First try of PS1 and PM5

bihealth · Sep 4, 2024 · 64379ca · 64379ca
1 parent 673955f
commit 64379ca
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Showing 5 changed files with 402 additions and 2 deletions.
diff --git a/src/bench/_stats.csv b/src/bench/_stats.csv
diff --git a/src/bench/stats.csv b/src/bench/stats.csv
diff --git a/src/defs/auto_pvs1.py b/src/defs/auto_pvs1.py
@@ -86,8 +86,8 @@ class PVS1PredictionStrucVarPath(AutoAcmgBaseEnum):
     "start_lost": SeqVarPVS1Consequence.InitiationCodon,
     "5_prime_utr_variant": SeqVarPVS1Consequence.NotSet,
     "5_prime_UTR_variant": SeqVarPVS1Consequence.NotSet,
-    "3_prime_utr_variant": SeqVarPVS1Consequence.NonsenseFrameshift,
-    "3_prime_UTR_variant": SeqVarPVS1Consequence.NonsenseFrameshift,
+    "3_prime_utr_variant": SeqVarPVS1Consequence.NotSet,
+    "3_prime_UTR_variant": SeqVarPVS1Consequence.NotSet,
     "splice_region_variant": SeqVarPVS1Consequence.SpliceSites,  # Can affect splicing
     "splice_donor_variant": SeqVarPVS1Consequence.SpliceSites,  # Canonical splice site
     "splice_donor_5th_base_variant": SeqVarPVS1Consequence.SpliceSites,  # Non-canonical splice site

diff --git a/src/seqvar/auto_ps1_pm5.py b/src/seqvar/auto_ps1_pm5.py
@@ -110,6 +110,28 @@ def _is_missense(var_data: AutoACMGSeqVarData) -> bool:
             return True
         return False
 
+    @staticmethod
+    def _affect_splicing(var_data: AutoACMGData) -> bool:
+        """
+        Check if the variant affects splicing.
+
+        Args:
+            var_data (AutoACMGData): The variant information.
+
+        Returns:
+            bool: True if the variant affects splicing, False otherwise.
+        """
+        score_checks = {
+            "spliceAI_acceptor_gain": var_data.thresholds.spliceAI_acceptor_gain,
+            "spliceAI_acceptor_loss": var_data.thresholds.spliceAI_acceptor_loss,
+            "spliceAI_donor_gain": var_data.thresholds.spliceAI_donor_gain,
+            "spliceAI_donor_loss": var_data.thresholds.spliceAI_donor_loss,
+        }
+        return any(
+            (getattr(var_data.scores.cadd, score_name) or 0) > threshold
+            for score_name, threshold in score_checks.items()
+        )
+
     def verify_ps1pm5(
         self, seqvar: SeqVar, var_data: AutoACMGSeqVarData
     ) -> Tuple[Optional[PS1PM5], str]:

diff --git a/src/vcep/cdh1.py b/src/vcep/cdh1.py
@@ -27,6 +27,38 @@
 
 class CDH1Predictor(DefaultSeqVarPredictor):
 
+    def predict_ps1pm5(
+        self, seqvar: SeqVar, var_data: AutoACMGData
+    ) -> Tuple[AutoACMGCriteria, AutoACMGCriteria]:
+        ps1 = AutoACMGCriteria(
+            name="PS1",
+            prediction=AutoACMGPrediction.NotApplicable,
+            strength=AutoACMGStrength.PathogenicSupporting,
+            summary="PS1 is not applicable for CDH1.",
+        )
+        if any(
+            cons in ["frameshift_variant", "stop_gained"] for cons in var_data.consequence.mehari
+        ) and self.undergo_nmd(
+            var_data.tx_pos_utr, var_data.hgnc_id, var_data.strand, var_data.exons
+        ):
+            pm5 = AutoACMGCriteria(
+                name="PM5",
+                prediction=AutoACMGPrediction.Met,
+                strength=AutoACMGStrength.PathogenicSupporting,
+                summary="Nonsense or frameshift variant predicted to undergo NMD. PM5 is met.",
+            )
+        else:
+            pm5 = AutoACMGCriteria(
+                name="PM5",
+                prediction=AutoACMGPrediction.NotMet,
+                strength=AutoACMGStrength.PathogenicSupporting,
+                summary=(
+                    "Consequence is not frameshift or nonsense or variant is not predicted to "
+                    "undergo NMD. PM5 is not met."
+                ),
+            )
+        return ps1, pm5
+
     def predict_pm1(self, seqvar: SeqVar, var_data: AutoACMGSeqVarData) -> AutoACMGCriteria:
         """Override predict_pm1 to return a not applicable status for PM1."""
         logger.info("Predict PM1")