NBEAL2

Chr 3AR

neurobeachin like 2

Also known as: BDPLT4, GPS

NCBI Gene: 23218 ENSG00000160796 UniProt: Q6ZNJ1 OMIM: 614169

The protein contains a BEACH domain and multiple WD40 domains and is involved in thrombopoiesis, specifically playing a role in the development or secretion of platelet alpha-granules that contain growth factors important for platelet biogenesis. Mutations cause gray platelet syndrome, which follows autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.32), indicating that such variants are likely pathogenic.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene contains a beige and Chediak-Higashi (BEACH) domain and multiple WD40 domains, and may play a role in megakaryocyte alpha-granule biogenesis. Mutations in this gene are a cause of gray platelet syndrome. [provided by RefSeq, Dec 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.321 OMIM phenotype

Clinical Summary— NBEAL2

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Gene-Disease Validity (ClinGen)

gray platelet syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

73 unique Pathogenic / Likely Pathogenic· 610 VUS of 955 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — NBEAL2

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.060

Z-score 8.09

OE 0.24 (0.18–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.39Z-score

OE missense 0.83 (0.80–0.87)

1385 obs / 1659.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.24 (0.18–0.32)

0≤0.351.4

Missense OE?0.83 (0.80–0.87)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 31 / 130.9Missense obs/exp: 1385 / 1659.3Syn Z: 0.00

ClinVar Variant Classifications

955 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34

Likely Pathogenic39

VUS610

Likely Benign115

Benign60

Conflicting40

Pathogenic

Likely Pathogenic

610

VUS

115

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	29	3	2	0	34
Likely Pathogenic	29	9	1	0	39
VUS	4	539	32	35	610
Likely Benign	0	24	22	69	115
Benign	1	7	30	22	60
Conflicting	—				40
Total	63	582	87	126	898

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap NBEAL2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →