| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Mendeliome v0.9098 | YARS2 | Zornitza Stark Marked gene: YARS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9098 | YARS2 | Zornitza Stark Gene: yars2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9098 | YARS2 | Zornitza Stark Phenotypes for gene: YARS2 were changed from to Myopathy, lactic acidosis, and sideroblastic anaemia 2 MIM# 613561; sideroblastic anaemia; muscle atrophy; myopathy; lactic acidosis; Hypertrophic cardiomyopathy; Hepatomegaly; Decreased cytochrome C oxidase activity | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9097 | YARS2 | Zornitza Stark Publications for gene: YARS2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9096 | YARS2 | Zornitza Stark Mode of inheritance for gene: YARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9095 | YARS2 | Zornitza Stark reviewed gene: YARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24430573, 24344687; Phenotypes: Myopathy, lactic acidosis, and sideroblastic anaemia 2 MIM# 613561, sideroblastic anaemia, muscle atrophy, myopathy, lactic acidosis, Hypertrophic cardiomyopathy, Hepatomegaly, Decreased cytochrome C oxidase activity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8306 | YARS | Zornitza Stark Phenotypes for gene: YARS were changed from Charcot-Marie-Tooth disease, dominant intermediate C 608323; Bi-allelic variants: ID, deafness, nystagmus to Charcot-Marie-Tooth disease, dominant intermediate C, MIM# 608323; MONDO:0012012; Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8305 | YARS | Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: Mono-allelic disease: More than 5 unrelated families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8305 | YARS | Zornitza Stark edited their review of gene: YARS: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8305 | YARS | Zornitza Stark edited their review of gene: YARS: Changed phenotypes: Charcot-Marie-Tooth disease, dominant intermediate C, MIM# 608323, MONDO:0012012, Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3643 | NARS |
Zornitza Stark gene: NARS was added gene: NARS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: NARS were set to 32738225 Phenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy Review for gene: NARS was set to GREEN Added comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model). Sources: Literature |
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| Mendeliome v0.2415 | YARS | Zornitza Stark Marked gene: YARS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2415 | YARS | Zornitza Stark Gene: yars has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2415 | YARS | Zornitza Stark Phenotypes for gene: YARS were changed from to Charcot-Marie-Tooth disease, dominant intermediate C 608323; Bi-allelic variants: ID, deafness, nystagmus | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2414 | YARS | Zornitza Stark Publications for gene: YARS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2413 | YARS | Zornitza Stark Mode of inheritance for gene: YARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2364 | YARS | Dean Phelan reviewed gene: YARS: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 30304524, 29232904, 27633801, 19561293; Phenotypes: peripheral neuropathy, multisystem disease, CMT; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | YARS2 |
Zornitza Stark gene: YARS2 was added gene: YARS2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: YARS2 was set to Unknown |
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| Mendeliome v0.0 | YARS |
Zornitza Stark gene: YARS was added gene: YARS was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: YARS was set to Unknown |
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