WAC
Basic information
Region (hg38): 10:28532493-28623112
Links
Phenotypes
GenCC
Source:
- DeSanto-Shinawi syndrome due to WAC point mutation (Strong), mode of inheritance: AD
- DeSanto-Shinawi syndrome due to WAC point mutation (Strong), mode of inheritance: AD
- DeSanto-Shinawi syndrome due to WAC point mutation (Supportive), mode of inheritance: AD
- DeSanto-Shinawi syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
DeSanto-Shinawi syndrome | 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 | Craniofacial; Gastrointestinal; Neurologic; Ophthalmologic | 25356899; 26264232 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (43 variants)
- DeSanto-Shinawi syndrome due to WAC point mutation (28 variants)
- Inborn genetic diseases (3 variants)
- DeSanto-Shinawi syndrome (2 variants)
- See cases (2 variants)
- Rare genetic intellectual disability (1 variants)
- WAC-related disorder (1 variants)
- Neurodevelopmental disorder (1 variants)
- Neurodevelopmental delay (1 variants)
- WAC-related neurodevelopmental disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the WAC 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 | 11 | |||||
missense | 77 | 17 | 100 | |||
nonsense | 22 | 30 | ||||
start loss | 0 | |||||
frameshift | 41 | 49 | ||||
inframe indel | 4 | |||||
splice donor/acceptor (+/-2bp) | 12 | |||||
splice region | 3 | 5 | 8 | |||
non coding | 28 | 33 | 68 | |||
Total | 69 | 20 | 91 | 51 | 43 |
Variants in WAC
This is a list of pathogenic ClinVar variants found in the WAC region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
10-28533444-A-C | Benign (Jul 03, 2018) | |||
10-28533531-C-G | Likely benign (Aug 03, 2020) | |||
10-28533561-A-G | Benign (Aug 30, 2020) | |||
10-28533574-G-T | Uncertain significance (Oct 12, 2022) | |||
10-28533577-T-C | DeSanto-Shinawi syndrome due to WAC point mutation;DeSanto-Shinawi syndrome | Uncertain significance (May 20, 2019) | ||
10-28533587-T-C | Uncertain significance (Jan 30, 2024) | |||
10-28533593-C-G | Uncertain significance (Dec 20, 2024) | |||
10-28533604-C-T | Pathogenic (Dec 12, 2018) | |||
10-28533604-CAG-C | DeSanto-Shinawi syndrome due to WAC point mutation | Pathogenic (Jul 08, 2021) | ||
10-28533610-C-T | DeSanto-Shinawi syndrome due to WAC point mutation | Uncertain significance (Jul 06, 2018) | ||
10-28533630-C-T | Likely benign (Aug 23, 2018) | |||
10-28533658-G-T | Benign (Jul 10, 2020) | |||
10-28533659-G-GGGC | Likely benign (Sep 23, 2020) | |||
10-28533659-G-GGGCGGC | Likely benign (Mar 19, 2020) | |||
10-28533812-C-T | Likely benign (Aug 10, 2018) | |||
10-28533924-G-A | Likely benign (Aug 10, 2018) | |||
10-28534011-AG-A | Pathogenic (Aug 09, 2024) | |||
10-28534011-A-AG | Uncertain significance (Jul 23, 2021) | |||
10-28534015-G-A | Inborn genetic diseases | Uncertain significance (Dec 14, 2023) | ||
10-28534022-G-T | WAC-related disorder | Likely benign (Sep 05, 2019) | ||
10-28534023-C-T | DeSanto-Shinawi syndrome due to WAC point mutation | Likely pathogenic (Jul 13, 2021) | ||
10-28534030-A-G | Inborn genetic diseases | Uncertain significance (Apr 12, 2023) | ||
10-28534035-G-A | DeSanto-Shinawi syndrome;DeSanto-Shinawi syndrome due to WAC point mutation | not provided (-) | ||
10-28534042-C-T | not specified | Uncertain significance (Oct 08, 2024) | ||
10-28534053-G-T | Benign (Jun 03, 2020) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
WAC | protein_coding | protein_coding | ENST00000354911 | 14 | 90620 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.00 | 0.00000294 | 124747 | 0 | 4 | 124751 | 0.0000160 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.51 | 262 | 341 | 0.769 | 0.0000171 | 4199 |
Missense in Polyphen | 78 | 125.17 | 0.62317 | 1639 | ||
Synonymous | -0.416 | 133 | 127 | 1.05 | 0.00000714 | 1270 |
Loss of Function | 5.53 | 0 | 35.6 | 0.00 | 0.00000196 | 405 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00 | 0.00 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.000112 | 0.000110 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.0000183 | 0.0000177 |
Middle Eastern | 0.000112 | 0.000110 |
South Asian | 0.00 | 0.00 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Acts as a linker between gene transcription and histone H2B monoubiquitination at 'Lys-120' (H2BK120ub1) (PubMed:21329877). Interacts with the RNA polymerase II transcriptional machinery via its WW domain and with RNF20-RNF40 via its coiled coil region, thereby linking and regulating H2BK120ub1 and gene transcription (PubMed:21329877). Regulates the cell-cycle checkpoint activation in response to DNA damage (PubMed:21329877). Positive regulator of amino acid starvation- induced autophagy (PubMed:22354037). Also acts as a negative regulator of basal autophagy (PubMed:26812014). Positively regulates MTOR activity by promoting, in an energy-dependent manner, the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex. This leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). May negatively regulate the ubiquitin proteasome pathway (PubMed:21329877). {ECO:0000269|PubMed:21329877, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:26812014}.;
- Disease
- DISEASE: DeSanto-Shinawi syndrome (DESSH) [MIM:616708]: An autosomal dominant syndrome characterized by developmental delay, hypotonia, behavioral problems, eye abnormalities, constipation, feeding difficulties, seizures and sleep problems. Patients exhibit dysmorphic features, including broad/prominent forehead, synophrys and/or bushy eyebrows, depressed nasal bridge and bulbous nasal tip. Additional variable features are posteriorly rotated ears, hirsutism, deep-set eyes, thin upper lip, inverted nipples, hearing loss and branchial cleft anomalies. {ECO:0000269|PubMed:25356899, ECO:0000269|PubMed:26264232}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in WAC are the cause of a form of intellectual disability characterized by hypotonia, behavioral problems and distinctive facial dysmorphisms including a square- shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. {ECO:0000269|PubMed:26757981}.;
- Pathway
- Post-translational protein modification;Metabolism of proteins;Protein ubiquitination;E3 ubiquitin ligases ubiquitinate target proteins
(Consensus)
Recessive Scores
- pRec
- 0.125
Intolerance Scores
- loftool
- 0.325
- rvis_EVS
- -0.87
- rvis_percentile_EVS
- 10.73
Haploinsufficiency Scores
- pHI
- 0.238
- hipred
- Y
- hipred_score
- 0.673
- ghis
- 0.659
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.466
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Wac
- Phenotype
Gene ontology
- Biological process
- cellular response to DNA damage stimulus;histone monoubiquitination;positive regulation of macroautophagy;protein ubiquitination;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;G1 DNA damage checkpoint;positive regulation of transcription, DNA-templated;histone H2B conserved C-terminal lysine ubiquitination
- Cellular component
- nucleus;nucleoplasm;spliceosomal complex;nuclear speck
- Molecular function
- RNA polymerase II complex binding;chromatin binding;protein binding