The Phenotypic variability of 16p11.2 distal BP2–BP3 deletion in a transgenerational family and in neurodevelopmentally ascertained samples
Bibliographic record
Abstract
BACKGROUND: We present genomic and phenotypic findings of a transgenerational family consisting of three male offspring, each with a maternally inherited distal 220 kb deletion at locus 16p11.2 (BP2-BP3). Genomic analysis of all family members was prompted by a diagnosis of autism spectrum disorder (ASD) in the eldest child, who also presented with a low body mass index. METHODS: All male offspring underwent extensive neuropsychiatric evaluation. Both parents were also assessed for social functioning and cognition. The family underwent whole-genome sequencing. Further data curation was undertaken from samples ascertained for neurodevelopmental disorders and congenital abnormalities. RESULTS: On medical examination, both the second and third-born male offspring presented with obesity. The second-born male offspring met research diagnostic criteria for ASD at 8 years of age and presented with mild attention deficits. The third-born male offspring was only noted as having motor deficits and received a diagnosis of developmental coordination disorder. Other than the 16p11.2 distal deletion, no additional contributing variants of clinical significance were observed. The mother was clinically evaluated and noted as having a broader autism phenotype. CONCLUSION: In this family, the phenotypes observed are most likely caused by the 16p11.2 distal deletion. The lack of other overt pathogenic mutations identified by genomic sequencing reinforces the variable expressivity that should be heeded in a clinical setting. Importantly, distal 16p11.2 deletions can present with a highly variable phenotype even within a single family. Our additional data curation provides further evidence on the variable clinical presentation among those with pathogenetic 16p11.2 (BP2-BP3) mutations.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".