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| DDG2P v3.12 | ZFYVE26 | Achchuthan Shanmugasundram reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: ; Publications: 18098276, 11342696, 19805727, 17661097; Phenotypes: SPASTIC PARAPLEGIA AUTOSOMAL RECESSIVE TYPE 15, OMIM:270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | TRAPPC4 | Achchuthan Shanmugasundram reviewed gene: TRAPPC4: Rating: GREEN; Mode of pathogenicity: ; Publications: 33011761, 32125366, 31794024; Phenotypes: Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, OMIM:618741; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | TMEM63C | Achchuthan Shanmugasundram reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: ; Publications: 35718349; Phenotypes: TMEM63C-associated hereditary spastic paraplegia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | TECPR2 | Achchuthan Shanmugasundram reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: 23176824; Phenotypes: HEREDITARY SPASTIC PARAPARESIS, OMIM:615031; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | SPTAN1 | Achchuthan Shanmugasundram reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: ; Publications: 36331550, 34590414, 22258530, 20493457, 29050398; Phenotypes: SPTAN1-related neurodevelopmental disorder with epilepsy and spastic paraplegia, OMIM:613477; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | SPG11 | Achchuthan Shanmugasundram reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: ; Publications: 19194956, 17322883, 18067136, 17717710; Phenotypes: SPASTIC PARAPLEGIA-11, OMIM:604360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | SPAST | Achchuthan Shanmugasundram reviewed gene: SPAST: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: SPAST-related developmental disorder (monoallelic); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | SLC1A4 | Achchuthan Shanmugasundram reviewed gene: SLC1A4: Rating: GREEN; Mode of pathogenicity: ; Publications: 27193218, 26041762, 31763347, 34174466; Phenotypes: SLC1A4-related Spastic tetraplegia, thin corpus callosum, and progressive microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | SELENOI | Achchuthan Shanmugasundram reviewed gene: SELENOI: Rating: GREEN; Mode of pathogenicity: ; Publications: 29500230, 28052917; Phenotypes: EPT1-related complex progressive hereditary spastic paraplegia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | SACS | Achchuthan Shanmugasundram reviewed gene: SACS: Rating: GREEN; Mode of pathogenicity: ; Publications: 10655055; Phenotypes: SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE, OMIM:270550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | PLP1 | Achchuthan Shanmugasundram reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 9056547, 8723686, 1384324, 11071483, 8786077, 7573159, 14452137, 8659540, 7574457, 8956049, 2773936, 1715570, 1605230, 7683951, 1720927, 8320699, 9489796, 17438221, 8696336, 2480601, 3827224, 1707231; Phenotypes: LEUKODYSTROPHY HYPOMYELINATING TYPE 1, OMIM:312080, SPASTIC PARAPLEGIA X-LINKED TYPE 2, OMIM:312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | PCYT2 | Achchuthan Shanmugasundram reviewed gene: PCYT2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32889549, 31637422; Phenotypes: COMPLEX HEREDITARY SPASTIC PARAPLEGIA, OMIM:615033; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | NRCAM | Achchuthan Shanmugasundram reviewed gene: NRCAM: Rating: GREEN; Mode of pathogenicity: ; Publications: 35108495; Phenotypes: NRCAM neurodevelopmental disorder with dysmorphic features, hypotonia and spasticity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | NOVA2 | Achchuthan Shanmugasundram reviewed gene: NOVA2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32197073; Phenotypes: Intellectual disability with ataxia/spasticity; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | NKX6-2 | Achchuthan Shanmugasundram reviewed gene: NKX6-2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28575651; Phenotypes: Progressive Spastic Ataxia and Hypomyelination; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | KIDINS220 | Achchuthan Shanmugasundram reviewed gene: KIDINS220: Rating: GREEN; Mode of pathogenicity: ; Publications: 27005418, 28934391, 32909676; Phenotypes: KIDINS220-related Developmental Disorder, biallelic, Spastic paraplegia, intellectual disability, nystagmus, and obesity., OMIM:617296; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | KANK1 | Achchuthan Shanmugasundram reviewed gene: KANK1: Rating: RED; Mode of pathogenicity: ; Publications: 16301218; Phenotypes: CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 2, OMIM:612900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | GBA2 | Achchuthan Shanmugasundram reviewed gene: GBA2: Rating: GREEN; Mode of pathogenicity: ; Publications: 23332917; Phenotypes: AUTOSOMAL-RECESSIVE CEREBELLAR ATAXIA WITH SPASTICITY.