Relatorio de Classificacao de Variantes Genéticas: Analise Clinica e Microarray

Classificação de variantes Composição do Relatório Classificação de variantes Composição do Relatório Dados Clínicos Sample Analysis Information Export Sample Type Blood constitutional Phenotype Deficiência intelectual Atraso desenvolvimento motor Atraso na fala Cariótipo normal TM normal Sexo Masculino Parâmetros de Qualidade Sample Info and QC Export Sample Info File 553663984011cy750Kcychp QC true snpQC CHP Summary 19661 mapd CHP Summary 0185 wavinessSd CHP Summary 0052 name Algorithm CYTO2 version Algorithm 220 sexCall Biology male autosomeGenomeLOH CHP Summary 0003881977 Karyoview Export Detalhe das alterações 750Kcyphp Copy Number State segments 750Kcyphp LOH segments 750Kcyphp SmoothSignal 750Kcyphp Weighted Log2 Ratio 750Kcyphp Allele Difference Common AOH blocksFullertonhg19aed CommonArtifactshg19bedaed 13 CIPHERDDG2P with genomic coordinates 20161010aed Descrição da alteração CN State 300 Type Gain Chromosome 9 Cytoband Start q332 Size kbp 165 Marker Count 67 Gene Count 6 Genes OR1J1 OR1J2 OR1J4 OR1N1 OR1N2 OR1L8 OMIM Genes Count 0 OMIM Genes Call Microarray Nomenclature arr hg19 9q332125182382125347866x3 Classificação de variantes Benigno A CNV foi relatada em várias publicações revisadas por várias fontes ou bancos de dados curados como uma variante benigna particularmente se a natureza da variação do número de cópias tiver sido bem caracterizada Patogênico A CNV é documentada como clinicamente significativa em várias publicações revisadas por várias fontes mesmo que a penetrância e a expressividade da CNV sejam conhecidas como variáveis Significado clínico incerto Esta representa uma categoria razoavelmente ampla e incluirá descobertas que mais tarde demonstraram ser claramente patogênicas ou claramente benignas No entanto se no momento do relato evidências insuficientes estiverem disponíveis para determinação inequívoca de significância clínica e a CNV Significado clinico incerto Provavelmente benigna Significado clinico incerto Provavelmente patogênica Significado clínico incerto provavelmente patogênico 1 A CNV é descrita em um único relato de caso mas com pontos de quebra e fenótipo bem definidos específicos e relevantes para os achados do paciente 2 Um gene dentro do intervalo CNV tem uma função gênica muito convincente que é relevante e específica para o motivo do encaminhamento do paciente Significado clínico incerto provavelmente benigno 1 A CNV não possui genes no intervalo mas é relatada porque excede o critério de tamanho que pode ser estabelecido pelo laboratório 2 A CNV é descrita em um pequeno número de casos em bancos de dados de variação na população geral Formato de laudo Formato de Laudos Descrição detalhada do achado Classificação da alteração Doenças associadas ou aspecto fenotípico esperado Aconselhamento genético Referencias bibliográficas RESULTADO FOI IDENTIFICADA ASEGUINTE ALTERACAO CROMOSSOMICA arrhg1913q1413q1434589185053947465x1 Genes de referencia Sao mapeados nessa regiao 92 genes CONCLUSAO A analise detalhada da amostra com o CytoScan 750K revelou uma delecao em 13q1413q143 de aproximadamente 8 Mb classificada como patogenica A delecao em 13q1413q143 inclui a regiao critica da CHROMOSOME 13q14 DELETION SYNDROME OMIM 613884 de heranca autossomica dominante INTERPRETACAO A delecao em 13q1413q143 inclui a regiao critica da sindrome de delecao 13q14 A sindrome de delecao do cromossomo 13q14 e uma sindrome de fenotipo variavel que depende do tamanho e posicao da alteracao Ela e caracterizada por