MedGenome Labs Ltd.
Sy. Nos. 94/1C and 94/2, Tower 1, Ground Floor, Veerasandra Village,
Attibele Hobli, Electronic City Phase-1, Electronics City, Bangalore,
Bangalore South, Karnataka, India, 560100.
Tel : 1800 296 9696, Web: [Link]
DNA TEST REPORT - MEDGENOME LABS
AARIV KHURANA
Full Name / Ref No: Order ID/Sample ID: 1367149/9256251
[APD1.0010994483]
Gender: Male Sample Type: Blood
Date of Birth / Age: 9 years Date of Sample Collection: 8th July 2025
Referring Clinician: Dr. Smita Malhotra, Date of Sample Receipt: 11th July 2025
Indraprastha Medical Corporation Date of Order Booking: 11th July 2025
Limited, New Delhi
Date of Report: 30th July 2025
Test Requested: Whole Exome Sequencing [80-100x]
CLINICAL DIAGNOSIS / SYMPTOMS / HISTORY
Master Aariv Khurana, presented with clinical indications of abdominal pain, vomiting, pancreatitis. His MRCP findings
suggestive of chronic calcific pancreatitis. USG findings showed fibrotic and atrophied pancreas. Master Aariv Khurana is
suspected to be affected with pancreatitis and has been evaluated for pathogenic variations.
RESULTS
VARIANTS OF UNCERTAIN SIGNIFICANCE RELATED TO THE GIVEN PHENOTYPE WERE DETECTED
SNV(s)/INDELS
Gene# (Transcript) Location Variant Zygosity Disease (OMIM) Inheritance Classification$
c.101A>G Uncertain
Exon 3 Homozygous Significance
(p.Asn34Ser)
(PP5)
c.195-69_195- Tropical calcific Uncertain
SPINK1 (-) Autosomal
Intron 3 66 dup Homozygous pancreatitis Significance
(ENST00000296695.10) recessive
(Intronic) (OMIM#608189) (PP5)
c.56-37T>C Uncertain
Intron 1 Homozygous Significance
(Intronic)
(PP5)
COPY NUMBER VARIANTS CNV(s)
No significant CNVs for the given clinical indications that warrants to be reported was detected.
VARIANT INTERPRETATION AND CLINICAL CORRELATION
VARIANT 1 (SPINK1 gene):
Variant description: A homozygous missense variant in exon 3 of the SPINK1 gene (chr5:g.147828115T>C; Depth: 77x)
that results in the amino acid substitution of Serine for Asparagine at codon 34 (p.Asn34Ser; ENST00000296695.10) was
Page 1 of 6
Name/Sample ID: Aariv Khurana [APD1.0010994483]/9256251
MedGenome Labs Ltd.
Sy. Nos. 94/1C and 94/2, Tower 1, Ground Floor, Veerasandra Village,
Attibele Hobli, Electronic City Phase-1, Electronics City, Bangalore,
Bangalore South, Karnataka, India, 560100.
Tel : 1800 296 9696, Web: [Link]
detected (Table). The observed variant has previously been reported in patients with acute to chronic pancreatitis [PMID:
12629264] and lies in the Kazal-type serine protease inhibitor domain of the SPINK1 protein [PF00050]. The p.Asn34Ser
variant has a minor allele frequency of 0.6%, 0.8%, 0.9%, 0.6% and 2.1% in the 1000 genomes, gnomAD (v3.1), gnomdAD
(v2), topmed and in our internal databases respectively. The reference codon is conserved across species.
Considering the fact that about 50% of TCP patients have a mutated SPINK1 gene with the majority having N34S
mutation as a founder mutation, patients with pancreatitis may be screened and informed about the risk of developing
the disease [PMID: 12011155].
Due to lack of segregation analysis$, this SPINK1 variation is classified as a variant of uncertain significance and has to
be carefully correlated with the clinical symptoms.
VARIANT 2 (SPINK1 gene):
Variant description: A homozygous variant in intron 3 of the SPINK1 gene (chr5:g.147824773_147824776dup; c.195-
69_195-66dup; Depth: 51x) was detected (Table). The observed variation has previously been reported (as IVS-
69insAAAA) in patients affected with pancreatitis [PMID: 12629264]. This variant has not been reported in the gnomdAD
(v2) databases and has a minor allele frequency of 0.5%, 0.8%, 0.6% and 1.7% in the 1000 genomes, gnomAD (v3.1),
topmed and in our internal databases respectively. The in silico prediction# of the variant is benign by MutationTaster2.
The reference base is conserved across species.
Due to lack of segregation analysis$, this SPINK1 variation is classified as a variant of uncertain significance and has to
be carefully correlated with the clinical symptoms.