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | GAD1 | Achchuthan Shanmugasundram reviewed gene: GAD1: Rating: RED; Mode of pathogenicity: Other; Publications: 15571623; Phenotypes: CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 1, OMIM:603513; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | ELOVL4 | Achchuthan Shanmugasundram reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: ; Publications: 22100072; Phenotypes: ICHTHYOSIS, SPASTIC QUADRIPLEGIA, AND INTELLECTUAL DEVELOPMENTAL DISORDER, OMIM:614457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | DSTYK | Achchuthan Shanmugasundram reviewed gene: DSTYK: Rating: GREEN; Mode of pathogenicity: ; Publications: 23862974, 28157540; Phenotypes: Autosomal Recessive Complicated Spastic Paraparesis SPG23, CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT, CAKUT1, OMIM:610805; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | DDHD2 | Achchuthan Shanmugasundram reviewed gene: DDHD2: Rating: GREEN; Mode of pathogenicity: ; Publications: 23176823; Phenotypes: COMPLEX HEREDITARY SPASTIC PARAPLEGIA, OMIM:615033; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | DDHD1 | Achchuthan Shanmugasundram reviewed gene: DDHD1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23176821, 15786464; Phenotypes: HEREDITARY SPASTIC PARAPLEGIA, OMIM:615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | DARS | Achchuthan Shanmugasundram reviewed gene: DARS: Rating: GREEN; Mode of pathogenicity: Other; Publications: 23643384; Phenotypes: HYPOMYELINATION WITH BRAIN STEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY., OMIM:615281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | CYP2U1 | Achchuthan Shanmugasundram reviewed gene: CYP2U1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23176821; Phenotypes: HEREDITARY SPASTIC PARAPLEGIA, OMIM:615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | ATL1 | Achchuthan Shanmugasundram reviewed gene: ATL1: Rating: GREEN; Mode of pathogenicity: ; Publications: 35925862; Phenotypes: ATL1-associated hereditary spastic paraplegia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | AP4S1 | Achchuthan Shanmugasundram reviewed gene: AP4S1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21620353; Phenotypes: CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 6, OMIM:614067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | AP4M1 | Achchuthan Shanmugasundram reviewed gene: AP4M1: Rating: GREEN; Mode of pathogenicity: ; Publications: 19559397; Phenotypes: CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 3, OMIM:612936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | AP4E1 | Achchuthan Shanmugasundram reviewed gene: AP4E1: Rating: GREEN; Mode of pathogenicity: ; Publications: 20972249; Phenotypes: CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 4, OMIM:613744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | AP4B1 | Achchuthan Shanmugasundram reviewed gene: AP4B1: Rating: GREEN; Mode of pathogenicity: ; Publications: 22290197, 21620353; Phenotypes: CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 5, OMIM:614066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | ALDH18A1 | Achchuthan Shanmugasundram reviewed gene: ALDH18A1: Rating: GREEN; Mode of pathogenicity: ; Publications: 26829900, 26297557, 26297558, 26320891, 28228640, 26026163; Phenotypes: INTELLECTUAL DEVELOPMENTAL DISORDER-JOINT HYPERMOBILITY-SKIN LAXITY WITH OR WITHOUT METABOLIC ABNORMALITIES, OMIM:612652, SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT, OMIM:601162, CUTIS LAXA, AUTOSOMAL DOMINANT 3, OMIM:616603; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | ABHD16A | Achchuthan Shanmugasundram reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: ; Publications: 34587489; Phenotypes: ABHD16A-associated spastic paraplegia, intellectual disability and thin corpus callosum; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.11 | TRAPPC4 |
