Cleft Lip/Cleft Palate Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10657 ABCA12 81479,81479 Order Options and Pricing
ABCA4 81408,81479
ACACB 81479,81479
ACBD5 81479,81479
ACSS2 81479,81479
ACTC1 81405,81479
ADH7 81479,81479
AHDC1 81479,81479
ALX1 81479,81479
AMELX 81479,81479
ANOS1 81406,81479
ARHGAP29 81479,81479
ARID5B 81479,81479
BMP2 81479,81479
BMP4 81479,81479
CADPS 81479,81479
CBFB 81479,81479
CDH1 81406,81479
CDH19 81479,81479
CDKN1C 81479,81479
CDON 81479,81479
CFAP57 81479,81479
CFDP1 81479,81479
CHD7 81407,81479
CHN2 81479,81479
CHRNA7 81479,81479
CLPTM1 81479,81479
CLPTM1L 81479,81479
COG5 81479,81479
COL11A1 81479,81479
COL11A2 81479,81479
COL2A1 81479,81479
COL9A1 81479,81479
COL9A2 81479,81479
COL9A3 81479,81479
COLEC11 81479,81479
CRISPLD2 81479,81479
CRYZ 81479,81479
CTNND1 81479,81479
DAB1 81479,81479
DEAF1 81479,81479
DENND4B 81479,81479
DHCR7 81405,81479
DHODH 81479,81479
DLG1 81479,81479
DLX4 81479,81479
DUSP22 81479,81479
DVL3 81479,81479
EFTUD2 81479,81479
ESCO2 81479,81479
ESRP2 81479,81479
EVC2 81479,81479
EYA1 81406,81405
FAM20C 81479,81479
FBLN1 81479,81479
FGD1 81479,81479
FGF10 81479,81479
FGF8 81479,81479
FGFR1 81405,81479
FGFR2 81479,81479
FGFR3 81479,81479
FLNA 81479,81479
FOXE1 81479,81479
FOXF2 81479,81479
FRAS1 81479,81479
FREM2 81479,81479
FZD6 81479,81479
GJA1 81479,81479
GLI2 81479,81479
GLI3 81479,81479
GPC6 81479,81479
GREM1 81479,81479
GRHL3 81479,81479
HYAL2 81479,81479
IFT88 81479,81479
IGF1R 81479,81479
INPPL1 81479,81479
IRF6 81479,81479
ISM1 81479,81479
JAG2 81479,81479
KDM6A 81479,81479
KLF4 81479,81479
KMT2D 81479,81479
LHX8 81479,81479
LRP8 81479,81479
MAFB 81479,81479
MASP1 81479,81479
MEIS2 81479,81479
MIB1 81479,81479
MN1 81479,81479
MSX1 81479,81479
MSX2 81479,81479
MYH3 81479,81479
NBAS 81479,81479
NECTIN1 81479,81479
NECTIN2 81479,81479
NEDD4L 81479,81479
NOTCH2 81479,81479
NTN1 81479,81479
NUDT6 81479,81479
PAX3 81479,81479
PAX7 81479,81479
PAX9 81479,81479
PDGFC 81479,81479
PDGFRA 81479,81479
PGM1 81479,81479
PHF8 81479,81479
PHYH 81479,81479
PIBF1 81479,81479
PIGA 81479,81479
PLEKHA5 81479,81479
PLEKHA7 81479,81479
POLR1C 81479,81479
POLR1D 81479,81479
PORCN 81479,81479
PPP1R21 81479,81479
PREPL 81479,81479
PRICKLE1 81479,81479
PTCH1 81479,81479
PTHLH 81479,81479
PTPRS 81479,81479
RIMS3 81479,81479
RIPK4 81479,81479
RPGRIP1L 81479,81479
RYK 81479,81479
RYR1 81408,81479
SATB2 81479,81479
SEMA3E 81479,81479
SF3B4 81479,81479
SHH 81479,81479
SIX3 81479,81479
SKI 81479,81479
SMAD2 81479,81479
SMAD3 81479,81479
SMC1A 81479,81479
SNAP29 81479,81479
SNTG1 81479,81479
SOX9 81479,81479
SP8 81479,81479
SPECC1L 81479,81479
SPRY2 81479,81479
SPRY4 81479,81479
SUMO1 81479,81479
TBX1 81479,81479
TBX10 81479,81479
TBX22 81479,81479
TCOF1 81479,81479
TFAP2A 81479,81479
TGDS 81479,81479
TGFB1 81479,81479
TGFB3 81479,81479
TGFBR2 81405,81479
TGIF1 81479,81479
TP63 81479,81479
TXNRD2 81479,81479
UFD1 81479,81479
UGT1A9 81479,81479
VAX1 81479,81479
WDR11 81479,81479
WDR35 81479,81479
WNT5A 81479,81479
WNT7A 81479,81479
YWHAE 81479,81479
ZBTB24 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10657Genes x (164)81479 81405, 81406, 81407, 81408, 81479 $1240 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Orofacial clefts are the most common type of congenital craniofacial anomaly identified in newborns occurring at a rate of 1-2 per 1,000 live births (IPDTOC Working Group. 2011. PubMed ID: 20507242; Mai et al. 2014. PubMed ID: 25399767). Orofacial clefts result from the failure of the facial prominences to grow or fuse appropriately during the fourth through to the twelfth week of embryogenesis (Burg et al. 2016. PubMed ID: 26973535, Deshpande and Goudy. 2019. PubMed ID: 30828634). The exact timing of the disruption determines the type of cleft (unilateral, bilateral, submucosal, microform, complete, or incomplete) and the degree of upper lip, alveolus, hard palate, soft palate, and uvula involvement (Worley et al. 2018. PubMed ID: 30396411). The common subclinical forms of orofacial clefts include cleft lip only (CLO), cleft lip and palate (CLP) and cleft palate only (CPO). Subclinical forms may present as an isolated primary anomaly (non-syndromic) or be accompanied by additional congenital anomalies or genetic syndromes (syndromic). Approximately 70% of cases with CLO or CLP are non-syndromic, whereas 50% of cases with CPO are non-syndromic (Shi et al. 2008. PubMed ID: 18383123).

