Carrier status determination, partner risk assessment, and prenatal CNV detection in one platform. ACMG-guided, high-throughput, and built for reproductive genomics labs running NGS-based workflows.
Carrier screening and prenatal testing have undergone a fundamental shift over the past decade. Targeted Sanger sequencing for a handful of conditions has given way to expanded NGS-based carrier panels covering hundreds of autosomal recessive and X-linked conditions. Karyotyping and microarray, the historical standard for prenatal chromosomal analysis, are increasingly supplemented or replaced by whole exome and whole genome sequencing when standard testing is inconclusive.
This transition creates two parallel demands on laboratory software. On the carrier screening side, labs classify variants across large gene panels rapidly and consistently, calculate partner-pair reproductive risk, and deliver standardized reports that genetic counselors and OB/GYNs can act on. On the prenatal side, labs detect aneuploidies and sub-microscopic CNVs directly from NGS data, integrate ultrasound and phenotype data, and manage secondary findings appropriately.
VarSeq handles both workflows in the same platform, using the same annotation framework, the same ACMG classification engine, and the same reporting infrastructure. A reproductive genomics program runs its carrier and prenatal components without maintaining separate tools. For the inheritance and classification concepts underlying these workflows, see the germline analysis guide.
Expanded carrier panels and partner-pair risk calculation define the carrier screening side of a reproductive genomics program. VarSeq automates the classification bottleneck while preserving pathologist sign-out.
Expanded carrier panels now routinely cover 200 to 500+ conditions, including cystic fibrosis (CFTR), spinal muscular atrophy (SMN1), sickle cell disease and other hemoglobinopathies (HBB), Fragile X (FMR1), and a long tail of rarer autosomal recessive conditions. At panel scale, manual variant review does not stay operationally viable.
VarSeq annotates carrier panel variants against ClinVar, gnomAD population frequency databases, and integrated literature sources. VSClinical applies the ACMG five-tier classification criteria, pre-populating each variant with supporting evidence and a preliminary classification. The interpreting scientist reviews and confirms or overrides before sign-out.
The clinical value of carrier screening is realized at the partner-pair level. A single carrier of an autosomal recessive condition carries no elevated reproductive risk unless their partner is also a carrier. VarSeq compares carrier status across both partners for each condition on the panel and calculates recurrence risk for shared conditions.
A couple where both partners carry a pathogenic CFTR variant face a 25% risk per pregnancy of an affected child. The platform surfaces this directly in the combined report. The genetic counselor reviews the result rather than performing the comparison by hand.
Carrier screening reports serve a downstream audience: genetic counselors, OB/GYNs, and in some cases patients directly. Report language needs to be clinically precise but accessible, and consistent across samples and interpreters.
VarSeq supports customizable report templates with standardized classification language, condition descriptions, and inheritance pattern documentation, configurable to match institutional reporting standards.
VarSeq detects aneuploidies and sub-microscopic CNVs directly from NGS data, integrates phenotype context, and manages secondary findings, all within the same analysis session as small variant calling.
Whole-chromosome aneuploidies, including trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome), and sex chromosome aneuploidies, are among the most clinically significant prenatal findings. VarSeq detects aneuploidy directly from NGS sequencing data using z-score and coverage-based analysis, validated for whole exome and whole genome assays.
For prenatal programs where exome or genome sequencing is the primary assay, this removes the need for a separate chromosomal microarray or FISH step in most cases.
Sub-microscopic CNVs below the resolution of standard karyotyping are a significant source of prenatal pathogenic findings. The VS-CNV algorithm detects pathogenic microdeletions and microduplications from NGS data, including clinically established syndromic regions: 22q11.2 deletion syndrome (DiGeorge), 5p deletion (Cri-du-chat), and 15q11-q13 (Prader-Willi/Angelman).
Detection from NGS data provides higher resolution than microarray and integrates with the small variant analysis workflow. Review the algorithm at CNV and structural variant analysis.
