UnitedHealthcare policy governing coverage of chromosome microarray testing (aCGH and SNP array) for non-oncology indications for members in Kentucky. Applies to ordering providers and laboratories serving Kentucky members.
Supporting Information, Clinical Evidence, and References sections were updated to reflect the most current information.
aCGH & SNPtest methods described as medically necessary
Prenatal/postnatalsettings specifically listed
ASD, DD/ID, CHDclinical indications listed as covered
Unprovencoverage stance for indications not listed
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Codes listed
example procedure/HCPCS codes provided
multiplereferences updated/added
Coverage Criteria
Medically necessary indications
Covered when ANY of the following indications apply:
Covered indications: Evaluation of an embryo/fetus; testing the products of conception following pregnancy loss; individuals undergoing invasive prenatal testing (amniocentesis, chorionic villus sampling, or fetal tissue sampling); autism spectrum disorder (ASD); multiple anomalies not specific to a Well‑Delineated Genetic Syndrome and not identifiable by clinical evaluation alone; isolated severe congenital heart disease; developmental delay/intellectual disability when a specific syndrome is not suspected; evaluation of a biological parent or sibling of a fetus or child with an abnormal or equivocal CMA result.
From Coverage Rationale (policy)
Unproven / Not medically necessary
Not medically necessary when the following applies:
Not medically necessary: Chromosome microarray testing using aCGH or SNP array is unproven and not medically necessary for populations and conditions other than those explicitly listed as covered due to insufficient evidence of efficacy.
From Coverage Rationale
Specific non‑covered situations: Use of CMA is not recommended as a first‑line test to evaluate first‑trimester pregnancy losses (per SMFM); routine CMA for individuals with ASD and their relatives solely for ASD management has insufficient evidence of clinical utility.
See SMFM Consult Series and Hayes evaluation
Clinical indications with evidence of increased diagnostic yield
Clinical contexts where CMA has demonstrated increased diagnostic yield in the provided literature:
Fetal structural anomalies: CMA shows higher diagnostic yield in fetuses with structural malformations (including congenital heart defects) compared with karyotype alone; incremental yields reported in multiple cohort and single‑center studies (example: 15.3% CMA vs 8.3% karyotype in one CHD cohort).example study yields: CMA 15.3% vs karyotype 8.3%
See Lu et al. and Ye et al. (chunks 34-35)
Fetal growth restriction (FGR/IUGR) with malformations: SNP‑based CMA identified substantially more pathogenic findings in fetuses with IUGR and structural malformations than karyotype; cohorts report higher detection when malformations are present (example: 35% abnormality detection in one series).example: 35% detection in IUGR with malformations
See Li et al. and Nguyen et al. (chunks 32-33)
Products of conception (POC) testing after pregnancy loss:
Indications supported by guidelines and evidence
Covered when any of the following guideline‑supported clinical indications are met:
Major fetal structural abnormality undergoing invasive prenatal diagnosis: Fetus with one or more major structural abnormalities identified on ultrasound who is undergoing invasive prenatal diagnostic testing — CMA is recommended and may replace karyotype.
ACOG/SMFM and ACMG practice resources (chunks 49-50, 67)
Stillbirth or intrauterine fetal death (IUFD): CMA of fetal tissue (amniotic fluid, placenta, or products of conception) is recommended in the evaluation of stillbirth/IUFD because of improved detection and higher success rates compared with karyotype.
ACOG/SMFM consensus (chunk 48-49)
Follow‑up of abnormal NIPS reporting small CNV: CMA testing should be utilized for follow‑up when small copy number changes are reported as positive on NIPS and may be performed on CVS or amniocentesis for confirmatory diagnosis or as a reflex to normal karyotype.
ACMG practice resource (chunk 47)
First-tier indications
Covered when criteria from professional societies are met; guidelines commonly state CMA is first‑tier in the following scenarios.