Pathogenic variants in the IRF6 gene are one of the most frequent underlying causes of orofacial clefting. IRF6-related disorders span a spectrum from isolated cleft lip and palate and Van der Woude syndrome (VWS) at the mild end to popliteal pterygium syndrome (PPS) at the more severe end.

Genetics

This test includes genes identified through literature, OMIM, and HGMD searches that have a reported association with orofacial cleft phenotypes.

Orofacial clefts represent a group of clinically and genetically heterogeneous disorders that may result from a chromosomal anomaly, a single gene disorder, a complex disorder resulting from interactions involving multiple genes, or a gestational exposure to environmental risk factors (Raminov et al. 2012. PubMed ID: 21545302). Despite this heterogeneous nature, orofacial clefts display strong familial aggregation, suggesting that heredity plays a major role (Sivertsen et al. 2008. PubMed ID: 18250102, Grosen et al. 2010. PubMed ID: 19752161). Mendelian forms may be inherited in an autosomal dominant (AD), autosomal recessive (AR), and X-linked (XL) manner, or arise de novo.

Van der Woude syndrome is the most common form of orofacial cleft and is frequently associated with missense and nonsense variants in the IRF6 gene (Brito et al. 2012. PubMed ID: 23213504). Pathogenic variants in the IRF6 gene have been reported in 69% (47/68) of patients with syndromic orofacial clefts and 3% (3/95) of patients with non-syndromic familial orofacial clefts (Desmyster et al. 2010. PubMed ID: 21045959). Beyond the IRF6 gene, pathogenic variants in the GRHL3, LRP6, TBX1, and TP63 genes have been detected via whole genome sequencing in 13% (6/46) of families with non-syndromic orofacial clefts (Basha et al. 2018. PubMed ID: 29500247).

Chromosomal abnormalities have been reported in a portion of individuals with orofacial clefts. A systematic review of published studies reported 0.5% to 13% of postnatal cases with syndromic orofacial cleft could be explained by an underlying chromosomal anomaly (Maarse et al. 2012. PubMed ID: 22889852). This rate was substantially reduced for non-syndromic cases, which ranged from 1.0% to 1.8% depending on the subclinical type of orofacial cleft.

See individual gene summaries for information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Due to the genetic heterogeneity of the disorders tested in this panel, the clinical sensitivity of this specific grouping of genes is difficult to estimate. Clinical sensitivity varies depending on the subclinical type of cleft, the presentation (syndromic versus non-syndromic), and the degree of familial aggregation (Brito et al. 2012. PubMed ID: 23213504; Raminov et al. 2012. PubMed ID: 21545302; Desmyster et al. 2010. PubMed ID: 21045959). Up to 69% of familial cases of syndromic orofacial cleft and up to 3% of familial cases of non-syndromic orofacial cleft may be explained by the IRF6 gene (Desmyster et al. 2010. PubMed ID: 21045959). In addition, up to 12.5% of cases of syndromic orofacial cleft and 2% of cases of non-syndromic orofacial cleft may be explained by chromosomal abnormalities (Maarse et al. 2012. PubMed ID: 22889852).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.3% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for testing include individuals with a syndromic or non-syndromic form of orofacial cleft, or a family history consistent with a familial form of orofacial clefting.