Prenatal variant interpretation is rarely made from sequencing data alone. Ultrasound anomalies, family history, and clinical phenotype provide essential context for prioritizing variants in a fetal exome or genome. VarSeq integrates phenotype using the PhoRank algorithm, which scores variant candidates against HPO (Human Phenotype Ontology) terms derived from ultrasound findings and clinical observations.
A fetal exome with a cardiac anomaly on ultrasound produces a different prioritization than the same variant list without phenotype context.
Prenatal exome and genome sequencing frequently generates incidental findings: pathogenic variants in adult-onset disease genes unrelated to the indication for testing. The ACMG maintains a list of genes for which reporting of secondary findings is recommended, currently 73+ genes. VarSeq includes built-in support for secondary findings management, including opt-out documentation and standardized reporting language for adult-onset conditions identified in a prenatal context.
For a deeper treatment of ACMG classification criteria and secondary findings frameworks, see the genome interpretation guide.
One platform spans preconception screening through structurally abnormal prenatal exomes, with a shared classification and reporting framework across every workflow.
High-throughput NGS panel analysis for 200 to 500+ autosomal recessive and X-linked conditions. ACMG carrier classification, partner comparison, automated risk calculation, and standardized reporting.
Couple-based screening prior to conception, with partner-pair reproductive risk assessment and cascade testing support for identified carriers.
Fetal exome analysis for structurally abnormal pregnancies where karyotype and microarray are non-diagnostic. Phenotype-guided prioritization using ultrasound findings and HPO terms, with aneuploidy and CNV detection integrated alongside small variant analysis.
Whole genome analysis when exome is non-diagnostic or broader coverage is indicated. Same classification and reporting framework as prenatal exome, with expanded variant scope including non-coding regions.
For programs transitioning from microarray to NGS-based prenatal CNV detection, VarSeq provides validated aneuploidy and microdeletion detection from WES or WGS data with equivalent or superior sensitivity for most syndromic CNV regions.
Representative conditions and genes across carrier screening and prenatal CNV detection. VarSeq analyzes any panel or assay that produces a VCF, so the conditions below illustrate scope rather than a fixed content list.
| Category | Representative Conditions | Key Genes |
|---|---|---|
| Carrier Screening: High Priority | Cystic Fibrosis, SMA, Sickle Cell, Fragile X | CFTR, SMN1, HBB, FMR1 |
| Carrier Screening: Expanded Panel | Gaucher, Canavan, Fanconi Anemia, Bloom Syndrome | GBA, ASPA, FANCA, BLM |
| Prenatal CNV: Chromosomal | Trisomy 21, 18, 13; sex chromosome aneuploidies | Whole-chromosome coverage |
| Prenatal CNV: Microdeletion/duplication | 22q11.2, 5p, 15q11-q13, 1p36, 4p | Region-based CNV detection |
| Secondary Findings (ACMG 73+) | Adult-onset conditions incidentally detected | BRCA1/2, MLH1, MSH2, others |
Carrier screening and prenatal testing are not isolated workflows. Labs running hereditary cancer panels, rare disease exomes, and carrier screening programs frequently share infrastructure: the same sequencing platform, the same bioinformatics pipeline, and ideally the same variant interpretation software. VarSeq is built for this multi-program reality. The platform that handles ACMG classification for hereditary cancer panels also handles carrier variant classification and prenatal CNV detection, without separate tool instances or duplicate validation efforts.
For labs running rare disease exomes alongside prenatal programs, the rare disease workflow is covered at rare disease analysis software. Labs running targeted carrier and prenatal panels can compare panel-specific filtering and reporting at targeted gene panel analysis, and programs scaling to broader coverage can move to whole exome analysis or whole genome analysis within the same validated environment.
Reproductive genomics labs operate under CAP/CLIA certification with specific requirements around variant classification consistency, report standardization, and audit trail documentation. Golden Helix supports three deployment models so labs can match the data governance requirements of any clinical environment.
Full deployment within the lab's own infrastructure. Fetal sequencing data under HIPAA and institutional governance never leaves the controlled environment. Complete data sovereignty for sites with strict policies against cloud-based PHI storage.
