Inheritest®500 PLUS with Repro Partners Report

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Updated on 10/29/2019
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Synonyms

  • Pan-ethnic carrier screening
  • Universal Carrier Screening

Special Instructions

This assay is not currently available in New York state.

Contact an Integrated Genetics laboratory genetic coordinator at 800-255-7357 with any questions.


Expected Turnaround Time

12 - 16 days


Related Documents

For more information, please view the literature below.

Inheritest®500 PLUS Panel Brochure

Inheritest® NGS Clinical Questionnaire


Specimen Requirements


Specimen

Whole blood


Volume

10 mL


Container

Yellow-top (ACD-A) tube (preferred) or lavender-top (EDTA) tube


Storage Instructions

Maintain at room temperature or refrigerate at 4°C.


Causes for Rejection

Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; yellow-top (ACD-B) tube


Test Details


Use

Carrier testing by analyzing 525 genes, each associated with a clinically relevant disorder, including Fragile X syndrome and spinal muscular atrophy.


Limitations

Technologies used do not detect germline mosaicism and do not rule out the presence of large chromosomal aberrations, including rearrangements, gene fusions, or variants in regions or genes not included in this test, or possible inter/intragenic interactions between variants. Variant classification and/or interpretation may change over time if more information becomes available. False positive or false negative results may occur for reasons that include: rare genetic variants, sex chromosome abnormalities, pseudogene interference, blood transfusions, bone marrow transplantation, somatic or tissue-specific mosaicism, mislabeled samples, or erroneous representation of family relationships.


Methodology

Single Nucleotide Polymorphism and Small Indel Sequencing Assessment: Genomic regions of interest are selected using a custom capture reagent for target enrichment and sequenced via the Illumina® next generation sequencing platform. Sequencing reads are aligned with the human genome reference GRCh37/hg19 build. Regions of interest include all exons and intron/exon junctions (+/-20 nucleotides) for each gene analyzed. A minimum of 99% of bases are covered at >15X. Analytical sensitivity is estimated to be >99% for single nucleotide variants, >97% for insertions/deletions less than six base pairs, and >95% for insertions/deletions between six and fifteen base pairs. Uncovered regions with known pathogenic variants are sequenced in a targeted manner. All reported variants are confirmed by a second method.

Copy Number Variant Assessment: Next Generation Sequencing is performed and the data are assessed with Illumina’s DRAGEN (Dynamic Read Analysis for GENomics) Bio-IT Platform. Reported variants are confirmed by a second method. Analytical sensitivity is estimated to be >95%.

Spinal Muscular Atrophy: This analysis will detect the copy number of exon 7 of the SMN1 gene. When no copies of SMN1 exon 7 are detected, SMN2 exon 7 copy number is assessed and reported. This test is unable to differentiate between two copies of the SMN1 gene on one allele (in cis) versus two copies of the gene on different alleles (in trans). When two copies of SMN1 exon 7 are detected, the data are assessed for the presence of the c.*3+80T>G “silent carrier” variant.

Congenital Adrenal Hyperplasia: This analysis will detect most large rearrangements/deletions/duplications within the CYP21A2 gene, as well as the presence of seven of the most common pathogenic variants in the gene: 1) c.518T>A (p.Ile173Asn), Chr6:32007203; 2) c.713T>A (p.Val238Glu); Chr6:32007587; 3) c.719T>A (p.Met240Lys); Chr6:32007593; 4) c.923dup (p.Leu308Phefs); Chr6:32007966; 5) c.293-13C/A>G; Chr6:32006858; 6) c.332_339delGAGACTAC (p.Gly111Valfs); Chr6:32006910-32006917; 7) c.-113G>A; Chr6:32006087. Other point mutations and small indels and reciprocal changes between CYP21A2 and CYP21A1P are not detected by this analysis. The analytical sensitivity of this assay is estimated to be >99%.

