Skip to content

POSTRE regulatory structural variant curation triage

Assessment date: 2026-09-21. Scope: the six Table 1 reference alleles and all 41 Table 2 proposed long-range cases, compared with the DisMech worktree. This is a curation worklist, not a pathogenicity adjudication or patient-level phenotype dataset. The initial Table 2 triage changed no KB entries; the follow-up below records subsequent curation.

Inputs and identity checks

The 41 input rows are 41 distinct chromosome/breakpoint/type tuples: 21 translocations, 15 deletions, three inversions and two duplications. They concern nine target-gene groups. All input coordinates are hg19/GRCh37, as specified by POSTRE. A comma-separated pair at one breakpoint is an interval supplied by the authors, not two SVs; it must not be converted to a nucleotide-resolved junction. For an intrachromosomal SV, the two breakpoint columns delimit the rearrangement. The table below preserves the deposited coordinate strings without coordinate-system conversion.

All 13 cited source abstracts were read. Relevant clinical/variant/assay sections of 12 full texts were inspected; the Ishibashi ARX paper remained abstract-only after its author-manuscript download returned HTTP 403. This is targeted triage, not a complete reassessment of every source’s supplementary data. Missing original patient IDs, individual phenotype assignments or assay results are explicitly unassessed below. Table2_SVs contains no detailed-phenotype column: only neurodevelopmental or limbs. Clinical summaries below come from identified original-paper passages or D’Haene’s coordinate-linked Table 1; a cohort description is not silently assigned to an individual.

Table 2 contains prior-literature mechanistic proposals with incomplete validation. POSTRE’s published standard-mode output calls 39 of these 41 pathogenic; it does not call NR2F2_Nr1 or CTNNA2_Nr1 pathogenic. Agreement with earlier proposals is not independent experimental confirmation. The paper’s LOF/GOF terminology includes changes in expression and cannot be copied directly into DisMech’s coding functional-impact or spatial/temporal expression enums.

Six reference alleles: deduplication and curation destination

These are Table 1 alleles, separate from the 41-row candidate set. Disease-level coverage does not imply that the particular benchmark allele has been recorded. The destinations below identify this tranche’s existing-entry extensions or new entries; the accompanying KB changes retain their own primary evidence and history.

POSTRE’s grouping of these six as reference cases does not establish equal experimental confidence for every mechanistic claim. In particular, Lohan’s SHH/ZRS duplication mechanism remains proposed, without an allele-specific SHH expression assay. Differences between deposited benchmark bounds and refined primary allele descriptions must be retained, not silently harmonized.

POSTRE reference Physical allele, hg19 Source / original identity Disease destination and allele decision
Patient_Nr1; TFAP2A Inversion chr6:10355280–99103873 Laugsch 2019, PMID:30982769; the single BOFS inversion proband, with no additional durable case/family label established. Primary-source coordinates match POSTRE. Branchiooculofacial syndrome; add this inversion allele. Patient-derived neural crest cells show monoallelic TFAP2A expression. Do not substitute another TFAP2A coding allele.
Patient_Nr2; SOX9 Deletion chr17:68663405–68738405, POSTRE’s older 75-kb input Long 2020, PMID:32991838; Benko family F1, refined by Gordon 2014, PMID:24934569 Isolated Pierre Robin syndrome; source refinement is hg19 chr17:68663923–68748011 with a 9-bp junction insertion. Preserve the distinct benchmark representation; do not assert identical bounds.
Patient_Nr3; KCNJ2 Duplication chr17:68020547–70038208, POSTRE-reported bounds Franke 2016, PMID:27706140; human Cooks fibroblast case; original patient/family label not provided in POSTRE or resolved in the reviewed main text Cooks syndrome; add the source-attributed allele. Do not equate it with mouse Dup-C/Dup-C2 or the differently bounded later human DD1 duplication.
Patient_Nr4; PAX3 Deletion chr2:221278232–223014332 Lupiáñez 2015, PMID:25959774; brachydactyly family; exact match to original family B1 remains unassessed Preaxial digit brachydactyly–webbed fingers; new regulatory disease context, not PAX3 Waardenburg disease. Keep exact family attribution unresolved until confirmed.
Patient_Nr5; IHH Duplication chr2:219907598–220954793, POSTRE-reported bounds Lupiáñez 2015, PMID:25959774, case P1; prior K1549/K1552 reports in Yuksel-Apak 2012, PMID:22234151 IHH-related polysyndactyly; primary hg18 chr2:219583780–220497443 spans 913,663 bp, whereas POSTRE’s hg19 span is approximately 1,047 kb. The discrepancy is unresolved; do not represent these as harmonized exact bounds.
Patient_Nr6; SHH Duplication chr7:156437229–156692706 Lohan 2014, PMID:24456159, family 1; Table 1 array bounds match POSTRE ZRS-related limb malformation; add the family 1 duplication. Junctions were sequenced for families 2 and 5, not this allele; ectopic SHH expression remains hypothetical here.