Deployment within the lab's own AWS or Azure environment. Full administrative control, geographic data residency selection, and elastic compute scaling for variable carrier and prenatal sample volumes.
Fully offline deployment for the most sensitive environments. All software, annotation databases, and licensing operate on an isolated internal network with the full feature set intact.
Quality system. Golden Helix operates under an ISO 13485-certified Quality Management System. The deterministic VarSeq pipeline supports CLIA validation documentation, and VSWarehouse stores carrier classification history for longitudinal consistency review. VarSeq Dx is CE marked under IVDR 2017/746. Review security and compliance capabilities.
Carrier screening and prenatal testing software: how the two workflows differ, how the platform scales, and how findings are managed.
Carrier screening software identifies individuals who carry one pathogenic copy of a recessive disease gene. They are unaffected but at risk of having an affected child if their partner is also a carrier. The primary workflow is high-throughput panel analysis with partner-pair comparison and reproductive risk calculation. Prenatal testing software analyzes sequencing data from a fetal sample, typically from amniocentesis or chorionic villus sampling, to identify chromosomal abnormalities, pathogenic CNVs, or causative variants for structural anomalies observed on ultrasound.
VarSeq handles both in the same platform, which is increasingly relevant as labs run both programs on the same NGS infrastructure.
VarSeq automates the annotation and ACMG classification steps that are the bottleneck in high-throughput carrier screening. Each variant is annotated against ClinVar, gnomAD, and integrated literature databases, and VSClinical pre-populates the five-tier ACMG classification with supporting evidence.
At high panel volume, the interpreting scientist reviews auto-classifications rather than building each classification from scratch, reducing per-sample interpretation time while preserving human sign-out before report generation.
Yes. The VS-CNV algorithm detects whole-chromosome aneuploidies (trisomy 21, 18, 13, and sex chromosome aneuploidies) and sub-microscopic CNVs directly from WES or WGS data. For programs transitioning from chromosomal microarray to NGS-based prenatal analysis, aneuploidy and microdeletion results are generated within the same analysis session as small variant results: no separate assay, no separate result delivery timeline.
Labs should validate detection sensitivity for their specific assay and coverage levels as part of their CLIA validation process.
VarSeq includes built-in secondary findings management aligned with the ACMG recommendations for reporting of incidental findings. Variants in ACMG-listed genes, currently 73+ genes including BRCA1/2, Lynch syndrome genes, and cardiac channelopathy genes, are flagged separately from the primary indication analysis.
The platform supports opt-out documentation, recording when a patient has declined secondary findings reporting, and generates separate report sections for secondary findings that meet the reporting threshold. This is configurable to match institutional policy and the consent framework in place for the testing program.
Yes. VarSeq compares carrier status across both partners for each condition on the screening panel and calculates recurrence risk for shared carrier conditions. For autosomal recessive conditions where both partners carry a pathogenic variant, the 25% recurrence risk per pregnancy is calculated and surfaced in the combined report.
For X-linked conditions, carrier risk for female partners and affected risk for male offspring are handled according to the inheritance pattern of the specific condition.
VarSeq uses the PhoRank algorithm to integrate phenotype data, including ultrasound anomalies, family history, and clinical observations expressed as HPO (Human Phenotype Ontology) terms, into variant prioritization for prenatal exome and genome cases. Variants are scored against the phenotype profile, so a fetal exome with a cardiac septal defect on ultrasound prioritizes variants in genes associated with congenital heart disease higher in the interpretation queue.
This is particularly valuable in structurally abnormal pregnancies where the variant list is long and clinical phenotype is the primary guide to interpretation.
On-premises, private cloud, and air-gapped configurations are all supported. Reproductive genomics labs handling fetal sequencing data under HIPAA and institutional data governance requirements typically prefer on-premises or private cloud deployment to keep all patient data within the lab's controlled environment.
All deployment modes support the full VarSeq feature set for carrier screening and prenatal analysis. See full security and compliance details.
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Run carrier screening and prenatal CNV detection in a single validated platform, from high-throughput preconception panels to structurally abnormal prenatal exomes.