Genes

Official Gene Symbol OMIM ID
ABCA12 607800
ABCA4 601691
ACACB 601557
ACBD5 616618
ACSS2 605832
ACTC1 102540
ADH7 600086
AHDC1 615790
ALX1 601527
AMELX 300391
ANOS1 300836
ARHGAP29 610496
ARID5B 608538
BMP2 112261
BMP4 112262
CADPS 604667
CBFB 121360
CDH1 192090
CDH19 603016
CDKN1C 600856
CDON 608707
CFAP57 614259
CFDP1 608108
CHD7 608892
CHN2 602857
CHRNA7 118511
CLPTM1 604783
CLPTM1L 612585
COG5 606821
COL11A1 120280
COL11A2 120290
COL2A1 120140
COL9A1 120210
COL9A2 120260
COL9A3 120270
COLEC11 612502
CRISPLD2 612434
CRYZ 123691
CTNND1 601045
DAB1 603448
DEAF1 602635
DENND4B 0
DHCR7 602858
DHODH 126064
DLG1 601014
DLX4 601911
DUSP22 616778
DVL3 601368
EFTUD2 603892
ESCO2 609353
ESRP2 612960
EVC2 607261
EYA1 601653
FAM20C 611061
FBLN1 135820
FGD1 300546
FGF10 602115
FGF8 600483
FGFR1 136350
FGFR2 176943
FGFR3 134934
FLNA 300017
FOXE1 602617
FOXF2 603250
FRAS1 607830
FREM2 608945
FZD6 603409
GJA1 121014
GLI2 165230
GLI3 165240
GPC6 604404
GREM1 603054
GRHL3 608317
HYAL2 603551
IFT88 600595
IGF1R 147370
INPPL1 600829
IRF6 607199
ISM1 615793
JAG2 602570
KDM6A 300128
KLF4 602253
KMT2D 602113
LHX8 604425
LRP8 602600
MAFB 608968
MASP1 600521
MEIS2 601740
MIB1 608677
MN1 156100
MSX1 142983
MSX2 123101
MYH3 160720
NBAS 608025
NECTIN1 600644
NECTIN2 600798
NEDD4L 606384
NOTCH2 600275
NTN1 601614
NUDT6 606261
PAX3 606597
PAX7 167410
PAX9 167416
PDGFC 608452
PDGFRA 173490
PGM1 171900
PHF8 300560
PHYH 602026
PIBF1 607532
PIGA 311770
PLEKHA5 607770
PLEKHA7 612686
POLR1C 610060
POLR1D 613715
PORCN 300651
PPP1R21 618159
PREPL 609557
PRICKLE1 608500
PTCH1 601309
PTHLH 168470
PTPRS 601576
RIMS3 611600
RIPK4 605706
RPGRIP1L 610937
RYK 600524
RYR1 180901
SATB2 608148
SEMA3E 608166
SF3B4 605593
SHH 600725
SIX3 603714
SKI 164780
SMAD2 601366
SMAD3 603109
SMC1A 300040
SNAP29 604202
SNTG1 608714
SOX9 608160
SP8 608306
SPECC1L 614140
SPRY2 602466
SPRY4 607984
SUMO1 601912
TBX1 602054
TBX10 604648
TBX22 300307
TCOF1 606847
TFAP2A 107580
TGDS 616146
TGFB1 190180
TGFB3 190230
TGFBR2 190182
TGIF1 602630
TP63 603273
TXNRD2 606448
UFD1 601754
UGT1A9 606434
VAX1 604294
WDR11 606417
WDR35 613602
WNT5A 164975
WNT7A 601570
YWHAE 605066
ZBTB24 614064
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
3MC syndrome 1 AR 257920
3MC syndrome 2 AR 265050
Aarskog Syndrome XL 305400
Abruzzo-Erickson syndrome XL 302905
Achondroplasia AD 100800
Acrofacial Dysostosis 1, Nager Type AD 154400
ADULT Syndrome AD 103285
Amelogenesis Imperfecta, Type Ie XL 301200
Apert Syndrome AD 101200
Arthrogryposis, Distal, Type 2B AD 601680
Arthrogryposis, distal, type 2B3 (Sheldon-Hall) AD 618436
Arthrogryposis, Distal, Type 8 AD 178110
Bamforth Syndrome AR 241850
Beckwith-Wiedemann Syndrome AD 130650
Bent bone dysplasia syndrome AD 614592
Bethlem Myopathy AD 158810
Bethlem Myopathy AD 158810
Blepharocheilodontic syndrome 1 AD 119580
Blepharocheilodontic syndrome 2 AD 617681
Brachydactyly Type A2 AD 112600
Brachydactyly, Type E2 AD 613382
Branchiooculofacial Syndrome AD 113620
Branchiootic syndrome 1 AD 602588
Branchiootorenal Syndrome 1, with or without Cataracts AD 113650