Achchuthan Shanmugasundram gene: TRAPPC4 was added gene: TRAPPC4 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: TRAPPC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAPPC4 were set to 33011761; 32125366; 31794024 Phenotypes for gene: TRAPPC4 were set to Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, OMIM:618741 |
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| DDG2P v3.11 | TMEM63C |
Achchuthan Shanmugasundram gene: TMEM63C was added gene: TMEM63C was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: TMEM63C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM63C were set to 35718349 Phenotypes for gene: TMEM63C were set to TMEM63C-associated hereditary spastic paraplegia |
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| DDG2P v3.11 | SPAST |
Achchuthan Shanmugasundram gene: SPAST was added gene: SPAST was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SPAST were set to SPAST-related developmental disorder (monoallelic) Mode of pathogenicity for gene: SPAST was set to Other |
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| DDG2P v3.11 | SLC1A4 |
Achchuthan Shanmugasundram gene: SLC1A4 was added gene: SLC1A4 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: SLC1A4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC1A4 were set to 27193218; 26041762; 31763347; 34174466 Phenotypes for gene: SLC1A4 were set to SLC1A4-related Spastic tetraplegia, thin corpus callosum, and progressive microcephaly |
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| DDG2P v3.11 | PCYT2 |
Achchuthan Shanmugasundram gene: PCYT2 was added gene: PCYT2 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCYT2 were set to 32889549; 31637422 Phenotypes for gene: PCYT2 were set to COMPLEX HEREDITARY SPASTIC PARAPLEGIA, OMIM:615033 |
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| DDG2P v3.11 | NRCAM |
Achchuthan Shanmugasundram gene: NRCAM was added gene: NRCAM was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: NRCAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NRCAM were set to 35108495 Phenotypes for gene: NRCAM were set to NRCAM neurodevelopmental disorder with dysmorphic features, hypotonia and spasticity |
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| DDG2P v3.11 | ATL1 |
Achchuthan Shanmugasundram gene: ATL1 was added gene: ATL1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: ATL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ATL1 were set to 35925862 Phenotypes for gene: ATL1 were set to ATL1-associated hereditary spastic paraplegia |
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| DDG2P v3.11 | ABHD16A |
Achchuthan Shanmugasundram gene: ABHD16A was added gene: ABHD16A was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABHD16A were set to 34587489 Phenotypes for gene: ABHD16A were set to ABHD16A-associated spastic paraplegia, intellectual disability and thin corpus callosum |
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| DDG2P v2.50 | ATG7 |
Dmitrijs Rots gene: ATG7 was added gene: ATG7 was added to DDG2P. Sources: Literature Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATG7 were set to PMID:34161705 Phenotypes for gene: ATG7 were set to developmental delay; ataxia Review for gene: ATG7 was set to GREEN Added comment: Zornitsa Stark wrote for this gene in Ataxia panel: "12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The more severely affected individuals had spastic paraplegia and inability to walk. Functional data including mouse model. " Should be also on ID panel. Sources: Literature |
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| DDG2P v2.50 | KPNA3 |
Dmitrijs Rots gene: KPNA3 was added gene: KPNA3 was added to DDG2P. Sources: Literature Mode of inheritance for gene: KPNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KPNA3 were set to PMID: 34564892 Phenotypes for gene: KPNA3 were set to Infantile onset spastic paraplegia; developmental delay Penetrance for gene: KPNA3 were set to unknown Mode of pathogenicity for gene: KPNA3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: KPNA3 was set to GREEN Added comment: 8 reported families with de novo missense variants, that segregates with pure HSP with infantile onset and some functional data PMID: 34564892 Sources: Literature |
