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Ataxia and cerebellar anomalies - narrow panel v4.64 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Ataxia and cerebellar anomalies - narrow panel v4.64 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Classified gene: ATP2B3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v4.63 ATP2B3 Achchuthan Shanmugasundram Gene: atp2b3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.62 ATP2B3 Achchuthan Shanmugasundram Publications for gene: ATP2B3 were set to
Ataxia and cerebellar anomalies - narrow panel v4.61 ATP2B3 Achchuthan Shanmugasundram Phenotypes for gene: ATP2B3 were changed from Spinocerebellar ataxia, X-linked 1 to ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Ataxia and cerebellar anomalies - narrow panel v4.60 ATP2B3 Achchuthan Shanmugasundram Mode of inheritance for gene: ATP2B3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: ATP2B3.
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram changed review comment from: There are six unrelated cases reported with X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases. There is also functional evidence available.

This gene has already been associated with ataxia in OMIM (MIM #302500), but not yet with any phenotypes in Gene2Phenotype.; to: There are six unrelated cases reported with five different X-linked recessive variants in ATP2B3 gene and with a phenotype comprising ataxia. However, the onset of the disease was during childhood in three of these cases, while detailed clinical information was not available for the other three cases. There is also functional evidence available.

This gene has already been associated with ataxia in OMIM (MIM #302500), but not yet with any phenotypes in Gene2Phenotype.
Ataxia and cerebellar anomalies - narrow panel v4.59 ATP2B3 Achchuthan Shanmugasundram reviewed gene: ATP2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25953895, 28807751, 36207321; Phenotypes: ?Spinocerebellar ataxia, X-linked 1, OMIM:302500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia and cerebellar anomalies - narrow panel v4.59 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Cerebellar ataxia, MONDO:0000437; Early-onset ataxia to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Dmitrijs Rots reviewed gene: ZFHX3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Sarah Leigh reviewed gene: ZFHX3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Sarah Leigh Tag STR tag was added to gene: ZFHX3.
Ataxia and cerebellar anomalies - narrow panel v4.58 ZFHX3 Sarah Leigh Phenotypes for gene: ZFHX3 were changed from syndromic intellectual disability to Spinocerebellar ataxia 4, OMIM:600223; spinocerebellar ataxia type 4, MONDO:0010847
Ataxia and cerebellar anomalies - narrow panel v4.57 ZFHX3 Sarah Leigh Entity copied from Intellectual disability - microarray and sequencing v5.499
Ataxia and cerebellar anomalies - narrow panel v4.57 ZFHX3 Sarah Leigh gene: ZFHX3 was added
gene: ZFHX3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: ZFHX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZFHX3 were set to 38412861; 38035881; 37292950
Phenotypes for gene: ZFHX3 were set to syndromic intellectual disability
Ataxia and cerebellar anomalies - narrow panel v4.56 MSTO1 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance should be changed to BIALLELIC, autosomal or pseudoautosomal.
Ataxia and cerebellar anomalies - narrow panel v4.56 MSTO1 Sarah Leigh Mode of inheritance for gene: MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.55 MSTO1 Sarah Leigh Tag Q1_24_MOI tag was added to gene: MSTO1.
Ataxia and cerebellar anomalies - narrow panel v4.55 MSTO1 Sarah Leigh Publications for gene: MSTO1 were set to 28554942; 28544275; 31604776; 31463572; 31130378; 30684668; 29339779
Ataxia and cerebellar anomalies - narrow panel v4.54 MSTO1 Sarah Leigh edited their review of gene: MSTO1: Added comment: Gal et al (2017) reported a family with autosomal dominant mitochondrial myopathy and ataxia caused by a monoallelic MSTO1 variant (PMID: 28554942). Subsequently, the variant involved (rs762798018) has been reclassified as a variant of unknown significance, this is because Gal et al (2023)(PMID:37431817) have retracted their claim that there is a direct link between the variant and the patients' myopathy and ataxia phenotypes.