retinoblastoma OMIM 180200 graus variaveis de comprometimento mental caracteristicas faciais distintas que imcluem testa alta e proeminente filtro longo e proeminente e lobulos de orelha antevertidos REFERENCIAS Baud 0 et al Dysmorphic phenotype and neurological impairment in 22 retinoblastoma patients with constitutional cytogenetic 13q deletion Clin Genet 55 478482 1999 Caselli R et al Retinoblastoma and mental retardation microdeletion syndrome clinical characterization and molecular dissection using array CGH J Hum Genet 52 535542 2007 DICAS 080989A3Phase4CustomerPanelCytoScanPS20110228CytoScanHDcychp Copy Number State segments 080989A3Phase4CustomerPanelCytoScanPS20110228CytoScanHDcychp Weighted Log2 Ratio 15 05 15 080989A3Phase4CustomerPanelCytoScanPS20110228CytoScanHDcychp Copy Number State 4 2 1 0 080989A3Phase4CustomerPanelCytoScanPS20110228CytoScanHDcychp Allele Peaks 15 05 05 15 OMIM 0 20000kb 40000kb 60000kb 80000kb 100000kb 120000kb 140000kb 160000kb 5 q112 q143 q15 q32 q34 A B 1st degree consanguinity IBD 25 Table 1 Correlation between percentage of LCSH and degree of parental relationship Parental Relationship Degree Coefficient of Inbreeding F LCSH IBD Predicted in Child a Parentchild First 025 25 Full siblings First 025 25 Half siblings Second 0125 125 Uncleniece or auntnephew Second 0125 125 Double first cousins Second 0125 125 Grandparentgrandchild Second 0125 125 First cousins Third 00625 6 First cousins once removed Fourth 003125 3 Second cousins Fifth 0015625 15 Third cousins Seventh 00039062 05 a Assuming outbred population Considerações sobre classificação A região contém um gene imprintado possivelmente levando a diferenças na patogenicidade há uma deleção em um alelo e uma mutação pontual no outro alelo A mesma deleção está presente em ambos os alelos portanto duas deleções heterozigotas benignas podem gerar uma deleção homozigótica deletéria Cada progenitor tem uma deleção diferente e benigna heterozigótica no mesmo gene que quando ambos são herdados causa um efeito deletério na prole heterozigoto composto A CNV está no cromossomo X e é herdada por um filho de uma mãe não afetada A CNV ocorre em combinação com outra CNV e juntos leva a um defeito patogênico DGV Database of Genomic Variants httpdgvtcagcadgvapphome Genomic Variants in Human Genome Build GRCh37 Feb 2009 hg19 800 kbp from chr77189018172690180 Browser Select Tracks Custom Tracks Preferences Search Landmark or Region chr77189018172690180 Search Examples chr77189018172690180 CFTR AC1081713 nsv529033 Data Source Genomic Variants in Human Genome Build GRCh37 Feb 2009 hg19 ScrollZoom Show 800 kbp Flip Filter variants study Filter Reset Overview Details Database of Genomic Variants A curated catalogue of human genomic structural variation Browser Select Tracks Custom Tracks Preferences Search Landmark or Region chr77189018172690180 Search Examples chr77189018172690180 CFTR AC1081713 nsv529033 Data Source Genomic Variants in Human Genome Build GRCh37 Feb 2009 hg19 Filter variants study Filter Reset chr7 chromosome chr7 800 kbp 200 kbp Cytogenetic Bands 7q1122 7q1123 DGV Structural Variants BlueGainRedLossBrownComplexPurpleInversionBlackUnknown nsv1146102 John2014 nsv5790 Kidd2008 nsv1029162 Coe2014 nsv607461 Cooper2011 nsv365909 Mills2006 nsv1114976 Alsmadi2014 esv1311182 Levy2007 nsv509206 Teague2010 esv3613679 nsv428170 Perry2008b nsv981520 Sudmant2013 nsv607467 Cooper2011 esv3571919 Uddin2014 nsv981664 Sudmant2013 dgv6466n10 nsv966844 Sudmant2013 esv3613663 1000GenomesConsortiumPhase3 nsv970526 Sudmant2013 nsv970528 Sudmant2013 