{ "@context": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/context/doc", "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086", "id": "CG-AC:AC086", "type": "ClinicalActionabilityReport", "metadata": { "schemaLabel": "AC-Sepio.Beta-1 (Unofficial)", "contentVersionId": "28757", "producedAtUTC": "Thu, 10 Sep 2026 19:39:03 -0000", "note": "DISCLAIMER: The SEPIO-inspired schema presented here is an initial prototype for Clinical Actionability curation summaries and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema." }, "description": "JSON-LD representation of ClinGen Actionability Stage 2 report modeled with SEPIO. The hierarchically structured document will include:\n1. Contextual & topic information, such as the **conditions/diseases** and the **genes**.\n2. Categorized **evidence narratives**, with references.\n\t* This content corresponds to the texts within the *Actionability Summary Report*\n4. **Outcome & Intervention** pairs, with **consensus scoring** in 5 dimensions:\n\t1. Outcome Severity\n\t2. Outcome Likelihood\n\t3. Intervention Effectiveness\n\t4. Nature of the Intervention\n\t5. Total (Overall) Score\n\n*( Note: The summary report does not include the **Screening Survey** which led to preparation of the actionability report. )", "condition": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/co", "id": "CG-AC:AC086/co", "type": "GeneticCondition", "label": "Pancreatic cancer/melanoma syndrome" }, "outcome": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ou/Morbidity%20and%20mortality%20from%20melanoma", "id": "CG-AC:AC086/ou/Morbidity and mortality from melanoma", "type": "Outcome", "label": "Morbidity and mortality from melanoma" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ou/Morbidity%20and%20mortality%20from%20pancreatic%20cancer", "id": "CG-AC:AC086/ou/Morbidity and mortality from pancreatic cancer", "type": "Outcome", "label": "Morbidity and mortality from pancreatic cancer" } ], "intervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/intv/Skin%20surveillance%20to%20detect%20melanoma%20and%20guide%20melanoma%20treatment", "id": "CG-AC:AC086/intv/Skin surveillance to detect melanoma and guide melanoma treatment", "type": "Intervention", "label": "Skin surveillance to detect melanoma and guide melanoma treatment" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/intv/Referral%20to%20specialist%20to%20guide%20surveillance%20plans%20for%20early%20detection%20of%20pancreatic%20cancer%20or%20precursors%20and%20guide%20pancreatic%20cancer%20treatment", "id": "CG-AC:AC086/intv/Referral to specialist to guide surveillance plans for early detection of pancreatic cancer or precursors and guide pancreatic cancer treatment", "type": "Intervention", "label": "Referral to specialist to guide surveillance plans for early detection of pancreatic cancer or precursors and guide pancreatic cancer treatment" } ], "clinicalActionabilityProfile": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/cap", "id": "CG-AC:AC086/cap", "type": "Assertion", "assertionMethod": "The ClinGen AWG developed a standardized protocol to generate evidence-based profiles of clinical actionability of genes and associated disorders in the form of summary reports and semiquantitative metric (SQM) scores.", "releaseDate": "Tue, 04 Oct 2022 00:00:00 -0000", "releaseNum": "2.0.0", "media": "call" }, "evidenceStatements": { "evidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/en/potgd", "id": "CG-AC:AC086/en/potgd", "type": "EvidenceNarrative", "narrative": "An accurate estimate of the prevalence of melanoma-pancreatic cancer syndrome (MPCS); aka Familial Atypical Multiple Mole Melanoma Syndrome) is difficult to make given the highly variable phenotype both between and within families and limited data available. Many CDKN2A pathogenic variants reported among families consist of founder variants, which are unique to specific populations and the geographic areas from which they originate. Pathogenic variants in CDKN2A have been estimated to account for up to 1-2% of unselected melanoma diagnoses. The frequency of pathogenic variants in CDKN2A in unselected pancreatic cancer patients has been estimated to be 0.89%.", "evidenceDomainTag": "Nature of the Threat.Prevalence of the Genetic Disorder", "publication": [ "CG-AC:RF000377", "CG-AC:RF000360", "CG-AC:RF000226", "CG-AC:RF003421", "CG-AC:RF003422", "CG-AC:RF003423", "CG-AC:RF003424", "CG-AC:RF003425" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/en/cf", "id": "CG-AC:AC086/en/cf", "type": "EvidenceNarrative", "narrative": "MPCS is a hereditary cancer predisposition syndrome associated with an increased risk of developing malignant melanoma and/or pancreatic cancer (mainly adenocarcinoma). Individuals