dc7ac233e8848cee5087dca606f4d638ca8a3be1
lrnassar
  Tue Apr 14 11:58:42 2026 -0700
Update InSiGHT scripts per v2.0.0 CSpec: fix PMS2 BS1 threshold, add PMS2 PVS1 Moderate region. refs #36582

diff --git src/hg/makeDb/scripts/insight/insightAFfrequencies.py src/hg/makeDb/scripts/insight/insightAFfrequencies.py
index bf22467a022..5e8a1df83c3 100644
--- src/hg/makeDb/scripts/insight/insightAFfrequencies.py
+++ src/hg/makeDb/scripts/insight/insightAFfrequencies.py
@@ -41,61 +41,61 @@
 # Gene to transcript mapping (coordinates will be queried from hgsql)
 TRANSCRIPTS = {
     'MLH1': 'NM_000249.4',
     'MSH2': 'NM_000251.3',
     'MSH6': 'NM_000179.3',
     'PMS2': 'NM_000535.7',
 }
 
 # ACMG thresholds per gene
 # Format: gene -> {'BA1': threshold, 'BS1': (lower, upper)}
 # PM2_supporting is for AF < lowest BS1 threshold but > 0
 THRESHOLDS = {
     'MLH1': {'BA1': 0.001, 'BS1_lower': 0.0001, 'BS1_upper': 0.001},
     'MSH2': {'BA1': 0.001, 'BS1_lower': 0.0001, 'BS1_upper': 0.001},
     'MSH6': {'BA1': 0.0022, 'BS1_lower': 0.00022, 'BS1_upper': 0.0022},
-    'PMS2': {'BA1': 0.0028, 'BS1_lower': 0.0001, 'BS1_upper': 0.001},
+    'PMS2': {'BA1': 0.0028, 'BS1_lower': 0.00028, 'BS1_upper': 0.0028},
 }
 
 # Colors (RGB)
 COLORS = {
     'PM2_supporting': '138,111,158',
     'BA1': '2,82,66',
     'BS1': '35,159,134',
 }
 
 # Rule text
 RULES = {
     'MLH1': {
         'PM2_supporting': 'Absent/extremely rare (<1 in 50,000) in gnomADv4',
         'BA1': 'gnomADv4 Grpmax AF ≥ 0.001 (0.1%)',
         'BS1': 'gnomADv4 Grpmax AF ≥ 0.0001 and < 0.001 (0.01-0.1%)',
     },
     'MSH2': {
         'PM2_supporting': 'Absent/extremely rare (<1 in 50,000) in gnomADv4',
         'BA1': 'gnomADv4 Grpmax AF ≥ 0.001 (0.1%)',
         'BS1': 'gnomADv4 Grpmax AF ≥ 0.0001 and < 0.001 (0.01-0.1%)',
     },
     'MSH6': {
         'PM2_supporting': 'Absent/extremely rare (<1 in 50,000) in gnomADv4',
         'BA1': 'gnomADv4 Grpmax AF ≥ 0.0022 (0.22%)',
         'BS1': 'gnomADv4 Grpmax AF ≥ 0.00022 and < 0.0022 (0.022-0.22%)',
     },
     'PMS2': {
         'PM2_supporting': 'Absent/extremely rare (<1 in 50,000) in gnomADv4',
         'BA1': 'gnomADv4 Grpmax AF ≥ 0.0028 (0.28%)',
-        'BS1': 'gnomADv4 Grpmax AF ≥ 0.0001 and < 0.001 (0.01-0.1%)',
+        'BS1': 'gnomADv4 Grpmax AF ≥ 0.00028 and < 0.0028 (0.028-0.28%)',
     },
 }
 
 # AutoSQL definition for the BED9+3 format
 AUTOSQL = """table InSiGHTAF
 "InSiGHT VCEP ACMG AF classifications for Lynch syndrome genes based on gnomAD v4.1 exomes"
    (
    string chrom;       "Reference sequence chromosome or scaffold"
    uint   chromStart;  "Start position in chromosome"
    uint   chromEnd;    "End position in chromosome"
    string name;        "HGVSc notation"
    uint score;         "Not used, all 0"
    char[1] strand;     "Not used, all ."
    uint thickStart;    "Same as chromStart"
    uint thickEnd;      "Same as chromEnd"