Description

Carrier screening comprehensive panel analyses 228 genes associated with genetic diseases that have moderate to severe well-defined phenotype and high cumulative frequency in individuals with unknown carrier status.

Genes tested

ABCD1, ACAD9, ACADM, ACOX1, ACSF3, ADAMTS2, AGA, AGL, AGPS, AGXT, AIRE, ALDH3A2, ALDOB, ALG6, ALMS1, ALPL, AMT, AQP2, ARSA, ASL, ASNS, ASPA, ASS1, ATM, ATP6V1B1, ATP7B, BBS1, BBS12, BCKDHB, BCS1L, BLM, BSND, BTD, CAPN3, CBS, CEP290, CERKL, CFTR, CHM, CHRNE, CIITA, CLN3, CLN5, CLN6, CLN8, CLRN1, CNGB3, COL4A3, COL4A5, COL7A1, CPT1A, CPT2, CRB1, CTNS, CTSK, CYBB, CYP11B2, CYP19A1, CYP27A1, DCLRE1C, DHCR7, DHDDS, DLD, DMD, DNAH5, DNAI1, DNAI2, DYSF, EDA, EIF2B5, EMD, ESCO2, ETFA, ETHE1, EYS, F11, F5, F9, FAH, FAM161A, FANCC, FANCG, G6PC, GAA, GALC, GALK1, GALT, GBA, GBE1, GCDH, GFM1, GJB2, GJB6, GLA, GLDC, GNE, GNPTAB, GNPTG, GNS, GRHPR, HADHA, HAX1, HBA1, HBA2, HBB, HEXA, HEXB, HJV, HGSNAT, HLCS, HMGCL, HOGA1, HPS1, HPS3, HSD17B4, HYAL1, HYLS1, IDS, ELP1, IL2RG, IVD, LAMC2, LCA5, LDLR, LHCGR, LHX3, LIFR, LIPA, LOXHD1, LPL, LRPPRC, MCCC1, MCCC2, MCOLN1, MEFV, MFSD8, MKS1, MLC1, MMAA, MMAB, MMACHC, MMADHC, MPI, MPV17, MTM1, MTRR, MTTP, MMUT, NAGLU, NAGS, NBN, NDUFAF5, NDUFS6, NPC1, NPC2, NPHS1, NPHS2, NR2E3, NTRK1, OAT, OPA3, OTC, PAH, PCDH15, PDHA1, PDHB, PEX1, PEX10, PEX2, PEX6, PEX7, PFKM, PHGDH, PKHD1, PMM2, PPT1, PROP1, PSAP, PTS, PUS1, PYGM, RAB23, RAG2, RAPSN, RARS2, RLBP1, RMRP, RPGR, RS1, SACS, SAMHD1, SEPSECS, SGCA, SGCB, SGCG, SLC12A6, SLC17A5, SLC25A13, SLC25A15, SLC26A2, SLC26A4, SLC35A3, SLC37A4, SLC4A11, SLC6A8, SLC7A7, SMARCAL1, SMPD1, STAR, SUMF1, TFR2, TGM1, TH, TMEM216, TPP1, TRMU, TSFM, TTPA, TYMP, UGT1A1, USH1C, USH2A, VPS13A, VPS45, VPS53, VRK1, VSX2, WNT10A

Technical specifications

• DMD: Deletion/Duplication analysis at single exon resolution is not offered for NM_004006.3 (DMD): exon 2, exon 15, exon 22, exon 23, exon 26, exon 27, exon 28, exon 32, exon 33, exon 34, exon 36, exon 38, exon 39, exon 40, exon 41, exon 42, exon 46, exon 54, exon 56, exon 58, exon 67, exon 68, exon 69, exon 71, exon 72, exon 73, exon 77, exon 78, exon 79.
• HBA1/2: the assay is designed to detect deletions and duplications of HBA1 and HBA2. All positive Copy Number Variations (CNVs) are confirmed using an orthogonal method. The test does not distinguish among the different HBA types of deletions/duplications, and any variant identified will be called as HBA loss/gain.

• Genomic regions not covered by this test:
  • NM_000383.4 (AIRE): exon 1
  • NM_000414.4 (HSD17B4): exon 5
  • NM_001352514.2 (HLCS): exon 1
  • NM_013339.4 (ALG6): exon 13
  • NM_014244.5 (ADAMTS2): exon 1
  • NM_025114.4 (CEP290): exons 5 and 23
  • NM_000233.4 (LHCGR): exon 1
  • NM_001384140.1 (PCDH15): exons 33, 34 and 35
  • NM_153818.2/NM_002617.4 (PEX10): exon 1
  • NM_032520.5 (GNPTG): exon 1
  • NM_000521.4 (HEXB): exon 4
  • NM_000232.5 (SGCB): exon 1
  • NM_020533.3 (MCOLN1): exon 1
  • NM_152419.3 (HGSNAT): exon 1

Technical limitations

The test aims to detect all variants relevant to the genes listed above by targeting all coding exons, of MANE or/and Canonical transcripts, and 12 bp of adjacent intronic sequence. Variants that fall outside of the targeted regions are not intended to be detected by this assay. Unless otherwise noted, sequence changes (SNVs and INDELS) in the promoter and other non-coding regions are not covered by this assay. Certain sequence changes (SNVs and INDELS) in non-coding regions of selected genes that are of clinical significance are also included in the analysis. In cases where two variants are identified in a gene, the test does not distinguish whether these are on one chromosome (in cis) or on different chromosomes (in trans). Certain types of genetic abnormalities such as inversions, rearrangements, polyploidy and epigenetic effects are not covered by this test. Certain sequence changes (SNVs and INDELS) in targeted regions containing repeats, sequences of high homology such as segmental duplications and pseudogenes, as well as regions of high/low GC-content may not be detected. Copy Number Variations (CNVs) are calculated using high quality, de-duplicated and uniquely aligned sequencing reads. CNVs are detected for a subset of the targeted regions using a depth of sequencing coverage approach by applying GC-content normalization. Genomic regions are called as variants if their normalised depth of coverage deviates significantly from the expected normalized coverage which is estimated from a set of reference clinical samples. The test can detect CNVs down to a few exons level resolution. The test cannot detect CNVs at genomic regions with either low mappability or containing repeats, pseudogenes and high/low GC-content. Detection of CNVs using NGS has lower sensitivity/specificity than orthogonal quantification methods, therefore the absence of reported CNVs does not guarantee the absence of CNVs. The lack of disease-causing variants in the targeted genes diminishes but does not exclude the possibility of a disease associated syndrome. Although the test is highly accurate there is still a possibility for false positive or false negative results.