LFS2
MCID: LFR007
MIFTS: 35

Li-Fraumeni Syndrome 2 (LFS2)

Categories: Cancer diseases, Endocrine diseases, Genetic diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Li-Fraumeni Syndrome 2

MalaCards integrated aliases for Li-Fraumeni Syndrome 2:

Name: Li-Fraumeni Syndrome 2 57 11 73 28 5 43 14 71
Lfs2 57 11 73
Li-Fraumeni Syndrome, Type 2 38
Li-Fraumeni Syndrome 71

Classifications:



External Ids:

Disease Ontology 11 DOID:0111504
OMIM® 57 609265
OMIM Phenotypic Series 57 PS151623
MeSH 43 C563755
MedGen 40 C1836482
UMLS 71 C0085390 C1836482

Summaries for Li-Fraumeni Syndrome 2

UniProtKB/Swiss-Prot: 73 A highly penetrant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.

MalaCards based summary: Li-Fraumeni Syndrome 2, also known as lfs2, is related to bone osteosarcoma and li-fraumeni syndrome 1. An important gene associated with Li-Fraumeni Syndrome 2 is CHEK2 (Checkpoint Kinase 2). The drugs Nicotinamide and Benzocaine have been mentioned in the context of this disorder. Affiliated tissues include breast, bone and brain, and related phenotypes are glioma and meningioma

Disease Ontology: 11 A Li-Fraumeni syndrome that has material basis in heterozygous mutation in CHEK2 on chromosome 22q12.1.

More information from OMIM: 609265 PS151623

Related Diseases for Li-Fraumeni Syndrome 2

Diseases in the Li-Fraumeni Syndrome family:

Li-Fraumeni Syndrome 2 Li-Fraumeni Syndrome 1

Diseases related to Li-Fraumeni Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 bone osteosarcoma 9.7 SNRNP25 CHEK2
2 li-fraumeni syndrome 1 9.4 SNRNP25 KRTAP10-1 DOCK5 CHEK2

Symptoms & Phenotypes for Li-Fraumeni Syndrome 2

Human phenotypes related to Li-Fraumeni Syndrome 2:

30
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 glioma 30 HP:0009733
2 meningioma 30 HP:0002858
3 sarcoma 30 HP:0100242
4 breast carcinoma 30 HP:0003002
5 stomach cancer 30 HP:0012126

Clinical features from OMIM®:

609265 (Updated 08-Dec-2022)

GenomeRNAi Phenotypes related to Li-Fraumeni Syndrome 2 according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-116 8.92 MATN3
2 Increased shRNA abundance (Z-score > 2) GR00366-A-177 8.92 CPQ
3 Increased shRNA abundance (Z-score > 2) GR00366-A-35 8.92 MATN3
4 Increased shRNA abundance (Z-score > 2) GR00366-A-43 8.92 CPQ

Drugs & Therapeutics for Li-Fraumeni Syndrome 2

Drugs for Li-Fraumeni Syndrome 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 21)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Nicotinamide Approved, Investigational Phase 1, Phase 2 98-92-0 936
2
Benzocaine Approved, Investigational Phase 1, Phase 2 1994-09-7, 94-09-7 2337
3
Tannic acid Approved Phase 1, Phase 2 1401-55-4 16129878 16129778
4
Folic acid Approved, Nutraceutical, Vet_approved Phase 1, Phase 2 59-30-3 6037
5
Niacin Approved, Investigational, Nutraceutical Phase 1, Phase 2 59-67-6 938
6 Folate Phase 1, Phase 2
7 Vitamins Phase 1, Phase 2
8 Vitamin B9 Phase 1, Phase 2
9 Vitamin B3 Phase 1, Phase 2
10 Trace Elements Phase 1, Phase 2
11 Nicotinic Acids Phase 1, Phase 2
12 Antimetabolites Phase 1, Phase 2
13 Vasodilator Agents Phase 1, Phase 2
14 Vitamin B Complex Phase 1, Phase 2
15 Hypolipidemic Agents Phase 1, Phase 2
16 Lipid Regulating Agents Phase 1, Phase 2
17 Micronutrients Phase 1, Phase 2
18
Phosphocreatine Nutraceutical Phase 1, Phase 2 67-07-2 587
19
Metformin Approved Phase 1 1115-70-4, 657-24-9 4091
20 Hypoglycemic Agents Phase 1
21 Anesthetics

Interventional clinical trials:

(show all 16)
# Name Status NCT ID Phase Drugs
1 LIFSCREEN : Evaluation of Whole Body MRI for Early Detection of Cancers in Subjects With P53 Mutation (Li-Fraumeni Syndrome) Completed NCT01464086 Phase 3
2 Exploratory Study of Nicotinamide Riboside on Mitochondrial Function in Li-Fraumeni Syndrome Completed NCT03789175 Phase 1, Phase 2
3 A Pilot Study of Metformin in Patients With a Diagnosis of Li-Fraumeni Syndrome Completed NCT01981525 Phase 1 Metformin
4 Metabolic Regulation by Tumor Suppressor p53 in Li-Fraumeni Syndrome Completed NCT00406445
5 Biomarker Monitoring for a Young Individual Carrying a TP53 Gene Mutation in a Familial High-Cancer Predisposition Setting Completed NCT02289326
6 Phenotype and Prognosis of Patients With Breast Cancer and Pathogenic Variants of TP53 (BREAST TP53) Completed NCT04966923
7 Magnetic Resonance Imaging Screening In Li Fraumeni Syndrome: An Exploratory Whole Body MRI Study Completed NCT01737255
8 Screening With Whole Body MRI For Detection Of Primary Tumors In Children And Adults With Li-Fraumeni Syndrome (LFS) And Other Cancer Predisposition Syndromes Recruiting NCT02950987
9 Clinical and Molecular Studies of Li-Fraumeni Syndrome and TP53-associated Disorders Recruiting NCT04367246
10 Familial Investigations of Childhood Cancer Predisposition Recruiting NCT03050268
11 Cardiovascular Disease Discovery Protocol Recruiting NCT01143454
12 Evaluate Willingness to Participate in a Trial Comparing Standard Genetic Counseling Versus Personalized Genetic Counseling Based on LFSPRO-ShinyApp Data Recruiting NCT05126810
13 Clinical, Epidemiologic, and Genetic Studies of Li-Fraumeni Syndrome Recruiting NCT01443468
14 Li-Fraumeni & TP53: Understanding and Progress (LiFT UP) Recruiting NCT04541654
15 Registry of Li Fraumeni and Li Fraumeni Like Syndromes - Registro Della Sindrome di Li Fraumeni Classica e Li Fraumeni Like Recruiting NCT04982744
16 Novel Approaches to Molecular and Clinical Surveillance in Li-Fraumeni Syndrome - Pilot Study. Enrolling by invitation NCT03176836

Search NIH Clinical Center for Li-Fraumeni Syndrome 2

Cochrane evidence based reviews: li-fraumeni syndrome 2

Genetic Tests for Li-Fraumeni Syndrome 2

Genetic tests related to Li-Fraumeni Syndrome 2:

# Genetic test Affiliating Genes
1 Li-Fraumeni Syndrome 2 28 CHEK2

Anatomical Context for Li-Fraumeni Syndrome 2

Organs/tissues related to Li-Fraumeni Syndrome 2:

MalaCards : Breast, Bone, Brain, Bone Marrow, Prostate
ODiseA: Blood And Bone Marrow, Mammary Gland, Brain

Publications for Li-Fraumeni Syndrome 2

Articles related to Li-Fraumeni Syndrome 2:

(show all 15)
# Title Authors PMID Year
1
p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. 57 5
11479205 2001
2
Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. 57 5
10617473 1999
3
A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer. 5
17085682 2006
4
CHEK2 I157T associates with familial and sporadic colorectal cancer. 5
16816021 2006
5
Interaction between CHEK2*1100delC and other low-penetrance breast-cancer susceptibility genes: a familial study. 5
16257342 2005
6
CHEK2 is a multiorgan cancer susceptibility gene. 5
15492928 2004
7
Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant. 5
15466005 2004
8
CHEK2 variant I157T may be associated with increased breast cancer risk. 5
15239132 2004
9
CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. 5
15122511 2004
10
The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. 5
12690581 2003
11
Mutations in CHEK2 associated with prostate cancer risk. 5
12533788 2003
12
A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. 5
12094328 2002
13
Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. 5
11967536 2002
14
Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome. 5
11719428 2001
15
A Prospective, Open-Label, Multicenter, Real-World Study of VYC-17.5L Hyaluronic Acid Dermal Filler in the Lips. 62
35795884 2022

Variations for Li-Fraumeni Syndrome 2

ClinVar genetic disease variations for Li-Fraumeni Syndrome 2:

