BICD2

Chr 9

BICD cargo adaptor 2

Also known as: SMALED2, SMALED2A, SMALED2B, bA526D8.1

NCBI Gene: 23299 ENSG00000185963 UniProt: Q8TD16

The protein mediates dynein-mediated transport along microtubules toward the minus end and functions at the Golgi apparatus. Loss-of-function mutations cause autosomal dominant spinal muscular atrophy, lower extremity-predominant types 2A and 2B. The high pLI score (0.98) indicates this gene is highly intolerant to loss-of-function variants, consistent with the dominant inheritance pattern where haploinsufficiency drives pathogenicity.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is one of two human homologs of Drosophila bicaudal-D and a member of the Bicoid family. It has been implicated in dynein-mediated, minus end-directed motility along microtubules. It has also been reported to be a phosphorylation target of NIMA related kinase 8. Two alternative splice variants have been described. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpinal muscular atrophy, lower extremity-predominant 2A, childhood onset, autosomal dominant

UniProtSpinal muscular atrophy, lower extremity-predominant, 2B, prenatal onset, autosomal dominant

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.983

Z-score 4.40

OE 0.13 (0.07–0.30)

Highly constrained

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

Missense Constraint?

2.20Z-score

OE missense 0.74 (0.68–0.80)

414 obs / 561.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.30)

0≤0.351.4

Missense OE?0.74 (0.68–0.80)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 4 / 30.0Missense obs/exp: 414 / 561.0Syn Z: -0.45

Background carrier burden — how many people carry a rare variant somewhere in BICD2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 67

953 rare PASS variants

Rare truncating (LoF)

1 in 5,000

53 rare PASS variants

Rare synonymous (reference)

1 in 74

536 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BICD2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