.
Ethical framework: sequencing & disclosure
Hereditary cancer (oncogenetics)
Hereditary cancer predispositions: indications and panels, variant classification, surveillance and carrier management. Excludes somatic oncology.
Indications, panels & variant classification
French recommendations: 13-gene panel of validated clinical utility (BRCA1/2, PALB2, TP53, CDH1, PTEN, RAD51C/D, MMR genes, EPCAM).
Gene-specific ACMG/AMP criteria for BRCA1/BRCA2 (ClinGen ENIGMA expert panel, calibrated evidence strengths).
International reference: genetic-testing criteria and management of hereditary cancer predispositions.
French reference database (frog-db.fr): harmonised classification of predisposition-gene variants, validated by GGC expert groups.
Surveillance & carrier management
Surveillance and risk-reducing surgery in BRCA1/2 carriers (e.g. RRSO at 35-40 y for BRCA1, 40-45 y for BRCA2).
French early-detection (breast, adnexa) and risk-reduction recommendations, accounting for carrier radiosensitivity.
Identification of germline TP53 variant carriers and multimodal surveillance (including whole-body MRI).
European guidelines (3rd 'Mallorca' edition): colonoscopic surveillance and management by MMR gene and sex.
Prophylactic total gastrectomy recommended in CDH1 carriers; endoscopic surveillance in expert centres as an alternative.
Curated, non-exhaustive list for orientation only. Always refer to the current version of each guideline. Somatic oncology (COSMIC, etc.) is out of scope.
Frequently asked questions
Which guidelines are covered?+
The structuring guidelines in constitutional genetics and hereditary cancer, grouped by theme: variant classification, secondary findings, sequencing indications, prenatal diagnosis, ethics. Sources include ACMG/AMP, ClinGen, ESHG, HAS, NCCN, ESMO, ENIGMA, GGC-Unicancer, among others.
Are these guidelines up to date?+
This is a curated, non-exhaustive list for orientation. Each row links to the official source; always refer to the current version of each guideline.
Is somatic oncology included?+
No. The scope is constitutional/germline. Somatic oncology (tumour testing, COSMIC, etc.) is out of scope.