VARIANT 3 (SPINK1 gene):
Variant description: A homozygous variant in intron 1 of the SPINK1 gene (chr5:g.147829667A>G; c.56-37T>C; Depth:
60x) was detected (Table). The observed variation has previously been reported (as IVS1-37T>C) in patients affected with
pancreatitis [PMID: 12629264]. This variant has a minor allele frequency of 0.5%, 0.7%, 0.8%, 0.6% and 1.5% in the 1000
genomes, gnomAD (v3.1), gnomdAD (v2), topmed and in our internal databases respectively. The in silico prediction# of
the variant is benign by MutationTaster2. The reference base is conserved across species.
Due to lack of segregation analysis$, this SPINK1 variation is classified as a variant of uncertain significance and has to
be carefully correlated with the clinical symptoms.
Literature evidence suggests that variant 3 (IVS1-37T>C) and variant 2 (IVS3-66- 65insTTTT) were seen in strong genetic
disequilibrium with the Asn34Ser variation (Variant 1). The significance of these variants must be clinically correlated
[PMID: 28670531].
OMIM phenotype: Tropical calcific pancreatitis (OMIM#608189) is caused by mutations in the SPINK1 gene
(OMIM*167790). TCP is an idiopathic, juvenile, nonalcoholic form of chronic pancreatitis widely prevalent in several
tropical countries. Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes secondary to TCP. TCP differs from
alcoholic pancreatitis by a younger age at onset, pancreatic calcification, a high incidence of insulin-dependent but
ketosis-resistant diabetes mellitus, and an exceptionally high incidence of pancreatic cancer [PMID: 18842627].
The significance/classification of the variant(s) may change based on the genetic testing in parents and other family
members.
ADDITIONAL INFORMATION
Page 2 of 6
Name/Sample ID: Aariv Khurana [APD1.0010994483]/9256251
MedGenome Labs Ltd.
Sy. Nos. 94/1C and 94/2, Tower 1, Ground Floor, Veerasandra Village,
Attibele Hobli, Electronic City Phase-1, Electronics City, Bangalore,
Bangalore South, Karnataka, India, 560100.
Tel : 1800 296 9696, Web: [Link]
• No other SNV(s)/INDELS or CNV(s) that warrants to be reported were detected. All the genes covered in this assay
have been screened for the given clinical indications. To view the coverage of all genes Click here. NGS test
methodology details of this assay are given in the appendix.
• $
Genetic test results are reported based on the recommendations of American College of Medical Genetics and
Genomics (ACMG) [PMID: 25741868, 31690835, 32906214].
• With regard to ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing
(PMID: 35802134; ACMG SF v3.1), we report significant pathogenic and/ or likely pathogenic variants in the
recommended genes for the recommended phenotypes, only if informed consent is given by the patient.
• Please write an email to [Link]@[Link] in case you need assistance for genetic counselling.
For any further technical queries please write an email to techsupport@[Link]
RECOMMENDATIONS
• Sequencing the variant(s) in the parents and the other affected and unaffected members of the family is
recommended to confirm the significance.
• Genetic counselling is advised for interpretation on the consequences of the variant(s).
• If results obtained do not match the clinical findings, additional testing should be considered as per referring
clinician's recommendations.
• The sensitivity of NGS assay to detect copy number variants (CNV) is 70-75%. We recommend discussing alternative
testing methodology options with MedGenome Tech Support (techsupport@[Link]) as required. In case
clinician is suspecting CNV as an important genetic etiology, alternate tests like microarray/ MLPA or qPCR may be
considered after discussing with the MedGenome TechSupport team.
Sandhya Nair, Ph.D Balaji Rajashekar, Ph.D Dr. Mallikarjun Patil DNB(Medical
Sr. Manager - Director - Clinical Bioinformatics Genetics), MD (Pediatrics), DCh
Variant Interpretation Consultant- Senior Clinical Geneticist
APPENDIX
TEST METHODOLOGY
Targeted gene sequencing: Selective capture and sequencing of the protein coding regions and clinically relevant in the
genome is performed. Variants identified in the exonic regions and splice-site are generally actionable compared to
variants that occur in non-coding regions. Targeted sequencing represents a cost-effective approach to detect variants
present in multiple/large genes in an individual.
DNA extracted from blood was used to perform targeted gene capture using a custom capture kit. The libraries were
sequenced to mean depth of >80-100X on Illumina sequencing platform. We follow the GATK best practices framework
for identification of germline variants in the sample using Sentieon [Sentieon]. The sequences obtained are aligned to
human reference genome (GRCh38) using BWA aligner [Sentieon, PMID:20080505] and analyzed using Sentieon for
removing duplicates, recalibration and re-alignment of indels [Sentieon]. Sentieon haplotype caller is then used to identify
variants in the sample. The germline variants identified in the sample is deeply annotated using VariMAT pipeline. Gene
annotation of the variants is performed using VEP program [PMID: 20562413] against the Ensembl release 104 human
Page 3 of 6
Name/Sample ID: Aariv Khurana [APD1.0010994483]/9256251
MedGenome Labs Ltd.