There are no further reports of monoallelic Myopathy, mitochondrial, and ataxia (OMIM:617675).; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.54 HMBS Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are three unrelated families reported with ataxia. Hence, this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: There are three unrelated families reported with ataxia. Hence, this gene can be promoted to green rating in the next GMS review.
Ataxia and cerebellar anomalies - narrow panel v4.54 HMBS Achchuthan Shanmugasundram Classified gene: HMBS as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.54 HMBS Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated families reported with ataxia. Hence, this gene can be promoted to green rating in the next GMS review.
Ataxia and cerebellar anomalies - narrow panel v4.54 HMBS Achchuthan Shanmugasundram Gene: hmbs has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.53 HMBS Achchuthan Shanmugasundram Phenotypes for gene: HMBS were changed from Leukoencephalopathy, HP:0002352; hereditary spastic paraplegia, MONDO:0019064 to Leukoencephalopathy, HP:0002352; cerebellar ataxia, MONDO:0000437
Ataxia and cerebellar anomalies - narrow panel v4.52 HMBS Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: HMBS.
Ataxia and cerebellar anomalies - narrow panel v4.52 HMBS Achchuthan Shanmugasundram edited their review of gene: HMBS: Changed phenotypes to: Leukoencephalopathy, HP:0002352, cerebellar ataxia, MONDO:0000437
Ataxia and cerebellar anomalies - narrow panel v4.52 HMBS Achchuthan Shanmugasundram gene: HMBS was added
gene: HMBS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: HMBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMBS were set to 27558376; 34089223
Phenotypes for gene: HMBS were set to Leukoencephalopathy, HP:0002352; hereditary spastic paraplegia, MONDO:0019064
Review for gene: HMBS was set to GREEN
Added comment: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

Monoallelic variants in HMBS gene have been associated with acute intermittent porphyria (MIM #176000) in OMIM, but biallelic variants have not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v4.51 PRICKLE1 Arina Puzriakova Phenotypes for gene: PRICKLE1 were changed from Progressive Myoclonus Epilepsy with Ataxia to Epilepsy, progressive myoclonic 1B, OMIM:612437
Ataxia and cerebellar anomalies - narrow panel v4.50 ACBD6 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.405
Ataxia and cerebellar anomalies - narrow panel v4.50 ACBD6 Arina Puzriakova gene: ACBD6 was added
gene: ACBD6 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Q1_24_promote_green tags were added to gene: ACBD6.
Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD6 were set to 21937992; 32108178; 36457943; 37951597
Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder, MONDO:0700092
Penetrance for gene: ACBD6 were set to Complete
Ataxia and cerebellar anomalies - narrow panel v4.49 ASL Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 patients including 2 out of 7 patients with ataxia (patients 25 and 33, c.437G>A; c.446+1G>A and c.348+1G>A; c.532G>A respectively). Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective analysis of patients with ASA prior to March 2013 and then prospective analysis of patients until December 2015. Ataxia was reported in 9 out of 52 patients studied. Ataxia was first noticed at a median age of 8.5 years. The genotype was available for 19 patients, including 3 of those with Ataxia (patients 1, 4 and 14) each with a different homozygous missense variant (c.35G>A;p.(Arg12Gln), c.377G>A;p.(Arg126G1n) and c.1138A>G;p.(Lys380Glu) respectively.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.
PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries, PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 patients including 2 out of 7 patients with ataxia (patients 25 and 33, c.437G>A; c.446+1G>A and c.348+1G>A; c.532G>A respectively). Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective analysis of patients with ASA prior to March 2013 and then prospective analysis of patients until December 2015. Ataxia was reported in 9 out of 52 patients studied. Ataxia was first noticed at a median age of 8.5 years. The genotype was available for 19 patients, including 3 of those with Ataxia (patients 1, 4 and 14) each with a different homozygous missense variant (c.35G>A;p.(Arg12Gln), c.377G>A;p.(Arg126G1n) and c.1138A>G;p.(Lys380Glu) respectively.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. )
Ataxia and cerebellar anomalies - narrow panel v4.49 ASL Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. Ataxia was first noticed at a median age of 8.5 years. The genotype was available for 19 patients, including 3 of those with Ataxia (patients 1, 4 and 14) each with a different homozygous missense variant.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 patients including 2 out of 7 patients with ataxia (patients 25 and 33, c.437G>A; c.446+1G>A and c.348+1G>A; c.532G>A respectively). Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective analysis of patients with ASA prior to March 2013 and then prospective analysis of patients until December 2015. Ataxia was reported in 9 out of 52 patients studied. Ataxia was first noticed at a median age of 8.5 years. The genotype was available for 19 patients, including 3 of those with Ataxia (patients 1, 4 and 14) each with a different homozygous missense variant (c.35G>A;p.(Arg12Gln), c.377G>A;p.(Arg126G1n) and c.1138A>G;p.(Lys380Glu) respectively.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. )
Ataxia and cerebellar anomalies - narrow panel v4.49 DLG4 Achchuthan Shanmugasundram Classified gene: DLG4 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.49 DLG4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are nine unrelated cases reported with monoallelic DLG4 variants and ataxia. Hence, this gene can be promoted to green rating in the next GMS review.
Ataxia and cerebellar anomalies - narrow panel v4.49 DLG4 Achchuthan Shanmugasundram Gene: dlg4 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.48 DLG4 Achchuthan Shanmugasundram Phenotypes for gene: DLG4 were changed from Intellectual developmental disorder, autosomal dominant 62 to Intellectual developmental disorder, autosomal dominant 62, OMIM:618793
Ataxia and cerebellar anomalies - narrow panel v4.47 DLG4 Achchuthan Shanmugasundram Publications for gene: DLG4 were set to PMID: 33597769
Ataxia and cerebellar anomalies - narrow panel v4.46 DLG4 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: DLG4.
Ataxia and cerebellar anomalies - narrow panel v4.46 DLG4 Achchuthan Shanmugasundram reviewed gene: DLG4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 62, OMIM:618793; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.46 ASL Eleanor Williams Tag Q4_23_promote_green tag was added to gene: ASL.
Tag Q4_23_NHS_review tag was added to gene: ASL.
Ataxia and cerebellar anomalies - narrow panel v4.46 ASL Eleanor Williams changed review comment from: Comment on list classification: Promoting this gene to amber as there are 2 cases of patients with ataxia and variants identified in the ASL gene (from PMID: 38044746 - Gurung et al 2023). Consulting with the Genomics England clinical team whether it would be appropriate to rate green.; to: Comment on list classification: Promoting this gene to amber with a recommendation for green rating as there are 5 cases of patients with ataxia and variants identified in the ASL gene (from PMID: 38044746 - Gurung et al 2023 and PMID: 28251416 - Baruteau et al 2017).
Ataxia and cerebellar anomalies - narrow panel v4.46 ASL Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. Ataxia was first noticed at a median age of 8.5 years. The genotype was available for 19 patients, including 3 of those with Ataxia (patients 1, 4 and 14) each with a different homozygous missense variant.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. )
Ataxia and cerebellar anomalies - narrow panel v4.46 ASL Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. )
Ataxia and cerebellar anomalies - narrow panel v4.46 ASL Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not mentioned as a phenotypic feature.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. )
Ataxia and cerebellar anomalies - narrow panel v4.46 ASL Eleanor Williams Classified gene: ASL as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.46 ASL Eleanor Williams Added comment: Comment on list classification: Promoting this gene to amber as there are 2 cases of patients with ataxia and variants identified in the ASL gene (from PMID: 38044746 - Gurung et al 2023). Consulting with the Genomics England clinical team whether it would be appropriate to rate green.