First‑tier indications (postnatal): CMA is recommended as a first‑line diagnostic test for individuals with developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD), multiple congenital anomalies not specific to a well‑delineated genetic syndrome, and apparently non‑syndromic DD/ID.
Prenatal and perinatal contexts where CMA is recommended:
Invasive prenatal diagnostic testing for major fetal anomalies: When invasive prenatal diagnostic testing is performed for major fetal structural abnormalities detected by ultrasound, CMA is the recommended primary test and may replace conventional karyotype.
ACOG/SMFM Practice Bulletin and Obstetric Care Consensus (chunks 49-50)
Evaluation of stillbirth/IUFD: CMA of fetal tissue or products of conception is recommended in the evaluation of stillbirth or intrauterine fetal demise when cytogenetic analysis is pursued, due to improved detection and higher test success rates compared with karyotype.
ACOG/SMFM guidance (chunk 48-49)
FGR/IUGR with malformations or late unexplained isolated FGR: Offer prenatal diagnostic testing including CMA when FGR is detected with fetal malformation or polyhydramnios; consider CMA for unexplained isolated FGR diagnosed at or after 32 weeks.
SMFM and SOGC recommendations (chunks 51-52)
Limitations / investigational situations
Situations limiting value of CMA or considered investigational:
When CMA is limited or investigational: CMA would not be considered medically necessary when a diagnosis of a disorder or syndrome is readily apparent based on clinical evaluation alone; when appropriate informed consent and genetic counseling are not obtained; or when there is inadequate knowledge about the test and follow‑up actions to address results.
AAN model coverage policy and policy rationale (chunks 65, 66, 2)
Technical limitations: CMA does not reliably detect balanced chromosomal rearrangements or certain structural variants without net copy‑number change; therefore it is not appropriate when balanced rearrangement detection is specifically required.
Policy and technical guidance (chunks 31, 47)
Chromosome microarray testing using array comparative genomic hybridization (aCGH) and/or single-nucleotide polymorphism (SNP) array is considered unproven and not medically necessary for populations and clinical indications other than those explicitly listed as covered in this policy. Coverage for indications not listed may be denied because evidence of clinical benefit is insufficient.
Chromosomal microarray analysis (CMA) detects copy number variations but may not detect balanced chromosomal rearrangements (i.e., translocations or inversions with no net gain or loss of chromosomal material). Additional testing (karyotype, FISH, or other cytogenetic methods) may be required when balanced rearrangements or uniparental disomy are suspected.
Society for Maternal-Fetal Medicine (SMFM) guidance states that the use of CMA is not recommended as a first-line test to evaluate first trimester pregnancy losses due to limited data (SMFM Consult Series GRADE 1C). When pregnancy loss evaluation is pursued, testing strategies should follow SMFM recommendations and local practice.
CMA would not be considered medically necessary when a diagnosis is readily apparent on clinical evaluation alone. In such cases, targeted testing or clinically driven management is preferred and CMA is of limited additional value.
No additional explicit exclusions are stated in the excerpted policy text. Coverage determinations must reference and comply with applicable federal, state, or contractual benefit requirements, which take precedence and may modify coverage decisions described here.
Chromosome microarray testing using aCGH or SNP array is unproven and not medically necessary for all other populations and conditions not specifically listed as covered in this policy because the available evidence does not demonstrate sufficient clinical benefit.
No explicit additional "not medically necessary" language beyond the statements already cited is present in the extracted portions of the document.
Routine use of CMA for all individuals with autism spectrum disorder (ASD) and for testing unaffected relatives lacks sufficient evidence of clinical utility to support coverage when used in isolation. Evaluations of ASD should follow guideline-directed assessment and consider CMA when clinically indicated rather than as a routine family screening test.
Ordering CMA outside the delineated, evidence-supported indications or without documented informed consent and appropriate pre- and post-test genetic counseling may render the test investigational or not medically necessary. Providers should ensure documented informed consent and counseling that addresses variants of uncertain significance, potential incidental findings (including adult-onset conditions), non-paternity, and implications for relatives before testing is performed.