Curation follow-up

The next curation tranche adds FOXG1_Nr5 (Mehrjouy P1) and MEF2C_Nr2/MEF2C_Nr3 (DGAP191/DGAP218), with qualitative affected regions and source-resolved allele descriptions. MEF2C-related disorder now supplies the missing disease context. Its MEF2C-AS1 breakpoint annotations preserve the later lncRNA interpretation alongside the proposed enhancer mechanism. Patient LCL results remain distinct from neuronal expression claims.

The SHFM1 extension records Allen family 2's deletion, not POSTRE DLX5&6_Nr7 (Allen family 1's translocation). Added PAX6, SHOX, and BMP2 examples likewise should not be counted as additional curated Table 2 rows. SOX9 family F1 now carries an EC1.45 feature annotation without equating that enhancer with the full deletion.

The coverage counts and case-by-case priorities below are the initial triage snapshot, retained for provenance. They do not override the three subsequent Table 2 allele additions above. The remaining MEF2C alleles still require individual assessment despite the new disease entry.

Coverage and evidence by target group at initial triage

The codes used in the case table are disease-scope matches, not allele matches. There are 19 cases with a direct disease/subtype destination, seven with related but incomplete disease scope, and 15 without an appropriate current disease entry. Gene mentions in unrelated disorders do not count as coverage.

Code Cases Current DisMech match Curation scope
S 6 Chromosome 2q32-q33 deletion syndrome Partial: entry discusses SATB2-associated syndrome but explicitly models a contiguous deletion. Resolve broader SATB2 syndrome placement before adding intact-target translocations/inversion.
A 1 Non-syndromic X-linked intellectual disability; related ARX-related XLAG Partial: a regulatory duplication cannot inherit the XLAG clinical profile. Recover P5’s clinical and allele details first.
F 11 FOXG1 disorder Direct disease destination; individual regulatory alleles need addition and source-specific evidence.
M 11 No MEF2C neurodevelopmental disease entry found New MEF2C-related neurodevelopmental disease context. MEF2C’s genetic record in Double Outlet Right Ventricle is a different phenotype/allele context.
D 7 Split hand/foot malformation, subtype SHFM1 Direct subtype destination. DYNC1I1 enhancer-disconnection mechanism and Allen 2014 are already cited; avoid duplicating that mechanism when adding alleles.
B 2 No BCL11B germline neurodevelopmental disease entry found New disease context; BCL11B activation in leukemia and incidental immune-disease mentions are not matches.
G 1 GLUT1 deficiency syndrome Direct disease destination subject to retrieving DGAP170’s individual clinical profile.
N 1 No appropriate NR2F2 regulatory neurodevelopmental entry found Candidate ASD-associated intergenic duplication. NR2F2 heart/diaphragm disease content is not this case.
C 1 No appropriate CTNNA2 regulatory disease entry found DD7 remains a mechanistic candidate; do not substitute the distinct biallelic coding CTNNA2 phenotype.

SATB2. Rainger 2014 connects three distinct rearrangements with craniofacial findings and enhancer experiments in mouse-derived cells and zebrafish. Those assays do not establish an expression change in the affected human developmental tissues. Nr3 reuses a previously described family, rather than identifying another independent allele each time the family is cited. Redin 2017 adds three separate breakpoints. Nr6 is especially unsuitable for a single asserted expression direction: POSTRE predicts simultaneous loss and gain of enhancer inputs. Nr4’s partner breakpoint also implicates PSD3 in Redin’s interpretation.

