Merge branch 'release-13.3.0'

docs/acmg_assignment.rst

@@ -7,8 +7,11 @@ ACMG Assignment
 Starting with version 13.1.0, Exomiser performs a partial categorisation of the variants contributing to the gene
 score for a mode of inheritance using the ACMG/AMP `Standards and guidelines for the interpretation of sequence
 variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association
-for Molecular Pathology <https://doi.org/10.1038/gim.2015.30>`_. The criteria are assigned and combined according to the
-`UK ACGS 2020 guidelines <https://www.acgs.uk.com/media/11631/uk-practice-guidelines-for-variant-classification-v4-01-2020.pdf>`_.
+for Molecular Pathology <https://doi.org/10.1038/gim.2015.30>`_. The criteria are assigned according to the
+`UK ACGS 2020 guidelines <https://www.acgs.uk.com/media/11631/uk-practice-guidelines-for-variant-classification-v4-01-2020.pdf>`_
+and scored according to the
+`ClinGen SVI <https://clinicalgenome.org/working-groups/sequence-variant-interpretation/>`_
+`updated 2020 guidelines <https://clinicalgenome.org/docs/fitting-a-naturally-scaled-point-system-to-the-acmg-amp-variant-classification-guidelines/>`_.
 
 It is important to be aware that these scores are not a substitute for manual assignment by a qualified clinical geneticist
 or clinician - The scores displayed utilise the data found in the Exomiser database and are a subset of the possible
@@ -60,15 +63,25 @@ at least two ancestors of the proband, none of whom are affected and none of who
 
 Population Data
 ===============
+
+For the population data criteria, all frequencies are considered using the populations set by the user in the
+:ref:`frequencysources`, apart from any bottle-necked populations not recommended for frequency filtering from gnomAD
+according to their `filtering allele frequency <https://gnomad.broadinstitute.org/help/faf>`_ document. This excludes
+the Ashkenazi Jewish (ASJ), European Finnish (FIN), Other (OTH), Amish (AMI) and Middle Eastern (MID) populations. In
+addition the LOCAL frequency will also not be used.
+
 BA1
 ---
 Given Exomiser will filter out alleles with an allele frequency of >= 2.0%, this is unlikely to be seen. However, alleles
-with a maximum frequency >= 5.0% in the frequency sources specified will be assigned the `BA1` criterion.
+with a maximum frequency >= 5.0% in the frequency sources specified will be assigned the `BA1` criterion. Variants listed
+as being excluded from this category by the ClinGen SVI working group `BA1 exclusion list <https://www.clinicalgenome.org/site/assets/files/3460/ba1_exception_list_07_30_2018.pdf>`_
+will not be marked as `BA1`, assuming they survived variant filtering.
 
 PM2
 ---
-Alleles not present in the ESP, ExAC and 1000 Genomes data sets (i.e. the allele must be absent from all three) are
-assigned the `PM2` criterion.
+In accordance with the `updated PM2 guidance <https://clinicalgenome.org/site/assets/files/5182/pm2_-_svi_recommendation_-_approved_sept2020.pdf>`_, variants absent from all of the user-defined :ref:`frequencysources`
+will be assigned the `PM2_Supporting` criterion. Additionally, for variants considered under a recessive mode of inheritance they
+can have a frequency of < 0.01% (0.0001) in all non-bottlenecked populations to be assigned `PM2_Supporting`.
 
 Allelic Data
 ============

docs/advanced_analysis.rst

@@ -38,8 +38,9 @@ Sample
 It is recommended to provide Exomiser the input sample as in `Phenopacket <https://phenopacket-schema.readthedocs.io/>`_ format.
 Exomiser will accept this in either JSON or YAML format.
 
-probandId:
+proband:
 ----------
+Identifier used for the proband in the VCF file.
 
 hpoIds:
 -------
@@ -247,8 +248,8 @@ gnomAD genomes:
     ``GNOMAD_G_OTH``,
     ``GNOMAD_G_SAS``
 
-We recommend using all databases if the proband population background is unknown, although removing the ``GNOMAD_E_ASJ`` and ``GNOMAD_G_ASJ``, unless your proband is
-known to come from an Ashkenazi population e.g.
+We recommend using all databases if the proband population background is unknown, although removing the ``GNOMAD_E_ASJ``
+and ``GNOMAD_G_ASJ``, unless your proband is known to come from an Ashkenazi population e.g.
 