Covered Indications and Supporting Evidence
List of covered indications
Covered indications (list): Prenatal evaluation of embryo/fetus; testing products of conception after pregnancy loss; invasive prenatal testing (amniocentesis, CVS, fetal tissue sampling); autism spectrum disorder (ASD); multiple anomalies not specific to a well‑delineated genetic syndrome; isolated severe congenital heart disease; developmental delay/intellectual disability without a suspected specific syndrome; evaluation of a biological parent or sibling of a fetus or child with an abnormal or equivocal CMA result.
Summarized list from Coverage Rationale (chunk 2)
Prenatal diagnosis for fetuses with structural malformations, fetal growth restriction with malformations, and POC for pregnancy loss
Higher CMA yield in prenatal structural malformations and POC: Multiple studies and a meta‑analysis indicate higher diagnostic yield of CMA versus karyotype for fetuses with structural malformations (including CHD), for fetal growth restriction with malformations, and for products of conception after pregnancy loss, supporting use of CMA in these prenatal contexts.see cited study yields (chunks 34, 36, 32)
Eligibility Requirements
Evaluation of a biological parent or sibling of a fetus or child with an abnormal or equivocal CMA result is supported and may be covered to aid interpretation and family counseling. Parental or familial testing can clarify whether a copy number variant is de novo versus inherited and inform clinical risk assessment.
Top-level eligibility requirements and detailed clinical decision nodes are not explicitly enumerated in the extracted portion; the policy emphasizes that genetic counseling is strongly recommended and that testing indications should be consistent with guideline-directed indications.
Eligibility aligns with professional practice resources such as the ACMG guidance that recommend CMA for evaluation of neurodevelopmental disability and congenital anomalies; specific plan-level eligibility details should follow the policy’s covered indications and any applicable benefit rules.
As noted elsewhere in the policy, testing of biological parents or siblings is supported when performed to resolve an abnormal or equivocal result in an affected fetus or child and to assist in interpretation and counseling.
The document provides evidence summaries (e.g., increased diagnostic yield in fetal congenital heart defects) that inform eligibility but does not list additional discrete top-level eligibility nodes in the extracted segments. Clinical judgment and guideline indications drive eligibility determinations.
Meta-analyses and systematic reviews demonstrating incremental CMA yield in fetal cardiovascular anomalies and other structural defects support eligibility for CMA in these prenatal settings when consistent with guideline recommendations.
Procedure and Diagnosis Codes
Applicable procedure/CPT/HCPCS codesmixed
0156U
Copy number intellectual disability, dysmorphology) , sequence analysis (e.g ,.
0209U
Cytogenomic constitutional (genome-wide) analysis, interrogation of genomic regions for copy number, structural changes and areas of homozygosity for chromosomal abnormalities.
81228
Cytogenomic (genome-wide) analysis for constitutional chromosomal abnormalities; interrogation of genomic regions for copy number variants, comparative genomic hybridization [CGH] microarray analysis.
81229
Cytogenomic (genome-wide) analysis for constitutional chromosomal abnormalities; interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants, comparative genomic hybridization (CGH) microarray analysis.
81349
Cytogenomic (genome-wide) analysis for constitutional chromosomal abnormalities; interrogation of genomic regions for copy number and loss-of-heterozygosity variants, loW-pass sequencing analysis.