Sy. Nos. 94/1C and 94/2, Tower 1, Ground Floor, Veerasandra Village,
Attibele Hobli, Electronic City Phase-1, Electronics City, Bangalore,
Bangalore South, Karnataka, India, 560100.
Tel : 1800 296 9696, Web: [Link]
gene model [PMID: 34791404]. In addition to SNVs and small Indels, copy number variants (CNVs) are detected from
targeted sequence data using the ExomeDepth method [PMID: 22942019]. This algorithm detects CNVs based on
comparison of the read-depths in the sample of interest with the matched aggregate reference dataset.
Clinically relevant mutations in both coding and non-coding regions are annotated using published variants in literature
and a set of diseases databases : ClinVar, OMIM, HGMD, LOVD, DECIPHER (population CNV) and SwissVar [PMID:
26582918, 18842627, 28349240, 21520333, 19344873, 20106818]. Common variants are filtered based on allele
frequency in 1000Genome Phase 3, gnomAD (v3.1 & 2.1.1), dbSNP (GCF_000001405.38), 1000 Japanese Genome,
TOPMed (Freeze_8), Genome Asia, and our internal Indian population database (MedVarDb v4.0) [PMID: 26432245,
32461613, 11125122, 26292667, 33568819, 31802016]. Non-synonymous variants effect is calculated using multiple
algorithms such as PolyPhen-2, SIFT, MutationTaster2 and LRT. Clinically significant variants are used for interpretation
and reporting.
Average sequencing Average on-target Percentage target base pairs covered
depth (x) sequencing depth (x)
0x 5x 20x
231 81.32 0.11 99.84 99.22
Total data generated (Gb) 8.67
Total reads aligned (%) 99.99
Reads that passed alignment (%) 82.81
Data Q30 (%) 97.58
$
The classification of the variants is done based on American College of Medical Genetics as described below
[PMID:25741868].
Variant A change in a gene. This could be disease causing (pathogenic) or not disease causing (benign).
A disease causing variant in a gene which can explain the patient's symptoms has been detected. This usually
Pathogenic
means that a suspected disorder for which testing had been requested has been confirmed.
A variant which is very likely to contribute to the development of disease however, the scientific evidence is
Likely
currently insufficient to prove this conclusively. Additional evidence is expected to confirm this assertion of
Pathogenic
pathogenicity.
A variant has been detected, but it is difficult to classify it as either pathogenic (disease causing) or benign
Variant of
(non-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. It is probable that their significance can be
Significance
assessed only with time, subject to availability of scientific evidence.
#
The transcript used for clinical reporting generally represents the canonical transcript (MANE Select), which is usually
the longest coding transcript with strong/multiple supporting evidence. However, clinically 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 in-silico predictions are based on Variant Effect Predictor (v104), [SIFT version - 5.2.2; PolyPhen - 2.2.2; LRT version
(November, 2009); CADD (v1.6); Splice AI; dbNSFPv4.2] and MutationTaster2 predictions are based on NCBI/Ensembl 66
build (GRCh38 genomic coordinates are converted to hg19 using UCSC LiftOver and mapped to MT2).
Diseases databases used for annotation includes ClinVar (updated on 17042023), OMIM (updated on 01092023), HGMD
(v2023.1), LOVD (Nov-18), DECIPHER (population CNV) and SwissVar.
Page 4 of 6
Name/Sample ID: Aariv Khurana [APD1.0010994483]/9256251
MedGenome Labs Ltd.
Sy. Nos. 94/1C and 94/2, Tower 1, Ground Floor, Veerasandra Village,
Attibele Hobli, Electronic City Phase-1, Electronics City, Bangalore,
Bangalore South, Karnataka, India, 560100.
Tel : 1800 296 9696, Web: [Link]
LIMITATIONS
• Genetic testing is an important part of the diagnostic process. However, genetic tests may not always give a definitive
answer. In some cases, testing may not identify a genetic variant even though one exists. This may be due to
limitations in current medical knowledge or testing technology. Accurate interpretation of test results may require
knowing the true biological relationships in a family. Failing to accurately state the biological relationships in {my/my
child's} family may result in incorrect interpretation of results, incorrect diagnoses, and/or inconclusive test results.
