Fix error in genotype given alleles mode when input alleles have geno…

…types (#5341)

* fix issue of alleles not being replaced with star alleles when the given allele variants have genotypes

* add unit test to replaceWithSpanDelVC

src/main/java/org/broadinstitute/hellbender/tools/walkers/haplotypecaller/HaplotypeCallerGenotypingEngine.java

@@ -216,18 +216,21 @@ public CalledHaplotypes assignGenotypeLikelihoods(final List<Haplotype> haplotyp
  activeRegionWindow,tracker,activeAllelesToGenotype,emitReferenceConfidence,maxMnpDistance,header,false);
  }
 
- private List<VariantContext> replaceSpanDels(final List<VariantContext> eventsAtThisLoc, final Allele refAllele, final int loc) {
+ @VisibleForTesting
+ static List<VariantContext> replaceSpanDels(final List<VariantContext> eventsAtThisLoc, final Allele refAllele, final int loc) {
  return eventsAtThisLoc.stream().map(vc -> replaceWithSpanDelVC(vc, refAllele, loc)).collect(Collectors.toList());
  }
 
- private VariantContext replaceWithSpanDelVC(final VariantContext variantContext, final Allele refAllele, final int loc) {
+ @VisibleForTesting
+ static VariantContext replaceWithSpanDelVC(final VariantContext variantContext, final Allele refAllele, final int loc) {
  if (variantContext.getStart() == loc) {
  return variantContext;
  } else {
  VariantContextBuilder builder = new VariantContextBuilder(variantContext)
  .start(loc)
  .stop(loc)
- .alleles(Arrays.asList(refAllele, Allele.SPAN_DEL));
+ .alleles(Arrays.asList(refAllele, Allele.SPAN_DEL))
+ .genotypes(GenotypesContext.NO_GENOTYPES);
  return builder.make();
  }
 

src/test/java/org/broadinstitute/hellbender/tools/walkers/haplotypecaller/HaplotypeCallerGenotypingEngineUnitTest.java

@@ -6,6 +6,7 @@
 import org.apache.commons.lang3.tuple.Pair;
 import org.broadinstitute.gatk.nativebindings.smithwaterman.SWOverhangStrategy;
 import org.broadinstitute.gatk.nativebindings.smithwaterman.SWParameters;
+import org.broadinstitute.hellbender.testutils.VariantContextTestUtils;
 import org.broadinstitute.hellbender.utils.QualityUtils;
 import org.broadinstitute.hellbender.utils.SimpleInterval;
 import org.broadinstitute.hellbender.utils.Utils;
@@ -559,4 +560,42 @@ public void testRemoveExcessiveAltAlleleFromVC(){
  Assert.assertEquals(reducedVC.getNAlleles(), 3);
  Assert.assertTrue(reducedVC.getAlleles().containsAll(Arrays.asList(Allele.create("A", true), Allele.create("T", false), Allele.create("C", false))));
  }
+
+ @Test
+ public void testReplaceWithSpanDelVC() {
+ final VariantContext snp = new VariantContextBuilder("source", "1", 1000000, 1000000,
+ Arrays.asList(Allele.create("A", true),
+ Allele.create("G", false))).make();
+ final VariantContext snpReplacement =
+ HaplotypeCallerGenotypingEngine.replaceWithSpanDelVC(snp, Allele.create("A", true), 1000000);
+
+ Assert.assertEquals(snpReplacement, snp);
+
+ final VariantContext spanDel = new VariantContextBuilder("source", "1", 999995, 1000005,
+ Arrays.asList(Allele.create("AAAAAAAAAAA", true),
+ Allele.create("A", false))).make();
+
+ final VariantContext spanDelReplacement =
+ HaplotypeCallerGenotypingEngine.replaceWithSpanDelVC(spanDel, Allele.create("A", true), 1000000);
+
+ final VariantContext expectedSpanDelReplacement = new VariantContextBuilder("source", "1", 1000000, 1000000,
+ Arrays.asList(Allele.create("A", true),
+ Allele.SPAN_DEL)).make();
+
+ VariantContextTestUtils.assertVariantContextsAreEqual(spanDelReplacement,
+ expectedSpanDelReplacement, Collections.emptyList());
+
+ final VariantContext spanDelWithGt = new VariantContextBuilder("source", "1", 999995, 1000005,
+ Arrays.asList(Allele.create("AAAAAAAAAAA", true),
+ Allele.create("A", false)))
+ .genotypes(new GenotypeBuilder("S1",
+ Arrays.asList(spanDel.getAlleles().get(0), spanDel.getAlleles().get(1))).make()).make();
+
+ final VariantContext spanDelWithGTReplacement =
+ HaplotypeCallerGenotypingEngine.replaceWithSpanDelVC(spanDelWithGt, Allele.create("A", true), 1000000);
+
+ VariantContextTestUtils.assertVariantContextsAreEqual(spanDelWithGTReplacement,
+ expectedSpanDelReplacement, Collections.emptyList());
+
+ }
 }