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| DDG2P v2.9 | SLC12A6 | Sarah Leigh commented on gene: SLC12A6: Associated with Agenesis of the corpus callosum with peripheral neuropathy 218000 in OMIM and as confirmed Gen2Phen gene. At least 10 biallelic variants were reported in at least 10 unrelated cases. 9/10 of these variants was terminating (PMID 12368912, 16606917, 17893295). Three de novo heterozygous missense variants have been identified in four unrelated cases with a milder phenotype of early- onset progressive Charcot- Marie-tooth disease (CMT) with or without spasticity (intermediate CMT)(PMID 31439721, 27485015). The authors of PMID 31439721 suggest that "autosomal- dominant inheritance of SLC12A6 variants also needs to be considered in patients with early- onset neuropathies". Furthermore, it will be important to understand the functional differences between the variants, as PMID 27485015 reported variant - p.Thr991Ala, resulted in increased potassium influx in Xenopus oocytes (gain-of-function), while the other missense variants identified so far had a loss-of-function effect in varying degrees (PMID 31439721). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.62 | ALDH18A1 | Rebecca Foulger Added comment: Comment on mode of inheritance: DDG2P MOI is monoallelic for CUTIS LAXA, AUTOSOMAL DOMINANT 3;biallelic for MENTAL RETARDATION-JOINT HYPERMOBILITY-SKIN LAXITY WITH OR WITHOUT METABOLIC ABNORMALITIES; monoallelic for SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT. All disorders have a confirmed Disease confidence rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.60 | GJC2 | Rebecca Foulger Added comment: Comment on mode of inheritance: In DDG2P, MOI is listed as biallelic for LEUKODYSTROPHY, HYPOMYELINATING, 2; monoallelic for LYMPHEDEMA, HEREDITARY, IC; monoallelic for SPASTIC PARAPLEGIA, 44. All disorders have a confirmed Disease confidence rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.15 | DSTYK | Rebecca Foulger Phenotypes for gene: DSTYK were changed from CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT, CAKUT1 610805 to CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT, CAKUT1 610805; Autosomal Recessive Complicated Spastic Paraparesis SPG23 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.14 | DSTYK | Rebecca Foulger commented on gene: DSTYK: Added 'watchlist' tag to highlight different Disease confidence ratings in DD-G2P: Confirmed for CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT, CAKUT1. Probable for Autosomal Recessive Complicated Spastic Paraparesis SPG23 (Added to G2P in March 2019). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.14 | DSTYK | Rebecca Foulger commented on gene: DSTYK: Multiple MOIs in Gene2Phenotype: 'monoallelic' for CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT, CAKUT1, and 'biallelic' for Autosomal Recessive Complicated Spastic Paraparesis SPG23. Kept MOI in PanelApp as 'monoallelic' because 'CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT, CAKUT1' is 'confirmed', and Autosomal Recessive Complicated Spastic Paraparesis SPG23 is 'probable'. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.14 | DSTYK | Rebecca Foulger commented on gene: DSTYK: New gene:disorder association added to DDG2P in March 2019: Autosomal Recessive Complicated Spastic Paraparesis SPG23. DDG2P Disease confidence: probable. DDG2P mode of pathogenicity/mutation consequence: loss of function. DDG2P mode of inheritance: biallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v0.95 | AFG3L2 | Rebecca Foulger commented on gene: AFG3L2: Kept rating as Amber to reflect DDG2P Disease confidence of 'child IF' for SPINOCEREBELLAR ATAXIA 28; ATAXIA, SPASTIC, 5, AUTOSOMAL RECESSIVE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v0.93 | UFC1 | Rebecca Foulger Added comment: Comment on mode of inheritance: No MOI is given in DDG2P for UFC1 Disease: Severe early-onset encephalopathy with progressive microcephaly. Set MOI to 'biallelic' to match OMIM 'Neurodevelopmental disorder with spasticity and poor growth, 618076'. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v0.1 | ZFYVE26 |
Rebecca Foulger gene: ZFYVE26 was added gene: ZFYVE26 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZFYVE26 were set to 11342696; 19805727; 18098276; 17661097 Phenotypes for gene: ZFYVE26 were set to SPASTIC PARAPLEGIA AUTOSOMAL RECESSIVE TYPE 15 270700 |
