Report Date: August 24, 2016 Software Annotation Version: 8 Genome Summary Name: (unknown) Genome ID: GFG_filtered_unphased_genotypes Sequencing Provider: (unknown) Sequencing Type: (unknown) Sequencing Coverage: Full Genome Genes Exons Protein-coding 0.018% 553,187 bases 0.029% 479,129 bases 0.283% 296,803 bases 0.685% 276,885 bases Variation Counts: Total number of variations: Heterozygous: Homozygous (x2): Rare variations (MAF <1%): SNV: MNV: Insertion: Deletion: 213,080 96,520 58,280 1,145 213,035 0 34 11 Nonsense: Frameshift: Misstart: Nonstop: Inframe Ins/Del: Missense: Splice site: Coding synonymous: mrna untranslated: Intron: 78 20 18 19 5 10,117 515 2,678 8,518 99,365 Known Phenotype Summary: 42,032 variations known to affect a disease or trait were assessed 106 disease or trait variations are found in this genome Phenotype variation coverage 8.7% Successfully sequenced 3,641 phenotype variations Missing data for 38,391 phenotype variations Clinical classification: Pathogenic Likely pathogenic Risk factor Drug response Association Protective 26 2 52 3 18 5 (Page 1 of 6)
Selected Phenotype Variation Details: Chr10: 126,100,579 G>T Pathogenic Phenotype: Ornithine aminotransferase deficiency Zygosity: Homozygous (x2) dbsnp ID: rs121965048 Population Allele Frequency: <0.01% Gene Impact: OAT INTRON MISSENSE N-54-K Supporting Publications: http://www.ncbi.nlm.nih.gov/pubmed/3375240 Gyrate atrophy of the choroid and retina due to deficiency of ornithine aminotransferase is clinically characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. Characteristic chorioretinal atrophy with progressive constriction of the visual fields leads to blindness at the latest during the sixth decade of life. Patients generally have normal intelligence (summary by Peltola et al., 2002). See 238970 for another hyperornithinemia syndrome. Chr1: 171,076,966 G>A Pathogenic Phenotype: Trimethylaminuria, mild Trimethylaminuria Zygosity: Heterozygous (x1) dbsnp ID: rs2266782 Population Allele Frequency: 38.28% Gene Impact: FMO3 MISSENSE E-158-K MISSENSE E-138-K MISSENSE E-95-K Supporting Publications: http://www.ncbi.nlm.nih.gov/pubmed/10485731 Trimethylaminuria is characterized by a fishy odor resembling that of rotten or decaying fish that results from excess excretion of trimethylamine in the urine, breath, sweat, and reproductive fluids. No physical symptoms are associated with trimethylaminuria. Affected individuals appear normal and healthy; however, the unpleasant odor often results in social and psychological problems. Symptoms are usually present from birth and may worsen during puberty. In females, symptoms are more severe just before and during menstruation, after taking oral contraceptives, and around the time of menopause. Chr1: 231,408,091 A>G Pathogenic Phenotype: Rhizomelic chondrodysplasia punctata type 2 Zygosity: Heterozygous (x1) Population Allele Frequency: 16.12% Gene Impact: GNPAT MISSENSE D-519-G dbsnp ID: rs11558492 (Page 2 of 6)
MISSENSE D-458-G Supporting Publications: http://www.ncbi.nlm.nih.gov/pubmed/11152660 Rhizomelic chondrodysplasia punctata (RCDP) is a peroxisomal disorder characterized by disproportionately short stature primarily affecting the proximal parts of the extremities, a typical facial appearance including a broad nasal bridge, epicanthus, high-arched palate, dysplastic external ears, and micrognathia, congenital contractures, characteristic ocular involvement, dwarfism, and severe mental retardation with spasticity. Biochemically, plasmalogen synthesis and phytanic acid alpha-oxidation are defective. Most patients die in the first decade of life. RCDP1 (215100) is the most frequent form of RCDP (summary by Wanders and Waterham, 2005). Whereas RCDP1 is a peroxisomal biogenesis disorder (PBD), RCDP2 is classified as a single peroxisome enzyme deficiency (Waterham and Ebberink, 2012). For a discussion of genetic heterogeneity of rhizomelic chondrodysplasia punctata, see 215100. Chr4: 187,158,034 G>A Pathogenic Phenotype: Prekallikrein deficiency Zygosity: Homozygous (x2) dbsnp ID: rs3733402 Population Allele Frequency: 53.62% Gene Impact: KLKB1 MISSENSE S-143-N Supporting Publications: http://www.ncbi.nlm.nih.gov/pubmed/17598838 Prekallikrein deficiency is a blood condition that usually causes no health problems. In people with this condition, blood tests show a prolonged activated partial thromboplastin time (PTT), a result that is typically associated with bleeding problems; however, bleeding problems generally do not occur in prekallikrein deficiency. The condition is usually discovered when blood tests are done for other reasons. A few people with prekallikrein deficiency have experienced health problems related to blood clotting such as heart attack, stroke, a clot in the deep veins of the arms or legs (deep vein thrombosis), nosebleeds, or excessive bleeding after surgery. However, these are common problems in the general population, and most affected individuals have other risk factors for developing