Gene: DICER1 PMCID: PMC8451242 PMID: 34552563 Pathogenic Inheritance Pattern: Autosomal Dominant MultipleDiseaseEntities Disease Entity: DICER1 syndrome, multinodular goitre, cystic nephroma, anaplastic renal sarcoma, Wilms tumour, differentiated thyroid carcinoma, gynandroblastoma, ciliary body medulloepithelioma, embryonal rhabdomyosarcoma, pineoblastoma, pituitary blastoma, kidney cyst, pulmonary cyst, Sertoli-Leydig Cell Tumor. Mutation: Germline MultipleGeneVariants Variant & Clinvar IDs: c.3452_3453del (485534), c.316del (no ClinVar ID), c.171_172insAC (no ClinVar ID), c.3434del (no ClinVar ID), c.988C>T (933007), c.5388dup (no ClinVar ID) Zygosity: None provided. Case: At time of operation, the goitre patients living in Denmark were ages 21, 12, 21, 8, 14, and 16. Four underwent total thyroidectomies, and two underwent partial thyroidectomies. The patient originally aged 21 previously had a kidney cyst at age 14 and a pulmonary cyst at an unknown age. The patient aged 14 at time of partial thyroidectomy later manifested a Sertoli-Leydig Cell Tumor at age 15. All six patients were female. CasePresentingHPO: None provided. CasePreviousTesting: thyroidectomy gnomAD: ENSG00000100697.10, https://gnomad.broadinstitute.org/gene/ENSG00000100697 Mutation Type: Frameshift, Nonsense

Gene Name: DICER1 PMCID: PMC5443331 PMID: 28323992 HGNCID: not found Inheritance Pattern: autosomal dominant Disease Entity: thyroid cancer and familial multinodular doiter Mutation: germline loss-of-function mutation Zygosity: not provided Variant: c.1870C>T; p.Arg624a, c.1870C>T; p.Arg624a, c.1870C>T; p.Arg624a, c.1870C>T; p.Arg624a, c.3726C>A; p.Tyr1242a, c.3675C>G; p.Tyr1225a, c.3675C>G; p.Tyr1225a Family Information: 145 individuals with a DICER1 germline mutation and 135 controls from 48 families Case: family members used; both males and females used and no significant differences seen among sex; ages range from 20-40 with carriers being significantly younger than controls; no significant differences seen among ethnicity but participants located from the US, UK, and Great Britain CasePresentingHPOs: thyroid cancer or MNG diagnosis common to those with a DICER! mutation but with no chemotherapy or radiation treatment yet CasePreviousTesting: tested levels of thyroid-stimulating hormone, thyroxine, thyroxine-binding globulin, and serum albumin; thyroid palpation; thyroid ultrasound; Sanger or next-generation sequencing assays gnomAD: n/a Mutation Type: missense

• Gene Name: DICER1 Syndrome (OMIM 606241, 601200)
• PMID: 34599283
• Hugo Gene Nomenclature Committee (HGNCID): N/A
• Inheritance Pattern: Autosomal Dominant
• Disease Entity: pleuropulmonary blastoma (PPB), Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma, DICER1-associated presacral malignant teratoid neoplasm and other non-neoplastic associations.
• Mutation: Germline
• Zygosity: Heterozygous
• Variant: has multiple variants associated with it
• Family Information: Germ cell tumors have been reported in family members
• Case: identified affected families w/ pleuropulmonary blastoma (PPB): germline and somatic DICER1 mutations also identified in other familial associated tumors
• CasePreviousTesting: numerous studies confirmed relationship b/t DICER1 variants in carriers and development of range neoplasms and non-neoplastic conditions

GeneName: DICER1 PMID: 30715996 HGNCID: N/A Inherritence pattern: autosomal dominant Disease Entity: multiple gene variants mutation: germline Zygosity: N/A Variant: Not found Family Info: N/A

