Added IUPAC ambuguity codes fix in REF for complex/deletions .

Author: PolinaBevad

src/main/java/com/astrazeneca/vardict/modules/ToVarsBuilder.java

@@ -993,9 +993,19 @@ else if (deletionLength < instance().conf.SVMINLEN) {
         }
     }
 
+    /**
+     * Validate reference allele according to VCF 4.3 specification in case if IUPAC ambiguity codes are present
+     * in reference.
+     * @param refallele sequence of reference bases that covers variant
+     * @return reference allele sequence where IUPAC ambuguity bases are changed to the one that is
+     * first alphabetically.
+     */
     String validateRefallele(String refallele) {
-        if (IUPAC_AMBIGUITY_CODES.containsKey(refallele)){
-            refallele = IUPAC_AMBIGUITY_CODES.get(refallele);
+        for (int i = 0; i < refallele.length(); i++) {
+            String refBase = substr(refallele, i, 1);
+            if (IUPAC_AMBIGUITY_CODES.containsKey(refBase)) {
+                refallele = refallele.replaceFirst(refBase, IUPAC_AMBIGUITY_CODES.get(refBase));
+            }
         }
         return refallele;
     }

src/test/java/com/astrazeneca/vardict/modules/ToVarsBuilderTest.java

@@ -139,5 +139,14 @@ public void testValidateRefAllele(){
             validatedAlleles.add(toVarsBuilder.validateRefallele(allele));
         }
         assertEquals(validatedAlleles, expected);
+
+        List<String> alleles_complex = Arrays.asList("ANYCGT", "MRACT", "CCGKBG");
+        List<String> expected_complex = Arrays.asList("ANCCGT", "AAACT", "CCGGCG");
+
+        validatedAlleles = new ArrayList<>();
+        for (String allele: alleles_complex) {
+            validatedAlleles.add(toVarsBuilder.validateRefallele(allele));
+        }
+        assertEquals(validatedAlleles, expected_complex);
     }
 }