5 (show top 50) (show all 61)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CHEK2 NM_007194.4(CHEK2):c.444+2T>C SNV Pathogenic
422638 rs560596101 GRCh37: 22:29121229-29121229
GRCh38: 22:28725241-28725241
2 CHEK2 NM_007194.4(CHEK2):c.444+1G>A SNV Pathogenic
Pathogenic
Pathogenic
128075 rs121908698 GRCh37: 22:29121230-29121230
GRCh38: 22:28725242-28725242
3 CHEK2 NM_007194.4(CHEK2):c.417C>A (p.Tyr139Ter) SNV Pathogenic
439092 rs200917541 GRCh37: 22:29121258-29121258
GRCh38: 22:28725270-28725270
4 CHEK2 NM_007194.4(CHEK2):c.409C>T (p.Arg137Ter) SNV Pathogenic
182452 rs730881701 GRCh37: 22:29121266-29121266
GRCh38: 22:28725278-28725278
5 CHEK2 NM_007194.4(CHEK2):c.216T>G (p.Tyr72Ter) SNV Pathogenic
141381 rs587781705 GRCh37: 22:29130494-29130494
GRCh38: 22:28734506-28734506
6 CHEK2 NM_007194.4(CHEK2):c.1283C>T (p.Ser428Phe) SNV Pathogenic
5603 rs137853011 GRCh37: 22:29091207-29091207
GRCh38: 22:28695219-28695219
7 CHEK2 NM_007194.4(CHEK2):c.1100del (p.Thr367fs) DEL Pathogenic
Pathogenic
128042 rs555607708 GRCh37: 22:29091857-29091857
GRCh38: 22:28695869-28695869
8 CHEK2 NM_007194.4(CHEK2):c.470T>C (p.Ile157Thr) SNV Pathogenic
Likely Pathogenic
5591 rs17879961 GRCh37: 22:29121087-29121087
GRCh38: 22:28725099-28725099
9 CHEK2 NM_007194.4(CHEK2):c.433C>T (p.Arg145Trp) SNV Pathogenic
5592 rs137853007 GRCh37: 22:29121242-29121242
GRCh38: 22:28725254-28725254
10 CHEK2 NM_007194.4(CHEK2):c.1425del (p.Phe475fs) DEL Pathogenic
5593 GRCh37: 22:29090056-29090056
GRCh38: 22:28694068-28694068
11 CHEK2 NM_007194.4(CHEK2):c.320-5T>A SNV Pathogenic
128070 rs121908700 GRCh37: 22:29121360-29121360
GRCh38: 22:28725372-28725372
12 CHEK2 NM_007194.4(CHEK2):c.592+3A>T SNV Pathogenic
142956 rs587782849 GRCh37: 22:29120962-29120962
GRCh38: 22:28724974-28724974
13 CHEK2 NM_007194.4(CHEK2):c.846+4_846+7del DEL Pathogenic
216652 rs764884641 GRCh37: 22:29105987-29105990
GRCh38: 22:28709999-28710002
14 CHEK2 NM_007194.4(CHEK2):c.339C>G (p.Tyr113Ter) SNV Pathogenic
530096 rs905674348 GRCh37: 22:29121336-29121336
GRCh38: 22:28725348-28725348
15 CHEK2 NM_007194.4(CHEK2):c.277del (p.Trp93fs) DEL Pathogenic
187085 rs786203458 GRCh37: 22:29130433-29130433
GRCh38: 22:28734445-28734445
16 CHEK2 NM_007194.4(CHEK2):c.349A>G (p.Arg117Gly) SNV Likely Pathogenic
128071 rs28909982 GRCh37: 22:29121326-29121326
GRCh38: 22:28725338-28725338
17 CHEK2 NM_007194.4(CHEK2):c.1555C>T (p.Arg519Ter) SNV Likely Pathogenic
128064 rs200432447 GRCh37: 22:29083962-29083962
GRCh38: 22:28687974-28687974
18 CHEK2 NM_007194.4(CHEK2):c.1238del (p.Ser412_Leu413insTer) DEL Likely Pathogenic
479550 rs765664259 GRCh37: 22:29091719-29091719
GRCh38: 22:28695731-28695731
19 CHEK2 NM_007194.4(CHEK2):c.757A>T (p.Lys253Ter) SNV Likely Pathogenic
491635 rs786201896 GRCh37: 22:29107932-29107932
GRCh38: 22:28711944-28711944
20 CHEK2 NM_007194.4(CHEK2):c.319+2T>A SNV Likely Pathogenic
142352 rs587782401 GRCh37: 22:29130389-29130389
GRCh38: 22:28734401-28734401
21 CHEK2 NM_007194.4(CHEK2):c.707T>C (p.Leu236Pro) SNV Likely Pathogenic
142448 rs587782471 GRCh37: 22:29107982-29107982
GRCh38: 22:28711994-28711994
22 CHEK2 NM_007194.4(CHEK2):c.917G>C (p.Gly306Ala) SNV Likely Pathogenic
128089 rs587780192 GRCh37: 22:29095917-29095917
GRCh38: 22:28699929-28699929
23 CHEK2 NM_007194.4(CHEK2):c.727T>C (p.Cys243Arg) SNV Uncertain Significance
140933 rs141776984 GRCh37: 22:29107962-29107962
GRCh38: 22:28711974-28711974
24 CHEK2 NM_007194.4(CHEK2):c.1053G>T (p.Glu351Asp) SNV Uncertain Significance
142151 rs587782268 GRCh37: 22:29092931-29092931
GRCh38: 22:28696943-28696943
25 CHEK2 NM_007194.4(CHEK2):c.479T>G (p.Ile160Arg) SNV Uncertain Significance
128076 rs72552323 GRCh37: 22:29121078-29121078
GRCh38: 22:28725090-28725090
26 CHEK2 NM_007194.4(CHEK2):c.1312G>T (p.Asp438Tyr) SNV Uncertain Significance
Uncertain Significance
