mirVAFC: A Web Server for Prioritizations of Pathogenic Sequence Variants from Exome Sequencing Data via Classifications.


:Exome sequencing has been widely used to identify the genetic variants underlying human genetic disorders for clinical diagnoses, but the identification of pathogenic sequence variants among the huge amounts of benign ones is complicated and challenging. Here, we describe a new Web server named mirVAFC for pathogenic sequence variants prioritizations from clinical exome sequencing (CES) variant data of single individual or family. The mirVAFC is able to comprehensively annotate sequence variants, filter out most irrelevant variants using custom criteria, classify variants into different categories as for estimated pathogenicity, and lastly provide pathogenic variants prioritizations based on classifications and mutation effects. Case studies using different types of datasets for different diseases from publication and our in-house data have revealed that mirVAFC can efficiently identify the right pathogenic candidates as in original work in each case. Overall, the Web server mirVAFC is specifically developed for pathogenic sequence variant identifications from family-based CES variants using classification-based prioritizations. The mirVAFC Web server is freely accessible at https://www.wzgenomics.cn/mirVAFC/.


Hum Mutat


Human mutation


Li Z,Liu Z,Jiang Y,Chen D,Ran X,Sun ZS,Wu J




Has Abstract


2017-01-01 00:00:00












  • Detection of sequence variants in the gene for human type II procollagen (COL2A1) by direct sequencing of polymerase chain reaction-amplified genomic DNA.

    abstract::The direct sequencing of the human type II procollagen (COL2A1) gene from polymerase chain reaction (PCR)-amplified genomic DNA is described. Thirty-two regions of the COL2A1 gene were asymmetrically amplified with intron primers which were specifically chosen to amplify a region spanning 500 to 800 bp of sequence enc...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Williams CJ,Harrison DA,Hopkinson I,Baldwin CT,Ahmad NN,Ala-Kokko L,Korn RM,Buxton PG,Dimascio J,Considine EL

    更新日期:1992-01-01 00:00:00

  • Overexpression of the C-type natriuretic peptide (CNP) is associated with overgrowth and bone anomalies in an individual with balanced t(2;7) translocation.

    abstract::Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. We report the molecular characterization of a de novo balanced t(2;7)(q37.1;q21.3) tr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bocciardi R,Giorda R,Buttgereit J,Gimelli S,Divizia MT,Beri S,Garofalo S,Tavella S,Lerone M,Zuffardi O,Bader M,Ravazzolo R,Gimelli G

    更新日期:2007-07-01 00:00:00

  • Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis.

    abstract::Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: García-García AB,Real JT,Puig O,Cebolla E,Marín-García P,Martínez Ferrandis JI,García-Sogo M,Civera M,Ascaso JF,Carmena R,Armengod ME,Chaves FJ

    更新日期:2001-11-01 00:00:00

  • Novel LOVD databases for hereditary breast cancer and colorectal cancer genes in the Chinese population.

    abstract::The Human Variome Project (HVP) is an international consortium of clinicians, geneticists, and researchers from over 30 countries, aiming to facilitate the establishment and maintenance of standards, systems, and infrastructure for the worldwide collection and sharing of all genetic variations effecting human disease....

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pan M,Cong P,Wang Y,Lin C,Yuan Y,Dong J,Banerjee S,Zhang T,Chen Y,Zhang T,Chen M,Hu P,Zheng S,Zhang J,Qi M

    更新日期:2011-12-01 00:00:00

  • Assessing the relative importance of the biophysical properties of amino acid substitutions associated with human genetic disease.

    abstract::The inclusion of a mutation in a pathology-based database such as the Human Gene Mutation Database (HGMD) is a two-stage process: first, the mutation must occur at the DNA level, then it must cause a clinically detectable disease state. The likelihood of the latter step, termed the relative clinical observation likeli...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Terp BN,Cooper DN,Christensen IT,Jørgensen FS,Bross P,Gregersen N,Krawczak M

    更新日期:2002-08-01 00:00:00

  • A novel nonstop mutation in TYMP does not induce nonstop mRNA decay in a MNGIE patient with severe neuropathy.

    abstract::The cellular quality control systems enable surveillance and selective degradation of nonsense, nonstop, and no-go mRNAs. In the case of nonstop mRNA, different mechanisms of nonstop-mediated decay (NSD) have been described for bacteria, yeast and mammals, but the molecular consequences of nonstop mutations have been ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Torres-Torronteras J,Rodriguez-Palmero A,Pinós T,Accarino A,Andreu AL,Pintos-Morell G,Martíí R

    更新日期:2011-04-01 00:00:00

  • Interpreting missense variants: comparing computational methods in human disease genes CDKN2A, MLH1, MSH2, MECP2, and tyrosinase (TYR).

    abstract::The human genome contains frequent single-basepair variants that may or may not cause genetic disease. To characterize benign vs. pathogenic missense variants, numerous computational algorithms have been developed based on comparative sequence and/or protein structure analysis. We compared computational methods that u...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chan PA,Duraisamy S,Miller PJ,Newell JA,McBride C,Bond JP,Raevaara T,Ollila S,Nyström M,Grimm AJ,Christodoulou J,Oetting WS,Greenblatt MS

    更新日期:2007-07-01 00:00:00

  • Screening for mutations in the uroporphyrinogen decarboxylase gene using denaturing gradient gel electrophoresis. Identification and characterization of six novel mutations associated with familial PCT.

    abstract::The two porphyrias, familial porphyria cutanea tarda (fPCT) and hepatoerythropoietic porphyria (HEP), are associated with mutations in the gene encoding the enzyme uroporphyrinogen decarboxylase (UROD). Several mutations, most of which are private, have been identified in HEP and fPCT patients, confirming the heteroge...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Christiansen L,Ged C,Hombrados I,Brons-Poulsen J,Fontanellas A,de Verneuil H,Hørder M,Petersen NE

    更新日期:1999-01-01 00:00:00

  • Lake Louise mutation detection meeting 2013: clinical translation of next-generation sequencing requires optimization of workflows and interpretation of variants.

    abstract::With the exponential reduction of the cost of next-generation sequencing (NGS), it is no longer the generation of data but the analysis and interpretation of massive amounts of sequencing data that are seen as key challenges for the effective integration of these technologies into clinical practice. Clinical geneticis...

    journal_title:Human mutation



    authors: Smith A,Boycott KM,Jarinova O

    更新日期:2014-02-01 00:00:00

  • Applying massive parallel sequencing to molecular diagnosis of Marfan and Loeys-Dietz syndromes.

    abstract::The Marfan (MFS) and Loeys-Dietz (LDS) syndromes are caused by mutations in the fibrillin-1 (FBN1) and Transforming Growth Factor Beta Receptor 1 and 2 (TGFBR1 and TGFBR2) genes, respectively. With the current conventional mutation screening technologies, analysis of this set of genes is time consuming and expensive. ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Baetens M,Van Laer L,De Leeneer K,Hellemans J,De Schrijver J,Van De Voorde H,Renard M,Dietz H,Lacro RV,Menten B,Van Criekinge W,De Backer J,De Paepe A,Loeys B,Coucke PJ

    更新日期:2011-09-01 00:00:00

  • Multiple LRRK2 variants modulate risk of Parkinson disease: a Chinese multicenter study.

    abstract::We and others found two polymorphic LRRK2 (leucine-rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first ...

    journal_title:Human mutation

    pub_type: 杂志文章,多中心研究


    authors: Tan EK,Peng R,Teo YY,Tan LC,Angeles D,Ho P,Chen ML,Lin CH,Mao XY,Chang XL,Prakash KM,Liu JJ,Au WL,Le WD,Jankovic J,Burgunder JM,Zhao Y,Wu RM

    更新日期:2010-05-01 00:00:00

  • Comprehensive evaluation of allele frequency differences of MC1R variants across populations.

    abstract::The melanocortin 1 receptor (MC1R), a member of the G protein-coupled receptors superfamily, mediates the response to melanocortins and is currently the best-described contributor to normal pigment variation in humans. A remarkably large number of natural polymorphisms, or variants, of the MC1R gene have been identifi...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Gerstenblith MR,Goldstein AM,Fargnoli MC,Peris K,Landi MT

    更新日期:2007-05-01 00:00:00

  • Two novel types of contiguous gene deletion of the AVPR2 and ARHGAP4 genes in unrelated Japanese kindreds with nephrogenic diabetes insipidus.

    abstract::Study of two families containing individuals with nephrogenic diabetes insipidus (NDI) indicated different types of 21.3 kb and 26.3 kb deletions involving the AVPR2 and ARHGAP4 (RhoGAP C1) genes. In the case of the 21.3 kb deletion, the deletion consensus motif (5'-TGAAGG-3') and polypurine runs, known as the arrest ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Demura M,Takeda Y,Yoneda T,Furukawa K,Usukura M,Itoh Y,Mabuchi H

    更新日期:2002-01-01 00:00:00

  • A novel splice site mutation of the EXT2 gene in a Finnish hereditary multiple exostoses family. Mutations in brief no. 197. Online.

    abstract::Hereditary multiple exostoses is a dominantly inherited disease characterized by multiple benign osteochondromas. The affected individuals have an increased risk of developing sarcoma. A large Finnish family with hereditary multiple exostosis was analyzed to find the disease-causing mutation. Blood samples were obtain...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wolf M,Hemminki A,Kivioja A,Sistonen P,Kaitila I,Ervasti H,Kinnunen J,Karaharju E,Knuutila S

    更新日期:1998-01-01 00:00:00

  • Diagnostic Exome Sequencing Identifies a Novel Gene, EMILIN1, Associated with Autosomal-Dominant Hereditary Connective Tissue Disease.

    abstract::Heritable connective tissue diseases are a highly heterogeneous family of over 200 disorders that affect the extracellular matrix. While the genetic basis of several disorders is established, the etiology has not been discovered for a large portion of patients, likely due to rare yet undiscovered disease genes. By per...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Capuano A,Bucciotti F,Farwell KD,Tippin Davis B,Mroske C,Hulick PJ,Weissman SM,Gao Q,Spessotto P,Colombatti A,Doliana R

    更新日期:2016-01-01 00:00:00

  • Whole-Genome Sequencing and Integrative Genomic Analysis Approach on Two 22q11.2 Deletion Syndrome Family Trios for Genotype to Phenotype Correlations.

    abstract::The 22q11.2 deletion syndrome (22q11DS) affects 1:4,000 live births and presents with highly variable phenotype expressivity. In this study, we developed an analytical approach utilizing whole-genome sequencing (WGS) and integrative analysis to discover genetic modifiers. Our pipeline combined available tools in order...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chung JH,Cai J,Suskin BG,Zhang Z,Coleman K,Morrow BE

    更新日期:2015-08-01 00:00:00

  • Ten novel mutations in the human neurofibromatosis type 1 (NF1) gene in Italian patients.

    abstract::The entire NF1 coding region was analyzed for mutations in a panel of 108 unrelated Italian NF1 patients. Using PTT, SSCP, and DNA sequencing, we found 10 mutations which have never been reported before. Clinical diagnosis of NF1 was established according to the NIH consensus criteria in 100 individuals, while 8 were ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Origone P,De Luca A,Bellini C,Buccino A,Mingarelli R,Costabel S,La Rosa C,Garrè C,Coviello DA,Ajmar F,Dallapiccola B,Bonioli E

    更新日期:2002-07-01 00:00:00

  • Common variation in GRB-associated Binding Protein 2 (GAB2) and increased risk for Alzheimer dementia.

    abstract::GRB-associated binding protein 2 (GAB2) was recently reported to be a modifier of late-onset Alzheimer dementia (AD) risk in carriers of the APOE epsilon4 allele in a genome-wide association analysis. We aimed to investigate this association in a well-characterized Belgian late-onset AD patient/control group: 528 Belg...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sleegers K,Bettens K,Brouwers N,Engelborghs S,van Miegroet H,De Deyn PP,Van Broeckhoven C

    更新日期:2009-02-01 00:00:00

  • Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients.

    abstract::The identification and interpretation of germline BRCA1/2 variants become increasingly important in breast and ovarian cancer (OC) treatment. However, there is no comprehensive analysis of the germline BRCA1/2 variants in a Chinese population. Here we performed a systematic review and meta-analysis on such variants fr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Gao X,Nan X,Liu Y,Liu R,Zang W,Shan G,Gai F,Zhang J,Li L,Cheng G,Song L

    更新日期:2020-03-01 00:00:00

  • Adapting crowdsourced clinical cancer curation in CIViC to the ClinGen minimum variant level data community-driven standards.

    abstract::Harmonization of cancer variant representation, efficient communication, and free distribution of clinical variant-associated knowledge are central problems that arise with increased usage of clinical next-generation sequencing. The Clinical Genome Resource (ClinGen) Somatic Working Group (WG) developed a minimal vari...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Danos AM,Ritter DI,Wagner AH,Krysiak K,Sonkin D,Micheel C,McCoy M,Rao S,Raca G,Boca SM,Roy A,Barnell EK,McMichael JF,Kiwala S,Coffman AC,Kujan L,Kulkarni S,Griffith M,Madhavan S,Griffith OL,Clinical Genome Resourc

    更新日期:2018-11-01 00:00:00

  • Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene.

    abstract::Hereditary diffuse gastric cancer (HDGC) is a cancer predisposition syndrome caused by germline mutation of the gene encoding the tumour-suppressor E-cadherin (CDH1). We describe the search for CDH1 mutations in 36 new diffuse gastric cancer families. All 16 CDH1 exons, neighbouring intronic sequence and an essential ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: More H,Humar B,Weber W,Ward R,Christian A,Lintott C,Graziano F,Ruzzo AM,Acosta E,Boman B,Harlan M,Ferreira P,Seruca R,Suriano G,Guilford P

    更新日期:2007-02-01 00:00:00

  • A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity.

    abstract::Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene. Recent studies on the subcellular localization revealed that the TRIM37 (KIAA0898) protein is located in peroxisomes. Ther...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Jagiello P,Hammans C,Wieczorek S,Arning L,Stefanski A,Strehl H,Epplen JT,Gencik M

    更新日期:2003-06-01 00:00:00

  • VAX1 mutation associated with microphthalmia, corpus callosum agenesis, and orofacial clefting: the first description of a VAX1 phenotype in humans.

    abstract::Vax1 and Vax2 have been implicated in eye development and the closure of the choroid fissure in mice and zebrafish. We sequenced the coding exons of VAX1 and VAX2 in 70 patients with anophthalmia/microphthalmia (A/M). In VAX1, we observed homozygosity for two successive nucleotide substitutions c.453G>A and c.454C>A, ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Slavotinek AM,Chao R,Vacik T,Yahyavi M,Abouzeid H,Bardakjian T,Schneider A,Shaw G,Sherr EH,Lemke G,Youssef M,Schorderet DF

    更新日期:2012-02-01 00:00:00

  • Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays.

    abstract::Chromosomal rearrangements such as microdeletions and interstitial duplications are the underlying cause of many human genetic disorders. These disorders can manifest in the form of multiple congenital anomalies (MCA), which are a significant cause of morbidity and mortality in children. The major limitations of cytog...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Ming JE,Geiger E,James AC,Ciprero KL,Nimmakayalu M,Zhang Y,Huang A,Vaddi M,Rappaport E,Zackai EH,Shaikh TH

    更新日期:2006-05-01 00:00:00

  • NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in "Brain-Lung-Thyroid Syndrome".

    abstract::NKX2-1 (NK2 homeobox 1) is a critical regulator of transcription for the surfactant protein (SP)-B and -C genes (SFTPB and SFTPC, respectively). We identified and functionally characterized two new de novo NKX2-1 mutations c.493C>T (p.R165W) and c.786_787del2 (p.L263fs) in infants with closely similar severe interstit...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Guillot L,Carré A,Szinnai G,Castanet M,Tron E,Jaubert F,Broutin I,Counil F,Feldmann D,Clement A,Polak M,Epaud R

    更新日期:2010-02-01 00:00:00

  • Pancreatic insufficiency and pulmonary disease in German and Slavic cystic fibrosis patients with the R347P mutation.

    abstract::Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) that codes for a cAMP-regulated chloride channel. The R347P is a missense mutation located within the first membrane spanning domain (MSD1) of the CFTR protein. This mutation occurs with an overal...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Varon R,Stuhrmann M,Macek M Jr,Kufardjieva A,Angelicheva D,Magdorf K,Jordanova A,Savov A,Wahn U,Macek M

    更新日期:1995-01-01 00:00:00

  • Propionic acidemia: analysis of mutant propionyl-CoA carboxylase enzymes expressed in Escherichia coli.

    abstract::Deficiency of propionyl-CoA carboxylase (PCC) results in propionic acidemia, an autosomal recessive disorder characterized by ketoacidosis sufficiently severe to cause neonatal death. PCC is involved in the catabolism of branched-chain amino acids, odd-chain fatty acids, and cholesterol. The enzyme is a biotin-depende...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chloupkova M,Maclean KN,Alkhateeb A,Kraus JP

    更新日期:2002-06-01 00:00:00

  • Y-position cysteine substitution in type I collagen (alpha1(I) R888C/p.R1066C) is associated with osteogenesis imperfecta/Ehlers-Danlos syndrome phenotype.

    abstract::The most common mutations in type I collagen causing types II-IV osteogenesis imperfecta (OI) result in substitution for glycine in a Gly-Xaa-Yaa triplet by another amino acid. We delineated a Y-position substitution in a small pedigree with a combined OI/Ehlers-Danlos Syndrome (EDS) phenotype, characterized by modera...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cabral WA,Makareeva E,Letocha AD,Scribanu N,Fertala A,Steplewski A,Keene DR,Persikov AV,Leikin S,Marini JC

    更新日期:2007-04-01 00:00:00

  • Genomic variation in a global village: report of the 10th annual Human Genome Variation Meeting 2008.

    abstract::The Centre for Applied Genomics of the Hospital for Sick Children and the University of Toronto hosted the 10th Human Genome Variation (HGV) Meeting in Toronto, Canada, in October 2008, welcoming about 240 registrants from 34 countries. During the 3 days of plenary workshops, keynote address, and poster sessions, a st...

    journal_title:Human mutation



    authors: Brookes AJ,Chanock SJ,Hudson TJ,Peltonen L,Abecasis G,Kwok PY,Scherer SW

    更新日期:2009-07-01 00:00:00

  • Characterization of a new disease-causing mutation of SH2D1A in a family with X-linked lymphoproliferative disease.

    abstract::Males with an expressed mutation in the SH2D1A gene that encodes an SH2 domain protein named SH2D1A or SAP (NP_002342; signaling lymphocyte activating molecule [SLAM]-associated protein), have an X-linked syndrome characterized by an increased vulnerability to infection with Epstein-Barr virus (EBV). We evaluated two ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Erdõs M,Uzvölgyi E,Nemes Z,Török O,Rákóczi E,Went-Sümegi N,Sümegi J,Maródi L

    更新日期:2005-05-01 00:00:00