Camptodactyly, Tall Stature, And Hearing Loss Syndrome AD 610474
Camptomelic Dysplasia AD 114290
Camurati-Engelmann Disease AD 131300
Catel-Manzke Syndrome AR 616145
CHARGE Association AD 214800
Cleft Lip/Palate-Ectodermal Dysplasia Syndrome AR 225060
Cleft Palate X-Linked XL 303400
Cleft palate, cardiac defects, and mental retardation AD 600987
Congenital Disorder of Glycosylation Type It AR 614921
Conotruncal Heart Malformations 217095
Contractures, pterygia, and variable skeletal fusions syndrome 1B AR 618469
Cornelia de Lange syndrome 2 XL 300590
Cranioectodermal Dysplasia 2 AR 613610
Craniometaphyseal dysplasia, autosomal recessive AR 218400
Craniosynostosis, Type 2 AD 604757
Crouzon Syndrome AD 123500
Culler-Jones Syndrome AD 615849
Cutis Gyrata Syndrome Of Beare And Stevenson AD 123790
Digeorge Sequence AD 188400
Ectodermal Dysplasia 3, Witkop Type AD 189500
Ectrodactyly, Ectodermal Dysplasia, And Cleft Lip/Palate Syndrome 3 AD 604292
Ellis-van Creveld Syndrome AR 225500
FG Syndrome 2 XL 300321
Fibrochondrogenesis AR 228520
Fibrochondrogenesis 2 AD 614524
Focal Dermal Hypoplasia XL 305600
Fraser Syndrome AR 219000
Fraser Syndrome 2 AR 617666
Freeman-Sheldon Syndrome AD 193700
Frontometaphyseal Dysplasia XL 305620
Frontonasal Dysplasia 3 AR 613456
Glass Syndrome AD 612313
Hajdu-Cheney Syndrome AD 102500
Harlequin Ichthyosis AR 242500
Hartsfield syndrome AD 615465
Hay-Wells Syndrome AD 106260
Holoprosencephaly 11 AD 614226
Holoprosencephaly 2 AD 157170
Holoprosencephaly 3 AD 142945
Holoprosencephaly 4 AD 142946
Holoprosencephaly 7 AD 610828
Holoprosencephaly 9 AD 610829
Hypertelorism, Teebi type AD 145420
Hypogonadotropic Hypogonadism 14 with or without Anosmia AD 614858
Hypogonadotropic Hypogonadism 17 with or without Anosmia AD 615266
Hypothalamic Hamartomas AD 241800
Ichthyosis, congenital, autosomal recessive 4A AR 601277
IMAGE Syndrome AD 614732
Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2 AR 614069
Insulin-Like Growth Factor 1 Resistance To AD 270450
Kabuki Syndrome 1 AD 147920
Kabuki Syndrome 2 XL 300867
Kallmann Syndrome 1 XL 308700
Kallmann Syndrome 2 AD 147950
Kallmann Syndrome 5 AD 612370
Kallmann Syndrome 6 AD 612702
Klein-Waardenberg's Syndrome AD 148820
Lacrimoauriculodentodigital Syndrome AD 149730
Limb-Mammary Syndrome AD 603543
Loeys-Dietz Syndrome 2 AD 610168
Loeys-Dietz Syndrome 3 AD 613795
Loeys-Dietz Syndrome 5 AD 615582
Mandibulofacial dysostosis, Guion-Almeida type AD 610536
Marshall Syndrome AD 154780
Meckel Syndrome 5 AR 611561
Melnick-Needles Syndrome XL 309350
Mental Retardation, Autosomal Dominant 24 AD 615828
Microphthalmia Syndromic 6 AD 607932
Microphthalmia, syndromic 11 AR 614402
Miller Syndrome AR 263750
Minicore Myopathy With External Ophthalmoplegia AR 255320
Mirror movements 4 AD 618264
Muenke Syndrome AD 602849
Multicentric carpotarsal osteolysis syndrome AD 166300
Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 XL 300868
Myasthenic syndrome, congenital, 22 AR 616224
Oculodentodigital Dysplasia AD 164200