128056 rs200050883 GRCh37: 22:29091178-29091178
GRCh38: 22:28695190-28695190
27 CHEK2 NM_007194.4(CHEK2):c.542G>A (p.Arg181His) SNV Uncertain Significance
Uncertain Significance
5598 rs121908701 GRCh37: 22:29121015-29121015
GRCh38: 22:28725027-28725027
28 CHEK2 NM_007194.4(CHEK2):c.1270T>C (p.Tyr424His) SNV Uncertain Significance
128054 rs139366548 GRCh37: 22:29091220-29091220
GRCh38: 22:28695232-28695232
29 CHEK2 NM_007194.4(CHEK2):c.1451C>T (p.Pro484Leu) SNV Uncertain Significance
140938 rs564605612 GRCh37: 22:29090030-29090030
GRCh38: 22:28694042-28694042
30 CHEK2 NM_007194.4(CHEK2):c.556A>C (p.Asn186His) SNV Uncertain Significance
141977 rs146198085 GRCh37: 22:29121001-29121001
GRCh38: 22:28725013-28725013
31 CHEK2 NM_007194.4(CHEK2):c.1556G>T (p.Arg519Leu) SNV Uncertain Significance
128066 rs587780180 GRCh37: 22:29083961-29083961
GRCh38: 22:28687973-28687973
32 CHEK2 NM_007194.4(CHEK2):c.980A>G (p.Tyr327Cys) SNV Uncertain Significance
128092 rs587780194 GRCh37: 22:29095854-29095854
GRCh38: 22:28699866-28699866
33 CHEK2 NM_007194.4(CHEK2):c.1336A>G (p.Asn446Asp) SNV Uncertain Significance
126909 rs121908705 GRCh37: 22:29091154-29091154
GRCh38: 22:28695166-28695166
34 CHEK2 NM_007194.4(CHEK2):c.1216C>T (p.Arg406Cys) SNV Uncertain Significance
142533 rs587782527 GRCh37: 22:29091741-29091741
GRCh38: 22:28695753-28695753
35 CHEK2 NM_007194.4(CHEK2):c.170C>T (p.Ser57Phe) SNV Uncertain Significance
182445 rs730881695 GRCh37: 22:29130540-29130540
GRCh38: 22:28734552-28734552
36 CHEK2 NM_007194.4(CHEK2):c.1534C>G (p.Leu512Val) SNV Uncertain Significance
141856 rs17882942 GRCh37: 22:29085131-29085131
GRCh38: 22:28689143-28689143
37 CHEK2 NM_007194.4(CHEK2):c.1525C>T (p.Pro509Ser) SNV Uncertain Significance
128063 rs587780179 GRCh37: 22:29085140-29085140
GRCh38: 22:28689152-28689152
38 CHEK2 NM_007194.4(CHEK2):c.1510G>C (p.Glu504Gln) SNV Uncertain Significance
142479 rs587782489 GRCh37: 22:29085155-29085155
GRCh38: 22:28689167-28689167
39 CHEK2 NM_007194.4(CHEK2):c.1420C>T (p.Arg474Cys) SNV Uncertain Significance
128059 rs540635787 GRCh37: 22:29090061-29090061
GRCh38: 22:28694073-28694073
40 CHEK2 NM_007194.4(CHEK2):c.1375+3A>G SNV Uncertain Significance
232607 rs876659868 GRCh37: 22:29091112-29091112
GRCh38: 22:28695124-28695124
41 CHEK2 NM_007194.4(CHEK2):c.1215C>A (p.Asn405Lys) SNV Uncertain Significance
128050 rs587780171 GRCh37: 22:29091742-29091742
GRCh38: 22:28695754-28695754
42 CHEK2 NM_007194.4(CHEK2):c.1178C>T (p.Pro393Leu) SNV Uncertain Significance
182435 rs730881690 GRCh37: 22:29091779-29091779
GRCh38: 22:28695791-28695791
43 CHEK2 NM_007194.4(CHEK2):c.1141A>G (p.Met381Val) SNV Uncertain Significance
140959 rs375130261 GRCh37: 22:29091816-29091816
GRCh38: 22:28695828-28695828
44 CHEK2 NM_007194.4(CHEK2):c.1133C>T (p.Thr378Ile) SNV Uncertain Significance
128046 rs587780167 GRCh37: 22:29091824-29091824
GRCh38: 22:28695836-28695836
45 CHEK2 NM_007194.4(CHEK2):c.1111C>T (p.His371Tyr) SNV Uncertain Significance
128044 rs531398630 GRCh37: 22:29091846-29091846
GRCh38: 22:28695858-28695858
46 CHEK2 NM_007194.4(CHEK2):c.1078G>A (p.Glu360Lys) SNV Uncertain Significance
230025 rs876658337 GRCh37: 22:29092906-29092906
GRCh38: 22:28696918-28696918
47 CHEK2 NM_007194.4(CHEK2):c.1036C>T (p.Arg346Cys) SNV Uncertain Significance
142222 rs201206424 GRCh37: 22:29092948-29092948
GRCh38: 22:28696960-28696960
48 CHEK2 NM_007194.4(CHEK2):c.1024G>A (p.Gly342Ser) SNV Uncertain Significance
182457 rs730881705 GRCh37: 22:29092960-29092960
GRCh38: 22:28696972-28696972
49 CHEK2 NM_007194.4(CHEK2):c.967A>C (p.Thr323Pro) SNV Uncertain Significance
420003 rs750984976 GRCh37: 22:29095867-29095867
GRCh38: 22:28699879-28699879
50 CHEK2 NM_007194.4(CHEK2):c.937G>A (p.Val313Met) SNV Uncertain Significance
410041 rs752302543 GRCh37: 22:29095897-29095897
GRCh38: 22:28699909-28699909