Applicable diagnosis codes (selected list from document)ICD-10
035.19X3
Maternal care for (suspected) chromosomal abnormality in fetus, other chromosomal abnormality, fetus
035.19X4
Maternal care for (suspected) chromosomal abnormality in fetus, other chromosomal abnormality, fetus
035.19X5
Maternal care for (suspected) chromosomal abnormality in fetus, other chromosomal abnormality, fetus
035.19X9
Maternal care for (suspected) chromosomal abnormality in fetus, other chromosomal abnormality, other fetus
035.2XXO
Maternal care for (suspected) hereditary disease in fetus, not applicable or unspecified
035.2XX1
Maternal care for (suspected) hereditary disease in fetus, fetus 1
035.2XX2
Maternal care for (suspected) hereditary disease in fetus, fetus 2
035.2XX3
Maternal care for (suspected) hereditary disease in fetus, fetus 3
035.2XX4
Maternal care for (suspected) hereditary disease in fetus, fetus 4
035.2XX5
Maternal care for (suspected) hereditary disease in fetus, fetus 5
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inv-21: Estimated risk for genomic disorders/pCNVs in products of conception and newborn incidence values.
Estimated incidence in products of conception (POC)Overall incidence of genomic disorders and syndromic pathogenic CNVs (pCNVs) in POC approximately 1/150.
POC diagnostic yield — chromosomal abnormalitiesMeta-analysis diagnostic yield for chromosomal abnormalities in POC: 49.9%.
POC diagnostic yield — pCNVs (overall)Meta-analysis diagnostic yield for pCNVs in POC: 2.5%.
POC diagnostic yield — genomic disorders/syndromic pCNVs (refined)Refined diagnostic yield for genomic disorders and syndromic pCNVs in POC: 0.8% (subset of pCNVs, ~31% of pCNVs detected).
Estimated newborn incidenceNewborn incidence of genomic disorders and syndromic pCNVs estimated at 1/540 (substantially lower than POC rate).
Provider Actions and Documentation
Documentation Required
Provider Actions and Documentation
The following provider actions and documentation requirements summarize coding, authorization, counseling, sequencing, and denial risks related to chromosomal microarray (CMA) testing. Reference the member’s applicable benefit documents and federal/state/contractual requirements when determining coverage and prior authorization applicability.
Code list (reference): See the policy's Applicable Codes section for procedure and diagnosis codes (e.g., CPT 81228, 81229, 81349, 81479; HCPCS S3870; proprietary molecular codes such as 0156U, 0209U) — listing is for reference only and does not itself determine coverage or reimbursement.
Prior authorization requirements: Prior authorization may be required per the member's benefit plan and applicable federal/state/contractual rules. Use InterQual/UHC criteria where applicable; when InterQual is not applicable, UnitedHealthcare Medical Policies/Coverage Determination Guidelines and Utilization Review Guidelines may be used. Verify prior authorization requirements with the patient’s benefit documents before testing.
Denial risk for unlisted indications: Testing performed for indications not explicitly supported by the policy's coverage criteria (or by applicable benefit documents) may be denied as not medically necessary.
None explicitly stated in this excerpt: Some benefit-specific administrative requirements (e.g., exact prior-auth process or forms) are not specified here — check the member's plan for operational details.
Informed consent and counseling: CMA should not be ordered without informed consent. Consent must include discussion of the potential to identify findings of uncertain significance, non-paternity, consanguinity, and adult-onset disease.
Not Covered / Investigational
Chromosome microarray testing for indications and populations not listed in the policy is considered not covered as unproven and not medically necessary. Tests ordered for unlisted indications may be denied.
Because CMA detects copy number changes but not balanced rearrangements, CMA is not suitable for detecting balanced chromosomal rearrangements; alternate cytogenetic testing (karyotype or other methods) should be used when balanced rearrangements are suspected.
CMA is not supported as a first-line test for evaluation of first trimester pregnancy loss per SMFM, and routine CMA for individuals with ASD and their relatives lacks sufficient evidence of clinical utility to support coverage solely for ASD management without other indications.
Use of CMA when a diagnosis is clinically apparent or when informed consent and counseling are not obtained may be considered investigational or not medically necessary. Providers should document counseling and consent when ordering CMA to avoid administrative or clinical concerns.