may develop either or both types of cancer. MPCS is classically a clinical diagnosis that includes cutaneous findings of a high total body nevi count (usually more than 50 and often into the hundreds; including some atypical nevi which may resemble early melanoma). The majority of the nevi will appear clinically typical. Controversy surrounds the pathologic significance of atypical nevi seen in MPCS syndrome; atypical nevi often regress and melanomas often develop on normal skin. The clinical and histopathologic characteristics of melanoma in MPCS are not different from those seen in sporadic cases. In addition to the head, neck, and trunk, melanoma may also occur in the eyes, ears, gastrointestinal tract, leptomeninges, and oral and genital mucous membranes. Evidence is also mixed regarding whether there is a difference in location of melanomas between those with CDKN2A pathogenic variants versus population-based controls. Some individuals exhibit all the classic MPCS characteristics while others will display few or none of the cutaneous features. The risk of melanoma also appears to be influenced by phenotypic risk factors, such as pigmentation, freckling and nevi and sun reactions but also exposure to UV radiation. Pancreatic cancer is the second most frequent cancer associated with MPCS. Presenting symptoms of pancreatic malignancies can include weight loss, jaundice, floating stools, pain, dyspepsia, nausea, vomiting, and occasionally pancreatitis; however, no early warning signs of pancreatic cancer have been established. A number of other malignancies have been reported in families with MPCS.", "evidenceDomainTag": "Nature of the Threat.Clinical Features", "publication": [ "CG-AC:RF000377", "CG-AC:RF000360", "CG-AC:RF003421", "CG-AC:RF003424", "CG-AC:RF003425", "CG-AC:RF003426", "CG-AC:RF003427" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/en/nh", "id": "CG-AC:AC086/en/nh", "type": "EvidenceNarrative", "narrative": "There is an earlier age of onset of melanoma in families with CDKN2A pathogenic variants compared with the general population. A median age of melanoma diagnosis has been observed between 33 and 45 years old; however, there are several documented individuals with melanoma occurring as early as the early teens and twenties. Individuals with MPCS may experience an earlier onset of pancreatic cancer than the general population. A median age of pancreatic cancer diagnosis has been reported between 65 and 70 years old.", "evidenceDomainTag": "Nature of the Threat.Natural History", "publication": [ "CG-AC:RF000377", "CG-AC:RF000360", "CG-AC:RF003421", "CG-AC:RF003422", "CG-AC:RF003424", "CG-AC:RF003426", "CG-AC:RF003427", "CG-AC:RF003428" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/en/ACMI2743", "id": "CG-AC:AC086/en/ACMI2743", "type": "EvidenceNarrative", "narrative": "Autosomal Dominant", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance", "publication": [ "CG-AC:RF000377", "CG-AC:RF000360", "CG-AC:RF003421", "CG-AC:RF003422", "CG-AC:RF003425" ] } ], "tieredEvidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ten/NOI2909", "id": "CG-AC:AC086/ten/NOI2909", "type": "TieredEvidenceNarrative", "narrative": "Surveillance interventions include the use of full body skin exams for melanoma and imaging to screen for pancreatic cancer. Treatment for melanoma in individuals with CDKN2A pathogenic variants is similar to sporadic melanoma and is largely based on surgery at initial stages. A recent systematic review found that among 77 high risk patients (12 with CDKN2A pathogenic variants, 15.6%) that underwent surgical intervention for concerning pancreatic lesions, no major post-operative complications were reported. However, the underreporting of postoperative data did not allow the extraction of reliable conclusions about postoperative morbidity or mortality after surgery. Patient selection for treatment is challenging, as surgery is associated with increased morbidity and mortality.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention", "publication": [ "CG-AC:RF003427", "CG-AC:RF003428", "CG-AC:RF003429" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ten/CDEC2920", "id": "CG-AC:AC086/ten/CDEC2920", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Some family members will display only part of the classic MPCS phenotype or will show no cutaneous characteristics but may later develop melanoma or pancreatic cancer. The anatomic location of the pancreas and late presenting, often nonspecific, initial symptoms of pancreatic cancer hinder the ability to detect masses at an early, resectable stage.