Ataxia and cerebellar anomalies - narrow panel v4.46 ASL Eleanor Williams Gene: asl has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.45 ASL Eleanor Williams Publications for gene: ASL were set to 38044746; 36994644; 28251416
Ataxia and cerebellar anomalies - narrow panel v4.44 ASL Eleanor Williams Phenotypes for gene: ASL were changed from Ataxia to Argininosuccinic aciduria, OMIM:207900; argininosuccinic aciduria, MONDO:0008815; Ataxia, HP:0001251
Ataxia and cerebellar anomalies - narrow panel v4.43 ASL Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not mentioned as a phenotypic feature.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals. 2 confirmed cases with ataxia and ASL variants are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not mentioned as a phenotypic feature.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. )
Ataxia and cerebellar anomalies - narrow panel v4.43 ASL Eleanor Williams commented on gene: ASL
Ataxia and cerebellar anomalies - narrow panel v4.43 THG1L Achchuthan Shanmugasundram Classified gene: THG1L as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.43 THG1L Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Ataxia and cerebellar anomalies - narrow panel v4.43 THG1L Achchuthan Shanmugasundram Gene: thg1l has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.42 THG1L Achchuthan Shanmugasundram Phenotypes for gene: THG1L were changed from Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800; Spinocerebellar ataxia, autosomal recessive 28, MONDO:0032923 to Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800, MONDO:0032923
Ataxia and cerebellar anomalies - narrow panel v4.41 THG1L Achchuthan Shanmugasundram Publications for gene: THG1L were set to 27307223; 30214071; 31168944
Ataxia and cerebellar anomalies - narrow panel v4.40 THG1L Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: THG1L.
Tag Q4_23_NHS_review tag was added to gene: THG1L.
Ataxia and cerebellar anomalies - narrow panel v4.40 THG1L Achchuthan Shanmugasundram reviewed gene: THG1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 27307223, 30214071, 31168944, 33682303, 37670026; Phenotypes: Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.40 ASL Nour Elkhateeb gene: ASL was added
gene: ASL was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: ASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASL were set to 38044746; 36994644; 28251416
Phenotypes for gene: ASL were set to Ataxia
Added comment: Ataxia has been reported in multiple individuals with argininosuccinic aciduria (PMID 38044746, 36994644, 28251416).
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v4.40 THG1L Hannah Knight reviewed gene: THG1L: Rating: AMBER; Mode of pathogenicity: None; Publications: 33682303, 33682303; Phenotypes: Spinocerebellar ataxia, autosomal recessive 28; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.40 DLG4 Dmitrijs Rots gene: DLG4 was added
gene: DLG4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: DLG4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLG4 were set to PMID: 33597769
Phenotypes for gene: DLG4 were set to Intellectual developmental disorder, autosomal dominant 62
Penetrance for gene: DLG4 were set to Complete
Review for gene: DLG4 was set to GREEN
Added comment: PMID: 33597769 described a large cohort with DLG4-synaptopathy, where at least 19 individuals are with movement disorders, and 9 are with ataxia.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v4.38 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Ataxia and cerebellar anomalies - narrow panel v4.38 FEM1C Eleanor Williams Tag gene-checked tag was added to gene: FEM1C.
Ataxia and cerebellar anomalies - narrow panel v4.38 FEM1C Eleanor Williams commented on gene: FEM1C: This gene currently has no phenotype listed in OMIM so checked PMID:36336956 to make sure the same gene name is listed. It is so added the gene-checked tag.
Ataxia and cerebellar anomalies - narrow panel v4.38 TECPR2 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: TECPR2.
Ataxia and cerebellar anomalies - narrow panel v4.38 SPTAN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: SPTAN1.
Ataxia and cerebellar anomalies - narrow panel v4.38 SPG7 Achchuthan Shanmugasundram Tag Q2_23_MOI was removed from gene: SPG7.
Ataxia and cerebellar anomalies - narrow panel v4.38 SLC52A2 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: SLC52A2.
Ataxia and cerebellar anomalies - narrow panel v4.38 SLC25A46 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: SLC25A46.
Ataxia and cerebellar anomalies - narrow panel v4.38 SCN2A Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: SCN2A.
Ataxia and cerebellar anomalies - narrow panel v4.38 NPTX1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: NPTX1.
Ataxia and cerebellar anomalies - narrow panel v4.38 NFASC Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: NFASC.
Ataxia and cerebellar anomalies - narrow panel v4.38 INTS11 Arina Puzriakova Phenotypes for gene: INTS11 were changed from Complex neurodevelopmental disorder, MONDO:0100038 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428
Ataxia and cerebellar anomalies - narrow panel v4.37 MAG Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: MAG.
