DYM

dymeclin, the group of Armadillo like helical domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 18:49036387-49461347

Links

ENSG00000141627 ∙ NCBI:54808 ∙ OMIM:607461 ∙ HGNC:21317 ∙ Uniprot:Q7RTS9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Dyggve-Melchior-Clausen disease (Definitive), mode of inheritance: AR
• Dyggve-Melchior-Clausen disease (Strong), mode of inheritance: AR
• Smith-McCort dysplasia 1 (Moderate), mode of inheritance: AR
• Dyggve-Melchior-Clausen disease (Supportive), mode of inheritance: AR
• Smith-McCort dysplasia (Supportive), mode of inheritance: AR
• Dyggve-Melchior-Clausen disease (Strong), mode of inheritance: AR
• Smith-McCort dysplasia 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dyggve-Melchior-Clausen disease; Smith-McCort dysplasia 1	AR	Musculoskeletal	Spinal cord compression due to atlantoaxial instability has been described, and awareness may allow screening and management to avoid potential sequelae	Musculoskeletal; Neurologic	21032395; 1008064; 401564; 679519; 2213845; 1486701; 12491225; 12554689; 16470731; 19005420; 20865280; 22090722

ClinVar

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

• not provided (12 variants)
• Dyggve-Melchior-Clausen syndrome (11 variants)
• Smith-McCort dysplasia 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYM 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			6	58	1	65
missense		1	105	3	1	110
nonsense	8	6	1			15
start loss						0
frameshift	8	2				10
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	10				12
splice region			3	12		15
non coding			12	17	37	66
Total	18	19	125	78	39

Highest pathogenic variant AF is 0.0000132

Variants in DYM

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

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

Position	Type	Phenotype	Significance	ClinVar
18-49043932-C-T		Smith-McCort dysplasia • Dyggve-Melchior-Clausen syndrome	Uncertain significance (Jun 14, 2016)
18-49044033-C-T		Smith-McCort dysplasia • Dyggve-Melchior-Clausen syndrome	Likely benign (Jun 14, 2016)
18-49044043-A-G		Smith-McCort dysplasia • Dyggve-Melchior-Clausen syndrome	Uncertain significance (Jun 14, 2016)
18-49044058-G-A		not specified	Benign/Likely benign (Dec 22, 2022)
18-49044060-C-T		Connective tissue disorder • Inborn genetic diseases	Uncertain significance (Nov 29, 2021)
18-49044061-G-A			Likely benign (Apr 26, 2023)
18-49044066-C-A		Dyggve-Melchior-Clausen syndrome • Smith-McCort dysplasia	Uncertain significance (Oct 31, 2022)
18-49044101-T-G			Likely benign (Sep 10, 2023)
18-49044108-C-T		Inborn genetic diseases	Uncertain significance (Sep 28, 2022)
18-49044115-T-C			Likely benign (Apr 14, 2023)
18-49044119-T-C			Uncertain significance (Sep 19, 2022)
18-49044122-T-C		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
18-49044122-TAGACA-T			Pathogenic (Nov 01, 2016)
18-49044139-A-G			Likely benign (Feb 22, 2022)
18-49044140-T-C		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
18-49044142-G-T			Likely benign (Jun 22, 2022)
18-49044177-C-T		Dyggve-Melchior-Clausen syndrome • Smith-McCort dysplasia	Uncertain significance (Jun 14, 2016)
18-49044186-AT-A		Dyggve-Melchior-Clausen syndrome	Pathogenic/Likely pathogenic (Oct 08, 2023)
18-49044209-A-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 31, 2023)
18-49044234-C-T			Benign (May 11, 2021)
18-49044292-C-T			Benign (May 11, 2021)
18-49044334-A-G			Benign (Nov 11, 2018)
18-49044502-C-G			Benign (Nov 10, 2018)
18-49097401-C-T		Dyggve-Melchior-Clausen syndrome	Pathogenic (Mar 17, 2024)
18-49097406-A-G		DYM-related disorder	Uncertain significance (Nov 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DYM	protein_coding	protein_coding	ENST00000269445	16	417679

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.59e-13	0.901	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.239	334	347	0.964	0.0000176	4365
Missense in Polyphen		110	130.51	0.84287		1705
Synonymous	-0.488	144	137	1.05	0.00000761	1281
Loss of Function	2.03	26	39.9	0.652	0.00000226	459

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000948	0.000948
Ashkenazi Jewish	0.00	0.00
East Asian	0.000490	0.000489
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000230	0.000229
Middle Eastern	0.000490	0.000489
South Asian	0.000262	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Necessary for correct organization of Golgi apparatus. Involved in bone development. {ECO:0000269|PubMed:21280149}.
• Disease: DISEASE: Dyggve-Melchior-Clausen syndrome (DMC) [MIM:223800]: A rare autosomal recessive disorder belonging to the group of spondyloepimetaphyseal dysplasias. DMC is characterized by progressive short stature with short trunk dwarfism, microcephaly, protruding sternum, and psychomotor retardation. Radiological features include a platyspondyly with double vertebral humps, an epiphyso-metaphyseal dysplasia and lacy pelvis iliac crests. {ECO:0000269|PubMed:12491225, ECO:0000269|PubMed:12554689, ECO:0000269|PubMed:18996921}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Smith-McCort dysplasia 1 (SMC1) [MIM:607326]: A rare autosomal recessive osteochondrodysplasia with skeletal features identical to those of Dyggve-Melchior-Clausen syndrome, but with normal intelligence and no microcephaly. It is characterized by short limbs and trunk with barrel-shaped chest. The radiographic phenotype includes platyspondyly, generalized abnormalities of the epiphyses and metaphyses, and a distinctive lacy appearance of the iliac crest. {ECO:0000269|PubMed:12491225, ECO:0000269|PubMed:18996921, ECO:0000269|PubMed:19005420}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.164

Intolerance Scores

• loftool: 0.191
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.67

Haploinsufficiency Scores

• pHI: 0.174
• hipred: N
• hipred_score: 0.267
• ghis: 0.568

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.616

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dym
• Phenotype: limbs/digits/tail phenotype; renal/urinary system phenotype; skeleton phenotype; growth/size/body region phenotype; craniofacial phenotype; cellular phenotype

Gene ontology

• Biological process: Golgi organization;bone development
• Cellular component: cytoplasm;Golgi apparatus;membrane
• Molecular function: protein binding;enzyme binding