Background
Chromosome microarray testing (array comparative genomic hybridization and SNP array) is a genome-wide method to detect copy number variants (CNVs) and regions of homozygosity. CMA analyzes multiple DNA sequences concurrently to identify deletions and duplications across the genome and is used in prenatal and postnatal diagnostic settings.
Definitions
inv-43: Definition — Developmental Delay (children <5 with delays in milestones).
DefinitionDevelopmental Delay: used to describe children younger than 5 years of age who present with delays in the attainment of developmental milestones at the expected age.
Age thresholdApplies to children younger than 5 years.
Clinical contextDescribes delays in attainment of developmental milestones compared with expected age norms.
DefinitionIntellectual Disability: a condition diagnosed before age 18 that includes below-average intellectual function and a lack of skills necessary for daily living.
Diagnostic age cutoffDiagnosis made before 18 years of age.
Supporting Literature and References
References
Supporting references: Multiple professional society guidelines, systematic reviews, meta‑analyses, and cohort studies support the use of CMA for diagnostic evaluation of developmental delay/intellectual disability, autism spectrum disorder, multiple congenital anomalies, fetal structural anomalies, fetal growth restriction, and prenatal diagnosis/fetal loss.
See References section (chunks 72-80)
Revision History
2025-07-01policy_updateLatest
Policy version CSO1ZKY.10 became effective; Supporting Information, Clinical Evidence, and References sections were updated and previous policy version CSO1ZKY.09 was archived.
References and the References list were updated as part of the policy revision; multiple professional society statements, systematic reviews, cohort studies, and technical standards are cited to support the recommendations and evidence summaries in this policy.
Note
Policy updated — verify effective date and current version
This policy has a material change effective 07/01/2025; ensure you are using the current policy version (CSO1ZKY.10) when ordering, billing, or requesting authorization.
Fetal cardiovascular anomalies: CMA is indicated for evaluation of fetal cardiovascular anomalies, particularly non‑isolated CHD and certain subtypes (e.g., septal defects, conotruncal defects) where higher rates of chromosome abnormalities are reported.
Systematic reviews and meta‑analyses report incremental yields (chunks 38, 41)
FGR with malformations or late unexplained isolated FGR: Offer prenatal diagnostic testing including CMA when FGR is detected with fetal malformation or polyhydramnios; consider CMA for unexplained isolated FGR diagnosed at or after 32 weeks.
SMFM and SOGC recommendations (chunks 32, 51, 52)
Postnatal neurodevelopmental disorders and multiple congenital anomalies: CMA is recommended as a first‑tier test in the evaluation of individuals with neurodevelopmental disability (DD/ID), autism spectrum disorder, and multiple congenital anomalies per ACMG and other professional societies.
ACMG, AAP, AACAP guidance (chunks 47, 63-67)
Pediatric congenital heart disease: Children with CHD — particularly those with additional clinical findings or syndromic features — should be evaluated with CMA given high rates of genomic disorders and CNVs detected in cohort studies.
Pediatric CHD cohort data (chunks 55, 61)
Evidence summarized from Lu et al., Peng et al., and Li et al.
Fetus with major structural abnormalities undergoing invasive prenatal diagnosis; stillbirth/IUFD evaluation; follow-up to abnormal NIPS indicating small CNV
Fetus with major structural abnormalities; stillbirth/IUFD; follow‑up to abnormal NIPS: CMA is recommended for fetuses with one or more major structural abnormalities undergoing invasive prenatal diagnosis; CMA of fetal tissue is recommended for stillbirth/IUFD evaluation; and CMA is the appropriate follow‑up for abnormal NIPS reporting small CNVs.
