percept ® is different... Australia’s most advanced and comprehensive non-invasive prenatal test

perce ® cell-free DNA pt prenatal test Why percept® percept is Australia’s most comprehensive non-invasive prenatal testing (NIPT) service. Advanced bioinformatics means percept is the only NATA/RCPA accredited Australian NIPT service to assess all 24 chromosomes, (chromosomes 1-22 and the X & Y chromosomes). This means we can identify additional genetic conditions like: • rare autosomal trisomies; • large segmental genetic imbalances like deletions and duplications. These are reported as additional findings; • maternal contributions to high risk results; • familial balanced translocation analysis; • all our tests are full supported by clinical interpretation and genetic counselling at no additional cost.

1. percept ® in numbers percept includes our fully integrated genetic counselling Frequency & clinical utility of percept Condition/s Frequency service, so patients and 1 in 74 Conventional NIPT (13, 18, 21) (based on VCGS data) health professionals are fully percept advanced NIPT Trisomy 13 1 in 436 informed and supported Trisomy 18 1 in 420 Trisomy 21 1 in 113 Additional analysis by percept Rare trisomies (other than 13, 18, 21) 1 in 280 Additional findings (dels & dups) 1 in 900

Combined frequency of additional analysis 1 in 214

Combined frequency of all 1 in 56

Additional cases detected by percept 4 in 1000

Compared to competitors micro-deletion syndromes Approximately 1 in 2,100 Micro-deletion syndrome panels (PPV 0-18%) 1-6

Therefore... Our analysis pipeline detects clinically significant genetic changes that occur more frequently and with a higher positive predictive value (PPV) than micro-deletion syndromes offered through other providers. Using a genome wide approach means genetic changes can be detected across all chromosomes and is not limited to a small number of targeted regions. The size of the genetic change detectable is dependent on a number of quality measures which includes fetal fraction and genomic location, but on average is approximately 10 mega bases in size. 2. Explained: rare autosomal trisomies & additional findings

Rare autosomal trisomies Additional findings • involve all chromosomes other than 13, 18, 21 & the • advanced bioinformatics means the entire length of every sex chromosomes; chromosome is analysed, representing an analysis similar • individually occur less frequently than 13, 18 & 21 but to a traditional karyotype; collectively are as frequent as trisomy 13 or 18; • large deletions & duplications can be associated with • up to 76% (46/60) of rare trisomies are clinically serious congenital malformations & intellectual disability; relevant to the pregnancy; • test sensitivity & genomic size of detectable imbalances • rare trisomies may be associated with miscarriages, is dependent on several factors, including fetal fraction; intra-uterine growth retardation, premature labour, • important to note that a low risk NIPT result does not compromised placental function, and as live birth exclude the presence of all deletions & duplications. with serious congenital anomalies.

Examples of additional findings from percept® Case report - Pallister-Killian syndrome

Chromosome imbalance Condition A. Chromosome 3 - partial monosomy 3p 10 Mb deletion Chromosome 4 - partial monosomy 4p Wolf-Hirschhorn syndrome Chromosome 5 - partial monosomy 5p Cri-du-chat syndrome Chromosome 9 - tetrasomy 9p Tetrasomy 9p syndrome Chromosome 10 - partial monosomy 10p 16 Mb deletion B. A: WISECONDOR plot showing Chromosome 10 - partial trisomy 10q 6 Mb duplication increased sequence counts for the Chromosome 11 - partial monosomy 11q Jacobsen syndrome p-arm of chromosome 12 (shown Chromosome 12 - tetrasomy 12p Pallister-Killian syndrome by red line & purple block). Chromosome 15 - maternal uniparental disomy Prader-Willi syndrome Chromosome 17 - partial monosomy 17p Miller-Dieker lissencephaly syndrome B: Conventional karyotyping on Chromosome 18 - tetrasomy 18p Tetrasomy 18p syndrome amniocytes confirmed this to Chromosome 22 - partial trisomy 22q 11 Mb duplication be mosaicism for tetrasomy of chromosome 12p. All confirmed by CVS or amniocentesis

