CRYBB2

crystallin beta B2, the group of Beta-gamma crystallins

Basic information

Region (hg38): 22:25212564-25231870

Previous symbols: [ "CCA2", "CRYB2A", "CRYB2" ]

Links

ENSG00000244752 ∙ NCBI:1415 ∙ OMIM:123620 ∙ HGNC:2398 ∙ Uniprot:P43320 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 3 multiple types (Definitive), mode of inheritance: AD
• cataract 3 multiple types (Strong), mode of inheritance: AD
• cataract 3 multiple types (Strong), mode of inheritance: AD
• cataract 3 multiple types (Strong), mode of inheritance: AD
• cataract - microcornea syndrome (Supportive), mode of inheritance: AD
• pulverulent cataract (Supportive), mode of inheritance: AD
• early-onset sutural cataract (Supportive), mode of inheritance: AD
• cerulean cataract (Supportive), mode of inheritance: AD
• early-onset nuclear cataract (Supportive), mode of inheritance: AD
• total early-onset cataract (Supportive), mode of inheritance: AD
• early-onset posterior subcapsular cataract (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 3, multiple types	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	2240043; 8812489; 9158139; 10634616; 11424921; 17234267; 18617901; 19649175; 21031021; 21245961; 22312185; 22846113

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRYBB2 gene.

• Cataract_3_multiple_types (56 variants)
• not_provided (28 variants)
• Inborn_genetic_diseases (23 variants)
• CRYBB2-related_disorder (9 variants)
• not_specified (4 variants)
• Developmental_cataract (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRYBB2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000496.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1			7	2	10
missense	3	10	52	3	1	69
nonsense	1		2			3
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)	1		3			4
Total	6	10	58	10	3

Highest pathogenic variant AF is 0.0000340732

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRYBB2	protein_coding	protein_coding	ENST00000398215	5	12348

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.390	0.609	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	91	125	0.730	0.00000779	1354
Missense in Polyphen		33	47.439	0.69563		490
Synonymous	-0.177	51	49.4	1.03	0.00000323	366
Loss of Function	2.66	3	13.6	0.221	8.76e-7	125

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000975	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.
• Disease: DISEASE: Cataract 3, multiple types (CTRCT3) [MIM:601547]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT3 includes congenital cerulean and sutural cataract with punctate and cerulean opacities, among others. Cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. Sutural cataract with punctate and cerulean opacities is characterized by white opacification around the anterior and posterior Y sutures, and grayish and bluish, spindle shaped, oval punctate and cerulean opacities of various sizes arranged in lamellar form. The spots are more concentrated towards the peripheral layers and do not delineate the embryonal or fetal nucleus. Phenotypic variation with respect to the size and density of the sutural opacities as well as the number and position of punctate and cerulean spots is observed among affected subjects. {ECO:0000269|PubMed:10634616, ECO:0000269|PubMed:9158139}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.445
• rvis_EVS: 0.3
• rvis_percentile_EVS: 72.01

Haploinsufficiency Scores

• pHI: 0.268
• hipred: Y
• hipred_score: 0.699
• ghis: 0.495

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Crybb2
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype

Gene ontology

• Biological process: visual perception;camera-type eye development;response to stimulus
• Molecular function: structural molecule activity;structural constituent of eye lens;identical protein binding;protein homodimerization activity