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF000377" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ten/ACPE4240", "id": "CG-AC:AC086/ten/ACPE4240", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "In 60 families with three or more melanoma patients (30 families with CDKN2A pathogenic variants), 7.7% of individuals with melanoma were diagnosed before age 20 years. Fifteen individuals, all from families with CDKN2A pathogenic variants, had multiple primary melanomas (MPM). Seven of the 15 MPM individuals had multiple melanomas before age 20 years.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF003424" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ten/ACPE4241", "id": "CG-AC:AC086/ten/ACPE4241", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Depending on the study design and target population, melanoma penetrance related to CDKN2A pathogenic variants differs widely. The penetrance of melanoma for individuals from multiple case families with CDKN2A pathogenic variants is estimated at 45% to 92% by 80 years of age and varies with geography. Penetrance has been estimated to be 14% by age 50 and 28% by age 80 years in a study using population-based cancer registries.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000377", "CG-AC:RF003422", "CG-AC:RF003424", "CG-AC:RF003425" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ten/RR2662", "id": "CG-AC:AC086/ten/RR2662", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "The risk for developing pancreatic cancer with a known pathogenic variant in CDKN2A, assessed in MPCS families, is increased 13- to 22- fold with some sources reporting a risk as high as 47-fold.", "evidenceDomainTag": "Threat Materialization Chances.Relative Risks", "publication": [ "CG-AC:RF000377", "CG-AC:RF000226", "CG-AC:RF003423", "CG-AC:RF003424", "CG-AC:RF003426" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ten/ACPE4239", "id": "CG-AC:AC086/ten/ACPE4239", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Studies of families with known CDKN2A pathogenic variants have estimated the penetrance for pancreatic cancer to be up to 17% in individuals with CDKN2A pathogenic variants by 75 years of age.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000377", "CG-AC:RF000360", "CG-AC:RF003424", "CG-AC:RF003426" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ten/EN2922", "id": "CG-AC:AC086/ten/EN2922", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "MPCS has a highly variable phenotype both between and within families. In some families, melanoma was the predominant malignancy while, in others, pancreatic cancer predominated the cancer presentation. There is significant heterogeneity in the cutaneous phenotype, some family members will display only part of the phenotype or will show no cutaneous characteristics but may later develop melanoma or pancreatic cancer.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF000377", "CG-AC:RF003421" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ten/EN2923", "id": "CG-AC:AC086/ten/EN2923", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Some individuals exhibit all of the classic MPCS characteristics while others will display few or none of the cutaneous features. Individuals may develop either or both types of cancer (melanoma and pancreatic cancer).", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF000377", "CG-AC:RF000360" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/ten/PGM2861", "id": "CG-AC:AC086/ten/PGM2861", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "No information on the prevalence of CDKN2A pathogenic variants in the general population was identified.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation" } ], "tieredRecommendations": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/tr/ACSU3803", "id": "CG-AC:AC086/tr/ACSU3803", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Routine testing via fasting blood glucose and/or HbA1C is recommended for pancreatic cancer screening.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF003428" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/tr/ACSU3804", "id": "CG-AC:AC086/tr/ACSU3804", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Consensus guidelines state that surveillance should be performed with endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) of the pancreas. It is recommended that this surveillance start at age 40-50 (depending on the guideline, with more recent guidelines suggesting age 40 to initiate screening) or 10 years prior to the earliest diagnosis of pancreatic cancer in the family, whichever is earlier. There is currently not a recommendation for when to stop surveillance. Pancreatic abnormalities that do not lead to immediate surgery should undergo additional testing such as EUS/fine-needle aspiration and should undergo close follow-up imaging