 .. code-block:: yaml
 

exomiser-cli/CHANGELOG.md

@@ -1,5 +1,15 @@
 # The Exomiser Command Line Executable - Changelog
 
+## 13.3.0 2023-10-17
+
+- Updated Jannovar version to 0.41 to fix incorrect MT codon table usage [#521](https://github.com/exomiser/Exomiser/issues/521)
+- Downgraded PM2 - PM2_Supporting for variants lacking frequency information [#502](https://github.com/exomiser/Exomiser/issues/502).
+- Updated AcmgEvidence to fit a Bayesian points-based system [#514](https://github.com/exomiser/Exomiser/issues/514)
+- Removed ASJ, FIN, OTH ExAC and gnomAD populations from presets and examples [#513](https://github.com/exomiser/Exomiser/issues/513).
+- Fix for regression causing `<INV>` variants to be incorrectly down-ranked
+- Fix for issue [#486](https://github.com/exomiser/Exomiser/issues/486) where VCF output includes whitespace in INFO field.
+- Logs will now display elapsed time correctly if an analysis runs over an hour (!). 
+
 ## 13.2.1 2023-06-30
 
 - Fix for bug where all `<INS>` structural variants were given a maximal variant score of 1.0 regardless of their position on a transcript.

exomiser-cli/pom.xml

@@ -32,7 +32,7 @@
     <parent>
         <groupId>org.monarchinitiative.exomiser</groupId>
         <artifactId>exomiser</artifactId>
-        <version>13.2.1</version>
+        <version>13.3.0</version>
     </parent>
 
 

exomiser-cli/src/main/resources/examples/NA19722_252900_AR_SGSH_1_NONSYNONYMOUS.yml

@@ -71,25 +71,26 @@ analysis:
 
       EXAC_AFRICAN_INC_AFRICAN_AMERICAN, EXAC_AMERICAN,
       EXAC_SOUTH_ASIAN, EXAC_EAST_ASIAN,
-      EXAC_FINNISH, EXAC_NON_FINNISH_EUROPEAN,
-      EXAC_OTHER,
+    #  EXAC_FINNISH,
+      EXAC_NON_FINNISH_EUROPEAN,
+    #  EXAC_OTHER,
 
       GNOMAD_E_AFR,
       GNOMAD_E_AMR,
-    #        GNOMAD_E_ASJ,
+    #  GNOMAD_E_ASJ,
       GNOMAD_E_EAS,
-      GNOMAD_E_FIN,
+    #  GNOMAD_E_FIN,
       GNOMAD_E_NFE,
-      GNOMAD_E_OTH,
+    #  GNOMAD_E_OTH,
       GNOMAD_E_SAS,
 
       GNOMAD_G_AFR,
       GNOMAD_G_AMR,
-    #        GNOMAD_G_ASJ,
+    #  GNOMAD_G_ASJ,
       GNOMAD_G_EAS,
-      GNOMAD_G_FIN,
+    #  GNOMAD_G_FIN,
       GNOMAD_G_NFE,
-      GNOMAD_G_OTH,
+    #  GNOMAD_G_OTH,
       GNOMAD_G_SAS
   ]
   # Possible pathogenicitySources: (POLYPHEN, MUTATION_TASTER, SIFT), (REVEL, MVP), CADD, REMM

exomiser-cli/src/main/resources/examples/NA19722_601952_AUTOSOMAL_RECESSIVE_POMP_13_29233225_5UTR_38.yml

@@ -55,25 +55,26 @@ analysis:
 
       EXAC_AFRICAN_INC_AFRICAN_AMERICAN, EXAC_AMERICAN,
       EXAC_SOUTH_ASIAN, EXAC_EAST_ASIAN,
-      EXAC_FINNISH, EXAC_NON_FINNISH_EUROPEAN,
-      EXAC_OTHER,
+    #  EXAC_FINNISH,
+      EXAC_NON_FINNISH_EUROPEAN,
+    #  EXAC_OTHER,
 
