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| Mendeliome v1.2271 | DMRT1 |
Zornitza Stark edited their review of gene: DMRT1: Added comment: DMRT1 gene exclusively expressed in male gonads. Thought not to affect ovarian development. Gene included three international studies - see PMID: 28295047 supplemental article Fig 1 patient 19, 46XY with hypoplastic labia, uterus present had DMRT1 c.251A>G p.Tyr84Cys maternally inherited VOUS PMID: 26005864: p.R111G also described in complete gonadal dysgenesis; Changed rating: AMBER; Changed publications: 31479588, 24934491, 29527098, 26005864, 28295047; Changed phenotypes: 46,XY disorder of sex development, MONDO:0020040 |
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| Mendeliome v1.1816 | ATXN7L3 |
Chirag Patel gene: ATXN7L3 was added gene: ATXN7L3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATXN7L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATXN7L3 were set to PMID: 38753057 Phenotypes for gene: ATXN7L3 were set to Neurodevelopmental disorder, MONDO_0100500 Review for gene: ATXN7L3 was set to GREEN gene: ATXN7L3 was marked as current diagnostic Added comment: This study reports 9 unrelated individuals with de novo heterozygous variants in ATXN7L3 identified through WES testing and GeneMatcher. Core clinical features included: global motor and language developmental delay, hypotonia, and dysmorphic features (hypertelorism, epicanthal folds, blepharoptosis, small nose, small mouth, and low-set posteriorly rotated ears). Variable features included: feeding difficulties, seizures, mild periventricular leukomalacia, and structural cardiac abnormalities. A recurrent nonsense variant [p.(Arg114Ter)] was found in 5/9 individuals. The other variants were 1 frameshift [p.(Ser112LysfsTer12)] and 3 missense variants [p.(Ile71Thr), p.(Ser92Arg), and p.(Leu106Pro)]. They investigated the effects of the recurrent nonsense variant [p.(Arg114Ter)] in fibroblasts of an affected individual. ATXN7L3 protein levels were reduced, and deubiquitylation was impaired (as indicated by an increase in histone H2Bub1 levels). This is consistent with the previous observation of increased H2Bub1 levels in Atxn7l3-null mouse embryos, which have developmental delay and embryonic lethality. Pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders (ND) and congenital abnormalities. ATXN7L3 is a component of the DUB module of the SAGA complex, and two other related DUB modules, and serves as an obligate adaptor protein of 3 ubiquitin-specific proteases (USP22, USP27X or USP51). Sources: Literature |
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| Mendeliome v1.1774 | ADAMTS18 | Zornitza Stark Marked gene: ADAMTS18 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1774 | ADAMTS18 | Zornitza Stark Gene: adamts18 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1774 | ADAMTS18 | Zornitza Stark Classified gene: ADAMTS18 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1774 | ADAMTS18 | Zornitza Stark Gene: adamts18 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1770 | ADAMTS18 |
Sangavi Sivagnanasundram gene: ADAMTS18 was added gene: ADAMTS18 was added to Mendeliome. Sources: Other Mode of inheritance for gene: ADAMTS18 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS18 were set to https://search.clinicalgenome.org/CCID:004057 Phenotypes for gene: ADAMTS18 were set to microcornea-myopic chorioretinal atrophy (MONDO:0014195) Review for gene: ADAMTS18 was set to GREEN Added comment: Classified DEFINITIVE by ClinGen Retina GCEP on 02/03/20222 - https://search.clinicalgenome.org/CCID:004057 Sources: Other |
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| Mendeliome v1.1401 | SEL1L |
Sarah Pantaleo gene: SEL1L was added gene: SEL1L was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SEL1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEL1L were set to PMID: 37943610; PMID: 37943617 Phenotypes for gene: SEL1L were set to Neurodevelopmental disorder, MONDO:0700092, SEL1L-related Penetrance for gene: SEL1L were set to Complete Added comment: Wang paper PMID: 37943610 SEL1L protein is involved in the SEL1L-HRD1 endoplasmic reticulum (ER)-associated degradation. Report two biallelic missense variants in SEL1L in six children from three independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia and/or ataxia (termed ERAD-associated neurodevelopment disorder with onset in infancy (ENDI). The variants were hypomorphic and impaired ERAD function. Identified by WES. Parents heterozygous and asymptomatic. P.(Gly585Asp) in Patient 1, p.(Met528Arg) in Patients 2 and 3 (siblings). All variants cause substrate accumulation. The extent of substrate accumulation in knockin cells was modest compared to those in knockout cells, pointing to a hypomorphic nature. They also had a variant in HRD1. Weis paper PMID: 37943617 Third variant p.(Cys141Tyr), biallelic, causing premature death in five patients from a consanguineous family with early-onset neurodevelopmental disorders and agammaglobulinaemia due to severe SEL1L-HRD1 ERAD dysfunction. This variant appears to have a more severe outcome, exhibiting B cell depletion and agammaglobulinaemia, causing the most severe dysfunction among all of the variants described by this group so far. They postulate that functionality of SEL1L-HRD1 ERAD is inversely correlated with disease severity in humans. Their symptoms were dev delay, neurological disorder and agammaglobulinaemia in childhood. Along with severe axial hypotonia, short stature and microcephaly. “Not a complete loss-of-function variant”. Sources: Literature |
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| Mendeliome v1.1313 | ADAMTS15 | Zornitza Stark Phenotypes for gene: ADAMTS15 were changed from Arthrogryposis (MONDO:0008779), ADMATS15-related to Arthrogryposis, distal, type 12, MIM# 620545 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1312 | ADAMTS15 | Zornitza Stark reviewed gene: ADAMTS15: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, distal, type 12, MIM# 620545; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1156 | APOO |
Zornitza Stark edited their review of gene: APOO: Added comment: PMID: 37649161 1 family, 2 individuals (male & female) with same NMD variant c.532G>T (p.E178*), maternally inherited (mother unaffected). Both died before 18 months of age with partial agenesis of the corpus callosum, bilateral congenital cataract, hypothyroidism, and severe immune deficiencies. Other phenotypes included partial syndactyly of the 2nd and 3rd toes, wrinkled palm, and sole skin. Functional studies included site directed mutagenesis. This mutation resulted in a highly unstable and degradation prone MIC26 protein, yet the remaining minute amounts of mutant MIC26 correctly localized to mitochondria and interacted physically with other MICOS subunits. MIC26 KO cells expressing MIC26 harboring the respective APOO/MIC26 mutation showed mitochondria with perturbed cristae architecture and fragmented morphology resembling MIC26 KO cells.; Changed publications: 37649161; Changed phenotypes: Mitochondrial disease, MONDO:0044970, APOO-related, Developmental delay, Lactic acidosis, Muscle weakness, Hypotonia, Repetitive infections, Cognitive impairment, Autistic behaviour |
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| Mendeliome v1.1071 | AQP4 |
Lucy Spencer gene: AQP4 was added gene: AQP4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AQP4 were set to 37143309 Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 Review for gene: AQP4 was set to AMBER Added comment: PMID: 37143309 Cohort of patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit. Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression. Sources: Literature |
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| Mendeliome v1.1001 | DCAF15 |
Chirag Patel gene: DCAF15 was added gene: DCAF15 was added to Mendeliome. Sources: Other Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome Review for gene: DCAF15 was set to AMBER Added comment: ESHG 2023: 3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child) Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment. WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3). Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli. Sources: Other |
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| Mendeliome v1.965 | SART3 |
Daniel Flanagan gene: SART3 was added gene: SART3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SART3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SART3 were set to PMID: 37296101 Phenotypes for gene: SART3 were set to Neurodevelopmental disorder (MONDO#0700092), SART3-related; 46,XY disorder of sex development (MONDO:0020040), SART3-related Review for gene: SART3 was set to GREEN Added comment: Nine individuals from six families presenting with intellectual disability, global developmental delay, a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Additionally, two individuals had seizures and two had epileptiform activity reported on EEG. Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro. Sources: Expert list |
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| Mendeliome v1.765 | NPPA |