them, so it is unclear whether their occurrence is related to prekallikrein deficiency. The remaining known phenotype variations affect the following traits and diseases: Obesity, association with Limb-girdle muscular dystrophy-dystroglycanopathy, type C3 Serum level of interleukin-6 soluble receptor Familial medullary thyroid carcinoma Hyperlipidemia, familial combined, susceptibility to Lupus nephritis, susceptibility to Prostate cancer, susceptibility to Venous thrombosis, susceptibility to Thyrotoxic periodic paralysis Legionellosis Lymphoproliferative disorders, susceptibility to Hypertension, essential, susceptibility to Fasting plasma glucose level quantitative trait locus 5 Ovarian response to FSH stimulation Fetal hemoglobin quantitative trait locus 5 Gastric cancer susceptibility after h. pylori infection Inflammatory bowel disease 10, susceptibility to Bilirubin, serum level of, quantitative trait locus 1 Human immunodeficiency virus type 1, rapid progression to AIDS Leanness, susceptibility to Recombination rate quantitative trait locus 1 Diabetes mellitus, noninsulindependent, association with Metabolic syndrome, protection against Systemic lupus erythmatosus, association with Congenital human immunodeficiency virus Bietti crystalline corneoretinal dystrophy Neural tube defects, folate-sensitive, susceptibility to Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive Familial hypercholesterolemia Low density lipoprotein cholesterol level quantitative trait locus 3 Asthma, susceptibility to Atopy, susceptibility to Hypertension, diastolic, resistance to Cancer progression and tumor cell motility C3HEX, ability to smell Myocardial infarction Asthma and atopy, susceptibility to Psoriasis susceptibility 13 Insulin resistance, susceptibility to Obesity Diabetes mellitus, insulin-dependent, 5 Estrogen resistance Superoxide dismutase 2 polymorphism Asthma-related traits, susceptibility to, 2 Bone mineral density quantitative trait locus 15 Coronary artery disease, susceptibility to Phenylthiocarbamide tasting Autism 15 Diabetes mellitus, type 2, susceptibility to Autoimmune thyroid disease 3... and more... Get full details on the remaining 102 known phenotype variations within the Enlis Genome software. (Page 3 of 6)
Interesting Variations of Uncertain Significance: Filter steps: Protein-disrupting variations (Nonsense, Frameshift, Misstart, Splice Disrupt) Phenotype Genes - Within a gene already implicated in a disease or trait Global allele frequency < 1% Uncertain clinical significance Results: Variation Gene Impact Allele Freq. Gene Phenotype Chr1: 237,804,287 T>A RYR2 NONSENSE 0.00% Arrhythmogenic right ventricular dysplasia Ventricular tachycardia Chr8: 101,232,564 T>G SPAG1 NONSENSE 0.00% Ciliary dyskinesia Chr9: 139,412,701 A>T NOTCH1 NONSENSE 0.00% Adams-Oliver syndrome Aortic valve disease Chr11: 116,661,635 T>A APOA5 NONSENSE 0.00% Hyperchylomicronemia Hypertriglyceridemia Chr12: 7,362,655 C>T PEX5 NONSENSE 0.01% Peroxisome biogenesis disorder + 3 additional variations Filter steps: Predicted deleterious variations Phenotype Genes - Within a gene already implicated in a disease or trait Global allele frequency < 1% Uncertain clinical significance Results: Variation Gene Impact Allele Freq. Chr1: 22,217,095 C>T HSPG2 MISSENSE 0.02% Chr1: 114,367,793 C>T RP5-1073O3. 2 MISSENSE 0.01% Chr1: 120,278,017 C>T PHGDH MISSENSE 0.03% Chr2: 167,145,152 G>A SCN9A MISSENSE 0.05% Chr2: 216,284,009 C>T FN1 MISSENSE 0.37% + 15 additional variations Gene Phenotype Dyssegmental dysplasia Schwartz- Jampel syndrome Neu-Laxova syndrome Phosphoglycerate dehydrogenase deficiency Dravet syndrome Epilepsy Erythermalgia Febrile seizures Insensitivity to pain Neuropathy, Hereditary sensory and autonomic Paroxysmal extreme pain disorder Small fiber neuropathy Glomerulopathy Plasma fibronectin deficiency (Page 4 of 6)
Notes * Mode of inheritance defintions: Autosomal Recessive Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i. e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity). Confidence Star Levels: Review Status: Classified by single submitter with no evidence provided, or multiple conficting interpretations Review Status: Classified by single submitter with evidence Review Status: Classified by multiple submitters Review Status: Reviewed by expert panel Review Status: Reviewed by professional society Human genome reference version: HomoSapiens_GRCh37 (Page 5 of 6)
Discover more with Enlis Genome software: Your data has been converted. It is now ready for analysis with the awardwinning Enlis Genome software! Comprehensive variation annotation Phenotype Explorer Tool - connect your data and generate PDF reports on over 6,000 diseases and traits Variation Filter - highly optimized with a point-and-click interface Gene Categories and Pathway Tool - evaluate over 20,000 built-in gene categories Homozygous Region Tool - to find regions associated with recessive disease and much more... Get started at: http://www.enlis.com (Page 6 of 6)