UniProtKB/Swiss-Prot genetic disease variations for Li-Fraumeni Syndrome 2:

73
# Symbol AA change Variation ID SNP ID
1 CHEK2 p.Arg145Trp VAR_008554 rs137853007

Cosmic variations for Li-Fraumeni Syndrome 2:

8
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM138972819 NOTCH2 soft tissue,breast,sarcoma,NS c.1028A>G p.N343S 1:119968196-119968196 3
2 COSM88406309 NOTCH2 soft tissue,breast,sarcoma,NS c.1145A>G p.N382S 1:119968196-119968196 3
3 COSM95516578 H3-3A soft tissue,bone,sarcoma,NS c.103G>T p.G35W 1:226064454-226064454 3
4 COSM95520543 H3-3A soft tissue,bone,sarcoma,NS c.103G>T p.G35W 1:226064454-226064454 3
5 COSM95523461 H3-3A soft tissue,bone,sarcoma,NS c.103G>T p.G35W 1:226064454-226064454 3
6 COSM95526780 H3-3A soft tissue,bone,sarcoma,NS c.103G>T p.G35W 1:226064454-226064454 3
7 COSM87494413 GNAQ soft tissue,bone,sarcoma,NS c.442C>T p.R148* 9:77815650-77815650 3

Expression for Li-Fraumeni Syndrome 2

Search GEO for disease gene expression data for Li-Fraumeni Syndrome 2.

Pathways for Li-Fraumeni Syndrome 2

GO Terms for Li-Fraumeni Syndrome 2

Sources for Li-Fraumeni Syndrome 2

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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