3. ® Why percept is different... VCGS Specialised Test Features percept NIPT other providers Routine analysis of all 24 chromosomes  ✘ Detection of rare autosomal trisomies  ✘ Additional findings (large segmental deletions/duplications)  ✘ VCGS is a not-for-profit Translocation analysis for known carriers *  ✘ Discrimination of maternal, fetal & placental mosaicism **  ✘ specialist genetics service; Co-twin demise *  ✘# all proceeds support Triplet pregnancies *  ✘ VCGS Key Service Features medical research Quick turn around time 3-5 days 4-10 days Fully integrated laboratory and clinical service  variable Lower limit of detection 2.5% fetal fraction up to 4% fetal fraction Low test failure rate 0.02% up to 2-3% Expert genetic data interrogation & interpretation  variable Clinical support provided with all testing  variable * Prior notification required. ** This is not always definitive but may be used to direct the care of the pregnancy. # Supported by one other provider.

Test Features No. detected Conditions detected Sensitivity PPV (n=30,000) Trisomy 21 267 >99% >99% Trisomy 18 72 >98% >95% Trisomy 13 69 >98% >85% 60 Rare trisomies LD 76%* (n=16,885)7 Additional findings 18 LD 61% (segmental aneuploidies >10Mb) (n=15,600)#

Translocation analysis No. cases No. detected Sensitivity PPV 45 11 100% 100% LD = limited data * This value represents both findings confirmed in the fetus and those confined to the placenta but considered clinically relevant.7 # VCGS NATA validation study (2017). VCGS data on file.

4. References 1. M. D. Pertile, M. Halks-Miller, N. Flowers, C. Barbacioru, S. L. Kinnings, D. Vavrek, W. K. Seltzer, D. W. Bianchi, Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggest increased risk of feto-placental disease. Sci Transl Med 9, Aug 30;9(405), (2017). 2. L. Hui, Cell-free DNA testing for 22q11.2 deletion syndrome: appraising the viability, effectiveness and appropriateness of screening. Ultrasound Obstet Gynecol; 47:137-141 (2016). 3. Y. Yaron, J. Jani, M. Schmid, D. Oepkes, Current state of testing for microdeletion syndromes and rare autosomal trisomies using cell-free DNA technology. Obsetrics and Gynecology 126; 5: 1095-1099 (2015). 4. S. G. Valderramos, R. R. Rao, E. W. Scibetta, N. S. Silverman, C. S. Han, L. D. Platt, Cell-free DNA screening in clinical practice: abnormal autosomal aneuploidy and microdeletion results. Am J Obs Gyn (2016). 5. S. J. Gross, M. Stosic, D. M. McDonald-McGinn, A.S. Bassett, A. Norvez, R. Dhamankar, K. Kobara, F. Kirkizlar, B. Zimmermann, N. Wayham, J. E. Babiarz, A. Ryan, K. N. Jinnett, Z. Demko, P. Benn, Clinical experience with single-nucleotide polymorphism- ® based non-invasive prenatal screening for 22q11.2 deletion syndrome.Ultrsound Obstet Gynecol; 47:177-183 (2016). perce cell-free DNA prenatal test 6. Martin, K., Iyengar, S., Kalyan, A., Lan, C., Simon, A.L., Stosic, M., Kobara, K., Ravi, H., Truong, T., Ryan, A. and Demko, Z.P., pt 2018. Clinical experience with a single nucleotide polymorphism based non invasive prenatal test for five clinically significant microdeletions. Clinical genetics, 93(2), pp.293-300. P) 1300 11 8247 E) [email protected] 7. National Library of Medicine (US). Genetics Home Reference [Internet]. Bethesda (MD). Available from: https://ghr.nlm.nih.gov/.

5.