From 976267afc33bee4cfd7a75627c096331945032f7 Mon Sep 17 00:00:00 2001 From: Gabriel Zinser Date: Tue, 2 Jun 2026 13:59:28 -0600 Subject: [PATCH 1/3] Adding conflicting evidence to FRA12A_DIP2B --- data/criTRia-curations.json | 25 ++++++++++++++++++------- 1 file changed, 18 insertions(+), 7 deletions(-) diff --git a/data/criTRia-curations.json b/data/criTRia-curations.json index 5a84c59c..f221e9be 100644 --- a/data/criTRia-curations.json +++ b/data/criTRia-curations.json @@ -1989,7 +1989,7 @@ "Description": "FRA12A is a rare, folate-sensitive chromosomal fragile site on chromosome 12 associated with intellectual developmental disorder, FRA12A type. The DIP2B CGG repeat expansion causes this folate-sensitive site and is associated with a broad phenotypic range, including intellectual disability, ataxia/movement disorder, and epilepsy; cardiovascular associations have also been reported but were not scored and are noted for completeness. For this curation, the neurodevelopmental and neurologic presentations (intellectual disability, ataxia/movement disorder, and epilepsy) were lumped as a single phenotypic spectrum, which supports the current score. If these phenotypes are treated as distinct entities, the evidence strength and resulting score may differ. Patients across multiple independent families and cohorts provide inheritance and functional support. Mechanistically, repeat expansions are associated with promoter hypermethylation, altered regulatory activity, and changes in DIP2B expression. Case-control studies report enrichment of DIP2B expansions in ataxia cohorts (OR = 2.8) and cardiovascular disease populations (OR = 2.7), and computational analyses support biological relevance through conservation and a predicted interaction with the DMAP1 methylation complex.", "Source": "criTRia", "SOP_version": "criTRia v0", - "Manual_evidence_level": null, + "Manual_evidence_level": "Disputed", "genetic_evidence_details": [ { "Evidence type": "Probands", @@ -2002,6 +2002,17 @@ "category_max_score": 6, "publication_dates": ["2025-03-01", "2007-02-01", "2021-01-01"] }, + { + "Evidence type": "Allele", + "Score": 0.0, + "Citation": "42205056", + "Evidence detail": "A cohort of 14 probands with expanded alleles identified no common phenotypic pattern. This included healthy probands with highly expanded alleles, and probands with various neurological and non neurological presentations. There was no clear association between size of expanded alleles and presence of neurological disorders, which contributes to the disputed classification of this locus.", + "evidence_category": "Collective Evidence", + "evidence_supercategory": "Genetic Evidence", + "evidence_max_score": 2, + "category_max_score": 3, + "publication_dates": ["2026-05-28"] + }, { "Evidence type": "Computational", "Score": 0.5, @@ -2027,14 +2038,14 @@ "experimental_evidence_details": [ { "Evidence type": "Regulatory impact", - "Score": 1.0, - "Citation": "pmid:37248219", - "Evidence detail": "Repeat expansion associated with promoter hypermethylation, loss of regulatory activity, and predicted allelic silencing. Expanded CGG repeat associated with promoter methylation and reduced DIP2B expression. Unmethylated expansion associated with overexpression.", + "Score": 0.5, + "Citation": "pmid:37248219; pmid:42205056", + "Evidence detail": "Repeat expansion associated with loss of regulatory activity, and predicted allelic silencing. Hypermethylation has been detected in expanded alleles, however another correlation analysis of long-read genomes shows no strong association between DIP2B CGG repeat length and promoter hypermethylation. Expanded CGG repeat associated with reduced DIP2B expression. Unmethylated expansion associated with overexpression.", "evidence_category": "Function", "evidence_supercategory": "Experimental Evidence", "evidence_max_score": 2, "category_max_score": 2, - "publication_dates": ["2023-05-29"] + "publication_dates": ["2023-05-29", "2026-05-28"] }, { "Evidence type": "Patient cells", @@ -2052,7 +2063,7 @@ "Singular Evidence": 6.0, "Collective Evidence": 0.5, "Statistics": 3.0, - "Function": 1.0, + "Function": 0.5, "Functional Alteration": 0.5, "Models": 0, "Rescue": 0 @@ -2065,7 +2076,7 @@ "total_score": 11.0, "publication_count": 5, "publication_interval_years": 18.08, - "classification": "Moderate" + "classification": "Disputed" }, { "Disease_ID": "DMD", From f69967625447d87b5b6163594dabb85b2e2ac2e7 Mon Sep 17 00:00:00 2001 From: Gabriel Zinser Date: Tue, 2 Jun 2026 14:06:44 -0600 Subject: [PATCH 2/3] fixing citation --- data/criTRia-curations.json | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/data/criTRia-curations.json b/data/criTRia-curations.json index f221e9be..d89af9d8 100644 --- a/data/criTRia-curations.json +++ b/data/criTRia-curations.json @@ -2005,7 +2005,7 @@ { "Evidence type": "Allele", "Score": 0.0, - "Citation": "42205056", + "Citation": "pmid:42205056", "Evidence detail": "A cohort of 14 probands with expanded alleles identified no common phenotypic pattern. This included healthy probands with highly expanded alleles, and probands with various neurological and non neurological presentations. There was no clear association between size of expanded alleles and presence of neurological disorders, which contributes to the disputed classification of this locus.", "evidence_category": "Collective Evidence", "evidence_supercategory": "Genetic Evidence", From eb969798d95535384454215c83d01b288b53602e Mon Sep 17 00:00:00 2001 From: gaberbz <182678422+gaberbz@users.noreply.github.com> Date: Tue, 2 Jun 2026 20:14:37 +0000 Subject: [PATCH 3/3] Update data --- data/STRchive-loci.json | 2 +- data/criTRia-curations.json | 8 ++++---- 2 files changed, 5 insertions(+), 5 deletions(-) diff --git a/data/STRchive-loci.json b/data/STRchive-loci.json index 30e17c29..dbfc88ff 100644 --- a/data/STRchive-loci.json +++ b/data/STRchive-loci.json @@ -1576,7 +1576,7 @@ "id": "FRA12A_DIP2B", "disease_id": "FRA12A", "gene": "DIP2B", - "evidence": ["Moderate"], + "evidence": ["Disputed"], "chrom": "chr12", "start_hg38": 50505001, "stop_hg38": 50505024, diff --git a/data/criTRia-curations.json b/data/criTRia-curations.json index d89af9d8..c70b5cc1 100644 --- a/data/criTRia-curations.json +++ b/data/criTRia-curations.json @@ -2070,12 +2070,12 @@ }, "supercategory_summary": { - "Experimental Evidence": 1.5, + "Experimental Evidence": 1.0, "Genetic Evidence": 9.5 }, - "total_score": 11.0, - "publication_count": 5, - "publication_interval_years": 18.08, + "total_score": 10.5, + "publication_count": 6, + "publication_interval_years": 19.32, "classification": "Disputed" }, {