ACOG/SMFM and ACMG practice resources (chunks 49, 47, 36)
Fetal cardiovascular anomalies — especially non‑isolated CHD, septal defects, and conotruncal defects — have demonstrated higher incremental diagnostic yields with CMA; consider CMA when karyotype/FISH is normal.pooled incremental yield examples e.g., 5.79% overall; higher in conotruncal defects
Meta‑analyses and cohort data (chunks 41, 38, 34)
Pediatric patients with CHD or neurodevelopmental disability/congenital anomalies — CMA is first-tier and shows substantial detection
Pediatric CHD and neurodevelopmental disability/congenital anomalies: Pediatric patients with congenital heart disease or neurodevelopmental disability and congenital anomalies should have CMA as a first‑tier test per ACMG and cohort studies show substantial detection of genomic disorders and CNVs in these populations.
Landis et al., Hussein et al., and ACMG guidance (chunks 55, 61)
Prenatal evaluation for major fetal structural abnormalities and evaluation of stillbirth/fetal demise (when invasive testing is performed)
Prenatal evaluation for major fetal structural abnormalities and stillbirth: ACMG and ACOG/SMFM recommend CMA for prenatal evaluation of major fetal structural abnormalities when invasive testing is performed and for evaluation of stillbirth/fetal demise when pursued.
ACMG technical standard and ACOG/SMFM guidance (chunks 67, 49, 51)
Congenital heart disease with additional clinical findings — higher diagnostic yields and genotype-phenotype associations
Congenital heart disease with additional findings: Congenital heart disease accompanied by additional clinical findings (e.g., extracardiac anomalies, dysmorphism) is associated with higher CMA diagnostic yields and identification of genotype–phenotype associations.
Cohort and retrospective studies (chunks 55, 61, 62)
Professional society practice parameters (AAN, AACAP) outline inclusion criteria and sequencing for genetic testing; when targeted testing is indicated by clinical or family history, perform that testing first and proceed to CMA if results are unrevealing and CMA is otherwise indicated.
Tests considered investigational when there is lack of clear value: CMA is considered investigational or not medically necessary when a diagnosis is clinically apparent, when targeted/alternative testing that is indicated has not been performed, or when the clinical indications fall outside enumerated, evidence-supported populations.
Conflict with contractual/state/federal terms may trigger denial: In the event of conflict between this policy and federal, state, or contractual benefit requirements, the federal/state/contractual terms govern and may require coverage or permit denial contrary to this policy.
Genetic counseling recommendation: Pre-test (and post-test) genetic counseling is strongly recommended and is considered essential when ordering CMA.
Genetic counseling documentation: Document pretest and posttest counseling by a provider with genetics expertise in the medical record; documentation may impact coverage and administrative decisions.
When a CNV of unknown significance is identified: Parental testing and clinical genetic evaluation/counseling are recommended to help determine de novo versus inherited status and clinical significance.
Reference governing benefit documents: Benefit coverage is determined by the patient’s federal, state, or contractual benefit requirements and applicable law; always check those documents before ordering/testing.
Testing sequence: For invasive prenatal diagnostic testing in a structurally normal fetus, either fetal karyotype or CMA may be performed; selection should be documented. For prenatal testing of fetuses with structural abnormalities, CMA is recommended and may replace standard karyotype.
Guideline-based sequencing: If a recognized genetic syndrome is suspected after counseling, perform targeted testing for that syndrome first. If targeted testing is negative, proceed to CMA and broader genomic testing as appropriate.
Functional componentsIncludes impaired intellectual functioning and deficits in adaptive skills needed for daily living.
inv-45: Definition — Well-delineated genetic syndrome (recognizable traits associated with a specific disease).
DefinitionWell-delineated genetic syndrome: a collection of recognizable traits or abnormalities that tend to occur together and are associated with a specific disease (examples: Down syndrome, Turner syndrome, Williams syndrome).
RecognitionDistinguishing characteristics may include specific facial features, other physical traits, laboratory tests, or family history.
ExamplesExamples listed in policy include Down syndrome, Klinefelter syndrome, Marfan syndrome, neurofibromatosis type 1, Prader-Willi syndrome, Rett syndrome, trisomy 13, trisomy 18, Turner syndrome, Williams syndrome.
inv-46: Definition — CMA, aCGH, SNP array (CMA includes array-CGH and SNP arrays).