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| DDG2P v0.1 | TECPR2 |
Rebecca Foulger gene: TECPR2 was added gene: TECPR2 was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TECPR2 were set to 23176824 Phenotypes for gene: TECPR2 were set to HEREDITARY SPASTIC PARAPARESIS 615031 |
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| DDG2P v0.1 | SPG11 |
Rebecca Foulger gene: SPG11 was added gene: SPG11 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPG11 were set to 17717710; 19194956; 17322883; 18067136 Phenotypes for gene: SPG11 were set to SPASTIC PARAPLEGIA-11 604360 |
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| DDG2P v0.1 | SELENOI |
Rebecca Foulger gene: SELENOI was added gene: SELENOI was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype Mode of inheritance for gene: SELENOI was set to Publications for gene: SELENOI were set to 28052917; 29500230 Phenotypes for gene: SELENOI were set to EPT1-related complex progressive hereditary spastic paraplegia |
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| DDG2P v0.1 | SACS |
Rebecca Foulger gene: SACS was added gene: SACS was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SACS were set to 10655055 Phenotypes for gene: SACS were set to SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE 270550 |
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| DDG2P v0.1 | PLP1 |
Rebecca Foulger Added phenotypes SPASTIC PARAPLEGIA X-LINKED TYPE 2 312920 for gene: PLP1 Publications for gene PLP1 were changed from 8659540; 8723686; 3827224; 9056547; 11071483; 1720927; 7574457; 1707231; 2773936; 1715570; 8696336; 8786077; 1384324; 7573159; 7683951; 1605230; 2480601 to 17438221; 9489796; 8320699; 8956049; 14452137 |
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| DDG2P v0.1 | NOVA2 |
Rebecca Foulger gene: NOVA2 was added gene: NOVA2 was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype Mode of inheritance for gene: NOVA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: NOVA2 were set to Intellectual disability with ataxia/spasticity |
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| DDG2P v0.1 | NKX6-2 |
Rebecca Foulger gene: NKX6-2 was added gene: NKX6-2 was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype Mode of inheritance for gene: NKX6-2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NKX6-2 were set to 28575651 Phenotypes for gene: NKX6-2 were set to Progressive Spastic Ataxia and Hypomyelination |
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| DDG2P v0.1 | L1CAM |
Rebecca Foulger Added phenotypes SPASTIC PARAPLEGIA X-LINKED TYPE 1 303350 for gene: L1CAM Publications for gene L1CAM were changed from 26916325 to 7920659; 7920660; 3460961 |
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| DDG2P v0.1 | KIDINS220 |
Rebecca Foulger gene: KIDINS220 was added gene: KIDINS220 was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype Mode of inheritance for gene: KIDINS220 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KIDINS220 were set to 27005418 Phenotypes for gene: KIDINS220 were set to Spastic paraplegia, intellectual disability, nystagmus, and obesity. |
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| DDG2P v0.1 | KANK1 |
Rebecca Foulger gene: KANK1 was added gene: KANK1 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype Mode of inheritance for gene: KANK1 was set to Publications for gene: KANK1 were set to 16301218 Phenotypes for gene: KANK1 were set to CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 2 612900 |
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| DDG2P v0.1 | GJC2 |
Rebecca Foulger Added phenotypes SPASTIC PARAPLEGIA, 44 613206 for gene: GJC2 Publications for gene GJC2 were changed from 20537300 to 19056803 |
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| DDG2P v0.1 | GBA2 |
Rebecca Foulger gene: GBA2 was added gene: GBA2 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: GBA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GBA2 were set to 23332917 Phenotypes for gene: GBA2 were set to AUTOSOMAL-RECESSIVE CEREBELLAR ATAXIA WITH SPASTICITY. |
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| DDG2P v0.1 | GAD1 |