Chern Lim changed review comment from: PMID: 36303204: - 1x Brugada patient with heterozygous R107X (NMD-predicted, 5 hets in gnomADv3), regarded as ACMG-LP. PMID: 19646991: - NPPA S64R missense in one fam with familial AF, heterozygous in two affected family members but was absent in unaffected family members and their controls. This variant has 195 hets in gnomADv3. PMID: 23275345: - Segregation of the homozygous p.R150Q mutation of the NPPA gene with the phenotype in the 6 families with autosomal recessive AD cardiomyopathy (ADCM). This variant has no homozygotes in gnomAD. ClinGen gene curation: for autosomal recessive DCM - No Known Disease Relationship (09/04/2020).; to: PMID: 36303204: - 1x Brugada patient with heterozygous R107X (NMD-predicted, 5 hets in gnomADv3), regarded as ACMG-LP. PMID: 19646991: - NPPA S64R missense in one fam with familial AF, heterozygous in two affected family members but was absent in unaffected family members and their controls. This variant has >200 hets in gnomADv3. PMID: 23275345: - Segregation of the homozygous p.R150Q mutation of the NPPA gene with the phenotype in the 6 families with autosomal recessive AD cardiomyopathy (ADCM). This variant has no homozygotes in gnomAD. ClinGen gene curation: for autosomal recessive DCM - No Known Disease Relationship (09/04/2020). |
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| Mendeliome v1.697 | SLC25A36 |
Krithika Murali gene: SLC25A36 was added gene: SLC25A36 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SLC25A36 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A36 were set to 34971397; 34576089; 31036718 Phenotypes for gene: SLC25A36 were set to Hyperinsulinemic hypoglycemia, familial, 8 - MIM#620211 Review for gene: SLC25A36 was set to GREEN Added comment: Solute carrier family 25 members 33 (SLC25A33) and 36 (SLC25A36) are the only known mitochondrial pyrimidine nucleotide carriers in humans PMID: 34971397 Sharoor et al 2022 report 2 siblings with hyperinsulinism, hypoglycemia and hyperammonemia from early infancy with homozygous SLC25A36 c.284 + 3 A > T variant identified through WES. Functional studies support LoF. PMID: 34576089 report a 12-year-old patient with hypothyroidism, hyperinsulinism, hyperammonemia, chronical obstipation, short stature, along with language and general developmental delay. WES identified SLC25A36 gene homozygous c.803dupT, p.Ser269llefs*35 variant. Functional analysis of mutant SLC25A36 protein in proteoliposomes showed a virtually abolished transport activity. Immunoblotting results suggest that the mutant SLC25A36 protein in the patient undergoes fast degradation. Supplementation with uridine lead to some improvement in clinical course. PMID: 31036718 deficiencies in SLC25A36 in mouse embryonic stem cells have been associated with mtDNA depletion as well as mitochondrial dysfunction Sources: Literature |
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| Mendeliome v1.629 | HTR2C |
Zornitza Stark gene: HTR2C was added gene: HTR2C was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HTR2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HTR2C were set to 36536256 Phenotypes for gene: HTR2C were set to Obesity disorder, MONDO:0011122, HTR2C-related Review for gene: HTR2C was set to GREEN Added comment: Exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Obesity was severe, childhood-onset. Knock-in male mice harboring a human loss-of-function HTR2C variant developed obesity and reduced social exploratory behavior; female mice heterozygous for the same variant showed similar deficits with reduced severity. Sources: Literature |
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| Mendeliome v1.484 | ADAMTS9 | Zornitza Stark Phenotypes for gene: ADAMTS9 were changed from Nephronophthisis-Related Ciliopathy to Nephropathy-related ciliopathy, MONDO:0022409, ADAMTS9-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.482 | ADAMTS9 | Chirag Patel Classified gene: ADAMTS9 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.482 | ADAMTS9 | Chirag Patel Gene: adamts9 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.481 | ADAMTS9 | Chirag Patel reviewed gene: ADAMTS9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.348 | FOSL2 |
Krithika Murali gene: FOSL2 was added gene: FOSL2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: FOSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOSL2 were set to 36197437 Phenotypes for gene: FOSL2 were set to Neurodevelopmental disorder, MONDO:0700092, FOSL2-related Review for gene: FOSL2 was set to GREEN Added comment: PMID 36197437 Cospain et al 2022 report 11 individuals from 10 families with heterozygous PTC variants in exon 4/4 of the FOSL2 gene. All variants were predicted to escape NMD resulting in a truncated protein, with the truncation occurring proximal to the C-terminal domain (supportive functional studies). In 10/11 families the variant occurred de novo in a single affected proband. In one family with 2 affected siblings, the variant was present in the siblings but absent in the unaffected parent likely due to gonadal mosaicism. Clinical features included: - Cutis aplasia congenital of the scalp (10/11) - Tooth enamel hypoplasia and discolouration (8/9) - Multiple other ectodermal features also noted e.g. small brittle nails, hypotrichosis/hypertrichosis, lichen sclerosis - 5 individuals had cataracts (mostly bilateral, congenital/early childhood onset) - 6/9 IUGR - 5/9 postnatal growth restriction - 7/9 developmental delay/ID - 5/7 ADHD/ASD - 2/9 seizures Sources: Literature |
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| Mendeliome v1.346 | ADAMTS19 | Zornitza Stark Phenotypes for gene: ADAMTS19 were changed from Non-syndromic heart valve disease to Cardiac valvular dysplasia 2, MIM# 620067 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.345 | ADAMTS19 | Zornitza Stark edited their review of gene: ADAMTS19: Changed phenotypes: Cardiac valvular dysplasia 2, MIM# 620067 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.342 | ATP7A |
Zornitza Stark changed review comment from: ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein.; to: ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein. Treatment for Menkes disease: subcutaneous injections of copper histidine or copper chloride ClinGen has assessed as moderate evidence for actionability. Neonatal treatment with subcutaneous copper-histidine (initiated before 30 days of life) is recommended for asymptomatic males with a diagnosis of MD, but is not recommended for symptomatic boys or after 30 days of life. Treatment should be continued indefinitely. In an open-label clinical trial, 12 patients with MD treated with copper-histidine within 22 days of life had 92% survival after a mean follow-up of 4.6 years compared to 13% in a historical control group of 15 patients treated after a late diagnosis (mean age at diagnosis: 163 ± 113 days, range: 42 to 390). Two of the 12 patients with earlier treatment had normal neurological development. A second open-label trial of 35 presymptomatic patients receiving copper-histidine at less than a month of age reported significant improvement of four major neurodevelopmental (gross motor, fine motor/adaptive, personal/social, and language) domains and a non-significant lower mortality (28.5% vs 50%) at age of 3 years (or age of death) compared to 22 patients treated later and after onset of symptoms. |
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| Mendeliome v1.337 | ADAMTS13 | Zornitza Stark Tag treatable tag was added to gene: ADAMTS13. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.332 | PTPA |
Zornitza Stark gene: PTPA was added gene: PTPA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PTPA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTPA were set to 36073231 Phenotypes for gene: PTPA were set to Intellectual disability, MONDO: 36073231, PTPA-related Review for gene: PTPA was set to AMBER Added comment: Biallelic PTPA pathogenic variants lead to a form of ID with later-onset parkinsonism based on 4 individuals from 2 families in the literature. Affected individuals were homozygous for missense variants demonstrated to result to reduced mRNA and protein levels as well as PP2A complex activation. Drosophila studies support an age-dependent locomotor dysfunction. Variants in other PP2A-complex-related genes also lead to NDDs. Summary provided below. There is currently no associated phenotype in OMIM, G2P, PanelApp UK or SysID. Consider inclusion in relevant panels (ID, Parkinsonism/movement disorders, etc) with amber rating pending further reports. ------ Fevga, Tesson et al (2022 - PMID: 36073231) describe the features of 4 individuals, from 2 unrelated families, with biallelic pathogenic PTPA variants. These presented with normal or delayed early milestones, learning disability and ID (mild to moderate) followed by progressive signs of parkinsonism (at the age of 11 yrs in 2 sibs, 15 yrs in another individual). Motor symptoms were responsive to levodopa and later to deep brain stimulation. Linkage analysis in one consanguineous family followed by exome revealed homozygosity for a missense PTPA variant (NM_178001:c.893T>G/p.Met298Arg). Exome sequencing in affected subjects from the 2nd family revealed homozygosity for a further missense variant (c.512C>A/p.Ala171Asp). There were no other candidate variants for the phenotype following parental / segregation studies. Role of the gene: As the authors discuss, PTPA (or PPP2R4) is ubiquitously expressed in all tissues incl. brain and encodes a phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase-2A (PP2A). PP2A in turn, is the major Ser/Thr phosphatase in brain targeting a large number of proteins involved in diverse functions. Activation of PP2A is dependent on its methylation, which is negatively regulated by the PP2A-specific methylesterase (PME-1). By binding to PME-1, PTPA counteracts the negative influence of the former on PP2A. Pathogenic variants in genes encoding subunits/regulators of the PP2A complex (e.g. PPP2R1A or PPP2CA) are associated with neurodevelopmental disorders. Variant studies: Upon overexpression of wt and both variants in a HEK-293 cell line the authors demonstrated that both variants resulted in significantly reduced mRNA and protein levels (which for Ala171Asp were attributed to increased proteasomal degradation). Both variants were shown to result in impaired PP2A complex activation compared to wt. Drosophila / animal models: Pan-neuronal RNAi-mediated knockdown of ptpa in Drosophila resulted in an age-dependent locomotor dysfunction, reversible with L-DOPA treatment. Previous studies in mice suggest cognitive/electrophysiological impairments upon downregulation of PP2A activity in transgenic mice. Sources: Literature |