       GNOMAD_E_AFR,
       GNOMAD_E_AMR,
-    #        GNOMAD_E_ASJ,
+    #  GNOMAD_E_ASJ,
       GNOMAD_E_EAS,
-      GNOMAD_E_FIN,
+    #  GNOMAD_E_FIN,
       GNOMAD_E_NFE,
-      GNOMAD_E_OTH,
+    #  GNOMAD_E_OTH,
       GNOMAD_E_SAS,
 
       GNOMAD_G_AFR,
       GNOMAD_G_AMR,
-    #        GNOMAD_G_ASJ,
+    #  GNOMAD_G_ASJ,
       GNOMAD_G_EAS,
-      GNOMAD_G_FIN,
+    #  GNOMAD_G_FIN,
       GNOMAD_G_NFE,
-      GNOMAD_G_OTH,
+    #  GNOMAD_G_OTH,
       GNOMAD_G_SAS
   ]
   # Possible pathogenicitySources: (POLYPHEN, MUTATION_TASTER, SIFT), (REVEL, MVP), CADD, REMM

exomiser-cli/src/main/resources/examples/preset-exome-analysis.yml

@@ -21,25 +21,26 @@ frequencySources: [
 
     EXAC_AFRICAN_INC_AFRICAN_AMERICAN, EXAC_AMERICAN,
     EXAC_SOUTH_ASIAN, EXAC_EAST_ASIAN,
-    EXAC_FINNISH, EXAC_NON_FINNISH_EUROPEAN,
-    EXAC_OTHER,
+  #  EXAC_FINNISH,
+    EXAC_NON_FINNISH_EUROPEAN,
+  #  EXAC_OTHER,
 
     GNOMAD_E_AFR,
     GNOMAD_E_AMR,
-  #        GNOMAD_E_ASJ,
+  #  GNOMAD_E_ASJ,
     GNOMAD_E_EAS,
-    GNOMAD_E_FIN,
+  #  GNOMAD_E_FIN,
     GNOMAD_E_NFE,
-    GNOMAD_E_OTH,
+  #  GNOMAD_E_OTH,
     GNOMAD_E_SAS,
 
     GNOMAD_G_AFR,
     GNOMAD_G_AMR,
-  #        GNOMAD_G_ASJ,
+  #  GNOMAD_G_ASJ,
     GNOMAD_G_EAS,
-    GNOMAD_G_FIN,
+  #  GNOMAD_G_FIN,
     GNOMAD_G_NFE,
-    GNOMAD_G_OTH,
+  #  GNOMAD_G_OTH,
     GNOMAD_G_SAS
 ]
 # Possible pathogenicitySources: (POLYPHEN, MUTATION_TASTER, SIFT), (REVEL, MVP), CADD, REMM

exomiser-cli/src/main/resources/examples/preset-genome-analysis.yml

@@ -21,25 +21,26 @@ frequencySources: [
 
     EXAC_AFRICAN_INC_AFRICAN_AMERICAN, EXAC_AMERICAN,
     EXAC_SOUTH_ASIAN, EXAC_EAST_ASIAN,
-    EXAC_FINNISH, EXAC_NON_FINNISH_EUROPEAN,
-    EXAC_OTHER,
+  #  EXAC_FINNISH,
+    EXAC_NON_FINNISH_EUROPEAN,
+  #  EXAC_OTHER,
 
     GNOMAD_E_AFR,
     GNOMAD_E_AMR,
-  #        GNOMAD_E_ASJ,
+  #  GNOMAD_E_ASJ,
     GNOMAD_E_EAS,
-    GNOMAD_E_FIN,
+  #  GNOMAD_E_FIN,
     GNOMAD_E_NFE,
-    GNOMAD_E_OTH,
+  #  GNOMAD_E_OTH,
     GNOMAD_E_SAS,
 
     GNOMAD_G_AFR,
     GNOMAD_G_AMR,
-  #        GNOMAD_G_ASJ,
+  #  GNOMAD_G_ASJ,
     GNOMAD_G_EAS,
-    GNOMAD_G_FIN,
+  #  GNOMAD_G_FIN,
     GNOMAD_G_NFE,
-    GNOMAD_G_OTH,
+  #  GNOMAD_G_OTH,
     GNOMAD_G_SAS
 ]
 # Possible pathogenicitySources: (POLYPHEN, MUTATION_TASTER, SIFT), (REVEL, MVP), CADD, REMM

exomiser-cli/src/main/resources/examples/test-analysis-exome.yml

@@ -56,25 +56,26 @@ analysis:
 
