CRYBA2

protein-coding

crystallin beta A2, the group of Beta-gamma crystallins

Gene summary

Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of the vertebrate eye, which function to maintain the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also defined as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Beta-crystallins, the most heterogeneous, differ by the presence of the C-terminal extension (present in the basic group but absent in the acidic group). Beta-crystallins form aggregates of different sizes and are able to form homodimers through self-association or heterodimers with other beta-crystallins. This gene is a beta acidic group member. Three alternatively spliced transcript variants encoding identical proteins have been reported. [provided by RefSeq, Jul 2008]

MANE transcript

NM_057093.2

Inheritance

SD, AD

ClinVar variants

U:34B:9

Top phenotype

Cataract 42

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr2:218,990,189-218,993,422

External References & Databases

Ensembl (ENSG00000163499)

Transcript & Mutation Effects

hg38 • Region Span ~3.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 42LIMITED

Inheritance Pattern: SD

Disease ID:MONDO:0007283

Submitter: Ambry Genetics

cataract 42LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007283

Submitter: Labcorp Genetics (formerly Invitae)

cataract 42STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007283

Submitter: G2P

early-onset nuclear cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020376

Submitter: Orphanet

early-onset anterior polar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020373

Submitter: Orphanet

Clinical Genomic Database (CGD)

Cataract 42AD

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 23508780

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRYBA2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 33

CRYBA2-related disorderTotal: 10

not providedTotal: 5

Early-onset anterior polar cataractTotal: 2

Cataract 42Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_057093.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar		5
missense			32 clinvar	3 clinvar	1 clinvar	36
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	34	8	1	43

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_057093.2	RefSeq	NP_476434.1	4	MANE Select
ENST00000295728.7	Ensembl	ENSP00000295728.2	4	MANE Select
NM_057094.2	RefSeq	NP_476435.1	4	Standard
ENST00000392096.6	Ensembl	ENSP00000375946.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

lens development in camera-type eye
biological_process

Molecular Function

molecular_function
structural constituent of eye lens
protein binding
protein homodimerization activity

Cellular Component

cellular_component

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295728
Coding exons: 4
Length: 3233
Individuals with no LoFs: 125636
Homozygous LoFs: 0
Heterozygous LoFs: 109
Defined: 125745
p: 0.000434

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.380	128	116	1.10	0.00000548	1278
Missense (PolyPhen)		38	42.592	0.89219		528
Synonymous	-0.238	50	47.9	1.04	0.00000233	377
Loss of Function	0.976	7	10.4	0.673	4.59e-7	99

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00058	0.00058	rare
Ashkenazi Jewish	0.0020	0.0020	notable
East Asian	0.00060	0.00060	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00045	0.00044	rare
South Asian	0.000033	0.000033	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.;
Disease: DISEASE: Cataract 42 (CTRCT42) [MIM:115900]: 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. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. {ECO:0000269|PubMed:23508780}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.570
RVIS EVS: -0.18
RVIS percentile EVS: 39.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.719

Gene Damage Prediction

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