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| Mendeliome v1.289 | TMEM147 |
Naomi Baker gene: TMEM147 was added gene: TMEM147 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMEM147 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM147 were set to PMID: 36044892 Phenotypes for gene: TMEM147 were set to Neurodevelopmental disorder (MONDO:0700092), TMEM147-related Review for gene: TMEM147 was set to GREEN Added comment: PMID: 36044892; Twelve different variants reported in 23 affected individuals from 15 unrelated families with biallelic variants. All individuals had global developmental delay and intellectual disability. Consistent facial dysmorphisms included coarse facies, prominent forehead, board depressed nasal root, tented mouth, long smooth philtrum, and low-set ears. In vitro studies of missense variants demonstrated accelerated protein degradation via the autophagy-lysosomal pathway, while analysis of primary fibroblasts and granulocytes provided functional evidence of ER and nuclear envelope dysfunction. Sources: Literature |
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| Mendeliome v1.289 | ADAMTS15 | Zornitza Stark Marked gene: ADAMTS15 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.289 | ADAMTS15 | Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.289 | ADAMTS15 | Zornitza Stark Classified gene: ADAMTS15 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.289 | ADAMTS15 | Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.283 | NOTCH1 | Zornitza Stark Phenotypes for gene: NOTCH1 were changed from Adams-Oliver syndrome 5 (MIM#616028) to Adams-Oliver syndrome 5 (MIM#616028); Genetic cerebral small vessel disease (MONDO:0018787), NOTCH1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.276 | ADAMTS15 |
Naomi Baker gene: ADAMTS15 was added gene: ADAMTS15 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS15 were set to PMID: 35962790 Phenotypes for gene: ADAMTS15 were set to Arthrogryposis (MONDO:0008779), ADMATS15-related Review for gene: ADAMTS15 was set to GREEN Added comment: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5). Sources: Literature |
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| Mendeliome v1.102 | IFNAR2 | Zornitza Stark edited their review of gene: IFNAR2: Added comment: Five children from Greenland, Canada, and Alaska presenting with viral diseases, including life-threatening COVID-19 or influenza, in addition to meningoencephalitis and/or hemophagocytic lymphohistiocytosis following live-attenuated viral vaccination; Changed rating: GREEN; Changed publications: 26424569, 35442417 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.35 | GIMAP6 |
Elena Savva gene: GIMAP6 was added gene: GIMAP6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GIMAP6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GIMAP6 were set to PMID: 35551368; 33328581 Phenotypes for gene: GIMAP6 were set to Autophagy, immune competence and inflammation Review for gene: GIMAP6 was set to AMBER Added comment: PMID: 35551368, PMID: 33328581 - K/O mice show autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)–containing lipids and die prematurely from microangiopathic glomerulosclerosis with immunodeficiency. - 2 unrelated families (3 patients) w/ a homozygous missense (p.Gly153Val) and nonsense (p.Trp86*). All unaffected siblings were heterozygous. Patient 1 (missense) presented with Coombs-positive hemolytic anemia, hepatosplenomegaly, Cranial MRI showed bilateral effusions, sulcal hyperintensity, and lateral parietal subcortical acute focal ischemic lesions. Patient 2 (nonsense) presented with recurrent purulent otitis media and a chronic wet cough, persistent jaundice, recurrent chest and ear infections, lingular consolidation, mild bronchiectasis, bibasilar bronchial wall thickening, right peribronchial consolidation, right lower lobe bronchiectasis, bilateral axillary lymphadenopathy, and splenomegaly. Patient 3 (nonsense) presented with suffered headaches, abdomen pain, mouth ulcers, and recurrent infections - Functional studies show patient 1 (missense) with reduced protein expression on western blot, and patient 2/3 (nonsense) with no protein expression. T cells of Pt 1 were similar to mouse K/O model (elevated basal LC3-II, reduced autophagic flux). gnomAD: 0 homozygous PTCs, but a very common canonical splice which is present in the non-canonical transcript Sources: Literature |
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| Mendeliome v0.14158 | RBPJ | Zornitza Stark Phenotypes for gene: RBPJ were changed from to Adams-Oliver syndrome 3, MIM# 614814 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14154 | RBPJ | Zornitza Stark reviewed gene: RBPJ: Rating: GREEN; Mode of pathogenicity: None; Publications: 22883147, 29924900; Phenotypes: Adams-Oliver syndrome 3, MIM# 614814; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14003 | ARHGAP31 | Elena Savva Phenotypes for gene: ARHGAP31 were changed from to Adams-Oliver syndrome 1, MIM#100300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14000 | ARHGAP31 | Elena Savva reviewed gene: ARHGAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33655927, 29924900; Phenotypes: Adams-Oliver syndrome 1, MIM#100300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13941 | DHH | Ain Roesley Phenotypes for gene: DHH were changed from 46XY partial gonadal dysgenesis, with minifascicular neuropathy, MIM# 607080 to 46XY gonadal dysgenesis with minifascicular neuropathy MIM#607080; 46XY sex reversal 7 MIM#233420 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13792 | CD164 |
Alison Yeung gene: CD164 was added gene: CD164 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CD164 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CD164 were set to 26197441; 35254497; 26197441 Phenotypes for gene: CD164 were set to Deafness, autosomal dominant 66, MIM# 616969 Review for gene: CD164 was set to GREEN Added comment: p.(Arg192Ter), a truncating variant that results in loss of 6 amino acids, was detected in two families (one Polish and one Korean) with hearing loss. Four affected (heterozygous) and two unaffected (neg) were tested, however 14 members had been diagnosed with HL in a large multi generational family (gene panel 237 genes). The second family (WES) had two affected heterozygous and no unaffected were tested. This same variant had previously been reported in a Danish family (12 affected heterozygous and 13 unaffected negative, but one younger member unaffected are heterozygous) with hearing loss (PMID: 26197441), for which functional studies in HEK cells demonstrated that the truncated protein was almost completely retained on the plasma cell membrane in contrast to the wild-type protein, which targeted primarily to the endo-lysosomal compartments. The YHTL motif, deleted by the c.574C>T nonsense mutation, is a canonical sorting motif known to be recognized by specific adaptor proteins in the cytosol, leading to subcellular trafficking of the transmembrane protein to endosomes and lysosomes. Sources: Literature |