GeneName: DICER1 PMID: 33552988 HGNCID: Unavailable Inheritance Pattern: Autosomal Dominant with reduced penetrance Disease Entity: Cystic nephroma, familial pleuropulmonary blastoma (PPB), ovarian Sertoli-Leydig cell tumor (SLCT), cervix embryonal rhabdomyosarcoma, multinodular goiter, Wilms' Tumor, Ciliary body medulloepithelioma, nasal chondromesenchymal hamartoma, differentiated thyroid carcinoma, pituitary blastoma, pineoblastoma, sarcomas of different sites. Mutation: germline mutation Zygosity: heterozygous Variant: ClinVar ID not listed Family Information: No family cases listed Case: No specific case mentioned gnomAD: N/A Mutation Type: Frameshift, Nonsense mutation

• GeneName: DICER1
• PMID (PubMed ID): 31952842
• HGNCID: N/A
• Inheritance Pattern: Autosomal dominant
• Disease Entity: Ovarian Sertoli-Leydig cell tumors or gynandroblastoma; cervical embryonal rhabdomyosarcoma; pleuropulmonary blastomas; ovarian tumors generally presented with virilization and amenorrhea during adolescence; metachronous ovarian tumors; thyroid disease; increases risk of thyroid cancer during pregnancy
• Mutation: Germline
• Zygosity: Heterozygous
• Variant: No variant
• Family Information: The pleuropulmonary blastoma locus was mapped to chromosome 14q using linkage analysis in families with multiple cases of pleuropulmonary blastoma, resulting in the identification of heterozygous germline variants in DICER. Sixty-four DICER1-carrier female patients from 32 predominantly non-Hispanic white families were confirmed to have a heterozygous germline DICER1 pathogenic variant and ranged in age from 2–72 years (median: 31 years).

-Gene: DICER1 -PMID: 29343557 -Inheritance Pattern: DICER1 is inherited as an autosomal dominant condition with decreased penetrance -Disease Entity: earlier onset disease, multisite disease, 0-2 site disease, cystic lung disease, familial disease, bilateral disease, stage IA/IB, bilateral disease -mutation: germline loss-of-function mutation, missense mutation, Intronic mutations, hotspot mutation, second somatic mutation, truncating mutations, biallelic mutation -zygosity: heterozygosity -Family History: -testing should be considered for those with a family history of DICER1-associated conditions so that appropriate surveillance can be undertaken. -Individuals at 50% risk of a germline pathogenic variant based on family history who do not pursue genetic testing should follow surveillance guidelines as -if they have a DICER1 mutation unless/until genetic testing confirms that they did not inherit the familial mutation When a pulmonary cyst is identified in a young child with a pathogenic germline -DICER1 variant or family history of a DICER1-associated condition, it should be assumed to be Type I PPB until proven otherwise

Other Information: -Case: Risk for most DICER1-associated neoplasms is highest in early childhood and decreases in adulthood -affected phenotype may simply result from probabilities of generating the characteristic “loss-of-function plus hotspot” two hit typical of a DICER1 syndrome neoplasm. -Caseprevioustesting: presymptomatic testing of a minor child, should be discussed and factored into the decision process, as some individuals may choose, and have the right to choose, not to know their/their child’s genetic status. -gnomAD: n/a

GeneName: DICER1 PMCID: PMC4398601, PMID: 25500911 HGNCID: not avaliable InheritancePattern: autosomal dominant DiseaseEthnicity: Pleuropulmonary blastoma Mutation: germline Zygosity: heterozygotes most common Variant: ClinVarID unavaliable FamilyInformation: family disease not mentioned gnomAD: not avaliable MutationType: missense