in 3-6 months (if they do not proceed to surgery after multidisciplinary review). Surveillance should be performed by multidisciplinary teams with appropriate expertise. Recommendations for screening are primarily based on evidence of increased risk, with the aim to detect early pancreatic lesions that can be intervened upon, rather than a proven efficacy of screening. Potential benefits of pancreatic cancer screening include a suggestion of downstaging, compared to historical data, in that 75%–90% of screen-detected pancreatic cancer has been surgically resectable at diagnosis (which is markedly higher than historical rates of resectability with pancreatic cancers detected due to symptoms). One study evaluated 178 asymptomatic patients with a pathogenic variant in CDKN2A in a screening program with annual MRI/MRCP with or without EUS. Mean age at the start of the program was 56 years (range: 37-75 years) and mean follow up time was 53 months (range: 0-169 months). A total of 866 MRIs and 106 EUSs were performed. Pancreatic ductal adenocarcinoma (PDAC) was detected in 13 (7.3%) patients. The mean age at diagnosis was 58 years (range: 39 to 74 years). The cumulative incidence of PDAC was 14% by age 70. The results showed increased rates in the identification of tumors in stages that allowed for treatment with resection. The resection rate of screen detected PDAC (75%) was much higher than reported for sporadic PDAC patients (15-20%) and compared to historical controls of patients with CDKN2A pathogenic variants with symptomatic PDAC (15%). The 5-year survival rate was substantially higher (24%) than the survival rate reported for patients with symptomatic sporadic PDAC (4-7%).", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF000226", "CG-AC:RF003422", "CG-AC:RF003428" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/tr/ACSU3802", "id": "CG-AC:AC086/tr/ACSU3802", "type": "TieredRecommendation", "evidenceSourceTier": "3", "recommendation": "Screening should begin at age 10 with a baseline total body skin examination including scalp, oral mucosa, genital area, and nail. Patients should be examined every 6 months initially to ensure nevi stability. Once stability is established these visits can be conducted annually or as needed if the patient detects an abnormality on self-exam. Thorough total body self-examination should be performed by the patient with assistance from a friend or family member every month. Observation of lesions may be aided by techniques such as full-body photography and dermoscopy. Nevi may become more unstable during puberty and pregnancy and may warrant increased frequency of physician examinations during these periods.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF000377", "CG-AC:RF003424" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/tr/ACPM5884", "id": "CG-AC:AC086/tr/ACPM5884", "type": "TieredRecommendation", "evidenceSourceTier": "3", "recommendation": "High-risk individuals should be educated about sun safety and warning signs of melanoma.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000377", "CG-AC:RF003424" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/tr/ACCA3502", "id": "CG-AC:AC086/tr/ACCA3502", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "All high-risk individuals should be counseled against smoking. As smoking has been shown to be an independent risk factor for pancreatic cancer in families with familial pancreatic cancer (not known to have pathogenic variants associated with cancer) (OR=3.7, 95% CI: 1.8-7.6) with smokers developing cancer one decade earlier than nonsmokers (59.6 vs. 69.1 years; p=0.01).", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF000226" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/tr/REC2177", "id": "CG-AC:AC086/tr/REC2177", "type": "TieredRecommendation", "evidenceSourceTier": "5", "recommendation": "A systematic review addressing physician visual screening for skin cancer identified limited evidence for the effectiveness of skin cancer screening on morbidity and mortality in average-risk individuals. One ecological study found that after the implementation of a population-based skin cancer screening program that screened 360,288 adults (about 19% of the eligible population, mean age 49.7 years) the population age- and sex-adjusted melanoma mortality decreased by 48% with an absolute mortality difference of 0.8 melanoma deaths per 100,000 persons. In two studies performing visual skin examination, sensitivity to detect melanoma was 40% when conducted by primary care physicians (n=16,383) and 49% when performed by dermatologists (n=7,436). Eight observational studies (n=236,485) examined the association between the degree of disease involvement (lesion thickness or stage at diagnosis) and mortality. All studies demonstrated a consistent linear increase in the risk of melanoma mortality with increasing disease involvement at diagnosis. Tumor thickness >4.0 mm was associated with an increased risk of melanoma mortality compared with thinner lesions.