FOXG1. Mehrjouy 2018 argues against enhancer adoption as the main explanation for Nr8/DECIPHER 260836 and supports disruption of a critical regulatory region. Its Nr5 and Nr6 equivalents have Sanger junction information finer than the intervals retained in POSTRE. Ellaway 2013 measured reduced FOXG1 RNA in whole blood for original cases 2 and 3, but no difference in case 1’s lymphoblastoid cells; the authors caution that technical triplicates are not biological replicates. The original figure uses hg18, whereas POSTRE supplies hg19. Mapping those original case numbers onto Nr9–11 remains unassessed here. These deletions also include PRKD1, so target-gene regulation and physical coding overlap must remain distinct.

MEF2C. Redin reports reduced MEF2C expression in lymphoblastoid cell lines for DGAP131, DGAP191, DGAP218 and DGAP222 (Nr1–4). This supports a position effect but leaves developing-brain relevance inferential. D’Haene 2019 maps promoter contacts and functionally tests neuronal enhancers; its Table 1 links the six deletion intervals to earlier patient/CNV publications. Those enhancer assays are not a recreation of each whole patient deletion. Nr10 traces to Engels 2009; Nr6–9 and Nr11 trace to Kaminsky 2011. Recover their original subject/accession identifiers before patient-level phenotype curation. Nr10 and Nr11 require separate consideration of NR2F1 coding loss; POSTRE lists both NR2F1 and MEF2C for these alleles.

DLX5/DLX6. Tayebi 2014 directly matches Nr1–4 to families 1–4. The first three deletion junctions were sequenced; family 4 has maximum array bounds without junction sequencing. Their deleted DYNC1I1 exons have enhancer activity, so these are regulatory SV examples even though coding exons are removed. Hearing loss occurs in family 2 and should not be transferred to the other families. Kouwenhoven 2010 supports a p63-bound regulatory element; POSTRE derives Nr5 from a figure and lifts its coordinates. Birnbaum 2012 links the SHSF12 inversion to incompletely penetrant SHFM/hearing loss and models tissue-specific enhancers, without validating the full human allele’s expression effects. Allen 2014 resolves Nr7’s translocation, including the ODC1 intron breakpoint and small junction insertions omitted from POSTRE’s two-coordinate input. Its family 2 deletion is a different allele and is not Nr7.

BCL11B and SLC2A1. Lessel 2018 identifies H:II-1 and I:II-2 as the two BCL11B translocation cases and measures approximately half-normal BCL11B RNA in blood cells. It does not demonstrate the proposed mechanism in developing brain. Redin’s DGAP170 has reduced SLC2A1 expression in lymphoblastoid cells; retrieve the individual clinical details before merging it with the general GLUT1 phenotype profile.

ARX, NR2F2 and CTNNA2. Ishibashi 2015 provides enhancer and zebrafish autoregulation evidence, but P5’s full patient/allele record was not accessible in this pass. Doan 2016 describes a de novo intergenic duplication upstream of NR2F2 in an ASD proband and cites reference ChIA-PET promoter contact; that is not an allele-specific expression measurement. Melo 2020 explicitly leaves DD7’s exact mechanism unresolved: lymphoblastoid-cell Hi-C and biological plausibility nominate CTNNA2. These latter two cases remain candidates regardless of POSTRE’s negative predictions.

Complete 41-case worklist

P1 means prioritize source-resolved allele curation or the required disease-scope decision; it is not a pathogenicity grade. P2 means resolve the specified clinical, mechanistic or source gap before curation. “Unassessed” means this review did not establish that field; it does not mean that the original study lacks it. Clinical details are intentionally abbreviated and are not exhaustive phenotype sets.

