SMN2
survival of motor neuron 2, centromeric, the group of Tudor domain containing|SMN complex
Basic information
Region (hg38): 5:70049638-70078522
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Spinal muscular atrophy, modifier of | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Musculoskeletal; Neurologic | 8900234; 9245983; 11791208; 16508748; 18337729; 18662980; 19716110; 19780763; 20301526 |
| Variants in SMN2 are most important in the context of individuals with SMN1 variants |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMN2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 1 | |||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 1 | 2 | 1 |
Variants in SMN2
This is a list of pathogenic ClinVar variants found in the SMN2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-70067122-A-G | not specified | Benign (-) | ||
| 5-70074624-C-T | Werdnig-Hoffmann disease | Uncertain significance (-) | ||
| 5-70076477-A-G | Werdnig-Hoffmann disease | Uncertain significance (-) | ||
| 5-70076521-G-A | not specified | Uncertain significance (Dec 19, 2022) | ||
| 5-70076526-T-C | Likely benign (Sep 01, 2024) | |||
| 5-70076545-G-C | Kugelberg-Welander disease • Spinal muscular atrophy, modifier of • Spinal muscular atrophy • not specified | Conflicting classifications of pathogenicity (Mar 12, 2024) | ||
| 5-70076555-C-G | Kugelberg-Welander disease | Likely benign (Sep 22, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SMN2 | protein_coding | protein_coding | ENST00000380743 | 8 | 29000 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.103 | 0.603 | 112942 | 9 | 12 | 112963 | 0.0000930 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.440 | 4 | 7.36 | 0.544 | 3.08e-7 | 1912 |
| Missense in Polyphen | 2 | 2.3345 | 0.85671 | 801 | ||
| Synonymous | -0.961 | 4 | 2.19 | 1.83 | 9.35e-8 | 565 |
| Loss of Function | 0.202 | 1 | 1.24 | 0.804 | 5.18e-8 | 207 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00200 | 0.00127 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000984 | 0.00000983 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000106 | 0.000106 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus. Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development. Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). {ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:23063131, ECO:0000269|PubMed:26700805, ECO:0000269|PubMed:9845364}.;
- Disease
- DISEASE: Spinal muscular atrophy 1 (SMA1) [MIM:253300]: A form of spinal muscular atrophy, a group of neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Autosomal recessive forms are classified according to the age of onset, the maximum muscular activity achieved, and survivorship. The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7- skipped transcripts and only low amount of full-length transcripts that encode for a protein identical to SMN1. Only about 4% of SMA patients bear one SMN1 copy with an intragenic mutation. SMA1 is a severe form, with onset before 6 months of age. SMA1 patients never achieve the ability to sit. {ECO:0000269|PubMed:10732817, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:15249625, ECO:0000269|PubMed:15580564, ECO:0000269|PubMed:7813012, ECO:0000269|PubMed:9147655}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy 2 (SMA2) [MIM:253550]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. It has intermediate severity, with onset between 6 and 18 months. Patients do not reach the motor milestone of standing, and survive into adulthood. {ECO:0000269|PubMed:10732802, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:9158159, ECO:0000269|PubMed:9837824}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy 3 (SMA3) [MIM:253400]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is after 18 months. Patients develop ability to stand and walk and survive into adulthood. {ECO:0000269|PubMed:10732817, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:9158159, ECO:0000269|PubMed:9837824}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy 4 (SMA4) [MIM:271150]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is in adulthood, disease progression is slow, and patients can stand and walk. {ECO:0000269|PubMed:7658877, ECO:0000269|PubMed:8551862}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- RNA transport - Homo sapiens (human);snRNP Assembly;Metabolism of RNA;Metabolism of non-coding RNA
(Consensus)
Recessive Scores
- pRec
- 0.131
Haploinsufficiency Scores
- pHI
- 0.140
- hipred
- N
- hipred_score
- 0.317
- ghis
- 0.515
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Smn1
- Phenotype
- growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);