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF000383" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/tr/REC2176", "id": "CG-AC:AC086/tr/REC2176", "type": "TieredRecommendation", "evidenceSourceTier": "5", "recommendation": "A retrospective case-control study compared the melanomas (n=40) of 32 unscreened index patients with a CDKN2A pathogenic variant with those melanomas (n=226) diagnosed in relatives after entering an annual screening program. The surveillance-detected melanomas were found to be thinner than those of the index patients indicating that they were detected in an earlier stage, except among patients who were not compliant with the surveillance protocol. Median Breslow thickness was 0.98 mm for index melanomas and 0.50 mm for surveillance melanomas. The probability of being diagnosed with a Breslow thickness >1.00 mm was significantly larger for index melanomas (OR: 3.1, CI: 1.2 – 8.1, p = 0.022). However, the majority of screen-detected melanomas were diagnosed in patients that were under intensified surveillance (every 3 to 6 months) because of a previous melanoma.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF000379" ] } ] }, "evidenceCategory": { "outcomeEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei", "id": "CG-AC:AC086/oei", "type": "EvidenceItem", "natureOfTheThreat": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei/nott", "id": "CG-AC:AC086/oei/nott", "type": "EvidenceLine", "prevalenceOfTheGeneticDisorder": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei/pgd", "id": "CG-AC:AC086/oei/pgd", "type": "EvidenceItem", "keyText": "Unknown", "sourceOfPopulation": "General population", "evidenceNarrative": { "@id": "CG-AC:AC086/en/potgd" } }, "clinicalFeatures": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei/cf", "id": "CG-AC:AC086/oei/cf", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC086/en/cf" } }, "naturalHistory": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei/nh", "id": "CG-AC:AC086/oei/nh", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC086/en/nh" } } }, "threatMaterializationChances": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei/tmc", "id": "CG-AC:AC086/oei/tmc", "type": "EvidenceLine", "modeOfInheritance": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei/moi", "id": "CG-AC:AC086/oei/moi", "type": "EvidenceItem", "keyText": "Autosomal Dominant", "evidenceNarrative": { "@id": "CG-AC:AC086/en/ACMI2743" } }, "prevalenceOfTheGeneticMutation": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei/pgm", "id": "CG-AC:AC086/oei/pgm", "type": "EvidenceItem", "keyText": "Unknown", "sourceOfPopulation": "General population", "tieredEvidenceNarrative": { "@id": "CG-AC:AC086/ten/PGM2861" } }, "penetrance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei/pe/ACPE4241", "id": "CG-AC:AC086/oei/pe/ACPE4241", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC086/ten/ACPE4241" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei/pe/ACPE4239", "id": "CG-AC:AC086/oei/pe/ACPE4239", "type": "EvidenceItem", "keyText": "5-39 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC086/ten/ACPE4239" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/oei/pe/ACPE4240", "id": "CG-AC:AC086/oei/pe/ACPE4240", "type": "EvidenceItem", "keyText": "Unknown", "tieredEvidenceNarrative": { "@id": "CG-AC:AC086/ten/ACPE4240" } } ], "relativeRisk": [ { "@id": 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"CG-AC:AC086/iei/su/ACSU3803", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC086/tr/ACSU3803" } } ] }, "conditionEscapeDetection": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/iei/ced", "id": "CG-AC:AC086/iei/ced", "type": "EvidenceLine", "chanceToEscapeDetection": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC086/iei/cted/CDEC2920", "id": "CG-AC:AC086/iei/cted/CDEC2920", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC086/ten/CDEC2920" } } ] } } }, "references": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000226", "id": "CG-AC:RF000226", "type": "Publication", "publicationType": "PMID", "citation": "Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. (2015) 110(2):223-62; quiz 263.