Ataxia and cerebellar anomalies - narrow panel v4.37 INTS11 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: INTS11.
Ataxia and cerebellar anomalies - narrow panel v4.37 GRN Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: GRN.
Ataxia and cerebellar anomalies - narrow panel v4.37 FRMD5 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: FRMD5.
Ataxia and cerebellar anomalies - narrow panel v4.37 FMR1 Achchuthan Shanmugasundram Tag Q4_22_demote_red was removed from gene: FMR1.
Ataxia and cerebellar anomalies - narrow panel v4.37 FEM1C Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: FEM1C.
Ataxia and cerebellar anomalies - narrow panel v4.37 COQ4 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: COQ4.
Ataxia and cerebellar anomalies - narrow panel v4.37 SUFU Achchuthan Shanmugasundram Tag watchlist_moi was removed from gene: SUFU.
Tag Q4_22_MOI was removed from gene: SUFU.
Tag Q4_22_promote_green was removed from gene: SUFU.
Tag Q4_22_expert_review was removed from gene: SUFU.
Ataxia and cerebellar anomalies - narrow panel v4.37 TECPR2 Eleanor Williams reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 SUFU Eleanor Williams reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 SPTAN1 Eleanor Williams reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.37 SPG7 Eleanor Williams edited their review of gene: SPG7: Added comment: The mode of inheritance of this gene has been updated to"BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal"following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 SLC52A2 Eleanor Williams reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 SLC25A46 Eleanor Williams reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 SCN2A Eleanor Williams reviewed gene: SCN2A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.37 NPTX1 Eleanor Williams reviewed gene: NPTX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.37 NFASC Eleanor Williams reviewed gene: NFASC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 MAG Eleanor Williams reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 INTS11 Eleanor Williams reviewed gene: INTS11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 GRN Eleanor Williams reviewed gene: GRN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 FRMD5 Eleanor Williams reviewed gene: FRMD5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ataxia and cerebellar anomalies - narrow panel v4.37 FMR1 Eleanor Williams reviewed gene: FMR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v4.37 FEM1C Eleanor Williams reviewed gene: FEM1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.37 COQ4 Eleanor Williams reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.36 SUFU Achchuthan Shanmugasundram Mode of inheritance for gene SUFU was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.35 TECPR2 Achchuthan Shanmugasundram Source Expert Review Green was added to TECPR2.
Source NHS GMS was added to TECPR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 SUFU Achchuthan Shanmugasundram Source Expert Review Green was added to SUFU.
Source NHS GMS was added to SUFU.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 SPTAN1 Achchuthan Shanmugasundram Source Expert Review Green was added to SPTAN1.
Source NHS GMS was added to SPTAN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 SPG7 Achchuthan Shanmugasundram Source NHS GMS was added to SPG7.
Mode of inheritance for gene SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.35 SLC52A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC52A2.
Source NHS GMS was added to SLC52A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 SLC25A46 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC25A46.
Source NHS GMS was added to SLC25A46.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 SCN2A Achchuthan Shanmugasundram Source Expert Review Green was added to SCN2A.
Source NHS GMS was added to SCN2A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 NPTX1 Achchuthan Shanmugasundram Source Expert Review Green was added to NPTX1.
Source NHS GMS was added to NPTX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 NFASC Achchuthan Shanmugasundram Source Expert Review Green was added to NFASC.
Source NHS GMS was added to NFASC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 MAG Achchuthan Shanmugasundram Source Expert Review Green was added to MAG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 INTS11 Achchuthan Shanmugasundram Source Expert Review Green was added to INTS11.
Source NHS GMS was added to INTS11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 GRN Achchuthan Shanmugasundram Source Expert Review Green was added to GRN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 FRMD5 Achchuthan Shanmugasundram Source Expert Review Green was added to FRMD5.
Source NHS GMS was added to FRMD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 FMR1 Achchuthan Shanmugasundram Source Expert Review Red was added to FMR1.
Source NHS GMS was added to FMR1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 FEM1C Achchuthan Shanmugasundram Source Expert Review Green was added to FEM1C.