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| Mendeliome v0.12737 | CACNA2D1 | Zornitza Stark reviewed gene: CACNA2D1: Rating: RED; Mode of pathogenicity: None; Publications: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12721 | ADAM22 | Alison Yeung Phenotypes for gene: ADAM22 were changed from Developmental and epileptic encephalopathy 61 (MIM#617933) to Developmental and epileptic encephalopathy 61 (MIM#617933) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12721 | ADAM22 | Alison Yeung Phenotypes for gene: ADAM22 were changed from Epileptic encephalopathy, early infantile, 61, MIM# 617933 to Developmental and epileptic encephalopathy 61 (MIM#617933) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12720 | ADAM22 | Alison Yeung Publications for gene: ADAM22 were set to 27066583; 30237576 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12719 | ADAM22 | Alison Yeung Classified gene: ADAM22 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12719 | ADAM22 | Alison Yeung Gene: adam22 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12713 | ADAM22 | Lucy Spencer reviewed gene: ADAM22: Rating: GREEN; Mode of pathogenicity: None; Publications: 35373813; Phenotypes: Developmental and epileptic encephalopathy 61 (MIM#617933); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11890 | NOTCH1 | Zornitza Stark Phenotypes for gene: NOTCH1 were changed from to Adams-Oliver syndrome 5 (MIM#616028) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11860 | NOTCH1 | Krithika Murali reviewed gene: NOTCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25963545, 25132448; Phenotypes: Adams-Oliver syndrome 5 (MIM#616028); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11755 | ADAMTS10 | Zornitza Stark Publications for gene: ADAMTS10 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11754 | ADAMTS10 | Zornitza Stark edited their review of gene: ADAMTS10: Changed publications: 15368195, 18567016, 19836009 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11730 | ADAT3 | Elena Savva Marked gene: ADAT3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11730 | ADAT3 | Elena Savva Gene: adat3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11730 | ADAT3 | Elena Savva Publications for gene: ADAT3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11730 | ADAT3 | Elena Savva Phenotypes for gene: ADAT3 were changed from to Mental retardation, autosomal recessive 36, MIM#615286 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11730 | ADAT3 | Elena Savva Mode of inheritance for gene: ADAT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11729 | ADAMTS10 | Elena Savva Phenotypes for gene: ADAMTS10 were changed from Weill-Marchesani syndrome 1, recessive, MIM#277600 to Weill-Marchesani syndrome 1, recessive, MIM#277600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11728 | ADAMTS10 | Elena Savva Phenotypes for gene: ADAMTS10 were changed from to Weill-Marchesani syndrome 1, recessive, MIM#277600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11727 | ADAMTS10 | Elena Savva Marked gene: ADAMTS10 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11727 | ADAMTS10 | Elena Savva Gene: adamts10 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11727 | ADAMTS10 | Elena Savva Mode of inheritance for gene: ADAMTS10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11726 | ADAM9 | Elena Savva Mode of inheritance for gene: ADAM9 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11725 | ADAM9 | Elena Savva Phenotypes for gene: ADAM9 were changed from Cone-rod dystrophy 9 MIM#612775 to Cone-rod dystrophy 9 MIM#612775 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11725 | ADAM9 | Elena Savva Publications for gene: ADAM9 were set to PMID: 25091951; 19409519 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11724 | ADAM9 | Elena Savva Publications for gene: ADAM9 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11724 | ADAM9 | Elena Savva Mode of inheritance for gene: ADAM9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11724 | ADAM9 | Elena Savva Phenotypes for gene: ADAM9 were changed from to Cone-rod dystrophy 9 MIM#612775 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11723 | ADAM9 | Elena Savva Marked gene: ADAM9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11723 | ADAM9 | Elena Savva Gene: adam9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11723 | ADAM9 | Elena Savva reviewed gene: ADAM9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25091951, 19409519; Phenotypes: Cone-rod dystrophy 9 MIM#612775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11331 | KCNE5 |
Zornitza Stark changed review comment from: Associated with Brugada is DISPUTED. Rare variants in KCNE5 reported in AF cohorts with some supportive functional data.; to: Association with Brugada is DISPUTED. Rare variants in KCNE5 reported in AF cohorts with some supportive functional data. |
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| Mendeliome v0.11076 | PPP2R3C |
Zornitza Stark gene: PPP2R3C was added gene: PPP2R3C was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPP2R3C were set to 30893644; 34714774; 34750818 Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419 Review for gene: PPP2R3C was set to GREEN Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility. Sources: Literature |
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| Mendeliome v0.10854 | ADAMTS1 | Zornitza Stark Marked gene: ADAMTS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10854 | ADAMTS1 | Zornitza Stark Gene: adamts1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10854 | ADAMTS1 | Zornitza Stark Classified gene: ADAMTS1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10854 | ADAMTS1 | Zornitza Stark Gene: adamts1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10846 | ADAMTS1 |
Paul De Fazio gene: ADAMTS1 was added gene: ADAMTS1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADAMTS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS1 were set to 34135477 Phenotypes for gene: ADAMTS1 were set to Nonsyndromic genetic hearing loss MONDO:0019497, ADAMTS1-related Review for gene: ADAMTS1 was set to RED gene: ADAMTS1 was marked as current diagnostic Added comment: Homozygous missense variant p.(Ser135Ala) identified in 3 affected siblings from a single consanguineous Pakistani family by WES. A fourth unaffected sibling was homozygous wild type. Variant is in gnomad (26 hets, 1 hom). RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only). Sources: Literature |
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| Mendeliome v0.10656 | STRADA | Zornitza Stark Marked gene: STRADA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10656 | STRADA | Zornitza Stark Gene: strada has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10656 | STRADA | Zornitza Stark Phenotypes for gene: STRADA were changed from to Polyhydramnios, megalencephaly, and symptomatic epilepsy, OMIM:611087; Polyhydramnios, megalencephaly, and symptomatic epilepsy, MONDO:0012611 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10655 | STRADA | Zornitza Stark Publications for gene: STRADA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10654 | STRADA | Zornitza Stark Mode of inheritance for gene: STRADA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10653 | STRADA | Zornitza Stark reviewed gene: STRADA: Rating: GREEN; Mode of pathogenicity: None; Publications: 17522105, 27170158, 28688840; Phenotypes: Polyhydramnios, megalencephaly, and symptomatic epilepsy, OMIM:611087, Polyhydramnios, megalencephaly, and symptomatic epilepsy, MONDO:0012611; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10337 | KCNJ8 | Zornitza Stark Phenotypes for gene: KCNJ8 were changed from Brugada syndrome to Cantú Syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10312 | ADAMTS2 | Zornitza Stark Marked gene: ADAMTS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10312 | ADAMTS2 | Zornitza Stark Gene: adamts2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10312 | ADAMTS2 | Zornitza Stark Phenotypes for gene: ADAMTS2 were changed from to Ehlers-Danlos syndrome, dermatosparaxis type (MIM# 225410) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10311 | ADAMTS2 | Zornitza Stark Publications for gene: ADAMTS2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10310 | ADAMTS2 | Zornitza Stark Mode of inheritance for gene: ADAMTS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10309 | ADAMTS2 | Zornitza Stark reviewed gene: ADAMTS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 26765342, 28306229; Phenotypes: Ehlers-Danlos syndrome, dermatosparaxis type (MIM# 225410); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10238 | EOGT | Zornitza Stark Phenotypes for gene: EOGT were changed from to Adams-Oliver syndrome 4, MIM#615297 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10235 | EOGT | Zornitza Stark reviewed gene: EOGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 23522784, 31368252, 29924900, 31368252; Phenotypes: Adams-Oliver syndrome 4, MIM#615297; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10156 | DOCK6 | Zornitza Stark Phenotypes for gene: DOCK6 were changed from to Adams-Oliver syndrome 2, MIM#614219 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10153 | DOCK6 | Zornitza Stark reviewed gene: DOCK6: Rating: GREEN; Mode of pathogenicity: None; Publications: 21820096, 23522784, 25132448, 25824905; Phenotypes: Adams-Oliver syndrome 2, MIM#614219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10044 | ECM1 |
