NBEAL2

neurobeachin like 2, the group of BEACH domain containing |Armadillo like helical domain containing|WD repeat domain containing

Basic information

Region (hg38): 3:46979665-47009704

Links

ENSG00000160796 ∙ NCBI:23218 ∙ OMIM:614169 ∙ HGNC:31928 ∙ Uniprot:Q6ZNJ1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• gray platelet syndrome (Supportive), mode of inheritance: AD
• gray platelet syndrome (Definitive), mode of inheritance: AR
• gray platelet syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Gray platelet syndrome	AR	Hematologic	Individuals may manifest with anemia (sometimes requiring RBC transfusions) due to bleeding tendencies, and preventive measures and treatment (eg, when surgery is needed) may be beneficial; Recognition of the development of myelofibrosis may also be beneficial in order to allow prompt management	Hematologic	5129551; 6156948; 3414674; 8192152; 20709904; 21765411; 21765412; 21765413; 23100277

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NBEAL2 gene.

• Gray platelet syndrome (257 variants)
• Inborn genetic diseases (133 variants)
• not provided (109 variants)
• not specified (59 variants)
• NBEAL2-related condition (8 variants)
• Thrombocytopenia;Abnormal bleeding (2 variants)
• Abnormal bleeding;Thrombocytopenia (2 variants)
• Thrombocytopenia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NBEAL2 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			40	21	21	82
missense		5	225	17	7	254
nonsense	7	2				9
start loss						0
frameshift	10	6				16
inframe indel			5			5
splice donor/acceptor (+/-2bp)	5	1				6
splice region		1	11		2	14
non coding			25	6	20	51
Total	22	14	295	44	48

Highest pathogenic variant AF is 0.0000131

Variants in NBEAL2

This is a list of pathogenic ClinVar variants found in the NBEAL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-46979684-G-A		Gray platelet syndrome	Uncertain significance (Jan 13, 2018)
3-46979700-C-T		Gray platelet syndrome	Uncertain significance (Jan 12, 2018)
3-46979742-C-G		Gray platelet syndrome	Uncertain significance (Apr 06, 2018)
3-46979786-G-A		Gray platelet syndrome	Uncertain significance (Jan 13, 2018)
3-46979842-G-GGCCGGA		Gray platelet syndrome	Uncertain significance (Jun 14, 2016)
3-46979898-C-T		Gray platelet syndrome	Uncertain significance (Oct 09, 2023)
3-46979900-C-T			Likely benign (Jun 15, 2018)
3-46979923-C-T		Gray platelet syndrome	Uncertain significance (Jan 13, 2018)
3-46988740-C-G		Gray platelet syndrome • NBEAL2-related disorder	Benign (Dec 31, 2019)
3-46988763-G-T		NBEAL2-related disorder	Likely benign (Dec 15, 2020)
3-46988849-G-A		Inborn genetic diseases	Uncertain significance (Mar 27, 2023)
3-46988866-C-T		Gray platelet syndrome	Uncertain significance (Jan 13, 2018)
3-46988869-G-A			Likely benign (Dec 31, 2019)
3-46988888-C-T		Gray platelet syndrome • NBEAL2-related disorder	Benign (Feb 23, 2021)
3-46988902-C-G			Likely benign (Jul 01, 2022)
3-46988950-GC-G			Likely pathogenic (Dec 01, 2020)
3-46989092-G-A		Gray platelet syndrome	Uncertain significance (Mar 30, 2018)
3-46989092-G-C		Inborn genetic diseases	Uncertain significance (Jun 13, 2023)
3-46989114-G-A		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
3-46989154-G-C			Uncertain significance (Sep 01, 2023)
3-46989276-C-G		Gray platelet syndrome	Uncertain significance (May 07, 2021)
3-46989279-C-T		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
3-46989287-C-T			Pathogenic (Jan 01, 2021)
3-46989292-C-G		Gray platelet syndrome • NBEAL2-related disorder	Benign (Jul 23, 2019)
3-46989295-G-A		NBEAL2-related disorder	Likely benign (Aug 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NBEAL2	protein_coding	protein_coding	ENST00000450053	54	30021

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0598	0.940	124761	3	534	125298	0.00215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.39	1385	1.66e+3	0.835	0.000109	17378
Missense in Polyphen		312	459.62	0.67882		5098
Synonymous	0.00237	706	706	1.00	0.0000450	5970
Loss of Function	8.09	31	131	0.237	0.00000678	1390

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00708	0.00682
Ashkenazi Jewish	0.000811	0.000795
East Asian	0.000803	0.000709
Finnish	0.000540	0.000509
European (Non-Finnish)	0.000551	0.000529
Middle Eastern	0.000803	0.000709
South Asian	0.0105	0.0103
Other	0.00135	0.00131

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably involved in thrombopoiesis. Plays a role in the development or secretion of alpha-granules, that contain several growth factors important for platelet biogenesis. {ECO:0000269|PubMed:21765411, ECO:0000269|PubMed:21765412}.
• Pathway: Neutrophil degranulation;Innate Immune System;Immune System (Consensus)

Intolerance Scores

• loftool: 0.763
• rvis_EVS: -3.12
• rvis_percentile_EVS: 0.46

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.563
• ghis: 0.555

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.141

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nbeal2
• Phenotype: skeleton phenotype; immune system 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); neoplasm; hematopoietic system phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: nbeal2
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: hemorrhagic

Gene ontology

• Biological process: platelet formation;neutrophil degranulation
• Cellular component: endoplasmic reticulum;plasma membrane;tertiary granule membrane;ficolin-1-rich granule membrane
• Molecular function: protein binding