src/test/resources/org/broadinstitute/hellbender/tools/haplotypecaller/expected.testGenotypeGivenAllelesMode.gatk4.vcf

@@ -31,3 +31,4 @@
 20 10004769 . TAAAACTATGC T 980.73 . AC=1;AF=0.500;AN=2;BaseQRankSum=1.603;DP=79;ExcessHet=3.0103;FS=3.758;MLEAC=1;MLEAF=0.500;MQ=52.37;MQRankSum=-6.625;QD=15.32;ReadPosRankSum=1.879;SOR=1.306 GT:AD:DP:GQ:PL 0/1:37,27:64:99:1018,0,1471
 20 10004771 . A *,T 998.77 . AC=1,0;AF=0.500,0.00;AN=2;BaseQRankSum=-1.270;DP=74;ExcessHet=3.0103;FS=2.397;MLEAC=1,0;MLEAF=0.500,0.00;MQ=51.81;MQRankSum=-6.325;QD=16.93;ReadPosRankSum=2.185;SOR=1.115 GT:AD:DP:GQ:PL 0/1:32,27,0:59:99:1027,0,1345,1162,1305,2852
 20 10006819 . AAAAC T 0 LowQual AC=0;AF=0.00;AN=2;DP=75;ExcessHet=3.0103;FS=0.000;MLEAC=0;MLEAF=0.00;MQ=61.14;SOR=0.572 GT:AD:DP:GQ:PL 0/0:75,0:75:99:0,244,2147483647
+20 10006823 . C *,G 0 LowQual AC=0,0;AF=0.00,0.00;AN=2;DP=73;ExcessHet=3.0103;FS=0.000;MLEAC=0,0;MLEAF=0.00,0.00;MQ=61.18;SOR=0.069 GT:AD:DP:GQ:PL 0/0:17,0,0:17:51:0,229,2147483647,51,819,590

src/test/resources/org/broadinstitute/hellbender/tools/haplotypecaller/testGenotypeGivenAllelesMode_givenAlleles.vcf

@@ -25,11 +25,12 @@
 ##INFO=<ID=SOR,Number=1,Type=Float,Description="Symmetric Odds Ratio of 2x2 contingency table to detect strand bias">
 ##contig=<ID=20,length=63025520>
 ##contig=<ID=21,length=48129895>
-#CHROM POS ID REF ALT QUAL FILTER INFO
-20 10000694 . G A . . .
-20 10001436 . A AAGGCT . . .
-20 10001661 . T C . . .
-20 10004094 . A T . . .
-20 10004769 . TAAAACTATGC T . . .
-20 10004771 . A T . . .
-20 10006819 . AAAAC T . . .
+#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT SAMPLE1
+20 10000694 . G A . . . GT 0|1
+20 10001436 . A AAGGCT . . . GT 0|1
+20 10001661 . T C . . . GT 0|1
+20 10004094 . A T . . . GT 0|1
+20 10004769 . TAAAACTATGC T . . . GT 0|1
+20 10004771 . A T . . . GT 0|1
+20 10006819 . AAAAC T . . . GT 0|1
+20 10006823 . C G . . . GT 0|1