Zornitza Stark changed review comment from: PMID: 11929856 - Hamada et al 2002 - looked at 6 different unrelated consanguineous families (from Saudi Arabia, Kuwait, Pakistan, The Netherlands, UK, and a group of South African families with a probable common ancestor) with a clinical diagnosis of Lipoid proteinosis (LP)/Urbach–Wiethe disease. They performed a genome-wide linkage analysis and identified a region and then looked at the expression of candidate genes in fibroblasts from patients compared to controls. ECM1 was found to have lower expression levels. 6 homozygous deletion variants were identified in the patients. In one family they established that the parents were heterozygous for the variant. PMID: 28720532 - Afifi et al 2017 - studied 12 patients from 10 unrelated consanguineous Egyptian families with a clinical diagnosis of lipoid proteinosis. The patients reported progressive hoarseness of voice and easily damaged skin by minor trauma or friction. Homozygous ECM1 variants were detected in affected members in all families: 1 family had a missense variant, 5 families had splice site variants and 4 families had indels predicted to cause frameshifts. Parents were found to be heterozygous for the variants. PMID: 33159951 - Zhu et al 2021 - a novel homozygous three-nucleotide duplication (c.506_508dupCTG) in ECM in two siblings affected with LP from a consanguineous Chinese family.; to: Lipoid proteinosis of Urbach and Wiethe is a rare autosomal recessive disorder typified by generalized thickening of skin, mucosae, and certain viscera. Classic features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. The disorder is clinically heterogeneous, with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurologic abnormalities such as temporal lobe epilepsy. Histologically, there is widespread deposition of hyaline (glycoprotein) material and disruption/reduplication of basement membrane PMID: 11929856 - Hamada et al 2002 - looked at 6 different unrelated consanguineous families (from Saudi Arabia, Kuwait, Pakistan, The Netherlands, UK, and a group of South African families with a probable common ancestor) with a clinical diagnosis of Lipoid proteinosis (LP)/Urbach–Wiethe disease. They performed a genome-wide linkage analysis and identified a region and then looked at the expression of candidate genes in fibroblasts from patients compared to controls. ECM1 was found to have lower expression levels. 6 homozygous deletion variants were identified in the patients. In one family they established that the parents were heterozygous for the variant. PMID: 28720532 - Afifi et al 2017 - studied 12 patients from 10 unrelated consanguineous Egyptian families with a clinical diagnosis of lipoid proteinosis. The patients reported progressive hoarseness of voice and easily damaged skin by minor trauma or friction. Homozygous ECM1 variants were detected in affected members in all families: 1 family had a missense variant, 5 families had splice site variants and 4 families had indels predicted to cause frameshifts. Parents were found to be heterozygous for the variants. PMID: 33159951 - Zhu et al 2021 - a novel homozygous three-nucleotide duplication (c.506_508dupCTG) in ECM in two siblings affected with LP from a consanguineous Chinese family. |
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| Mendeliome v0.10013 | ARPC4 |
Bryony Thompson gene: ARPC4 was added gene: ARPC4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ARPC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARPC4 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100072 Phenotypes for gene: ARPC4 were set to Microcephaly; mild motor delays; significant speech impairment Review for gene: ARPC4 was set to GREEN Added comment: 7 affected individuals from 6 families (gonadal mosaicism was confirmed in the mother of the 2 affected siblings) with a recurrent missense variant (NM_005718.4:c.472C>T; p.R158C). The variant was associated with a decreased amount of F-actin in cells from two affected individuals. Sources: Literature |
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| Mendeliome v0.9667 | DLL4 | Zornitza Stark Phenotypes for gene: DLL4 were changed from to Adams-Oliver syndrome 6, MIM#616589 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9664 | DLL4 | Zornitza Stark reviewed gene: DLL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26299364, 33899511, 31261205, 29924900; Phenotypes: Adams-Oliver syndrome 6 MIM#616589; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9569 | KIAA0391 |
Lucy Spencer changed review comment from: Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes. -1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism. -1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5. -1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL. -an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches. All variants are in p.400s. Sources: Literature; to: Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes. -1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism. -1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5. -1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL. -an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches. All variants are in p.400s. Sources: Literature |
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| Mendeliome v0.9567 | KIAA0391 |
Lucy Spencer gene: KIAA0391 was added gene: KIAA0391 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIAA0391 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA0391 were set to PMID: 34715011 Added comment: Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes. -1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism. -1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5. -1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL. -an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches. All variants are in p.400s. Sources: Literature |
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| Mendeliome v0.9563 | SPRED2 |
Dean Phelan gene: SPRED2 was added gene: SPRED2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPRED2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPRED2 were set to PMID: 34626534 Phenotypes for gene: SPRED2 were set to developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt Review for gene: SPRED2 was set to GREEN Added comment: PMID: 34626534 Homozygosity for three different variants c.187C>T (p.Arg63∗), c.299T>C (p.Leu100Pro), and c.1142_1143delTT (p.Leu381Hisfs∗95) were identified in four subjects from three families. All variants severely affected protein stability, causing accelerated degradation, and variably perturbed SPRED2 functional behaviour. The clinical phenotype of the four affected individuals included developmental delay, intellectual disability, cardiac defects, short stature, skeletal anomalies, and a typical facial gestalt as major features, without the occurrence of the distinctive skin signs characterizing Legius syndrome. Sources: Literature |
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| Mendeliome v0.9522 | ADAMTS17 | Zornitza Stark Marked gene: ADAMTS17 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9522 | ADAMTS17 | Zornitza Stark Gene: adamts17 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9522 | ADAMTS17 | Zornitza Stark Phenotypes for gene: ADAMTS17 were changed from to Weill-Marchesani 4 syndrome, recessive, MIM# 613195 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9521 | ADAMTS17 | Zornitza Stark Publications for gene: ADAMTS17 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9520 | ADAMTS17 | Zornitza Stark Mode of inheritance for gene: ADAMTS17 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9519 | ADAMTS17 | Zornitza Stark reviewed gene: ADAMTS17: Rating: GREEN; Mode of pathogenicity: None; Publications: 19836009, 22486325, 24940034, 30712880; Phenotypes: Weill-Marchesani 4 syndrome, recessive, MIM# 613195; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9366 | NLRP5 |
Zornitza Stark edited their review of gene: NLRP5: Added comment: 'Maternal effect gene' Part of the subcortical maternal complex Report of five mothers carrying either monoallelic or biallelic variants in NLRP5, who had both unaffected offspring and offspring with BWS-MLID (Doherty 2015). Report of one family where the mother carried biallelic variants in NLRP5, had one offspring with BWS, one unaffected offspring and multiple miscarriages (Sparago 2019). Reports of at least three unrelated individuals with recurrent early embryonic arrest carrying biallelic variants in NLRP5. Functional work suggesting protein degradation in affected human cell lines (Mu 2019, Xu 2020).; Changed rating: GREEN; Changed publications: 32222962, 31829238, 30877238, 26323243, 34440388; Changed phenotypes: Early embryonic arrest, Multi locus imprinting disturbance in offspring; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v0.8522 | SYNCRIP |
Zornitza Stark gene: SYNCRIP was added gene: SYNCRIP was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SYNCRIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SYNCRIP were set to 34157790; 30504930; 27479843; 23020937 Phenotypes for gene: SYNCRIP were set to Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology Review for gene: SYNCRIP was set to GREEN Added comment: Semino et al (2021 - PMID: 34157790) provide clinical details on 3 unrelated individuals with de novo SYNCRIP variants and provide a review of 5 additional subjects previously identified within large cohorts in the literature and databases. Features included DD, ID (7/7 for whom this information was available), ASD or autistic features (4/7). MRI abnormalities were observed in 3 (widening of CSF spaces, periventricular nodular heterotopia, prominent lat. ventricles). Epilepsy (myoclonic-astatic epilepsy / Doose syndrome) was reported for 2(/8) individuals. The 3 patients here reported were identified following trio/singleton exome with Sanger confirmation of the variants and their de novo occurrence. Variants are in almost all cases de novo (7/7 for whom this was known) and in 5/8 cases were pLoF, in 2/8 missense SNVs while a case from DECIPHER had a 77.92 kb whole gene deletion not involving other genes with unknown inheritance. Overall the variants reported to date include [NM_006372.5]: 1 - c.858_859del p.(Gly287Leufs*5) 2 - c.854dupA p.(Asn285Lysfs*8) 3 - c.734T>C p.(Leu245Pro) 4 - chr6:85605276-85683190 deletion (GRCh38) 5 - c.629T>C p.(Phe210Ser) 6 - c.1573_1574delinsTT p.(Gln525Leu) 7 - c.1247_1250del p.(Arg416Lysfs*145) 8 - c.1518_1519insC p.