Source NHS GMS was added to FEM1C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 COQ4 Achchuthan Shanmugasundram Source Expert Review Green was added to COQ4.
Source NHS GMS was added to COQ4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.34 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ATP6.
Ataxia and cerebellar anomalies - narrow panel v4.34 DAB1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark, there is only one case reported with cerebellar ataxia and identified with biallelic DAB1 variants. Hence, this gene should remain red in this panel.; to: As reviewed by Zornitza Stark, there is only one case reported with cerebellar ataxia and identified with biallelic DAB1 variants. Hence, this gene should remain red in this panel.

Note that repeat expansions in this gene have an established association with disease (MIM #615945) and it is caused by monoallelic inheritance.
Ataxia and cerebellar anomalies - narrow panel v4.34 DAB1 Achchuthan Shanmugasundram Phenotypes for gene: DAB1 were changed from Spinocerebellar ataxia 37 to cerebellar ataxia, MONDO:0000437
Ataxia and cerebellar anomalies - narrow panel v4.33 DAB1 Achchuthan Shanmugasundram Mode of inheritance for gene: DAB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.32 DAB1 Achchuthan Shanmugasundram reviewed gene: DAB1: Rating: RED; Mode of pathogenicity: None; Publications: 33928188; Phenotypes: cerebellar ataxia, MONDO:0000437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.32 TRIP4 Achchuthan Shanmugasundram Classified gene: TRIP4 as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v4.32 TRIP4 Achchuthan Shanmugasundram Gene: trip4 has been classified as Red List (Low Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.31 TRIP4 Achchuthan Shanmugasundram reviewed gene: TRIP4: Rating: RED; Mode of pathogenicity: None; Publications: 34075209; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.31 RFXANK Achchuthan Shanmugasundram Classified gene: RFXANK as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.31 RFXANK Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, this gene should be rated amber with the current evidence.
Ataxia and cerebellar anomalies - narrow panel v4.31 RFXANK Achchuthan Shanmugasundram Gene: rfxank has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.30 RFXANK Achchuthan Shanmugasundram reviewed gene: RFXANK: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Bare lymphocyte syndrome, type II, complementation group B, OMIM:209920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.30 COQ4 Achchuthan Shanmugasundram Phenotypes for gene: COQ4 were changed from Childhood-onset spinocerebellar ataxia; Adult-onset ataxia-spasticity spectrum disease; Hereditary spastic paraparesis, MONDO:0019064; Cerebellar ataxia, MONDO:0000437 to Coenzyme Q10 deficiency, primary, 7, OMIM:616276
Ataxia and cerebellar anomalies - narrow panel v4.29 COQ4 Achchuthan Shanmugasundram edited their review of gene: COQ4: Changed phenotypes to: Coenzyme Q10 deficiency, primary, 7, OMIM:616276
Ataxia and cerebellar anomalies - narrow panel v4.29 SPTAN1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Although there are three unrelated cases reported with biallelic SPTAN1 variants and hereditary spastic paraplegia, they do not present with ataxia (PMID:31515523; PMID:34526651). Hence, the MOI should remain as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Ataxia and cerebellar anomalies - narrow panel v4.29 SPTAN1 Achchuthan Shanmugasundram Mode of inheritance for gene: SPTAN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.28 SPTAN1 Sarah Leigh Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064 to Developmental and epileptic encephalopathy 5, OMIM:613477; developmental and epileptic encephalopathy, 5, MONDO:0013277
Ataxia and cerebellar anomalies - narrow panel v4.27 LETM1 Sarah Leigh Entity copied from Possible mitochondrial disorder - nuclear genes v3.41
Ataxia and cerebellar anomalies - narrow panel v4.27 LETM1 Sarah Leigh gene: LETM1 was added
gene: LETM1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review,Expert Review Amber
Q3_23_promote_green, Q3_23_MOI tags were added to gene: LETM1.
Mode of inheritance for gene: LETM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LETM1 were set to 36055214; 33815143
Phenotypes for gene: LETM1 were set to Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089
Ataxia and cerebellar anomalies - narrow panel v4.26 AGTPBP1 Achchuthan Shanmugasundram Classified gene: AGTPBP1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.26 AGTPBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating at the next major update.
