Two Novel Protein‐Truncating Variants in <i>NLRP2</i> and Their Functional Impacts on the Subcortical Maternal Complex
Bibliographic record
Abstract
Female infertility is a prevalent reproductive disorder with high genetic heterogeneity. Previous reports have demonstrated the causal role of biallelic pathogenic variants in the Subcortical Maternal Complex (SCMC) genes in female reproductive failure with some leading to infertility, early embryonic loss, and molar pregnancies, while others are compatible with live birth with and without multilocus imprinting disorders (MLID). Here, we report two deleterious protein-truncating variants, c.1326delG, p.Leu443Phefs*78 and c.2802_2803del, p.Arg935Metfs*15, in heterozygous state in the NLRP2 gene of a patient with primary infertility, four early miscarriages, and one failed attempt of intracytoplasmic sperm injection. We show that the two variants mediate mRNA decay in EBV-transformed lymphoblastoid cells from the patient, lead to decreased NLRP2 protein levels, and alter NLRP2 interactions with other members of the SCMC in vitro. This study emphasizes the importance of performing clinical exomes for patients with recurrent reproductive failure and reporting their variants and reproductive histories to improve patient counseling.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".