         EXAC_AFRICAN_INC_AFRICAN_AMERICAN, EXAC_AMERICAN,
         EXAC_SOUTH_ASIAN, EXAC_EAST_ASIAN,
-        EXAC_FINNISH, EXAC_NON_FINNISH_EUROPEAN,
-        EXAC_OTHER,
+      #  EXAC_FINNISH,
+        EXAC_NON_FINNISH_EUROPEAN,
+      #  EXAC_OTHER,
 
         GNOMAD_E_AFR,
         GNOMAD_E_AMR,
-#        GNOMAD_E_ASJ,
+      #  GNOMAD_E_ASJ,
         GNOMAD_E_EAS,
-        GNOMAD_E_FIN,
+      #  GNOMAD_E_FIN,
         GNOMAD_E_NFE,
-        GNOMAD_E_OTH,
+      #  GNOMAD_E_OTH,
         GNOMAD_E_SAS,
 
         GNOMAD_G_AFR,
         GNOMAD_G_AMR,
-      #        GNOMAD_G_ASJ,
+      #  GNOMAD_G_ASJ,
         GNOMAD_G_EAS,
-        GNOMAD_G_FIN,
+      #  GNOMAD_G_FIN,
         GNOMAD_G_NFE,
-        GNOMAD_G_OTH,
+      #  GNOMAD_G_OTH,
         GNOMAD_G_SAS
     ]
   # Possible pathogenicitySources: (POLYPHEN, MUTATION_TASTER, SIFT), (REVEL, MVP), CADD, REMM

exomiser-cli/src/main/resources/examples/test-analysis-genome.yml

@@ -46,25 +46,26 @@ analysis:
 
         EXAC_AFRICAN_INC_AFRICAN_AMERICAN, EXAC_AMERICAN,
         EXAC_SOUTH_ASIAN, EXAC_EAST_ASIAN,
-        EXAC_FINNISH, EXAC_NON_FINNISH_EUROPEAN,
-        EXAC_OTHER,
+      #  EXAC_FINNISH,
+        EXAC_NON_FINNISH_EUROPEAN,
+      #  EXAC_OTHER,
 
         GNOMAD_E_AFR,
         GNOMAD_E_AMR,
-#        GNOMAD_E_ASJ,
+      #  GNOMAD_E_ASJ,
         GNOMAD_E_EAS,
-        GNOMAD_E_FIN,
+      #  GNOMAD_E_FIN,
         GNOMAD_E_NFE,
-        GNOMAD_E_OTH,
+      #  GNOMAD_E_OTH,
         GNOMAD_E_SAS,
 
         GNOMAD_G_AFR,
         GNOMAD_G_AMR,
-      #        GNOMAD_G_ASJ,
+      #  GNOMAD_G_ASJ,
         GNOMAD_G_EAS,
-        GNOMAD_G_FIN,
+      #  GNOMAD_G_FIN,
         GNOMAD_G_NFE,
-        GNOMAD_G_OTH,
+      #  GNOMAD_G_OTH,
         GNOMAD_G_SAS
     ]
   # Possible pathogenicitySources: (POLYPHEN, MUTATION_TASTER, SIFT), (REVEL, MVP), CADD, REMM

exomiser-cli/src/main/resources/examples/test-analysis-multisample.yml

@@ -45,25 +45,26 @@ analysis:
 
         EXAC_AFRICAN_INC_AFRICAN_AMERICAN, EXAC_AMERICAN,
         EXAC_SOUTH_ASIAN, EXAC_EAST_ASIAN,
-        EXAC_FINNISH, EXAC_NON_FINNISH_EUROPEAN,
-        EXAC_OTHER,
+      #  EXAC_FINNISH,
+        EXAC_NON_FINNISH_EUROPEAN,
+      #  EXAC_OTHER,
 
         GNOMAD_E_AFR,
         GNOMAD_E_AMR,
-#        GNOMAD_E_ASJ,
+      #  GNOMAD_E_ASJ,
         GNOMAD_E_EAS,
-        GNOMAD_E_FIN,
+      #  GNOMAD_E_FIN,
         GNOMAD_E_NFE,
-        GNOMAD_E_OTH,
+      #  GNOMAD_E_OTH,
         GNOMAD_E_SAS,
 
