SMOC2

SPARC related modular calcium binding 2, the group of SPARC family

Basic information

Region (hg38): 6:168441150-168673445

Links

ENSG00000112562 ∙ NCBI:64094 ∙ OMIM:607223 ∙ HGNC:20323 ∙ Uniprot:Q9H3U7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dentin dysplasia type I (Strong), mode of inheritance: AR
• dentin dysplasia type I (Strong), mode of inheritance: AR
• atypical dentin dysplasia due to SMOC2 deficiency (Supportive), mode of inheritance: AR
• dentin dysplasia type I (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dentin dysplasia, type I	AR	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	Dental	22152679; 23317772

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMOC2 gene.

• not provided (56 variants)
• Inborn genetic diseases (19 variants)
• Dentin dysplasia type I (2 variants)
• Dentin dysplasia, type I, with extreme microdontia and misshapen teeth (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMOC2 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				9	7	16
missense			25	2	2	29
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region			1	3	1	5
non coding					24	24
Total	1	1	25	11	33

Variants in SMOC2

This is a list of pathogenic ClinVar variants found in the SMOC2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-168441267-C-T			Benign (Jun 19, 2021)
6-168441334-A-G			Benign (Jun 19, 2021)
6-168441383-C-T			Pathogenic (Mar 20, 2023)
6-168441422-C-G		not specified	Uncertain significance (Aug 08, 2023)
6-168441427-G-T			Likely benign (Nov 29, 2022)
6-168441430-C-G		SMOC2-related disorder	Likely benign (Jul 29, 2022)
6-168441433-T-G			Benign (Jan 29, 2024)
6-168441447-C-T		not specified	Uncertain significance (May 23, 2023)
6-168441455-G-T		Dentin dysplasia, type I, with extreme microdontia and misshapen teeth	Pathogenic (Oct 01, 2017)
6-168509763-C-G			Benign (Nov 12, 2018)
6-168509964-C-T			Uncertain significance (Dec 19, 2021)
6-168509966-G-A		not specified	Uncertain significance (Sep 17, 2021)
6-168509970-C-T		not specified	Uncertain significance (Feb 23, 2023)
6-168510017-C-T			Uncertain significance (Apr 25, 2022)
6-168510033-G-A		not specified	Uncertain significance (Jan 22, 2024)
6-168510063-T-C		not specified	Uncertain significance (Dec 03, 2021)
6-168510072-G-A		not specified	Uncertain significance (Apr 17, 2023)
6-168510073-A-G			Likely benign (Oct 04, 2023)
6-168510340-T-A			Benign (Nov 12, 2018)
6-168526105-G-A			Benign (Nov 12, 2018)
6-168526358-G-A			Uncertain significance (May 31, 2017)
6-168526374-G-A			Benign (Mar 01, 2023)
6-168526391-C-T		not specified	Uncertain significance (Sep 22, 2023)
6-168526393-C-T		not specified	Uncertain significance (Apr 03, 2023)
6-168526417-A-T		not specified	Uncertain significance (Apr 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMOC2	protein_coding	protein_coding	ENST00000354536	13	232154

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00253	0.997	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.642	254	284	0.893	0.0000186	2956
Missense in Polyphen		72	97.044	0.74193		900
Synonymous	0.0349	122	122	0.996	0.00000912	859
Loss of Function	3.00	9	25.3	0.356	0.00000107	318

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000182	0.000181
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.00	0.00
South Asian	0.0000983	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes matrix assembly and cell adhesiveness (By similarity). Can stimulate endothelial cell proliferation, migration, as well as angiogenesis. {ECO:0000250, ECO:0000269|PubMed:16774925}.
• Disease: DISEASE: Dentin dysplasia 1 (DTDP1) [MIM:125400]: A dental defect in which both primary and secondary dentitions are affected. The clinical crowns of both permanent and deciduous teeth are of normal shape, form and color in most cases, although they may be slightly opalescent and blue or brown. Teeth may be very mobile and exfoliate spontaneously because of inadequate root formation. On radiographs, the roots are short and may be more pointed than normal. Pulp chambers are usually absent except for a chevron- shaped remnant in the crown. Root canals are usually absent. {ECO:0000269|PubMed:22152679}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gastric Cancer Network 1 (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.696
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.82

Haploinsufficiency Scores

• pHI: 0.0972
• hipred: Y
• hipred_score: 0.604
• ghis: 0.520

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.793

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Smoc2
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; digestive/alimentary phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: smoc2
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: positive regulation of endothelial cell migration;positive regulation of cell-substrate adhesion;extracellular matrix organization;positive regulation of vascular wound healing;positive regulation of fibroblast growth factor receptor signaling pathway;positive regulation of angiogenesis;positive regulation of mitotic cell cycle;positive regulation of vascular endothelial growth factor signaling pathway;positive regulation of DNA biosynthetic process;positive regulation of endothelial cell chemotaxis
• Cellular component: basement membrane;interstitial matrix;extracellular space;cell periphery
• Molecular function: calcium ion binding;heparin binding