Case ID Physical SV and hg19 breakpoints Original reference / patient or provenance Clinical detail assessed KB match Priority and next curation action / evidence limit
SATB2_Nr1 Translocation; chr2:200000820,200010665 / chr11:33461914,33544317 Rainger 2014; Rainger case 1 ID, micrognathia, cleft palate S (partial) P1 — Map to SATB2-associated syndrome; breakpoint intervals, model-enhancer evidence; no patient craniofacial expression assay.
SATB2_Nr2 Translocation; chr2:199380000,199390000 / chr3:181460016,181526605 Rainger 2014; Rainger case 2 Severe ID, Pierre Robin sequence S (partial) P1 — Preserve the separate chr3 breakpoint near SOX2; do not attribute the whole phenotype to SATB2.
SATB2_Nr3 Translocation; chr1:51292287 / chr2:199214552,199261488 Rainger 2014; Reanalysed Ghassibe-Sabbagh family; father/son Cleft palate, micrognathia, microstomia, oligodontia S (partial) P1 — One familial allele, not independent father/son alleles; FAF1 is physically interrupted; SATB2 regulation is the proposed alternative.
SATB2_Nr4 Translocation; chr2:200092423,200092424 / chr8:18574077,18574078 Redin 2017; DGAP237 Neurodevelopmental; individual clinical profile unassessed S (partial) P2 — Inspect supplementary expression result and PSD3 disruption; assay listed in methods is not itself a positive result.
SATB2_Nr5 Translocation; chr2:199943781,199943805 / chr11:121638616,121642346 Redin 2017; DGAP249 Neurodevelopmental; individual clinical profile unassessed S (partial) P2 — Recover primary phenotype and derivative structure before adding an allele-specific regulatory chain.
SATB2_Nr6 Inversion; chr2:105990245,105990246 / chr2:199613232,199613234 Redin 2017; NIJ12 Neurodevelopmental; individual clinical profile unassessed S (partial) P2 — POSTRE predicts both lost and gained enhancer inputs; retain competing effects rather than choose an expression direction.
ARX_Nr1 Duplication; chrX:24351258 / chrX:24900393 Ishibashi 2015; P5 Neurodevelopmental; P5 clinical detail unassessed A (partial) P2 — Abstract only; resolve duplicated functional ARX sequence versus enhancer dosage and clinical subtype before curation.
FOXG1_Nr1 Translocation; chr3:36969141,36969450 / chr14:29745315,29745323 Redin 2017; DGAP245 Neurodevelopmental; individual clinical profile unassessed F P2 — Add only after checking original patient phenotype and the second breakpoint; position effect is proposed.
FOXG1_Nr2 Translocation; chr8:79810404,79810407 / chr14:29765534,29765537 Redin 2017; NIJ1 Neurodevelopmental; individual clinical profile unassessed F P2 — Same requirement as Nr1; distinct allele, not a duplicate based on FOXG1.
FOXG1_Nr3 Translocation; chr1:81860987 / chr14:29609215 Redin 2017; DGAP294 Neurodevelopmental; individual clinical profile unassessed F P2 — Same requirement as Nr1; resolve breakpoint precision from the primary report.
FOXG1_Nr4 Translocation; chr4:65690635 / chr14:29725054 Redin 2017; DGAP246 Neurodevelopmental; individual clinical profile unassessed F P2 — Preserve possible NPAS3 contribution at the partner breakpoint; do not transfer all features to FOXG1.
FOXG1_Nr5 Translocation; chr9:94269066,94269642 / chr14:29738715,29739465 Mehrjouy 2018; P1; SCV000576475 FOXG1-like phenotype; primary clinical description available F P1 — Use primary Sanger-defined junctions for allele curation; POSTRE stores broader mate-pair intervals.
FOXG1_Nr6 Translocation; chr4:114869960,114871254 / chr14:29630531,29631032 Mehrjouy 2018; P2; SCV000576474 FOXG1-like phenotype; primary clinical description available F P1 — Use Sanger junctions; chr4 breakpoint truncates ARSJ, separate from the intact FOXG1 regulatory target.
FOXG1_Nr7 Translocation; chr2:224764222,224765719 / chr14:29263288,29263828 Mehrjouy 2018; P3; SCV000576473 Developmental delay, hypotonia, microcephaly F P1 — Keep unresolved breakpoint interval; WDFY1 and a noncoding RNA are physically interrupted.
FOXG1_Nr8 Deletion; chr14:29538005 / chr14:30335064 Mehrjouy 2018; P4; DECIPHER 260836 Severe delay, microcephaly, absent language F P1 — Curate the explicit competing-mechanism history; enhancer adoption is challenged, not experimentally established.
FOXG1_Nr9 Deletion; chr14:29695258 / chr14:30872374 Ellaway 2013; Ellaway deletion; original case-number mapping unassessed Rett-like cohort; individual correspondence unassessed F P1 — Reconcile hg18 original figure to hg19 interval; assign blood/LCL expression only after identifying the original case.
FOXG1_Nr10 Deletion; chr14:29337429 / chr14:30487998 Ellaway 2013; Ellaway deletion; original case-number mapping unassessed Rett-like cohort; individual correspondence unassessed F P1 — Same mapping requirement as Nr9; do not assume all three cases had reduced measured expression.
FOXG1_Nr11 Deletion; chr14:29429541 / chr14:30316719 Ellaway 2013; Ellaway deletion; original case-number mapping unassessed Rett-like cohort; individual correspondence unassessed F P1 — Same mapping requirement as Nr9; retain PRKD1 deletion and technical-replicate limitations.
MEF2C_Nr1 Translocation; chr1:86157131,86157132 / chr5:88829562,88829564 Redin 2017; DGAP131 Delay, seizures, hypotonia, dysmorphic features M (gap) P1 — New disease context needed; reduced MEF2C measured in LCLs, not developing brain.