• Test results are interpreted in the context of clinical findings, family history and other laboratory data. Only variants
in genes potentially related to the proband's medical condition are reported. Rare polymorphisms may lead to false
negative or positive results. Misinterpretation of results may occur if the information provided is inaccurate or
incomplete.
• Specific events like copy number variants, translocations, repeat expansions and chromosomal rearrangements may
not be reliably detected with whole exome sequencing. Variants in untranslated region, promoters and intronic
variants are not assessed using this method.
• Genetic testing is highly accurate. Rarely, inaccurate results may occur for various reasons. These reasons include,
but are not limited to: mislabeled samples, inaccurate reporting of clinical/medical information, rare technical errors
or unusual circumstances such as bone marrow transplantation, blood transfusion; or the presence of change(s) in
such a small percentage of cells that may not be detectable by the test (mosaicism).
• The variant population allele frequencies and in silico predictions for GRCh38 version of the Human genome is
obtained after lifting over the coordinates from hg19 genome build. The existing population allele frequencies
(1000Genome, gnomAD-Exome) are currently available for hg19 genome version only. This might result in some
discrepancies in variant annotation due to the complex changes in some regions of the genome.
• It is assumed that the clinician ordering a genetic test is fully aware of these limitations and MedGenome shall not
be responsible in case any inappropriate panel/test methodology is selected.
DISCLAIMERS
• Interpretation of variants in this report is performed to the best knowledge of the laboratory based on the
information available at the time of reporting. The classification of variants can change over time and MedGenome
cannot be held responsible for this. Please feel free to contact MedGenome Labs (techsupport@[Link])
in the future to determine if there have been any changes in the classification of any variants. Re-analysis of variants
in previously issued reports in light of new evidence is not routinely performed but may be available upon request.
• The sensitivity of this assay to detect large deletions/duplications of more than 10 bp or copy number variants (CNV)
is 70-75%. The CNVs detected have to be confirmed by alternate method.
• Due to inherent technology limitations of the assay, not all bases of the exome can be covered by this test.
Accordingly, variants in regions of insufficient coverage may not be identified and/or interpreted. Therefore, it is
possible that pathogenic variants are present in one or more of the genes analyzed but have not been detected. The
variants not detected by the assay that was performed may impact the phenotype.
• It is also possible that a pathogenic variant is present in a gene that was not selected for analysis and/or
interpretation in cases where insufficient phenotypic information is available.
• Genes with pseudogenes, paralog genes and genes with low complexity may have decreased sensitivity and
specificity of variant detection and interpretation due to inability of the data and analysis tools to unambiguously
determine the origin of the sequence data in such regions.
• The variant(s) have not been validated/confirmed by Sanger sequencing.
• Incidental or secondary findings (if any) that meet the ACMG guidelines [PMID: 27854360] can be given upon request.
Page 5 of 6
Name/Sample ID: Aariv Khurana [APD1.0010994483]/9256251
MedGenome Labs Ltd.
Sy. Nos. 94/1C and 94/2, Tower 1, Ground Floor, Veerasandra Village,
Attibele Hobli, Electronic City Phase-1, Electronics City, Bangalore,
Bangalore South, Karnataka, India, 560100.
Tel : 1800 296 9696, Web: [Link]
• The report shall be generated within turnaround time (TAT), however, such TAT may vary depending upon the
complexity of test(s) requested. MedGenome under no circumstances will be liable for any delay beyond
aforementioned TAT.
• It is hereby clarified that the report(s) generated from the test(s) do not provide any diagnosis or opinion or
recommends any cure in any manner. MedGenome hereby recommends the patient and/or the guardians of the
patients, as the case may be, to take assistance of the clinician or a certified physician or doctor, to interpret and to
communicate the report(s) thus generated. MedGenome hereby disclaims all liability arising in connection with the
report(s).
• In a very few cases genetic test may not show the correct results, e.g. because of the quality of the material provided
to MedGenome. In case where any test provided by MedGenome fails for unforeseeable or unknown reasons that
cannot be influenced by MedGenome in advance, MedGenome shall not be responsible for the incomplete,
potentially misleading or even wrong result of any testing if such could not be recognized by MedGenome in advance.
• Variants of uncertain significance (VUS) which are mentioned in the report need to be further correlated with the
clinical phenotype, reports of other investigations, segregation analysis in the parents or affected/unaffected family
members. MedGenome shall not be responsible for the inappropriate interpretation/ communication/ clinical
actions/ reproductive decisions based on the VUS reported. The classification of VUS may change as the clinical
phenotype evolves or more information is available in the scientific literature/ annotated databases.
• This is a laboratory developed test and the development and the performance characteristics of this test was
determined by MedGenome.
END OF REPORT
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Name/Sample ID: Aariv Khurana [APD1.0010994483]/9256251