(Ala507Argfs*14) [P1-3: this report, P4: DECIPHER 254774, P5-6: Guo et al 2019 - PMID: 30504930, P7: Lelieveld et al 2016 - PMID: 27479843, P8: Rauch et al 2012 - PMID: 23020937 / all other Refs not here reviewed, clinical details summarized by Semino et al in table 1] SYNCRIP (also known as HNRNPQ) encodes synaptotagmin‐binding cytoplasmic RNA‐interacting protein. As the authors note, this RNA-binding protein is involved in multiple pathways associated with neuronal/muscular developmental disorders. Several references are provided for its involvement in regulation of RNA metabolism, among others sequence recognition, pre-mRNA splicing, translation, transport and degradation. Mutations in other RNA-interacting proteins and hnRNP members (e.g. HNRNPU, HNRNPD) are associated with NDD. The missense variant (p.Leu245Pro) is within RRM2 one of the 3 RNA recognition motif (RRM) domains of the protein. These 3 domains, corresponding to the central part of the protein (aa 150-400), are relatively intolerant to variation (based on in silico predictions and/or variation in gnomAD). Leu245 localizes within an RNA binding pocket and in silico modeling suggests alteration of the tertiary structure and RNA-binding capacity of RRM2. There are no additional studies performed. Overall haploinsufficiency appears to be the underlying disease mechanism based on the truncating variants and the gene deletion. [pLI in gnomAD : 1, %HI : 2.48%] Animal models are not discussed. There is no associated phenotype in OMIM. This gene is included in the DD panel of G2P (monoallelic LoF variants / SYNCRIP-related developmental disorder). SysID also lists SYNCRIP within the current primary ID genes. Sources: Literature |
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| Mendeliome v0.8316 | ADA | Zornitza Stark Marked gene: ADA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8316 | ADA | Zornitza Stark Gene: ada has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8316 | ADA | Zornitza Stark Phenotypes for gene: ADA were changed from to Severe combined immunodeficiency due to ADA deficiency, MIM# 102700; MONDO:0007064 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8315 | ADA | Zornitza Stark Publications for gene: ADA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8314 | ADA | Zornitza Stark Mode of inheritance for gene: ADA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8313 | ADA | Zornitza Stark reviewed gene: ADA: Rating: GREEN; Mode of pathogenicity: None; Publications: 3007108, 3475710, 8178821, 8227344, 2783588; Phenotypes: Severe combined immunodeficiency due to ADA deficiency, MIM# 102700, MONDO:0007064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8014 | ADA2 | Zornitza Stark Marked gene: ADA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8014 | ADA2 | Zornitza Stark Gene: ada2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8014 | ADA2 | Zornitza Stark Phenotypes for gene: ADA2 were changed from to Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome, MIM# 615688 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8013 | ADA2 | Zornitza Stark Publications for gene: ADA2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8012 | ADA2 | Zornitza Stark Mode of inheritance for gene: ADA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8011 | ADA2 | Zornitza Stark commented on gene: ADA2: Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome (VAIHS) is an autosomal recessive multisystem disorder with onset in childhood. The phenotype is highly variable, but most patients have features of a systemic vascular inflammatory disorder with skin ulceration and recurrent strokes affecting the small vessels of the brain resulting in neurologic dysfunction. Other features may include recurrent fever, elevated acute-phase proteins, myalgias, lesions resembling polyarteritis nodosa, and/or livedo racemosa or reticularis with an inflammatory vasculitis on biopsy. Some patients may have renal and/or gastrointestinal involvement, hypertension, aneurysms, or ischemic necrosis of the digits. Some affected individuals have immunodeficiency. At least 10 unrelated families reported, the p.Gly47Arg variant is a common founder variant in the Jewish population. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8011 | ADA2 | Zornitza Stark reviewed gene: ADA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24552284, 24552285, 33791889; Phenotypes: Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome, MIM# 615688; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7917 | ADAMTSL2 | Zornitza Stark Marked gene: ADAMTSL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7917 | ADAMTSL2 | Zornitza Stark Gene: adamtsl2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7917 | ADAMTSL2 | Zornitza Stark Phenotypes for gene: ADAMTSL2 were changed from to Geleophysic dysplasia 1, MIM# 231050; Dermatosparaxic Ehlers Danlos syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7916 | ADAMTSL2 | Zornitza Stark Publications for gene: ADAMTSL2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7915 | ADAMTSL2 | Zornitza Stark Mode of inheritance for gene: ADAMTSL2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7914 | ADAMTSL2 | Zornitza Stark reviewed gene: ADAMTSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33369194, 26879370, 21415077; Phenotypes: Geleophysic dysplasia 1, MIM# 231050, Dermatosparaxic Ehlers Danlos syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6679 | ADAMTS13 | Zornitza Stark Marked gene: ADAMTS13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6679 | ADAMTS13 | Zornitza Stark Gene: adamts13 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6679 | ADAMTS13 | Zornitza Stark Phenotypes for gene: ADAMTS13 were changed from to Thrombotic thrombocytopenic purpura, hereditary, MIM# 274150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6678 | ADAMTS13 | Zornitza Stark Publications for gene: ADAMTS13 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6677 | ADAMTS13 | Zornitza Stark Mode of inheritance for gene: ADAMTS13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6676 | ADAMTS13 | Zornitza Stark reviewed gene: ADAMTS13: Rating: GREEN; Mode of pathogenicity: None; Publications: 11586351, 30312976; Phenotypes: Thrombotic thrombocytopenic purpura, hereditary, MIM# 274150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5357 | ADAR | Zornitza Stark Marked gene: ADAR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5357 | ADAR | Zornitza Stark Gene: adar has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5357 | ADAR | Zornitza Stark Phenotypes for gene: ADAR were changed from to Aicardi-Goutieres syndrome 6, MIM# 615010; Dyschromatosis symmetrica hereditaria, MIM# 127400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5356 | ADAR | Zornitza Stark Mode of inheritance for gene: ADAR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5355 | ADAR | Zornitza Stark reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 6, MIM# 615010, Dyschromatosis symmetrica hereditaria, MIM# 127400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5254 | FBXO31 |
Kristin Rigbye changed review comment from: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.; to: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression. Extended patient phenotypes: Spastic diplegia, with esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus (patient 1); Spastic paraplegia with ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation (patient 2). |
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| Mendeliome v0.5198 | ODC1 | Zornitza Stark commented on gene: ODC1: Fifth individual reported in PMID 30239107: de novo nonsense variant identified, molecular modeling suggested that due to lack of a C terminus in the mutant protein, antizyme binding does not induce ODC degradation, leading to accumulation of active protein. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5191 | ALPK1 | Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5190 | ALPK1 | Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979 to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5189 | ALPK1 | Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5188 | ALPK1 | Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndromeROSAH syndrome, MIM#614979 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4317 | Zornitza Stark removed gene:ADAT1 from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4316 | ADAT1 | Zornitza Stark Marked gene: ADAT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4316 | ADAT1 | Zornitza Stark Gene: adat1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4316 | ADAT1 | Zornitza Stark Classified gene: ADAT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4316 | ADAT1 | Zornitza Stark Gene: adat1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4315 | ADAT1 |
Zornitza Stark gene: ADAT1 was added gene: ADAT1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ADAT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAT1 were set to 28180185; 29390050; 29659736 Phenotypes for gene: ADAT1 were set to Hyperekplexia 4, MIM#618011 Review for gene: ADAT1 was set to GREEN Added comment: Hyperekplexia-4 is an autosomal recessive severe neurologic disorder apparent at birth. Three unrelated families reported. Affected infants have extreme hypertonia and appear stiff and rigid. They have little if any development, poor or absent visual contact, and no spontaneous movement, consistent with an encephalopathy. Some patients have early-onset refractory seizures. Sources: Expert list |
