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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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