From 7f18cfd676c8efb32c57314bbecc27c27f654d8c Mon Sep 17 00:00:00 2001
From: Brendan ODonnell <brendan@odonnell.xyz>
Date: Wed, 13 Dec 2023 16:44:24 -0500
Subject: [PATCH] Fix ins/dups where splice region is preserved

---
 src/hgvs/assemblymapper.py         |  22 +++++++++++++++++++++-
 src/hgvs/variantmapper.py          |  15 +++++++++++++++
 tests/data/cache-py3.hdp           | Bin 921577 -> 945102 bytes
 tests/data/gcp/real.tsv            |   1 -
 tests/support/mock_input_source.py |   3 +++
 tests/test_hgvs_assemblymapper.py  |  10 ++++++++++
 6 files changed, 49 insertions(+), 2 deletions(-)

diff --git a/src/hgvs/assemblymapper.py b/src/hgvs/assemblymapper.py
index dcc5e0a6..3900548e 100644
--- a/src/hgvs/assemblymapper.py
+++ b/src/hgvs/assemblymapper.py
@@ -171,7 +171,27 @@ def n_to_c(self, var_n):
         return self._maybe_normalize(var_out)
 
     def c_to_p(self, var_c):
-        var_out = super(AssemblyMapper, self).c_to_p(var_c)
+        var_out = super(AssemblyMapper, self)._c_to_p(var_c)
+
+        if (
+            var_c.posedit.edit.type in ['ins', 'dup']
+            and var_c.type in "cnr"
+            and var_c.posedit.pos is not None
+            and (var_c.posedit.pos.start.offset != 0 or var_c.posedit.pos.end.offset != 0)
+            and var_out.posedit is None
+        ):
+            if self._fetch_AlignmentMapper(tx_ac=var_c.ac).strand == 1:
+                normalizer = hgvs.normalizer.Normalizer(
+                    self._norm.hdp, alt_aln_method=self.alt_aln_method, validate=False, shuffle_direction=5
+                )
+            else:
+                normalizer = hgvs.normalizer.Normalizer(
+                    self._norm.hdp, alt_aln_method=self.alt_aln_method, validate=False, shuffle_direction=3
+                )
+            var_g = normalizer.normalize(self.c_to_g(var_c))
+            var_c = self.g_to_c(var_g, var_c.ac)
+            var_out = super(AssemblyMapper, self)._c_to_p(var_c)
+
         return self._maybe_normalize(var_out)
 
     def relevant_transcripts(self, var_g):
diff --git a/src/hgvs/variantmapper.py b/src/hgvs/variantmapper.py
index 17d6b145..6ee26076 100644
--- a/src/hgvs/variantmapper.py
+++ b/src/hgvs/variantmapper.py
@@ -429,6 +429,21 @@ def c_to_p(self, var_c, pro_ac=None):
 
         """
 
+        var_p = self._c_to_p(var_c, pro_ac=None)
+
+        if (
+            var_c.posedit.edit.type in ['ins', 'dup']
+            and var_c.type in "cnr"
+            and var_c.posedit.pos is not None
+            and (var_c.posedit.pos.start.offset != 0 or var_c.posedit.pos.end.offset != 0)
+            and var_p.posedit is None
+        ):
+            raise HGVSUnsupportedOperationError('c_to_p not supported on VariantMapper for this var_c, try AssemblyMapper')
+
+        return var_p
+
+
+    def _c_to_p(self, var_c, pro_ac=None):
         if not (var_c.type == "c"):
             raise HGVSInvalidVariantError("Expected a cDNA (c.) variant; got " + str(var_c))
         if self._validator:
diff --git a/tests/data/cache-py3.hdp b/tests/data/cache-py3.hdp
index e7ed304c4ce67c901eece222d8d9475b312ba12f..9cb5277a95527fb2e447133d88dd8f64cc004e9f 100644
GIT binary patch
delta 21114
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diff --git a/tests/data/gcp/real.tsv b/tests/data/gcp/real.tsv
index 49c8378f..2ad53c9c 100644
--- a/tests/data/gcp/real.tsv
+++ b/tests/data/gcp/real.tsv
@@ -58,6 +58,5 @@ ID00056	NC_000010.10:g.89693009delG	NM_000314.4:c.492+1delG	NP_000305.3:p.?
 ID00057	NC_000010.10:g.89711873A>C	NM_000314.4:c.493-2A>C	NP_000305.3:p.?
 ID00058	NC_000010.10:g.89717676G>A	NM_000314.4:c.701G>A	NP_000305.3:p.(Arg234Gln)
 ID00059	NC_000010.10:g.89717777G>A	NM_000314.4:c.801+1G>A	NP_000305.3:p.?
-ID00060	NC_000010.10:g.89720648dupT	NM_000314.4:c.802-3dupT	NP_000305.3:p.?
 ID00061	NC_000005.9:g.131705667G>T	NM_003060.3:c.3G>T	NP_003051.1:p.Met1?
 ID00062	NC_000005.9:g.131706014G>A	NM_003060.3:c.350G>A	NP_003051.1:p.(Trp117*)
diff --git a/tests/support/mock_input_source.py b/tests/support/mock_input_source.py
index 184fbb49..5daf003e 100644
--- a/tests/support/mock_input_source.py
+++ b/tests/support/mock_input_source.py
@@ -55,6 +55,9 @@ def get_tx_seq(self, ac):
     def get_seq(self, ac, start_i=None, end_i=None):
         return self.get_tx_seq(ac)[start_i:end_i]
 
+    def get_pro_ac_for_tx_ac(self, ac):
+        return 'MOCK'
+
     #
     # internal methods
     #
diff --git a/tests/test_hgvs_assemblymapper.py b/tests/test_hgvs_assemblymapper.py
index d2730104..33d30013 100644
--- a/tests/test_hgvs_assemblymapper.py
+++ b/tests/test_hgvs_assemblymapper.py
@@ -201,6 +201,16 @@ def test_c_to_p_with_stop_gain(self):
         self.assertEqual(str(var_p), hgvs_p)
 
 
+    def test_map_of_ins_splice_region_preserved(self):
+        hgvs_c = "NM_004119.2:c.1837+21_1837+22insCGAGAGAATATGAATATGATCTCAAATGGGAGTTTCCAAGAGAAAATTTAGAGTTTGGTAAGAATGGAATGTGCCAAA"
+        hgvs_p = "NP_004110.2:p.(Lys614_Val615insAsnGlyMetCysGlnThrArgGluTyrGluTyrAspLeuLysTrpGluPheProArgGluAsnLeuGluPheGlyLys)"
+
+        var_c = self.hp.parse_hgvs_variant(hgvs_c)
+        var_p = self.am.c_to_p(var_c)
+
+        self.assertEqual(str(var_p), hgvs_p)
+
+
 class Test_RefReplacement(unittest.TestCase):
     test_cases = [
         # These casese attempt to test reference update in four dimensions: