ni#enoaeLabLS.

3rd Hoor, Narayana Dldrralaya Buildirg, Narayara Health City,

*Z58,lA\ Bornnmandra, H6Jr Road, Bangalore - 560 0!X), India
Td : +91 (0)80 67154989 / 990. WS: www.medqenome.com + MTDGENoMT

DiIA TEST REPORT - ffiEBGEIIOHE tABOIATO$ES

BABY OF AJITHA
f r,i ::+i.,::, ;: r-,.i;. ,..iij 85915/224609
Is63767G]
1..:;;-' 1: l'. ,:' Maie Blood
1 year NA
Dr. Sony M., 7rh December 2018, 4:15 PM
Christian Medical College and 8th December 2018
Hospital, Vellore 18th January 2019, 6:30 PM
'i*i;i *r:i)**ai*a*: Clinical Exome

C$HICAT rlrAB[rosrs 1srsrpT0t$s I HrsT$ay

Baby of Ajitha, born of a non-consanguineous marriage, presented with clinical indications of global developmental delay,
delayed speech, delayed motor milestones, hyperactivity, mild dysmorphism (mild coarse facies, prominent forehead,
depressed nasal bridge and wide mouth) and small umbilical hernia. His audiogram is suggestive of low-frequency hearing
loss in right ear more than left ear. Baby of Ajitha has been evaluated for pathogenic gene variations.

AIlDlTr0t{AL Flt{Dltrr6s: H0 vAftlAt{I{s}0r ux(EnlAtil stcl{tFttA}ttt (vus}tDtilTtnED

YAR]AHT I HTERPRETATIOil A]ID CtIIIIfi[ CORRELATIOI*

Itlo mriations likely to k causatiue of the clinical synptom serc &tected.
No other variant that warrants to be reported was detected. Variations with high minor allele frequencies which are likely
to be benign will be given upon request.

All the genes covered in the dinkal exonre asay haue been screened for the giren dinical indicatiom. The coverage of
the clinicel exo{re assay 6enes *dll be provided upon r€quesL

RECOITIME}IDATIONS

Th6-felfrshfuityof t*Gskedaesay+todetecthrge heterozygoudehtions,/duplications is lt n and an alternate rnethd

is recommended.

Genetic counselling is advised.

TEST &IETHODOI.OGY

Targeted gene sequencing: Selectirc capture and sequencing of the protein coding regions of the genomelgenes is
performed. Mutations identified in the exonic regions are generally actionable compared to variations that occur in non-
coding rqions. Targeted sequencing represents a csst-effective approach to detect variants preserlt in multiplellarge
genes in an individual.

Page 1 of 4
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Name/Sample ID: Baby crf Alitha [563767G]/22.t509
.,':v, -:\ r

l'-atr4 *MEe{1r@,
MedGenome Labs Ltd.
3rd Floor, Narayana Nethralai.ra Building, Narayana Health City,
#25BlA, Bommasandra, Hosur Road, Bangalore - 56C 099, India.
€= MrDsENoMtr
Tei ; +91 (0)80 67154S89 1 990, Webr

DNA extracted frcm blood was used to perform targeted gene crpture using a custom capture kit- The libraries wert:
sequenced to mean >80-100X coverage on lllumina sequencing piatform. The sequences obtained are aligned to human
reference genome (CRCh37/hg19) using B\i/A program [2, 3] and analyzed using Picard and GATK version 3.6 [4, 5] to
identify variants relevant io the clinical indlcation. \l/e follow the GATK best practices framework for identilication cf
variants in the sample. Gene annotaticn of the variants is performed using VEP pragram [6] against the Ensembl release
87 human gene model [7]. Clinically relevant mutations \,vere annotated using published varienis in iiterature and a set
of diseases databases - ClinVar, OMIM, GWAS, HGMD and SwissVar [8-15]. Con':mon \rariants are filtered based on allele
frequency in 1000Genome Phase 3, ExAC, EVS, dbSNP147, LU00 Lapanese Genanre and our internal lndian population
database [16-20]. Non-synonymous variants effect is calculated using multiple algorithrns such as Poii:Phg6-2,51a1-,
Mutation Taste12, Mutation Assessor, and LRT. Only ncn-synonymous and splice site variants found in the clinical exorne
panel consisting of 8332 genes were used for clinical interpretation. Silent variations that do not result rn any change in
amino acid in the coding region are not reported.

Total data generated {Gb} 5.55

Total reads aliened {%} 99.99
Reads that passed alisnment (76) 93 .3.r
g61s : Q30 (%) C1 C
'

*Genetic test results are reported based on the recommendations of American College of Medical Genetics
[1], as
described below:

Va ria nt A change in a gene. rhis could be disease causing ipathogenic) or not disease causing (benign).

A disease causing variation in a gene which can explain the patiehts' symptoms has been detected. This
Pathogenic
usually means that a suspected disorder for which testing had been requested has been confirmed.

A variant which is very likelyto contribute to the development of disease however. the scientific evidence is
Likely
currently insufficient to prove this conclusively. Additional evidence is expected to co*firm this assertion of
Pathogenic
pathogenicity.

A variant has been detected, but it is difficult to classifo it as either pathogenic {disease causing} or benign
Variant of
inon-disease causing) based on current available scientific evidence. Further testing of the patient or family
Uncertain
members as recommended by your clinician may be needed. lt is probable that their significance can be
Significance
assessed only with time, sub.iect to availability of scientific evidence.

SThe transcript used for clinical reporting generally represents the canonical transcript (according
to Ensembl release 87 gene modei),
which is usually the lcngest.adingtranscript urith stronglmultiple supporting evidence. Howevel clinicatty relevant variants annotated
in alternate complete coding transcripts could also be reported.

Variants annotated on incomplete and nonsense mediated decay transcripts will not be reported.

#The rn sill'co predictions are based on Variant Efiect Predictor, Ensembl release 87 (SIFT version - 5.2.2; PolyPhen - 2.2"2); LRT version
- November. 2O09 release from dbNSFtu3.1 and Mutation Taster2 based on build NCBI 371Ensembl 69 [21"].

For arry further technical queries phase contad techsupgort@medgenome.com.

DISCLAIf$IER

r The classification of variants of unknown significance can change over time and MedGenome cannot be held
responsible for this. Please contact MedGenome at a later date to inquire about any changes.
a lntronic variants are not assessed using this method.
a Large deletions of more than 1O bp or copy number variations fchromosomal rearrangements cannot be assessed
using this method.

Certain genes may not be covered completely and few mutations could be missed. Variants not detected by the assay
that was performed may impact the phenotype.

Page 2 of 4
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Name/Sample ID: Baby of Ajiiha [563767G]i 22160S
 MedGenome Labs Ltd.

+
3rd Floor. Narayana Nethralaya Building, Narayana Health Crty-,
#25BlA, Bonrmasandra, Hosur Road, Bangalore _ 560 099, india.
Tel : +91 (0)80 671549891990, Web: ..
ilrrDGENoMr
a The mutations have not been validated by Sanger sequencing.
a lncidental or secondary findings {if any} that meet the ACMG guidelines
[22] can also be given upon request.
a This is a laboratory developed test and the development and
the performance characteristics of this test was
determined by MedGenome.

.at
{ u;'"*
&.*'*i ,,t+".dl
3,,--t- ffieu
Dr. Udhoyo H.l(orerho, ffD
Associsle Direclor- Senior Bioinformofirs t00 tob Direrlor
Dicgnostirs {Puediofrirs}, Fellawship in
Screntisl ll
S€dksl Genetirs.
fonsgltonl - flinitol Genafirist

END OF REPORT

RETEREIICES

1' Richards s' Aziz N, Sale s, et a/- 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,
Genetics in Medicine, ZOlS May;17(5):u105_24
2' Li' H- and R' Durbin- Fast and accurate long-read alignment with Burrows-wheelertransform.
Bioinformatics, 20L0. 26{5i: p- 5gg-
95.
3' It/leyer, L'fl', eraJ', The ucsc Genome Srowser database:
extensions and updates 2013. Nucleic Acids Res, 2013.41(D1l: p.
D64-

4' McKenna' A', er al', The Genome Analysis Tootkit: a MapReduce

framework for analyzing ne)d-generation DNA sequencing data.
Genorne Req 2010. 20{9}: p. 129?_303.
5' elaL, The Sequence Alignment/Map format and SAMtools. BioinformaticE
Li, H',
2009. 25(16): p. 2078-9.
6' Mclaren' w'' ef a/', Derivingthe consequences of genomic variants
with the Ensembl Apl and sNp Effect predictor. Bioinformatics,
2010- 26{16}: p- 2069-70-
]. ENSEMBL:http://www.ensembl.orq
8' Landrum, M J', et aL, clinvar: public archive of interpretations
of clinically relevant variants. Nucleic Acids Res., 2015.
s' online Mendelian lnheritance in Man (oMlM), a knowtedgebase of
human genes and genetic disorders,
i,i,[|il,,*;ilrll''
10. OMIM:http://www.omim.orp
11. GwAS: h,ttp;#ivwW,eh.i. af .Hk/gwas/
12' welter D', et at',The NHGRI GwAs catatog, a curated resource of SNp-trait associations. Nucleic Acids Res., 2014.
13' stenson, P' D', eta'', Human Gene Mutation Database
{HGMDR):2003 update. Hum. Mutat. 21, s77-5g1.
14. HGMD,
* retrieval of single amino-acid polvmorphisms and phenotype
information using swissvar. Bioinformatics,
ff*t;tiilii'rT*
16' A global reference for human genetic variation.
Nature, 2015. 526(7s71): p. 6g-74.
17.Analysisofprotein.codinggeneticyariationin6o,706humans.2o15,@

Page 3 of 4 /-.^ n
\-A H
Namelsampte ID: Baby of Ajitha 1563767G1122460g
:. a i:::'. i::
}l#*noreLabLid.
3rd Hoor, Nard)rana Nethralaya Building, Narayana Health City.
#258ff\ Bommasandra, Hosur Road, Bangalore - 560 099, India.
Td : +91 (0)80 671549891 990, Webr www.medgeilome.com €fo r',tr*firru*nrtr
18. t{HLair https://esp.gs.washinqton.eduldrupal
19. Nagasaki, M., Rare variant discovery by deep wholegenome sequencing of 1,070 Japanese individuals. Nat. Commun. 2015.

2O. dbSt{P: http ://www. ncbi. nlm. nih.eov/SN P/

21. Mutation Taster2: httD://www.mutationtaster.org/
22. Green R. c., et oL, American Collqe of Medical Genetics and Genomics. ACMG recomrnendations for reporting of incidenfal
findings in clinical exome and genome sequencing. Genet Med.2O13 Jul;1S(7):565-74.

Page 4 of 4 /-An
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Name/Sample ID: Baby of Ajitha [563767G]i 22-1609

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