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| Mendeliome v0.4201 | DHX37 | Zornitza Stark Phenotypes for gene: DHX37 were changed from 46,XY gonadal dysgenesis; testicular regression syndrome (TRS) to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS); Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, MIM#618731 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4198 | DHX37 |
Zornitza Stark changed review comment from: Seventeen individuals with 46,XY gonadal dysgenesis reported in two studies. Sources: Literature; to: Mono-allelic disease: Seventeen individuals with 46,XY gonadal dysgenesis reported in two studies. Sources: Literature |
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| Mendeliome v0.4198 | DHX37 | Zornitza Stark edited their review of gene: DHX37: Added comment: Bi-allelic disease: 5 unrelated families with bi-allelic variants, all with ID as part of the phenotype, which also includes congenital anomalies particularly affecting the vertebrae and heart, but also some with microcephaly, brain anomalies.; Changed publications: 31337883, 31745530, 26539891, 31256877; Changed phenotypes: 46,XY gonadal dysgenesis, testicular regression syndrome (TRS), Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, MIM#618731; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4093 | ADARB1 | Zornitza Stark Phenotypes for gene: ADARB1 were changed from Intellectual disability; microcephaly; seizures to Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862; Intellectual disability; microcephaly; seizures | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4092 | ADARB1 | Zornitza Stark Publications for gene: ADARB1 were set to 32220291 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4091 | NOTCH3 |
Eleanor Williams gene: NOTCH3 was added gene: NOTCH3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NOTCH3 were set to 31960911 Phenotypes for gene: NOTCH3 were set to CADASIL Review for gene: NOTCH3 was set to AMBER Added comment: PMID: 31960911 - Gravesteijn et al 2020 - describe a family with a unique cysteine-altering NOTCH3 variant in exon 9 in 5 individuals, which is predicted to cause natural exon 9 skipping. This mimics the therapeutic NOTCH3 cysteine correction approach and allows the effect of cysteine corrective exon skipping on NOTCH3 protein aggregation and disease severity in humans to be studied. In this family the CADASIL phenotype was mild. Note this gene is rated green on the Neurodegenerative disorders - adult onset panel in the Genomics England instance of PanelApp https://panelapp.genomicsengland.co.uk/panels/474/gene/NOTCH3/ Sources: Literature |
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| Mendeliome v0.4091 | TRPM7 | Eleanor Williams commented on gene: TRPM7: PMID: 31423533 - Cartwright et al 2020 - functional studies on four heterozygous nonsynonymous variants that were observed in TRPM7 in four individual cases of unexplained still birth which were screened for variants in 35 candidate genes in PMID: 29874177 (Munroe et al 2018). TRPM7 is a ubiquitously expressed ion channel known to regulate cardiac development and repolarization in mice. They found two variants in TRPM7, p.G179V and p.T860M, reduce ion channel current expression, which in the case of p.T860M is likely due to rapid degradation mediated by the proteasome. In addition, the p.R494Q TRPM7 variant significantly increases TRPM7 ion channel current, in a cell-type specific manner. They believe that TRPM7 may play a key role in ensuring correct cardiac development of the fetus. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4091 | ADARB1 | Arina Puzriakova reviewed gene: ADARB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32220291, 32719099; Phenotypes: Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3261 | ADAMTSL4 | Zornitza Stark Marked gene: ADAMTSL4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3261 | ADAMTSL4 | Zornitza Stark Gene: adamtsl4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3261 | ADAMTSL4 | Zornitza Stark Phenotypes for gene: ADAMTSL4 were changed from to Ectopia lentis, isolated, autosomal recessive, MIM# 225100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3260 | ADAMTSL4 | Zornitza Stark Publications for gene: ADAMTSL4 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3259 | ADAMTSL4 | Zornitza Stark Mode of inheritance for gene: ADAMTSL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3258 | ADAMTSL4 | Zornitza Stark Tag founder tag was added to gene: ADAMTSL4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3258 | ADAMTSL4 | Zornitza Stark reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19200529, 20564469, 20141359, 21051722; Phenotypes: Ectopia lentis, isolated, autosomal recessive, MIM# 225100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3191 | ADAMTS19 | Zornitza Stark Publications for gene: ADAMTS19 were set to 31844321 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3190 | ADAMTS19 | Zornitza Stark Classified gene: ADAMTS19 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3190 | ADAMTS19 | Zornitza Stark Gene: adamts19 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3189 | ADAMTS19 | Zornitza Stark reviewed gene: ADAMTS19: Rating: GREEN; Mode of pathogenicity: None; Publications: 32323311, 31844321; Phenotypes: Heart valve disease (HVD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3189 | ADAMTS3 | Zornitza Stark Marked gene: ADAMTS3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3189 | ADAMTS3 | Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3189 | ADAMTS3 | Zornitza Stark Classified gene: ADAMTS3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3189 | ADAMTS3 | Zornitza Stark Gene: adamts3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3188 | ADAMTS3 |
Zornitza Stark gene: ADAMTS3 was added gene: ADAMTS3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS3 were set to 28985353; 30450763 Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3 (618154) Review for gene: ADAMTS3 was set to GREEN Added comment: Two families reported, supportive functional data. Sources: Expert list |
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| Mendeliome v0.2940 | KCNJ8 | Zornitza Stark Phenotypes for gene: KCNJ8 were changed from to Brugada syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2936 | KCNJ8 | Zornitza Stark reviewed gene: KCNJ8: Rating: RED; Mode of pathogenicity: None; Publications: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2936 | KCNE3 | Zornitza Stark Phenotypes for gene: KCNE3 were changed from to Brugada syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2932 | KCNE3 | Zornitza Stark reviewed gene: KCNE3: Rating: RED; Mode of pathogenicity: None; Publications: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2630 | DHX37 |
Zornitza Stark gene: DHX37 was added gene: DHX37 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: DHX37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DHX37 were set to 31337883; 31745530 Phenotypes for gene: DHX37 were set to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS) Review for gene: DHX37 was set to GREEN Added comment: Seventeen individuals with 46,XY gonadal dysgenesis reported in two studies. Sources: Literature |
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| Mendeliome v0.2629 | ALPK1 | Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2625 | ALPK1 | Zornitza Stark edited their review of gene: ALPK1: Added comment: Six unrelated families reported with same recurrent missense variant c.710C>T, (p.Thr237Met) and ROSAH syndrome phenotype. Pancytopaenia and recurrent infections present in some.; Changed rating: GREEN; Changed publications: 31053777, 30967659, 31939038; Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, ROSAH syndrome, retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2620 | GALM |
Hazel Phillimore gene: GALM was added gene: GALM was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALM were set to PMID: 30451973; 30910422 Phenotypes for gene: GALM were set to galactosaemia; type IV galactosaemia Review for gene: GALM was set to GREEN Added comment: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia. In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973) In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422) Sources: Literature |
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| Mendeliome v0.2416 | ADAMTS19 | Alison Yeung Marked gene: ADAMTS19 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2416 | ADAMTS19 | Alison Yeung Gene: adamts19 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2416 | ADAMTS19 | Alison Yeung Classified gene: ADAMTS19 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2416 | ADAMTS19 | Alison Yeung Gene: adamts19 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2401 | ADAMTS19 | Crystle Lee edited their review of gene: ADAMTS19: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2375 | DHH | Zornitza Stark Phenotypes for gene: DHH were changed from to 46XY partial gonadal dysgenesis, with minifascicular neuropathy, MIM# 607080 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2365 | ADAMTS19 |
Crystle Lee changed review comment from: PMID: 31844321; Wünnemann 2020: 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review; to: Borderline amber/green PMID: 31844321; Wünnemann 2020: 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review |