nsv970530 Sudmant2 nsv1019397 Coe2014 esv3613666 1000GenomesConsortiumPhase3 nsv1018460 Coe2014 nsv971391 Sudmant2013 esv3541892 Boomsma2014 nsv469716 Locke2006 nsv469793 Locke2006 nsv469664 Locke2006 nsv1074517 Thareja2015 esv2759537 Redon2006 nsv1074516 Thareja2015 esv3613665 1000GenomesConsortiumPhase3 nsv1030447 Coe2014 dgv3854e59 1000GenomesConsortiuml nsv366857 Mills2006 esv3613667 1000GenomesConsortiumPhase3 nsv1018175 Coe2014 nsv970529 Sudmant2013 nsv1109890 Alsmadi2014 esv3613668 1000GenomesConsortiumPhase3 nsv1161563 Lou2015 dgv6459n100 Coe2014 nsv970527 Sudmant2013 nsv8135 Perry2008 esv3362186 1000Genc nsv1161562 Lou2015 nsv981523 Sudmant2013 nsv981663 Sudmant2013 esv3613680 nsv966845 Sudmant2013 dgv6463n100 Coe2014 esv3613674 1000GenomesConsortiumPhase3 nsv8137 Perry2008 dgv1923e212 Uddin2014 nsv1124229 Alsmadi2014 nsv970876 Sudmant2013 nsv950548 Dogan nsv1019945 Coe2014 nsv8133 Perry2008 nsv967332 Sudmant2013 nsv981526 Sudmant nsv1020209 Coe2014 nsv981521 Sudmant2013 esv2764061 Vogler2010 dgv6460n100 Coe2014 esv3571921 Uddin2014 nsv981524 Sudmant2013 esv2761093 Vogler2010 nsv967330 Sudmant2013 esv3384196 1000GenomesConsortiumPilot nsv442053 McCarroll12008 nsv981662 Sudmant2013 esv3327489 1000GenomesConsortiumPilot dgv1116n67 Park2010 esv3613678 1000GenomesConsortiumPhase3 Decipher httpsdeciphersangeracukbro wserq206203754262103993l ocation206194576762195767 DECIPHER GRCh37 About Browse DDDUK Search DECIPHER Join Login Genome Browser 206203754262103993 Jump to position gene or band Go Tracks Chr 20 p13 p123 p122 p121 p1123 p1121 q1121 q1122 q1123 q12 q1312 q1313 q132 q1333 8196 Mb 8198 Mb 8200 Mb 8202 Mb 8204 Mb 8206 Mb 8208 Mb 8210 Mb 8212 Mb 8214 Mb 8216 Mb 8218 Mb Genes CHRNA4 KCNQ2 EEF1A2 PPDPF SRMS PTKB HE Genes Legend pLl ranges 00 Less intolerant 01 02 03 04 05 Intolerance to LoF mutation 06 07 08 09 1 More intolerant No pLl score Morbid Genes CHRNA4 KCNQ2 EEF1A2 Sequence DECIPHER CopyNumber Variants DECIPHER CopyNumber Variants Legend Gain Pathogenic Loss Pathogenic Gain Likely pathogenic Loss Likely pathogenic Tracks Chr 20 p13 p123 p122 p121 p1123 p1121 q1121 q1122 q1123 q12 q1312 q1313 q132 q1333 My query position 8196 Mb 8198 Mb 8200 Mb 8202 Mb 8204 Mb 8206 Mb 8208 Mb 8210 Mb 8212 Mb 8214 Mb 8216 Mb 8218 Mb Genes CHRNA4 KCNQ2 EEF1A2 PPDPF SRMS PTKB HE Genes Legend pLl ranges 00 Less intolerant 01 02 03 04 05 Intolerance to LoF mutation 06 07 08 09 1 More intolerant No pLl score Morbid Genes CHRNA4 KCNQ2 EEF1A2 DECIPHER CopyNumber Variants DECIPHER CopyNumber Variants Legend Gain Pathogenic Loss Pathogenic Gain Likely pathogenic Loss Likely pathogenic Overview Genotype 1 Phenotype 3 Assessments 0 Karyotype Citations 0 Contacts Sequence Variants No records found Filter Location Gene Transcript Annotation Inheritance Genotype Pathogenicity Contribution Links No data available in table CopyNumber Variants 1 to 1 of 1 Filter Location Class Mean Ratio Size Genes Inheritance Genotype Pathogenicity Contribution DS Score Sampling Probability Links 20 61468347 62908674 Deletion 1 144 Mb 61 De novo constitutive Heterozygous Pathogenic Full Score Sampling probability 331 1 View Browser Genes 61 Matching Patients 184 Matching CNV Syndromes 0 Tracks Chr 20 p13 p123 p122 p121 p1123 p1121 q1121 q1122 q1123 q12 q1312 q1313 q132 q1333 8120 Mb 8140 Mb 8160 Mb 8180 Mb 8200 Mb 8220 Mb 8240 Mb 8260 Mb 8280 Mb Genes Some features are currently hidden resize to see all YTHDF1 COL20A1 KCNQ2 PPDPF STMN3 LIME1 ABHD10B SAMD10 RGSI9 PCMTD2 NTSR1 OGFR SLC17A9 BIRC7 CHRNA4 EEF1A2 GMEB2 TNFRSF8 TPDS2L2 PRPF6 OPRL1 