Rebecca Foulger gene: GAD1 was added gene: GAD1 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype Mode of inheritance for gene: GAD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GAD1 were set to 15571623 Phenotypes for gene: GAD1 were set to CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 1 603513 Mode of pathogenicity for gene: GAD1 was set to Other - please provide details in the comments |
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| DDG2P v0.1 | ELOVL4 |
Rebecca Foulger gene: ELOVL4 was added gene: ELOVL4 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: ELOVL4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ELOVL4 were set to 22100072 Phenotypes for gene: ELOVL4 were set to ICHTHYOSIS, SPASTIC QUADRIPLEGIA, AND MENTAL RETARDATION 614457 |
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| DDG2P v0.1 | DDHD2 |
Rebecca Foulger gene: DDHD2 was added gene: DDHD2 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: DDHD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DDHD2 were set to 23176823 Phenotypes for gene: DDHD2 were set to COMPLEX HEREDITARY SPASTIC PARAPLEGIA 615033 |
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| DDG2P v0.1 | DDHD1 |
Rebecca Foulger gene: DDHD1 was added gene: DDHD1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: DDHD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DDHD1 were set to 15786464; 23176821 Phenotypes for gene: DDHD1 were set to HEREDITARY SPASTIC PARAPLEGIA 615030 |
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| DDG2P v0.1 | DARS |
Rebecca Foulger gene: DARS was added gene: DARS was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: DARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DARS were set to 23643384 Phenotypes for gene: DARS were set to HYPOMYELINATION WITH BRAIN STEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY. 615281 Mode of pathogenicity for gene: DARS was set to Other - please provide details in the comments |
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| DDG2P v0.1 | CYP2U1 |
Rebecca Foulger gene: CYP2U1 was added gene: CYP2U1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: CYP2U1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CYP2U1 were set to 23176821 Phenotypes for gene: CYP2U1 were set to HEREDITARY SPASTIC PARAPLEGIA 615030 |
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| DDG2P v0.1 | AP4S1 |
Rebecca Foulger gene: AP4S1 was added gene: AP4S1 was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype Mode of inheritance for gene: AP4S1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP4S1 were set to 21620353 Phenotypes for gene: AP4S1 were set to CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 6 614067 |
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| DDG2P v0.1 | AP4M1 |
Rebecca Foulger gene: AP4M1 was added gene: AP4M1 was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype Mode of inheritance for gene: AP4M1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP4M1 were set to 19559397 Phenotypes for gene: AP4M1 were set to CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 3 612936 |
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| DDG2P v0.1 | AP4E1 |
Rebecca Foulger gene: AP4E1 was added gene: AP4E1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: AP4E1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP4E1 were set to 20972249 Phenotypes for gene: AP4E1 were set to CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 4 613744 |
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| DDG2P v0.1 | AP4B1 |
Rebecca Foulger gene: AP4B1 was added gene: AP4B1 was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype Mode of inheritance for gene: AP4B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP4B1 were set to 21620353; 22290197 Phenotypes for gene: AP4B1 were set to CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 5 614066 |
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| DDG2P v0.1 | ALDH18A1 |
Rebecca Foulger gene: ALDH18A1 was added gene: ALDH18A1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: ALDH18A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: ALDH18A1 were set to SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT 601162 |
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| DDG2P v0.1 | AFG3L2 |
Rebecca Foulger Added phenotypes ATAXIA, SPASTIC, 5, AUTOSOMAL RECESSIVE 614487 for gene: AFG3L2 Publications for gene AFG3L2 were changed from 20208537 to 22964162 |
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