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| Mendeliome v0.2365 | ADAMTS19 |
Crystle Lee changed review comment from: PMID: 31844321; Wünnemann 2020: 4 affected in unrelated 2 consanguineous family with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review; to: PMID: 31844321; Wünnemann 2020: 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review |
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| Mendeliome v0.2365 | ADAMTS19 |
Crystle Lee gene: ADAMTS19 was added gene: ADAMTS19 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: ADAMTS19 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS19 were set to 31844321 Phenotypes for gene: ADAMTS19 were set to Non-syndromic heart valve disease Review for gene: ADAMTS19 was set to GREEN Added comment: PMID: 31844321; Wünnemann 2020: 4 affected in unrelated 2 consanguineous family with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Expert Review |
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| Mendeliome v0.2361 | DHH | Naomi Baker reviewed gene: DHH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31018998, 29471294, 11017805; Phenotypes: gonadal dysgenesis, minifascicular neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2213 | ADAM22 | Zornitza Stark Marked gene: ADAM22 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2213 | ADAM22 | Zornitza Stark Gene: adam22 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2213 | ADAM22 | Zornitza Stark Classified gene: ADAM22 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2213 | ADAM22 | Zornitza Stark Gene: adam22 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1900 | NSMCE2 |
Tiong Tan gene: NSMCE2 was added gene: NSMCE2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NSMCE2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NSMCE2 were set to 25105364 Phenotypes for gene: NSMCE2 were set to SECKEL SYNDROME 10 Penetrance for gene: NSMCE2 were set to Complete Review for gene: NSMCE2 was set to AMBER Added comment: Biallelic hypomorphic variants in two unrelated women with microcephalic primordial dwarfism, insulin-resistant diabetes, fatty liver, and hypertriglyceridemia developing in childhood; and primary gonadal failure. Good quality functional evidence. No additional confirmatory cases since 2014 publication Sources: Literature |
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| Mendeliome v0.1887 | ADARB1 | Zornitza Stark Marked gene: ADARB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1887 | ADARB1 | Zornitza Stark Gene: adarb1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1887 | ADARB1 | Zornitza Stark Classified gene: ADARB1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1887 | ADARB1 | Zornitza Stark Gene: adarb1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1886 | ADARB1 |
Zornitza Stark gene: ADARB1 was added gene: ADARB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADARB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADARB1 were set to 32220291 Phenotypes for gene: ADARB1 were set to Intellectual disability; microcephaly; seizures Review for gene: ADARB1 was set to GREEN Added comment: Four unrelated individuals with bi-allelic variants in this gene. Sources: Literature |
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| Mendeliome v0.1792 | ADAM17 | Zornitza Stark Marked gene: ADAM17 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1792 | ADAM17 | Zornitza Stark Gene: adam17 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1792 | ADAM17 | Zornitza Stark Phenotypes for gene: ADAM17 were changed from to Inflammatory neonatal-onset skin and bowel disease, MIM#614328 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1791 | ADAM17 | Zornitza Stark Publications for gene: ADAM17 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1790 | ADAM17 | Zornitza Stark Mode of inheritance for gene: ADAM17 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1789 | ADAM17 | Zornitza Stark Classified gene: ADAM17 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1789 | ADAM17 | Zornitza Stark Gene: adam17 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1774 | ADAM17 | Lauren Akesson reviewed gene: ADAM17: Rating: AMBER; Mode of pathogenicity: None; Publications: 22010916, 25804906, 21041656, 22236242; Phenotypes: Inflammatory neonatal-onset skin and bowel disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1352 | KRT14 | Zornitza Stark Phenotypes for gene: KRT14 were changed from to Epidermolysis bullosa simplex, recessive 1, 601001; Dermatopathia pigmentosa reticularis, 125595; Epidermolysis bullosa simplex, Dowling-Meara type, 131760; Epidermolysis bullosa simplex, Koebner type, 131900; Epidermolysis bullosa simplex, Weber-Cockayne type, 131800; Naegeli-Franceschetti-Jadassohn syndrome, 161000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1348 | KRT14 | Zornitza Stark reviewed gene: KRT14: Rating: GREEN; Mode of pathogenicity: None; Publications: 16960809, 18049449; Phenotypes: Epidermolysis bullosa simplex, recessive 1, 601001, Dermatopathia pigmentosa reticularis, 125595, Epidermolysis bullosa simplex, Dowling-Meara type, 131760, Epidermolysis bullosa simplex, Koebner type, 131900, Epidermolysis bullosa simplex, Weber-Cockayne type, 131800, Naegeli-Franceschetti-Jadassohn syndrome, 161000; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.815 | ADAMTS9 | Zornitza Stark Marked gene: ADAMTS9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.815 | ADAMTS9 | Zornitza Stark Gene: adamts9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.815 | ADAMTS9 | Zornitza Stark Classified gene: ADAMTS9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.815 | ADAMTS9 | Zornitza Stark Gene: adamts9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.814 | ADAMTS9 |
Zornitza Stark gene: ADAMTS9 was added gene: ADAMTS9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADAMTS9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS9 were set to 30609407 Phenotypes for gene: ADAMTS9 were set to Nephronophthisis-Related Ciliopathy Review for gene: ADAMTS9 was set to GREEN Added comment: Two families reported with functional evidence Sources: Literature |
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| Mendeliome v0.565 | ADAM22 |
Zornitza Stark gene: ADAM22 was added gene: ADAM22 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAM22 were set to 27066583; 30237576 Phenotypes for gene: ADAM22 were set to Epileptic encephalopathy, early infantile, 61, MIM# 617933 Review for gene: ADAM22 was set to AMBER Added comment: Two families reported; the second one as part of a large consanguineous cohort. Sources: Expert list |
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| Mendeliome v0.0 | STRADA |
Zornitza Stark gene: STRADA was added gene: STRADA was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: STRADA was set to Unknown |
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| Mendeliome v0.0 | ADAT3 |
Zornitza Stark gene: ADAT3 was added gene: ADAT3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADAT3 was set to Unknown |
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| Mendeliome v0.0 | ADAR |
Zornitza Stark gene: ADAR was added gene: ADAR was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADAR was set to Unknown |
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| Mendeliome v0.0 | ADAMTSL4 |
Zornitza Stark gene: ADAMTSL4 was added gene: ADAMTSL4 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADAMTSL4 was set to Unknown |
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| Mendeliome v0.0 | ADAMTSL2 |
Zornitza Stark gene: ADAMTSL2 was added gene: ADAMTSL2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADAMTSL2 was set to Unknown |
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| Mendeliome v0.0 | ADAMTS2 |
Zornitza Stark gene: ADAMTS2 was added gene: ADAMTS2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADAMTS2 was set to Unknown |
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| Mendeliome v0.0 | ADAMTS17 |
Zornitza Stark gene: ADAMTS17 was added gene: ADAMTS17 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADAMTS17 was set to Unknown |
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| Mendeliome v0.0 | ADAMTS13 |
Zornitza Stark gene: ADAMTS13 was added gene: ADAMTS13 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADAMTS13 was set to Unknown |
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| Mendeliome v0.0 | ADAMTS10 |
Zornitza Stark gene: ADAMTS10 was added gene: ADAMTS10 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADAMTS10 was set to Unknown |
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| Mendeliome v0.0 | ADAM9 |
Zornitza Stark gene: ADAM9 was added gene: ADAM9 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADAM9 was set to Unknown |
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| Mendeliome v0.0 | ADAM17 |
Zornitza Stark gene: ADAM17 was added gene: ADAM17 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADAM17 was set to Unknown |
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| Mendeliome v0.0 | ADA2 |
Zornitza Stark gene: ADA2 was added gene: ADA2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADA2 was set to Unknown |
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| Mendeliome v0.0 | ADA |
Zornitza Stark gene: ADA was added gene: ADA was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ADA was set to Unknown |
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