         GNOMAD_G_AFR,
         GNOMAD_G_AMR,
-      #        GNOMAD_G_ASJ,
+      #  GNOMAD_G_ASJ,
         GNOMAD_G_EAS,
-        GNOMAD_G_FIN,
+      #  GNOMAD_G_FIN,
         GNOMAD_G_NFE,
-        GNOMAD_G_OTH,
+      #  GNOMAD_G_OTH,
         GNOMAD_G_SAS
     ]
   # Possible pathogenicitySources: (POLYPHEN, MUTATION_TASTER, SIFT), (REVEL, MVP), CADD, REMM

exomiser-core/CHANGELOG.md

@@ -1,5 +1,29 @@
 # The Exomiser - Core Library Changelog
 
+## 13.3.0 2023-10-17
+
+- Updated Jannovar version to 0.41 to fix incorrect MT codon table usage [#521](https://github.com/exomiser/Exomiser/issues/521)
+- Downgraded PM2 - PM2_Supporting for variants lacking frequency information [#502](https://github.com/exomiser/Exomiser/issues/502).
+- Updated Acgs2020Classifier and Acmg2015Classifier to allow for PVS1 and PM2_Supporting to be sufficient to trigger LIKELY_PATHOGENIC
+- Updated AcmgEvidence to fit a Bayesian points-based system [#514](https://github.com/exomiser/Exomiser/issues/514)
+- Removed ASJ, FIN, OTH ExAC and gnomAD populations from presets and examples [#513](https://github.com/exomiser/Exomiser/issues/513).
+- Fix for regression causing `<INV>` variants to be incorrectly down-ranked 
+- Fix for issue [#486](https://github.com/exomiser/Exomiser/issues/486) where VCF output includes whitespace in INFO field.
+- Logs will now display elapsed time correctly if an analysis runs over an hour (!).
+- Updated exomiser-phenotype-data to take annotations from phenotype.hpoa [#351](https://github.com/exomiser/Exomiser/issues/351), [#373](https://github.com/exomiser/Exomiser/issues/373), [#379](https://github.com/exomiser/Exomiser/issues/379)
+- Updated application.properties and ResourceConfigurationProperties to remove unused fields.
+- Updated DiseaseInheritanceCacheReader and DiseasePhenotypeReader to parse phenotype.hpoa file
+- Updated DiseaseResourceConfig to use hpoa resource
+
+New APIs:
+
+- New `Acmg2020PointsBasedClassifier` class
+- New `FrequencyData.size()` method
+- New `FrequencyData.isEmpty()` method
+- New `FrequencyData.containsFrequencySource()` method
+- New `FrequencyData.getMaxFreqForPopulation()` method
+- New `FrequencySource.NON_FOUNDER_POPS` method
+
 ## 13.2.1 2023-06-30
 
 - Fix for bug where all `<INS>` structural variants were given a maximal variant score of 1.0 regardless of their position on a transcript.

exomiser-core/pom.xml

@@ -30,7 +30,7 @@
     <parent>
         <groupId>org.monarchinitiative.exomiser</groupId>
         <artifactId>exomiser</artifactId>
-        <version>13.2.1</version>
+        <version>13.3.0</version>
     </parent>
 
     <dependencies>

exomiser-core/src/main/java/org/monarchinitiative/exomiser/core/analysis/AbstractAnalysisRunner.java

@@ -148,7 +148,11 @@ public AnalysisResults run(Sample sample, Analysis analysis) {
 
         Duration duration = Duration.between(timeStart, Instant.now());
         long ms = duration.toMillis();
-        logger.info("Finished analysis in {}m {}s {}ms ({} ms)", (ms / 1000) / 60 % 60, ms / 1000 % 60, ms % 1000, ms);
+        int hoursPart = duration.toHoursPart();
+        if (hoursPart > 0) {
+            logger.info("Finished analysis in {}h {}m {}s {}ms ({} ms)", hoursPart, duration.toMinutesPart(), duration.toSecondsPart(), duration.toMillisPart(), ms);
+        }
+        logger.info("Finished analysis in {}m {}s {}ms ({} ms)", duration.toMinutesPart(), duration.toSecondsPart(), duration.toMillisPart(), ms);
         return analysisResults;
     }