FBN2

fibrillin 2, the group of Fibrillins

Basic information

Region (hg38): 5:128257908-128659185

Previous symbols: [ "CCA" ]

Links

ENSG00000138829 ∙ NCBI:2201 ∙ OMIM:612570 ∙ HGNC:3604 ∙ Uniprot:P35556 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital contractural arachnodactyly (Definitive), mode of inheritance: AD
• congenital contractural arachnodactyly (Strong), mode of inheritance: AD
• carpal tunnel syndrome (Limited), mode of inheritance: AD
• congenital contractural arachnodactyly (Strong), mode of inheritance: AD
• congenital contractural arachnodactyly (Supportive), mode of inheritance: AD
• congenital contractural arachnodactyly (Strong), mode of inheritance: AD
• macular degeneration, early-onset (Limited), mode of inheritance: AD
• macular degeneration, early-onset (Limited), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital contractural arachnodactyly (Beals syndrome)	AD	Cardiovascular	The condition may be clinically recognizable in most individuals, but individuals may have cardiovascular manifestations including aortic root dilatation, and surveillance and early interventions may reduce morbidity and mortality	Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Ophthalmologic	7493032; 7633409; 8900230; 9106527; 9714438; 10797416; 11754102; 16531736; 20301560; 24899048

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBN2 gene.

• Congenital contractural arachnodactyly (1924 variants)
• not provided (1075 variants)
• Familial thoracic aortic aneurysm and aortic dissection (637 variants)
• not specified (294 variants)
• Ehlers-Danlos syndrome (108 variants)
• Connective tissue disorder (89 variants)
• Congenital contractural arachnodactyly;Macular degeneration, early-onset (40 variants)
• FBN2-related condition (25 variants)
• Cardiovascular phenotype (22 variants)
• Macular degeneration, early-onset (14 variants)
• Macular degeneration, early-onset;Congenital contractural arachnodactyly (12 variants)
• Inborn genetic diseases (7 variants)
• Marfan syndrome (2 variants)
• See cases (2 variants)
• Arterial dissection (1 variants)
• 7 conditions (1 variants)
• Neurodevelopmental abnormality (1 variants)
• Primary dilated cardiomyopathy (1 variants)
• Loeys-Dietz syndrome (1 variants)
• Congenital contractural arachnodactyly;Marfan syndrome (1 variants)
• Ehlers-Danlos syndrome, type 4 (1 variants)
• Brain aneurysm (1 variants)
• Marfanoid habitus and intellectual disability (1 variants)
• Craniosynostosis syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBN2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			24	517	29	570
missense	12	44	933	122	38	1149
nonsense	2	3	21			26
start loss						0
frameshift			16			16
inframe indel		2	7			9
splice donor/acceptor (+/-2bp)	6	13	20			39
splice region	2		61	86	7	156
non coding	1	1	38	302	151	493
Total	21	63	1059	941	218

Highest pathogenic variant AF is 0.0000131

Variants in FBN2

This is a list of pathogenic ClinVar variants found in the FBN2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-128257923-C-T		Congenital contractural arachnodactyly	Benign (Jan 13, 2018)
5-128257948-T-C		Congenital contractural arachnodactyly	Uncertain significance (Jan 13, 2018)
5-128258033-C-CTT		Congenital contractural arachnodactyly	Uncertain significance (Jun 14, 2016)
5-128258035-T-G		Congenital contractural arachnodactyly	Uncertain significance (Jan 13, 2018)
5-128258040-C-T		Congenital contractural arachnodactyly	Benign (Jan 12, 2018)
5-128258140-G-C		Congenital contractural arachnodactyly	Uncertain significance (Jan 13, 2018)
5-128258178-C-T		Congenital contractural arachnodactyly	Benign (Jan 12, 2018)
5-128258216-T-C		Congenital contractural arachnodactyly	Uncertain significance (Jan 13, 2018)
5-128258264-G-A		Congenital contractural arachnodactyly	Benign (Jan 13, 2018)
5-128258323-T-C		Congenital contractural arachnodactyly	Benign (Jan 13, 2018)
5-128258337-A-G		Congenital contractural arachnodactyly	Uncertain significance (Jan 13, 2018)
5-128258344-G-A		Congenital contractural arachnodactyly	Uncertain significance (Jan 13, 2018)
5-128258344-G-T		Congenital contractural arachnodactyly	Uncertain significance (Jan 12, 2018)
5-128258353-C-T		Congenital contractural arachnodactyly	Uncertain significance (Jan 13, 2018)
5-128258390-A-AAAC		Congenital contractural arachnodactyly	Uncertain significance (Jun 14, 2016)
5-128258446-T-C		Congenital contractural arachnodactyly	Uncertain significance (Jan 13, 2018)
5-128258493-G-C		Congenital contractural arachnodactyly	Benign (Jan 13, 2018)
5-128258576-G-A		Congenital contractural arachnodactyly	Uncertain significance (Jan 13, 2018)
5-128258636-T-C		Congenital contractural arachnodactyly	Benign (Jan 12, 2018)
5-128258710-G-C		Congenital contractural arachnodactyly	Uncertain significance (Jan 12, 2018)
5-128258722-A-T		Congenital contractural arachnodactyly	Benign (Jan 13, 2018)
5-128258739-T-C		Congenital contractural arachnodactyly	Uncertain significance (Apr 27, 2017)
5-128258769-G-A		Congenital contractural arachnodactyly	Uncertain significance (Jan 12, 2018)
5-128258784-C-T		Congenital contractural arachnodactyly	Uncertain significance (Jan 13, 2018)
5-128258813-T-C		Congenital contractural arachnodactyly	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBN2	protein_coding	protein_coding	ENST00000508053	65	401278

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.24e-9	125707	0	41	125748	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.55	1456	1.63e+3	0.892	0.0000935	19376
Missense in Polyphen		373	597.85	0.6239		7149
Synonymous	-1.07	626	593	1.06	0.0000369	5241
Loss of Function	9.83	22	153	0.143	0.00000784	1965

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000543	0.000543
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000163	0.000163
South Asian	0.000262	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Fibrillin-2: Fibrillins are structural components of 10- 12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles. Fibrillin-2-containing microfibrils regulate the early process of elastic fiber assembly. Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively. {ECO:0000250|UniProtKB:Q61555}.
• Disease: DISEASE: Macular degeneration, early-onset (EOMD) [MIM:616118]: An ocular disorder characterized by macular changes resulting in progressive loss of visual acuity. {ECO:0000269|PubMed:24899048}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hypothesized Pathways in Pathogenesis of Cardiovascular Disease;Extracellular matrix organization;Elastic fibre formation (Consensus)

Recessive Scores

• pRec: 0.229

Intolerance Scores

• loftool: 0.00785
• rvis_EVS: -1.87
• rvis_percentile_EVS: 2.02

Haploinsufficiency Scores

• pHI: 0.654
• hipred: Y
• hipred_score: 0.652
• ghis: 0.433

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.778

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fbn2
• Phenotype: growth/size/body region phenotype; muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: fbn2b
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: extracellular matrix organization;embryonic limb morphogenesis;positive regulation of bone mineralization;sequestering of TGFbeta in extracellular matrix;camera-type eye development;positive regulation of osteoblast differentiation;embryonic eye morphogenesis;bone trabecula formation
• Cellular component: microfibril;extracellular region;extracellular matrix;collagen-containing extracellular matrix
• Molecular function: extracellular matrix structural constituent;calcium ion binding;protein binding;extracellular matrix constituent conferring elasticity