Whole Exome Sequencing Gene package Multiple congenital anomalie, version 7, 18‐2‐2019 Technical information DNA was enriched using Agilent SureSelect Clinical Research Exome V2 capture and paired‐end sequenced on the Illumina platform (outsourced). The aim is to obtain 8.1 Giga base pairs per exome with a mapped fraction of 0.99. The average coverage of the exome is ~50x. Duplicate reads are excluded. Data are demultiplexed with bcl2fastq Conversion Software from Illumina. Reads are mapped to the genome using the BWA‐MEM algorithm (reference: http://bio‐bwa.sourceforge.net/). Variant detection is performed by the Genome Analysis Toolkit HaplotypeCaller (reference: http://www.broadinstitute.org/gatk/). The detected variants are filtered and annotated with Cartagenia software and classified with Alamut Visual. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes). HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x A4GALT [Blood group, P1Pk system, P(2) phenotype], 111400[Blood group, P1Pk system, p phenotype], 111400NOR po 607922 141 100 100 99 AAAS Achalasia‐addisonianism‐alacrimia syndrome, 231550 605378 88 100 100 100 AAGAB Keratoderma, palmoplantar, punctate type IA, 148600 614888 51 100 100 89 AARS Charcot‐Marie‐Tooth disease, axonal, type 2N, 613287 601065 78 100 99 93 Epileptic encephalopathy, early infantile, 29, 616339 AARS2 Combined oxidative phosphorylation deficiency 8, 614096 612035 117 100 100 100 Leukoencephalopathy, progressive, with ovarian failure, 615889 AASS Hyperlysinemia, 238700 605113 56 100 96 86 Saccharopinuria, 268700 ABAT GABA‐transaminase deficiency, 613163 137150 95 100 99 94 ABCA1 {Coronary artery disease in familial hypercholesterolemia, protection against}, 143890 600046 81 100 99 94 HDL deficiency, type 2, 604091 Tangier disease, 205400 ABCA12 Ichthyosis, congenital, autosomal recessive 4A, 601277 607800 58 100 99 90 Ichthyosis, congenital, autosomal recessive 4B (harlequin), 242500 ABCA3 Surfactant metabolism dysfunction, pulmonary, 3, 610921 601615 104 100 100 97 Whole exome sequencing Gene package Multiple congenital anomalie version 7, 18‐2‐2019 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x ABCA4 Cone‐rod dystrophy 3, 604116 601691 85 100 99 95 Fundus flavimaculatus, 248200 {Macular degeneration, age‐related, 2}, 153800 Retinal dystrophy, early‐onset severe, 248200 Retinitis pigmentosa 19, 601718 Stargardt disease 1, 248200 ABCB11 Cholestasis, benign recurrent intrahepatic, 2, 605479 603201 56 100 99 90 Cholestasis, progressive familial intrahepatic 2, 601847 ABCB4 Cholestasis, intrahepatic, of pregnancy, 3, 614972 171060 57 100 98 85 Cholestasis, progressive familial intrahepatic 3, 602347 Gallbladder disease 1, 600803 ABCB6 [Blood group, Langereis system], 111600 605452 96 100 100 98 Dyschromatosis universalis hereditaria 3, 615402 Microphthalmia, isolated, with coloboma 7, 614497 Pseudohyperkalemia, familial, 2, due to red cell leak, 609153 ABCB7 Anemia, sideroblastic, with ataxia, 301310 300135 53 100 98 81 ABCC2 Dubin‐Johnson syndrome, 237500 601107 64 100 99 91 ABCC6 Arterial calcification, generalized, of infancy, 2, 614473 603234 124 100 100 99 Pseudoxanthoma elasticum, 264800 Pseudoxanthoma elasticum, forme fruste, 177850 ABCC8 Diabetes mellitus, noninsulin‐dependent, 125853 600509 99 100 100 98 Diabetes mellitus, permanent neonatal, 606176 Diabetes mellitus, transient neonatal 2, 610374 Hyperinsulinemic hypoglycemia, familial, 1, 256450 Hypoglycemia of infancy, leucine‐sensitive, 240800 ABCC9 Atrial fibrillation, familial, 12, 614050 601439 55 100 98 90 Cardiomyopathy, dilated, 1O, 608569 Hypertrichotic osteochondrodysplasia, 239850 ABCD1 Adrenoleukodystrophy, 300100 300371 75 85 76 72 Adrenomyeloneuropathy, adult, 300100 ABCD4 Methylmalonic aciduria and homocystinuria, cblJ type, 614857 603214 98 100 100 98 ABCG5 Sitosterolemia, 210250 605459 70 100 100 98 ABCG8 {Gallbladder disease 4}, 611465 605460 138 100 97 95 Sitosterolemia, 210250 ABHD12 Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract, 612674 613599 57 100 100 91 ABHD5 Chanarin‐Dorfman syndrome, 275630 604780 62 100 100 95 ABL1 Congenital heart defects and skeletal malformations syndrome, 617602 189980 129 100 100 99 Leukemia, Philadelphia chromosome‐positive, resistant to imatinib Whole exome sequencing Gene package Multiple congenital anomalie version 7, 18‐2‐2019 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x ACAD8 Isobutyryl‐CoA dehydrogenase