MCFD2
Basic information
Region (hg38): 2:46901870-46941855
Links
Phenotypes
GenCC
Source:
- factor 5 and Factor VIII, combined deficiency of, 2 (Strong), mode of inheritance: AR
- factor 5 and Factor VIII, combined deficiency of, 2 (Strong), mode of inheritance: AR
- combined deficiency of factor V and factor VIII (Supportive), mode of inheritance: AR
- factor 5 and Factor VIII, combined deficiency of, 2 (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Factor V and Factor VIII, combined deficiency of, 2 | AR | Hematologic | Preventive measures and prompt treatment of bleeding diathese may reduce morbidity; Medical treatment to replace absent factors can be effective (eg, with FFP for FV, Desmopression or FVIII concentrates/recombinant products/plasma-derived factor for FVIII) | Hematologic | 12717434; 15333032; 16304051; 19141160; 18391077; 21492322; 22535353 |
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 MCFD2 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 | 4 | |||||
| missense | 12 | 13 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 70 | 41 | 120 | |||
| Total | 0 | 2 | 85 | 10 | 41 |
Variants in MCFD2
This is a list of pathogenic ClinVar variants found in the MCFD2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MCFD2 | protein_coding | protein_coding | ENST00000409105 | 3 | 39986 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.100 | 0.783 | 125737 | 0 | 10 | 125747 | 0.0000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.575 | 91 | 76.8 | 1.18 | 0.00000378 | 978 |
| Missense in Polyphen | 15 | 17.979 | 0.8343 | 275 | ||
| Synonymous | -0.519 | 36 | 32.2 | 1.12 | 0.00000188 | 267 |
| Loss of Function | 1.21 | 2 | 4.87 | 0.411 | 2.10e-7 | 64 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000246 | 0.000246 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000264 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000980 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: The MCFD2-LMAN1 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins. Plays a role in the secretion of coagulation factors. {ECO:0000269|PubMed:12717434}.;
- Disease
- DISEASE: Factor V and factor VIII combined deficiency 2 (F5F8D2) [MIM:613625]: A blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal. {ECO:0000269|PubMed:12717434, ECO:0000269|PubMed:18590741, ECO:0000269|PubMed:18685427, ECO:0000269|PubMed:20491958}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Cargo concentration in the ER;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport
(Consensus)
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- loftool
- 0.0726
- rvis_EVS
- -0.16
- rvis_percentile_EVS
- 41.25
Haploinsufficiency Scores
- pHI
- 0.175
- hipred
- Y
- hipred_score
- 0.510
- ghis
- 0.588
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mcfd2
- Phenotype
- homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- endoplasmic reticulum to Golgi vesicle-mediated transport;protein transport;COPII vesicle coating
- Cellular component
- Golgi membrane;endoplasmic reticulum membrane;ER to Golgi transport vesicle membrane;endoplasmic reticulum-Golgi intermediate compartment membrane
- Molecular function
- calcium ion binding;protein binding