MEF2C_Nr2 Translocation; chr5:88706882,88706887 / chr7:94007560,94007567 Redin 2017; DGAP191 ID, seizures, hypotonia, sensorineural deafness M (gap) P1 — New disease context needed; LCL expression supports regulation but cannot assign every clinical feature to MEF2C.
MEF2C_Nr3 Inversion; chr5:24272298,24272302 / chr5:88400843,88400848 Redin 2017; DGAP218 Delay, seizures, hypotonia, autism M (gap) P1 — New disease context needed; inversion and reduced LCL expression must remain separate from inferred neural enhancer effects.
MEF2C_Nr4 Translocation; chr1:53133119 / chr5:89055498,89055499 Redin 2017; DGAP222 Delay, microcephaly, dysmorphic features M (gap) P1 — New disease context needed; LCL expression is not a patient neuronal assay.
MEF2C_Nr5 Translocation; chr5:88793025,88793026 / chr15:94759893,94759898 Redin 2017; ROC1 Developmental delay M (gap) P2 — No LCL result established here; assess partner breakpoint and additional CHD2 model prediction.
MEF2C_Nr6 Deletion; chr5:89453519 / chr5:89767052 D’Haene 2019; D’Haene Table 1 → Kaminsky 2011 Cerebral white-matter abnormality, autism M (gap) P1 — Recover original CNV accession; tested enhancers are not a recreation of this complete deletion.
MEF2C_Nr7 Deletion; chr5:88348147 / chr5:88783092 D’Haene 2019; D’Haene Table 1 → Kaminsky 2011 Developmental and/or morphological abnormality; nonspecific source wording M (gap) P1 — Recover original CNV accession and individual phenotype; avoid importing a generic cohort description as specific findings.
MEF2C_Nr8 Deletion; chr5:89208994 / chr5:89855436 D’Haene 2019; D’Haene Table 1 → Kaminsky 2011 ID, myopathy M (gap) P1 — Recover original CNV accession; distinguish intact MEF2C target from genes physically removed.
MEF2C_Nr9 Deletion; chr5:89523963 / chr5:90412409 D’Haene 2019; D’Haene Table 1 → Kaminsky 2011 Developmental and/or morphological abnormality; nonspecific source wording M (gap) P1 — Recover original CNV accession and phenotype; enhancer assays alone do not establish this allele’s full effect.
MEF2C_Nr10 Deletion; chr5:88412388 / chr5:91996699 D’Haene 2019; D’Haene Table 1 → Engels 2009 Severe ID, seizures, hypotonia M (gap) P1 — Resolve original patient; assess NR2F1 coding deletion alongside MEF2C regulatory loss.
MEF2C_Nr11 Deletion; chr5:88232587 / chr5:93437723 D’Haene 2019; D’Haene Table 1 → Kaminsky 2011 Delay, seizures, hypotonia M (gap) P1 — Recover original CNV accession; large mixed-effect deletion also removes NR2F1, precluding single-target phenotype attribution.
DLX5&6_Nr1 Deletion; chr7:95615187 / chr7:95783313 Tayebi 2014; Tayebi family 1 Non-syndromic SHFM D P1 — Extend SHFM1 with breakpoint-sequenced deletion; DYNC1I1 coding exons host the regulatory elements.
DLX5&6_Nr2 Deletion; chr7:95624825 / chr7:96135521 Tayebi 2014; Tayebi family 2 SHFM with hearing loss D P1 — Keep additional deleted interval and hearing phenotype family-specific; enhancer-to-hearing assignment remains inferential.
DLX5&6_Nr3 Deletion; chr7:95667046 / chr7:95872044 Tayebi 2014; Tayebi family 3 Non-syndromic SHFM D P1 — Extend SHFM1 with its distinct sequenced allele; do not merge the overlapping deletions.
DLX5&6_Nr4 Deletion; chr7:95693341 / chr7:95862369 Tayebi 2014; Tayebi family 4 Non-syndromic SHFM D P1 — Array maximum bounds only: original authors could not sequence breakpoints; preserve this uncertainty.
DLX5&6_Nr5 Deletion; chr7:95552064 / chr7:96432064 Kouwenhoven 2010; Kouwenhoven Figure 3 patient SHFM D P1 — POSTRE coordinates were lifted to hg19 from a figure; verify allele bounds and enhancer identity before structured entry.
DLX5&6_Nr6 Inversion; chr7:29076632 / chr7:96348018 Birnbaum 2012; SHSF12 family SHFM and sensorineural hearing loss D P1 — Familial inversion with incomplete penetrance; POSTRE coordinates are lifted from hg18; avoid transferring absent craniofacial findings.
DLX5&6_Nr7 Translocation; chr2:10585833 / chr7:96229309 Allen 2014; Allen family 1/proband 1 SHFM affecting three limbs, sensorineural deafness D P1 — Existing SHFM1 citation covers this mechanism; add the allele once, with chr2 ODC1 interruption separate from DLX5/6 targeting.
BCL11B_Nr1 Translocation; chr4:24332309,24332315 / chr14:98758653,98758657 Lessel 2018; H:II-1 Neurodevelopmental delay/ID with speech impairment B (gap) P1 — New germline disease context needed; approximately half BCL11B RNA in blood supports regulation, not neural-tissue validation.
BCL11B_Nr2 Translocation; chr4:148252852,148252854 / chr14:99097976,99097980 Lessel 2018; I:II-2 Neurodevelopmental delay/ID with speech impairment B (gap) P1 — Distinct translocation from Nr1; same blood-versus-brain limitation; do not map to the leukemia entry.
SLC2A1_Nr1 Translocation; chr1:43493587,43493589 / chr19:7512323,7512335 Redin 2017; DGAP170 Neurodevelopmental; individual clinical profile unassessed G P1 — Extend GLUT1 only after retrieving clinical profile; decreased LCL expression supports a position effect, with neural context unresolved.
NR2F2_Nr1 Duplication; chr15:96550000 / chr15:96620000 Doan 2016; Doan Figure 3b; individual ID unassessed Autism cohort proband N (gap) P2 — Candidate intergenic duplication and reference ChIA-PET contact; no allele-specific expression demonstrated; POSTRE did not call pathogenic.
CTNNA2_Nr1 Translocation; chr4:176067000 / chr2:82047000 Melo 2020; DD7 ID and developmental delay C (gap) P2 — Primary study leaves mechanism unresolved; Hi-C in LCLs suggests a candidate target; POSTRE did not call pathogenic.

