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| Mendeliome v1.2129 | APOA4 |
Zornitza Stark gene: APOA4 was added gene: APOA4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: APOA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: APOA4 were set to 38096951 Phenotypes for gene: APOA4 were set to Hereditary amyloidosis, MONDO:0018634, APOA4-related Review for gene: APOA4 was set to GREEN Added comment: 5 families with autosomal dominant medullary amyloidosis. WGS/WES identified 2 different variants in the APOA4 gene (p.D33N in 3 families and p.L66V in 2 families). The variants were absent in gnomAD, located at the structurally flexible N-terminal domain of APOA4, and segregated with disease. There were 48 genotype +ve individuals with 44/48 having an eGFR <60. All clinically affected individuals presented with a bland urinary sediment, CKD, and no clinical evidence of systemic amyloidosis. Mean age of dialysis/transplantation was 58+/-11yrs. Routine kidney biopsies limited to the kidney cortex showed tubulointerstitial fibrosis and secondary glomerulosclerosis and no amyloid deposition. Four affected individuals were shown to have isolated medullary deposition of amyloid, with mass spectrometry showing the mutated Apoa4 as the primary constituent in 3 available cases. Plasma total ApoA4 levels were increased for patients (n=15) with ApoA4 mutations versus controls (n=49). They hypothesize that the amino acid substitutions alter the tertiary or quaternary structure of the mutated ApoA4, leading to increased plasma and primary urine concentrations and isolated medullary amyloid deposition. Sources: Literature |
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| Mendeliome v1.1381 | KDR |
Zornitza Stark edited their review of gene: KDR: Added comment: PMID 34113005: Exome sequencing in a family with two siblings affected by ToF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants. Rare variant burden analysis conducted in a set of 1,569 patients of European descent with ToF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 × 10-11). At this stage MOI unclear and insufficient evidence for either MOI.; Changed publications: 31980491, 29650961, 18931684, 34113005; Changed phenotypes: Pulmonary hypertension, Haemangioma, capillary infantile, somatic 602089, Tetralogy of Fallot, MONDO:0008542; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v1.1311 | EGF | Zornitza Stark commented on gene: EGF: LIMITED by ClinGen. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14471 | MEGF8 | Zornitza Stark Marked gene: MEGF8 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14471 | MEGF8 | Zornitza Stark Gene: megf8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14471 | MEGF8 | Zornitza Stark Phenotypes for gene: MEGF8 were changed from to Carpenter syndrome, MIM#614976 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14470 | MEGF8 | Zornitza Stark Publications for gene: MEGF8 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14469 | MEGF8 | Zornitza Stark Mode of inheritance for gene: MEGF8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14468 | MEGF8 | Zornitza Stark reviewed gene: MEGF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 23063620; Phenotypes: Carpenter syndrome, MIM#614976; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11583 | VEGFA | Zornitza Stark Marked gene: VEGFA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11583 | VEGFA | Zornitza Stark Gene: vegfa has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11583 | VEGFA | Zornitza Stark Phenotypes for gene: VEGFA were changed from to {Microvascular complications of diabetes 1} 603933 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11582 | VEGFA | Zornitza Stark Classified gene: VEGFA as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11582 | VEGFA | Zornitza Stark Gene: vegfa has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11581 | VEGFA | Zornitza Stark reviewed gene: VEGFA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Microvascular complications of diabetes 1} 603933; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6207 | EGFR | Eleanor Williams changed review comment from: PMID: 33326033 - Akhavanfard et al 2020 - identified a heterozygous germline variant in EGFR (c.3238 G>A, p.Asp1080Asn) in a 21 year old female with metastatic bilateral Adrenocortical carcinoma (ACC). Then they analyzed germline exome data from 21 children, 32 adolescents and young adults (15-39y), and 60 adult participants with ACC. 3.5% of all 113 ACC cases had at least a highly prioritized VUS germline EGFR variant, compared to only 0.3% in a non-TCGA (The Cancer Genome Atlas) ExAC control group (P < 0.0001). No segregation data.; to: PMID: 33326033 - Akhavanfard et al 2020 - identified a heterozygous germline variant in EGFR (c.3238 G>A, p.Asp1080Asn) in a 21 year old female with metastatic bilateral Adrenocortical carcinoma (ACC). Then they analyzed germline exome data from 21 children, 32 adolescents and young adults (15-39y), and 60 adult participants with ACC. 3.5% of all 113 ACC cases had at least a highly prioritized VUS germline EGFR variant, compared to only 0.3% in a non-TCGA (The Cancer Genome Atlas) ExAC control group (P < 0.0001). In the adolescents and young adults group 6.2% had ECGR variants. No segregation data. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6207 | EGFR | Eleanor Williams reviewed gene: EGFR: Rating: AMBER; Mode of pathogenicity: None; Publications: 33326033; Phenotypes: Adrenocortical carcinoma; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5781 | VEGFC | Zornitza Stark Marked gene: VEGFC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5781 | VEGFC | Zornitza Stark Gene: vegfc has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5781 | VEGFC | Zornitza Stark Phenotypes for gene: VEGFC were changed from to Lymphatic malformation 4, MIM#615907 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5780 | VEGFC | Zornitza Stark Publications for gene: VEGFC were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5779 | VEGFC | Zornitza Stark Mode of inheritance for gene: VEGFC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5778 | VEGFC | Elena Savva reviewed gene: VEGFC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23410910, 24744435, 30071673; Phenotypes: Lymphatic malformation 4, MIM#615907; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4935 | MEGF10 | Zornitza Stark Marked gene: MEGF10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4935 | MEGF10 | Zornitza Stark Gene: megf10 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4935 | MEGF10 | Zornitza Stark Phenotypes for gene: MEGF10 were changed from to Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, MIM# 614399 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4934 | MEGF10 | Zornitza Stark Publications for gene: MEGF10 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4933 | MEGF10 | Zornitza Stark Mode of inheritance for gene: MEGF10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4932 | MEGF10 | Zornitza Stark reviewed gene: MEGF10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22101682, 22371254, 30802937; Phenotypes: Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, MIM# 614399; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3325 | TBC1D2B |
Zornitza Stark gene: TBC1D2B was added gene: TBC1D2B was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBC1D2B were set to 32623794 Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality Review for gene: TBC1D2B was set to GREEN Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. All were born to non-consanguineous couples and additional investigations were performed in some. Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24. Sources: Expert Review |
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| Mendeliome v0.1042 | EGFR | Zornitza Stark Marked gene: EGFR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1042 | EGFR | Zornitza Stark Gene: egfr has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1042 | EGFR | Zornitza Stark Phenotypes for gene: EGFR were changed from to Inflammatory skin and bowel disease, neonatal, 2; OMIM # 616069 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1041 | EGFR | Zornitza Stark Publications for gene: EGFR were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1040 | EGFR | Zornitza Stark Mode of inheritance for gene: EGFR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1039 | EGFR | Zornitza Stark Classified gene: EGFR as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1039 | EGFR | Zornitza Stark Gene: egfr has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1038 | EGFR | Zornitza Stark reviewed gene: EGFR: Rating: RED; Mode of pathogenicity: None; Publications: 24691054; Phenotypes: Inflammatory skin and bowel disease, neonatal, 2, OMIM # 616069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1030 | EGF | Zornitza Stark Marked gene: EGF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1030 | EGF | Zornitza Stark Gene: egf has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1030 | EGF | Zornitza Stark Mode of inheritance for gene: EGF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1029 | EGF | Zornitza Stark Phenotypes for gene: EGF were changed from to Hypomagnesemia 4, renal, MIM#611718 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1028 | EGF | Zornitza Stark Publications for gene: EGF were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1027 | EGF | Zornitza Stark Classified gene: EGF as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1027 | EGF | Zornitza Stark Gene: egf has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1026 | EGF | Zornitza Stark reviewed gene: EGF: Rating: RED; Mode of pathogenicity: None; Publications: 17671655; Phenotypes: Hypomagnesemia 4, renal, MIM#611718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | VEGFC |
Zornitza Stark gene: VEGFC was added gene: VEGFC was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: VEGFC was set to Unknown |
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| Mendeliome v0.0 | VEGFA |
Zornitza Stark gene: VEGFA was added gene: VEGFA was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: VEGFA was set to Unknown |
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| Mendeliome v0.0 | MEGF8 |
Zornitza Stark gene: MEGF8 was added gene: MEGF8 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: MEGF8 was set to Unknown |
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| Mendeliome v0.0 | MEGF10 |
Zornitza Stark gene: MEGF10 was added gene: MEGF10 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: MEGF10 was set to Unknown |
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| Mendeliome v0.0 | EGFR |
Zornitza Stark gene: EGFR was added gene: EGFR was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: EGFR was set to Unknown |
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| Mendeliome v0.0 | EGF |
Zornitza Stark gene: EGF was added gene: EGF was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: EGF was set to Unknown |
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