NKAIN4 ARFGAP1 PTK6 RTEL1 SLCAA4RG DNAJC5 LINC00176 MYT1 SOX18 SRMS UCKL1 Genes Legend pLl ranges 00 Less intolerant 01 02 03 04 05 Intolerance to LoF mutation 06 07 08 09 1 More intolerant No pLl score Morbid Genes COL9A3 SLC17A9 CHRNA4 EEF1A2 RTEL1 DNAJC5 SOX18 KCNQ2 PRPF6 OMIM Online Mendelian Inheritance in Man OMIM Online Mendelian Inheritance in Man An Online Catalog of Human Genes and Genetic Disorders Updated May 11 2018 httpswwwomimorg 607837 Table of Contents CLN8 GENE CLN8 HGNC Approved Gene Symbol CLN8 Cytogenetic location 8p233 Genomic coordinates GRCh38 817557771786569 from NCBI GenePhenotype Relationships Location Phenotype Phenotype MIM number Inheritance Phenotype mapping key 8p233 Ceroid lipofuscinosis neuronal 8 600143 AR 3 Ceroid lipofuscinosis neuronal 8 Northern epilepsy variant 610003 AR 3 TEXT Cloning and Expression Ranta et al 1999 reported the positional cloning of a novel gene CLN8 in the critical region of chromosome 8p for progressive epilepsy with mental retardation EPMR 610003 or Northern epilepsy The CLN8 gene encodes a deduced 286amino acid transmembrane protein with a molecular mass of 80 kD Ranta et al 1999 also cloned mouse Cln8 To determine the intracellular localization of CLN8 Lonka et al 2000 transiently transfected BHK cell lines with CLN8 cDNA Using CLN8 and cell organellespecific antibodies with confocal immunofluorescence microscopy they showed that the CLN8 protein localizes primarily in the ER with partial localization in the ERGolgi intermediate compartment ERGIC The ERERGIC localization was not altered in the CLN8 protein containing a human CLN8 mutation 6001430001 However the truncated murine mnd mutant protein was found only in the ER Mutations in the ER retrieval signal KKRP resulted in localization of CLN8 to the Golgi apparatus The authors concluded that CLN8 is an ER resident protein that recycles between ER and ERGIC httpsgenesfariorgdatabasecnv As of December 19 2019 SFARI Genes scoring criteria changed and we will only be updating certain modules To view the previous version visit the SFARI Gene Archive SFARI GENE DATABASE ABOUT TOOLS USER GUIDE NEWS ARCHIVE Latest Release 2020 Q2 Search this table 54 rows in table TYPE TITLE AUTHOR YEAR 1 Major Arraybased comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spe Jacquemont ML et al 2006 2 Major Screening for genomic rearrangements and methylation abnormalities of the 15q11q13 region in autism spectrum disorders Depienne C et al 2009 3 Major Autism genomewide copy number variation reveals ubiquitin and neuronal genes Glessner JT et al 2009 5 Major Functional impact of global rare copy number variation in autism spectrum disorders Pinto D et al 2010 6 Major Copy number variations associated with autism spectrum disorders contribute to a spectrum of neurodevelopmental disorders Rosenfeld JA et al 2010 7 Major A genotype resource for postmortem brain samples from the Autism Tissue Program Wintle RF et al 2011 8 Major Rare de novo and transmitted copynumber variation in autistic spectrum disorders Levy D et al 2011 9 Major An evidencebased approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili Kaminsky EB et al 2011 10 Major Identification and characterization of three inherited genomic copy number variations associated with familial schizophrenia Liao HM et al 2012 12 Major De novo interstitial duplication of 15q112q131 with complex maternal uniparental trisomy for the 15q11q13 region in a patient with PraderWilli Burrage LC et al 2012 EXTERNAL LINKS UCSC Genome Browser NCBI Map Viewer DECIPHER DECIPHER