deficiency, 611283 604773 163 100 100 100 ACAD9 Mitochondrial complex I deficiency due to ACAD9 deficiency, 611126 611103 88 100 100 99 ACADM Acyl‐CoA dehydrogenase, medium chain, deficiency of, 201450 607008 58 100 99 90 ACADS Acyl‐CoA dehydrogenase, short‐chain, deficiency of, 201470 606885 118 100 100 100 ACADSB 2‐methylbutyrylglycinuria, 610006 600301 59 100 99 86 ACADVL VLCAD deficiency, 201475 609575 109 100 100 97 ACAN Short stature and advanced bone age, with or without early‐onset osteoarthritis and/or osteochondritis 155760 221 100 100 98 dissecans, 165800 ?Spondyloepimetaphyseal dysplasia, aggrecan type, 612813 ?Spondyloepiphyseal dysplasia, Kimberley type, 608361 ACAT1 Alpha‐methylacetoacetic aciduria, 203750 607809 62 100 98 89 ACE [Angiotensin I‐converting enzyme, benign serum increase] 106180 99 100 100 99 {Microvascular complications of diabetes 3}, 612624 {Myocardial infarction, susceptibility to} Renal tubular dysgenesis, 267430 {SARS, progression of} {Stroke, hemorrhagic}, 614519 ACO2 Infantile cerebellar‐retinal degeneration, 614559 100850 138 100 97 94 ?Optic atrophy 9, 616289 ACOX1 Peroxisomal acyl‐CoA oxidase deficiency, 264470 609751 95 100 100 98 ACP5 Spondyloenchondrodysplasia with immune dysregulation, 607944 171640 133 100 100 100 ACSF3 Combined malonic and methylmalonic aciduria, 614265 614245 144 100 100 99 ACSL4 Mental retardation, X‐linked 63, 300387 300157 49 100 98 83 ACSL6 Myelodysplastic syndrome 604443 74 100 100 95 Myelogenous leukemia, acute ACTA1 Myopathy, actin, congenital, with cores, 161800 102610 126 100 100 100 Myopathy, actin, congenital, with excess of thin myofilaments, 161800 Myopathy, congenital, with fiber‐type disproportion 1, 255310 ?Myopathy, scapulohumeroperoneal, 616852 Nemaline myopathy 3, autosomal dominant or recessive, 161800 ACTA2 Aortic aneurysm, familial thoracic 6, 611788 102620 163 100 100 100 Moyamoya disease 5, 614042 Multisystemic smooth muscle dysfunction syndrome, 613834 ACTB Baraitser‐Winter syndrome 1, 243310 102630 208 100 100 100 ?Dystonia, juvenile‐onset, 607371 Whole exome sequencing Gene package Multiple congenital anomalie version 7, 18‐2‐2019 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x ACTC1 Atrial septal defect 5, 612794 102540 180 100 100 100 Cardiomyopathy, dilated, 1R, 613424 Cardiomyopathy, hypertrophic, 11, 612098 Left ventricular noncompaction 4, 613424 ACTG1 Baraitser‐Winter syndrome 2, 614583 102560 174 100 100 100 Deafness, autosomal dominant 20/26, 604717 ACTN1 Bleeding disorder, platelet‐type, 15, 615193 102575 109 100 100 99 ACTN4 Glomerulosclerosis, focal segmental, 1, 603278 604638 112 100 100 99 ACVR1 Fibrodysplasia ossificans progressiva, 135100 102576 65 100 100 96 ACVR1B Pancreatic cancer, somatic 601300 68 100 100 96 ACVR2B Heterotaxy, visceral, 4, autosomal, 613751 602730 100 100 100 97 ACVRL1 Telangiectasia, hereditary hemorrhagic, type 2, 600376 601284 92 100 100 94 ACY1 Aminoacylase 1 deficiency, 609924 104620 99 100 100 100 ADA Adenosine deaminase deficiency, partial, 102700 608958 79 100 100 95 Severe combined immunodeficiency due to ADA deficiency, 102700 ADA2 Polyarteritis nodosa, childhood‐onset, 615688 607575 91 100 100 97 ?Sneddon syndrome, 182410 ADAM10 {Alzheimer disease 18, susceptibility to}, 615590 602192 49 100 98 82 Reticulate acropigmentation of Kitamura, 615537 ADAM17 ?Inflammatory skin and bowel disease, neonatal, 1, 614328 603639 58 100 98 89 ADAM9 Cone‐rod dystrophy 9, 612775 602713 50 100 98 84 ADAMTS10 Weill‐Marchesani syndrome 1, recessive, 277600 608990 103 100 100 99 ADAMTS13 Thrombotic thrombocytopenic purpura, familial, 274150 604134 92 98 97 95 ADAMTS17 Weill‐Marchesani 4 syndrome, recessive, 613195 607511 96 97 96 93 ADAMTS18 Microcornea, myopic chorioretinal atrophy, and telecanthus, 615458 607512 69 100 99 96 ADAMTS2 Ehlers‐Danlos syndrome, dermatosparaxis type, 225410 604539 108 100 100 99 ADAMTSL2 Geleophysic dysplasia 1, 231050 612277 89 100 100 97 ADAMTSL4 Ectopia lentis et pupillae, 225200 610113 110 100 100 99 Ectopia lentis, isolated, autosomal recessive, 225100 ADAR Aicardi‐Goutieres syndrome 6, 615010 146920 79 100 100 98 Dyschromatosis symmetrica hereditaria, 127400 ADAT3 Mental retardation, autosomal recessive 36, 615286 615302 126 100 100 100 ADCY5 Dyskinesia, familial, with facial myokymia, 606703 600293 109 99 96 93 ADGRG1 Polymicrogyria, bilateral frontoparietal, 606854 604110 112 100 100 99 Polymicrogyria, bilateral perisylvian, 615752