Oculodentodigital Dysplasia, Autosomal Recessive AR 257850
Oculomaxillofacial Dysostosis AD 600251
Omodysplasia 1 AR 258315
Opitz GBBB syndrome, type II AD 145410
Opsismodysplasia AR 258480
Orofacial Cleft 10 613705
Orofacial Cleft 11 AD 600625
Orofacial cleft 15 AD 616788
Orofacial Cleft 5 AD 608874
Orofacial Cleft 6, Susceptibility To AD 608864
Orofacial cleft 8 AD 618149
Osteoglophonic Dysplasia AD 166250
Oto-Palato-Digital Syndrome Type 1 XL 311300
Oto-Palato-Digital Syndrome, Type II XL 304120
Otofaciocervical Syndrome AD 166780
Otospondylomegaepiphyseal Dysplasia AR 215150
Pallister-Hall Syndrome AD 146510
Parietal Foramina AD 168500
Parietal Foramina With Cleidocranial Dysplasia AD 168550
Periventricular Nodular Heterotopia 7 AD 617201
Pfeiffer Syndrome AD 101600
Popliteal Pterygium Syndrome AD 119500
Popliteal pterygium syndrome 2, lethal type AR 263650
Raine Syndrome AR 259775
Rapp-Hodgkin Ectodermal Dysplasia Syndrome AD 129400
Roberts Syndrome AR 268300
Roberts-SC Phocomelia Syndrome AR 269000
Robinow Syndrome AD 180700
Robinow syndrome, autosomal dominant 3 AD 616894
Saethre-Chotzen Syndrome AD 101400
Scaphocephaly, Maxillary Retrusion, And Mental Retardation AD 609579
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies AD 617877
Short-Rib Thoracic Dysplasia 7 with or without Polydactyly AR 614091
Shprintzen-Goldberg Syndrome AD 182212
Siderius X-Linked Mental Retardation Syndrome XL 300263
Single Upper Central Incisor AD 147250
Smith-Lemli-Opitz Syndrome AR 270400
Stickler Syndrome Type 1 AD 108300
Stickler Syndrome, Type 2 AD 604841
Stickler Syndrome, Type 3 AD 184840
Stickler Syndrome, Type 4 AD 614134
Stickler Syndrome, Type 5 AR 614284
Stickler Syndrome, Type I, Nonsyndromic Ocular AD 609508
Terminal Osseous Dysplasia XL 300244
Tooth Agenesis, Selective, 1 AD 106600
Tooth Agenesis, Selective, 3 AD 604625
Treacher Collins Syndrome AD 154500
Treacher Collins Syndrome 2 AD 613717
Treacher Collins syndrome 3 AR 248390
Ulna And Fibula Absence Of With Severe Limb Deficiency AR 276820
Van Der Woude Syndrome AD 119300
Van Der Woude Syndrome 2 AD 606713
Velocardiofacial Syndrome AD 192430
Waardenburg Syndrome Type 1 AD 193500
Weyers Acrofacial Dysostosis AD 193530
Xia-Gibbs syndrome AD 615829

Related Tests

Name
PGxome®
IRF6-Related Disorders via the IRF6 Gene
Van der Woude Syndrome (VWS) via the GRHL3 Gene
X-linked Cleft Palate via the TBX22 Gene

Citations

  • Basha et al. 2018. PubMed ID: 29500247
  • Brito et al. 2012. PubMed ID: 23213504
  • Burg et al. 2016. PubMed ID: 26973535
  • Deshpande and Goudy. 2019. PubMed ID: 30828634
  • Desmyter et al. 2010. PubMed ID: 21045959
  • Grosen et al. 2010. PubMed ID: 19752161
  • IPDTOC Working Group. 2011. PubMed ID: 20507242
  • Maarse et al. 2012. PubMed ID: 22889852
  • Mai et al. 2014. PubMed ID: 25399767
  • Rahimov et al. 2012. PubMed ID: 21545302
  • Shi et al. 2008. PubMed ID: 18383123
  • Sivertsen et al. 2008. PubMed ID: 18250102
  • Worley et al. 2018. PubMed ID: 30396411

Ordering/Specimens

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