DefinitionCMA (chromosomal microarray analysis): a genome-wide method to detect copy number variants (CNVs) and areas of homozygosity; includes array comparative genomic hybridization (aCGH) and single-nucleotide polymorphism (SNP) array approaches.
aCGHArray comparative genomic hybridization: detects CNVs by comparing patient DNA hybridization to control DNA and identifying unequal hybridization signals.
SNP arraySingle-nucleotide polymorphism (SNP) array: detects CNVs using probes specific to single-base sites and comparison to a reference DNA sequence.
inv-47: Definition — Copy number variation (CNV) — deletions/duplications detectable by CMA.
DefinitionCopy number variation (CNV): an alteration that includes deletion and/or duplication of one or more sections of DNA that may be benign or pathogenic and can be detected by CMA.
Detection methodsCNVs are detected by aCGH (unequal hybridization) or SNP array (differences vs reference DNA).
Clinical significanceCNVs may be benign with no phenotype or pathogenic leading to a variety of phenotypic abnormalities; interpretation uses genomic databases and may require parental testing.
inv-48: Definition — pCNV (pathogenic copy number variant) — submicroscopic deletion/duplication identified by CMA.
DefinitionpCNV (pathogenic copy number variant): a submicroscopic deletion or duplication identified by CMA that is classified as pathogenic and associated with disease.
Context in POCPolicy meta-analysis reports pCNV diagnostic yield in products of conception (POC) of 2.5% overall, with a refined genomic-disorder/syndromic pCNV yield of 0.8%.
Follow-upPathogenic classification may require additional workup (parental testing, clinical correlation) per ACMG guidance.
inv-49: Definition — POC (products of conception) — tissue from miscarriage or pregnancy loss.
DefinitionPOC (products of conception): tissue from miscarriage or pregnancy loss used for cytogenetic or genomic testing to evaluate causes of pregnancy loss.
UseCMA of POC can identify chromosomal abnormalities and pCNVs and inform the probable genetic cause of pregnancy loss.
EvidenceMeta-analysis of CMA on POC reported chromosomal abnormality yield 49.9% and pCNV yield 2.5%.
inv-50: Definition — CMA (chromosomal microarray testing) including array-CGH and SNP array.
DefinitionCMA (chromosomal microarray testing): includes array-CGH and SNP array platforms used to detect copy-number variants and loss of heterozygosity in prenatal and postnatal settings.
ApplicationsUsed prenatally (requires invasive sampling for diagnostic CMA), for POC testing, and postnatally for developmental disorders, ASD, and congenital anomalies.
LimitationsCMA may not detect balanced rearrangements or UPD reliably and platform-specific limitations should be understood by ordering clinicians.
inv-51: Definition — CNV classification follow-up — parental testing and clinical genetic evaluation recommended for uncertain CNVs.
RecommendationCNV classification follow-up: when a CNV of uncertain significance is identified, parental testing and clinical genetic evaluation and counseling are recommended to determine de novo versus inherited status and clarify clinical significance.
RationaleParental testing can aid interpretation by showing inheritance pattern; ACMG practice resources recommend this approach.
Clinical stepsFollow-up may include cytogenetic/FISH confirmation, targeted testing, and detailed phenotype-genotype correlation by genetics experts.
inv-52: Definition — CMA (alternate reference) repeated in document.
DefinitionCMA (alternate reference): chromosomal microarray analysis (CMA) described in multiple ACMG technical standards and consensus statements as a first-tier diagnostic test for developmental disabilities and congenital anomalies.
StandardsACMG technical standards (2021 revision) and consensus statements outline CMA interpretation, reporting, and recommended follow-up actions.
SynonymCMA is also referred to as array-CGH and SNP array in policy literature and guidance documents.