Test Catalog

Test ID: SMNCS    
Spinal Muscular Atrophy Carrier Screening, Deletion/Duplication Analysis, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

General population carrier screening for spinal muscular atrophy (SMA)


Carrier screening for reproductive partners of known SMA carriers


Carrier screening for parents of a child with a known deletion of the survival motor neuron 1 gene (SMN1) or other family history of SMA

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

SMN1 exon 7 copy number and SMN2 exon 7 copy number are determined. Also ascertains whether the g.27134T>G polymorphism is present or absent in patients found to have 2 copies of SMN1.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For tissue cultures only: If skin biopsy is received, fibroblast culture for genetic test will be added per laboratory protocol and charged separately.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by motor neuron degeneration leading to muscular atrophy with progressive paralysis. It is a genetically complex condition that is traditionally divided into 5 subtypes, depending on the age at which symptoms present and the motor milestones that are achieved. Presentation can range from in utero joint contractures and lack of fetal movement (type 0), to loss of ambulation in adolescence or adulthood (type IV). All patients with SMA develop symmetrical loss of muscle control, most commonly affecting proximal muscles. The American College of Medical Genetics (ACMG) and The American College of Obstetricians and Gynecologists (ACOG) currently recommend offering SMA carrier screening to all couples, regardless of race or ethnicity, before conception or early in pregnancy.


The most common form of SMA is associated with the loss of Survival Motor Neuron (SMN) protein, which is encoded by 2 or more genes on chromosome 5. The majority of SMN protein is expressed by the SMN1 gene but a small portion of SMN is also contributed by the SMN2 gene. In fact, SMN1 produces more than 90% of SMN protein, while SMN2 produces about less than 10% of residual SMN protein. This occurs because SMN2 differs from SMN1 by 5 nucleotide changes, 1 of which leads to alternative exon 7 splicing, and a reduction of SMN2 expression. Most individuals have 2 copies of SMN1, but individuals with as many as 5 copies of SMN1 have been observed. In addition, individuals may also have 0 to 5 copies of SMN2.


SMA is most commonly caused by a homozygous deletion of exon 7 in SMN1. However, some patients with this disorder may be compound heterozygotes, with a deletion of 1 copy of SMN1 and a point mutation in the other allele. The severity of a patient's disease is associated with the number of copies of SMN2 that are present and 3 or more SMN2 copies are associated with a milder SMA phenotype.


As the SMA test is a quantitative assay for the number of SMN1 exon 7 deletions, any result showing 2 SMN1 copies may in fact have 2 normal copies of SMN1 in cis (on the same chromosome) and a copy of SMN1 with the exon 7 deletion on the other chromosome (in trans). This is called the "2+0" carrier genotype. The frequency of the "2+0" carrier genotype differs by ancestry. Previously, it was not possible to distinguish a "2+0" carrier from an individual with 1 copy of SMN1 on each chromosome. However, following a study performed by Luo et al,(6) it is now possible to provide an adjusted genetic residual carrier risk specific to one’s ancestry, based on the presence or absence of the SMN1 polymorphism g.27134T>G. The presence of this polymorphism is linked to being a "2+0" carrier in the Ashkenazi Jewish and Asian populations and it increases the chances that one is a "2+0" carrier in other populations. Please see the table below for details.


SMA carrier residual risk estimates.(6) 


Carrier frequency

Detection rate based on copy number alone

Residual risk after detection of 2 copies of SMN1

Detection rate with addition of SMN1 g.27134T>G

Residual risk  of being a 2+0 carrier after absence of SMN1 g.27134T>G

Residual risk of being a 2+0 carrier after presence of SMN1 g.27134T>G

Ashkenazi Jewish

1 in 41.1


1 in 345


1 in 580

2+0 Carrier


1 in 53


1 in 628


1 in 701.8

2+0 Carrier

African American

1 in 66


1 in 121


1 in 395.7

1 in 33.5


1 in 117


1 in 1,061


1 in 1,762

1 in 139.6


1 in 35


1 in 632


1 in 769.3

1 in 28.6


Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Point mutations are undetectable by this assay. Nor can this assay definitively discriminate between 2 copies of survival motor neuron 1 (SMN1) on the same chromosome versus 2 copies on separate chromosomes for patients of most ancestries.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match clinical findings, additional testing should be considered.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. D'Amico A, Mercuri E, Tiziano FD, Bertini E: Spinal muscular atrophy. Orphanet J Rare Dis 2011;6:71

2. Hendrickson BC, Donohoe C, Akmaev VR, et al: Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet 2009;46:641-644

3. Carre A, Empey C: Review of Spinal Muscular Atrophy (SMA) for Prenatal and Pediatric Genetic Counselors. 2016;25:32-43

4. Committee on Genetics: Committee Opinion No. 690: Carrier Screening in the Age of Genomic Medicine. Obstet Gynecol 2017;129:e35-e40

5. Committee on Genetics: Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol March 2017;129;e41-e55

6. Luo M, Liu L, Peter I, et al: An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med 2014;16:149-156

7. Prior TW, Nagan N: Spinal muscular atrophy: overview of molecular diagnostic approaches. Curr Protoc Hum Genet 2016;1:88 unit 9.27

8. Prior TW, Nagan N, Sugarman EA, et al: Technical standards and guidelines for spinal muscular atrophy testing. Genet Med 2011;13:686-694

Special Instructions Library of PDFs including pertinent information and forms related to the test