Deduplication limits and next pass

No candidate is discarded merely because its target gene, disorder or cited publication is already present. Within Table 2, the deposited type/chromosome/breakpoint tuples are distinct. The worktree search found no explicit paired-coordinate record for these 41 deposited alleles; generic mechanism coverage, including the Allen SHFM1 citation, remains separately identified above. This literal-coordinate screen is a lower-bound check, not proof of absence: a different assembly, refined breakpoint or differently named prior report could represent the same allele.

The pre-existing local benchmark/ directory contains 1,842 PhenoSV simulation CSVs. A manifest identifying the 193 source cases was not readily available, and the simulation files were not used as a substitute for source-case provenance. Allele-level overlap with the PhenoSV 193-case set remains unassessed. Before using this list as an independent evaluation set, reconcile original study/patient identifiers, assemblies and breakpoint intervals across datasets; overlapping intervals or shared genes alone are insufficient.

After the follow-up above, remaining candidates include the other SHFM1 family alleles, FOXG1 Nr6–8 and the blood/LCL-supported BCL11B, MEF2C and SLC2A1 cases. Resolve the missing BCL11B disease entry and SATB2 disease scope before adding those alleles. Retrieve individual phenotype records for the Redin cases and original CNV accessions for the D’Haene-derived deletions. Keep the NR2F2 and CTNNA2 cases as explicit hypotheses until evidence justifies a stronger assertion.

For each eventual KB allele, separate the physical rearrangement and any overlapping genes from the intact regulatory target; identify the tested enhancer and assay system; distinguish measured RNA abundance from proposed spatial/temporal misexpression; and preserve competing explanations and mixed coding/regulatory effects. A POSTRE score alone does not establish a mechanistic edge or justify LOE, mLOE or GOE.