Gene: DICER1 PMID: 30672147 HGNCID: n/a Inheritance Pattern: autosomal dominant Disease Entity: Pleuropulmonary Blastoma, Cystic Nephroma, Sertoli-Leydig tumors, Multinodular goiter, thyroid cancer, rhabdomysarcoma, pineoblastoma Mutation: Germline Zygosity: n/a MultipleGeneVariants Variant: p.Gly1824Val, p.Ser1160Tyr, p.Ala1578Thr, p.Leu1469Pro, p.Ser1160Tyr, p.Ile528Thr, p.Pro1836Leu, p.Glu904*, p.Tyr1835Ser, p.Ile528Thr, p.Arg1342His, p.Phe1650Cys, p.Trp1481Arg, p.Arg201His, p.Asp1390His, p.Trp1397Arg, p.Ala1578Thr <br /> Family Info: n/a gnomAD: n/a

Gene: DICER1 PMID: 30672147 HGNCID: Not found Inheritance Pattern: autosomal dominant Disease Entity: Pleuropulmonary Blastoma, Cystic Nephroma, Sertoli-Leydig tumors, Multinodular goiter, thyroid cancer, rhabdomysarcoma, pineoblastoma Mutation: germline Zygosity: not stated Variant: p.Asp1810Asn, c.4206+1G>C [splice],p.Gly1824Val, p.Ser1160Tyr, p.Ala1578Thr, p.Leu1469Pro, p.Ser1160Tyr, p.Ile528Thr, p.Pro1836Leu, p.Glu904, p.Tyr1835Ser, p.Ile528Thr, p.Arg1342His, p.Phe1650Cys, p.Trp1481Arg, p.Arg201His, p.Asp1390His, p.Asp1810Asn c.4206+1G>C, p.Trp1397Arg, p.Ala1578Thr Family Info: none provided

Gene Name: OMIN PMID: 34599283 Autosomal Dominant Gynandroblastoma cERMS Pediatric Paratesticular Sarcomas nephrolithiasis or nephrocalcinonsis Cystic Nephroma Anaplastic Sarcoma of Kidney Wilms tumor Cystic Hepatic Neoplasm Hamartomatous polyps

Germline mutation heterozygosity Multiple Gene Variants There is usually a family history or a carrier for the mutation it rarely occurs out of nowhere.

GeneName: DICER1 PMID (PubMed ID): 29762508 HGNCID: Unavailable Inheritance Pattern: Autosomal Dominant Disease Entity: cancer, rare genetic disorder, pleuroplumonary blastomas, cystic nephroma, rhabdomyosarcoma, multinodular goiter, thyroid cancer, overian Sertoli-Leydig cell tumors, and other meoplasias Mutations: Germline mutations or Somatic mutations Zygosity: Heterozygosity Variant: unregistered Family Information: Cystic nephromas has been reported in approximately 12% of children with pleuripulmonary blastomas or those with a family member with cystic nephroma. Patient with two DICER1 mutations and several of his family members shared these mutations. All members developed a least one type of tumor with differing origins. The patient was an 11-year old boy with a rare Hodgkin lymphoma with DICER1 in 2016. (c.5299delC and c.4616C>T).

GeneName = DICER1 PMID = 29762508 HGNCID = Can't find Inheritance pattern = Autosomal dominant Disease entity = cancer, multinodular goiter, pleuropulmonary blastoma, cystic nephroma, ovarian Sertoli-Leydig cell tumor Mutation = germline OR somatic Zygosity = causes loss of heterozygosity Variant = unregistered Family = those with the mutation almost always passed it on

GeneName:DICER1 PMID (PubMed ID): PMCID: PMC6418698 PMID: 30672147 HGNCID: NOT LISTED<br /> Inheritance Pattern: Autosomal Dominant Disease Entity: Cancer; benign and malignant tumors including pleuropulmonary blastoma, cystic nephroma, Sertoli-Leydig cell tumors, multinodular goiter, Thryoid cancer, rhabdomyosarcoma, and pineoblastoma. Mutation: Somatic missense variation Mutation type: missense Zygosity: None stated Variant: unregistered…. Family Information: Characterize germline variants in familial early-onset clorectal cancer patients; The observation of germline DICER1 variation with uterine corpus endometrial carcinoma merits additional investigation. CasePresentingHPOs: uterine and rectal cancers in germline mutation