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=25645574", "xdbref": [ "PMID:25645574" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000360", "id": "CG-AC:RF000360", "type": "Publication", "publicationType": "OMIM", "citation": "Online Medelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. Melanoma-pancreatic cancer syndrome. MIM: 6067192012 Aug 22. ", "webUrl": "https://www.omim.org/entry/606719", "xdbref": [ "OMIM:606719" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000377", "id": "CG-AC:RF000377", "type": "Publication", "publicationType": "PMID", "citation": "Eckerle Mize D, Bishop M, Resse E, Sluzevich J. Familial Atypical Multiple Mole Melanoma Syndrome. (2009)", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=21249757", "xdbref": [ "PMID:21249757" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000379", "id": "CG-AC:RF000379", "type": "Publication", "publicationType": "PMID", "citation": "van der Rhee JI, de Snoo FA, Vasen HF, Mooi WJ, Putter H, Gruis NA, Kukutsch NA, Bergman W. Effectiveness and causes for failure of surveillance of CDKN2A-mutated melanoma families. J Am Acad Dermatol. (2011) 65(2):289-96.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=21570154", "xdbref": [ "PMID:21570154" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000383", "id": "CG-AC:RF000383", "type": "Publication", "publicationType": "PMID", "citation": "Wernli KJ, Henrikson NB, Morrison CC, Nguyen M, Pocobelli G, Blasi PR. Screening for Skin Cancer in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. (2016) 316(4):436-47.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=27458949", "xdbref": [ "PMID:27458949" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003421", "id": "CG-AC:RF003421", "type": "Publication", "publicationType": "Orphanet", "citation": "Familial atypical multiple mole melanoma syndrome. Orphanet encyclopedia [Internet]", "xdbref": [ "Orphanet:404560" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003422", "id": "CG-AC:RF003422", "type": "Publication", "publicationType": "Other", "citation": "true. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic cancer (version 2.2022). (2022) Accessed: 2022-06-03. ", "webUrl": "https://www.nccn.org/guidelines/guidelines-detail?category=2&id=1503" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003423", "id": "CG-AC:RF003423", "type": "Publication", "publicationType": "PMID", "citation": "Astiazaran-Symonds E, Goldstein AM. A systematic review of the prevalence of germline pathogenic variants in patients with pancreatic cancer. J Gastroenterol. (2021) 56(1435-5922):713-721.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=34255164", "xdbref": [ "PMID:34255164" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003424", "id": "CG-AC:RF003424", "type": "Publication", "publicationType": "Other", "citation": "true. Genetics of skin cancer (pdq(r)): nci. pdq cancer information summaries. (2022) Accessed: 2022-06-03. ", "webUrl": "https://www.cancer.gov/types/skin/hp/skin-genetics-pdq" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003425", "id": "CG-AC:RF003425", "type": "Publication", "publicationType": "OMIM", "citation": "Online Medelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. Melanoma, cutaneous malignant, susceptibility to, 2; cmm2. MIM: 1556012013 Nov 11. ", "webUrl": "https://www.omim.org/entry/155601", "xdbref": [ "OMIM:155601" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003426", "id": "CG-AC:RF003426", "type": "Publication", "publicationType": "Other", "citation": "true. Pancreatic cancer (version 1.2022). (2022) Accessed: 2022-06-03. ", "webUrl": "https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003427", "id": "CG-AC:RF003427", "type": "Publication", "publicationType": "Orphanet", "citation": "Familial melanoma. Orphanet encyclopedia [Internet]", "xdbref": [ "Orphanet:618" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003428", "id": "CG-AC:RF003428", "type": "Publication", "publicationType": "PMID", "citation": "Goggins M, Overbeek KA, Brand R, Syngal S, Del Chiaro M, Bartsch DK, Bassi C, Carrato A, Farrell J, Fishman EK, Fockens P, Gress TM, van Hooft JE, Hruban RH, Kastrinos F, Klein A, Lennon AM, Lucas A, Park W, Rustgi A, Simeone D, Stoffel E, Vasen HFA, Cahen DL, Canto MI, Bruno M, International Cancer of the Pancreas Screening (CAPS) consortium. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. (2020) 69(1468-3288):7-17.", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=31672839", "xdbref": [ "PMID:31672839" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF003429", "id": "CG-AC:RF003429", "type": "Publication", "publicationType": "PMID", "citation": "Bagias G, Kanavidis P, Vailas M, Despotidis M, Sotiropoulou M, Katsaros I, Maroulis I, Filippou D, Schizas D. Surgical management of familial pancreatic cancer: a systematic review of the literature. ANZ J Surg. (2022)", "webUrl": "https://www.ncbi.nlm.nih.gov/pubmed/?term=35758214", "xdbref": [ "PMID:35758214" ] } ] }