Alpha thalassemia: Variants included in the analysis of the alpha-globin (HBA) gene cluster are the Constant Spring non-deletion variant and the following deletions: -alpha3.7, -alpha4.2, --alpha20.5, --SEA, --FIL, --THAI, --MED, and the HS-40 regulatory region.

Fragile X Syndrome: Repeat-primed PCR is used to detect the number of CGG repeats on each allele of the FMR1 gene. The reportable range is 5-200 repeats. Alleles with expansions above 200 repeats are reported as >200. In females, excluding prenatal specimens, alleles between 55 and 90 repeats are assessed by a PCR assay to determine the number and position of AGG interruptions within the CGG repeats.

Reported Variants and Risk Revisions: Pathogenic and likely pathogenic variants are reported after confirmation by an appropriate technology. Variants in GJB2, GJB6, and OPA3 that act in a dominant fashion are not reported. NEB variants occurring in exons 82-105 may not be reliably detected by this analysis and are not reported. Nondeletion variants are specified using the numbering and nomenclature recommended by the Human Genome Variation Society. Variants of uncertain significance, likely benign, and benign variants are not reported. Variant classification is consistent with ACMG standards and guidelines. When provided, carrier rates and detection rates are derived from gnomAD and ClinVar. For unknown or mixed ethnicities, the ethnic background with the most conservative risk estimate is used. For a complete list of residual risks for all genes on this panel, visit www.integratedgenetics.com.


References

den Dunnen JT. Describing Sequence Variants Using HGVS Nomenclature. Methods Mol Biol. 2017;1492:243-251.27822869
Monaghan KG, Lyon E, Spector EB; American College of Medical Genetics and Genomics. ACMG Standards and Guidelines for fragile X testing: a revision to the disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics and Genomics. Genet Med. 2013 Jul;15(7):575-586.23765048
Richards S, Aziz N, Bale S. 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. Genet Med. 2015 May;17(5):405-424.25741868

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
630217 Inheritest(R)500PLUS w/Partner 630218 Genetic Counselor N/A
630217 Inheritest(R)500PLUS w/Partner 630219 Specimen Type Female 31208-2
630217 Inheritest(R)500PLUS w/Partner 630246 Specimen Type Male 31208-2
630217 Inheritest(R)500PLUS w/Partner 630220 Ethnicity Female 42784-9
630217 Inheritest(R)500PLUS w/Partner 630247 Ethnicity Male N/A
630217 Inheritest(R)500PLUS w/Partner 630221 Indication Female 42349-1
630217 Inheritest(R)500PLUS w/Partner 630248 Indication Male N/A
630217 Inheritest(R)500PLUS w/Partner 630222 Result 51969-4
630217 Inheritest(R)500PLUS w/Partner 630223 Summary N/A
630217 Inheritest(R)500PLUS w/Partner 630224 Addl Clinical Information 55752-0
630217 Inheritest(R)500PLUS w/Partner 630225 Comments 8251-1
630217 Inheritest(R)500PLUS w/Partner 630226 Method/Limitations 49549-9
630217 Inheritest(R)500PLUS w/Partner 630227 Information Table N/A
630217 Inheritest(R)500PLUS w/Partner 630229 Disclaimer 62364-5
630217 Inheritest(R)500PLUS w/Partner 630230 Electronically Signed By 72486-4
630217 Inheritest(R)500PLUS w/Partner 630231 Image 51969-4
630217 Inheritest(R)500PLUS w/Partner 630233 GC Review N/A
630217 Inheritest(R)500PLUS w/Partner 630234 Partner Name N/A
630217 Inheritest(R)500PLUS w/Partner 630235 Partner Spec ID N/A
630217 Inheritest(R)500PLUS w/Partner 630237 Patient Gender 76691-5
Reflex Table for Patient Gender
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 630241 NGS + Fragile X 630238 NGSBC N/A
Reflex Table for Patient Gender
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 630241 NGS + Fragile X 630240 FRAXBC N/A
Reflex Table for Patient Gender
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 630238 NGSBC 630238 NGSBC N/A

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