Ataxia and cerebellar anomalies - narrow panel v4.26 AGTPBP1 Achchuthan Shanmugasundram Gene: agtpbp1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.25 AGTPBP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: AGTPBP1.
Ataxia and cerebellar anomalies - narrow panel v4.25 AGTPBP1 Achchuthan Shanmugasundram gene: AGTPBP1 was added
gene: AGTPBP1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: AGTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGTPBP1 were set to 30420557
Phenotypes for gene: AGTPBP1 were set to Neurodegeneration, childhood-onset, with cerebellar atrophy, OMIM:618276
Review for gene: AGTPBP1 was set to GREEN
Added comment: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Five unrelated patients had ataxia and all patients had cerebellar atrophy. In addition, functional studies with mouse models have recapitulated the human phenotype.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v4.24 DNAJC3 Achchuthan Shanmugasundram Classified gene: DNAJC3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.24 DNAJC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated families identified with biallelic DNAJC3 variants and reported with gait ataxia since childhood/ adolescence. Hence, this gene can be promoted to Green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v4.24 DNAJC3 Achchuthan Shanmugasundram Gene: dnajc3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.23 DNAJC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DNAJC3.
Ataxia and cerebellar anomalies - narrow panel v4.23 DNAJC3 Achchuthan Shanmugasundram gene: DNAJC3 was added
gene: DNAJC3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: DNAJC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC3 were set to 25466870; 28940199; 32738013; 33486469; 34654017
Phenotypes for gene: DNAJC3 were set to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192
Review for gene: DNAJC3 was set to GREEN
Added comment: PMID:25466870 - Five individuals from two different families were identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)) and reported with gait ataxia as one of the clinical manifestations. The onset of gait disturbances was during childhood/ adolescence for four of these cases.

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with gait ataxia since 15 years of age.

PMID:32738013 - Two unrelated children were identified with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with gait ataxia.

PMID:33486469 - Two unrelated patients were identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (patient 2: p.Arg393Ter) variants, of which patient 1 had ataxia.

PMID:34654017 - Two siblings (aged 10 and 5 years) identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with gait ataxia.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v4.22 UCHL1 Sarah Leigh Tag Q3_23_MOI tag was added to gene: UCHL1.
Ataxia and cerebellar anomalies - narrow panel v4.22 UCHL1 Sarah Leigh commented on gene: UCHL1: Childhood onset cerebellar ataxia and has been reported in both Spastic paraplegia 79A, autosomal dominant, OMIM:620221 and Spastic paraplegia 79B, autosomal recessive, OMIM:615491, therefore, the mode of inheritance for this gene should be: BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Ataxia and cerebellar anomalies - narrow panel v4.22 UCHL1 Sarah Leigh edited their review of gene: UCHL1: Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v4.22 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209 to Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Ataxia and cerebellar anomalies - narrow panel v4.21 EN1 Eleanor Williams Tag watchlist tag was added to gene: EN1.
Ataxia and cerebellar anomalies - narrow panel v4.21 EN1 Eleanor Williams commented on gene: EN1: This gene was copied from the Skeletal dysplasia panel to the Ataxia and cerebellar anomalies - narrow panel panel. The Genomics England clinical team have agreed that Fetal anomalies is an appropriate panel for this gene and the rating should currently be amber.
Ataxia and cerebellar anomalies - narrow panel v4.21 EN1 Eleanor Williams Entity copied from Skeletal dysplasia v4.10
Ataxia and cerebellar anomalies - narrow panel v4.21 EN1 Eleanor Williams gene: EN1 was added
gene: EN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: EN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EN1 were set to 33568816
Phenotypes for gene: EN1 were set to ENDOVE syndrome, limb-only type, MIM# 619217; ENDOVE syndrome, limb-brain type, MIM# 619218
Ataxia and cerebellar anomalies - narrow panel v4.20 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.20 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are eight unrelated cases associating monoallelic variants in DAGLA with ataxia. Hence, this gene should be promoted to Green rating at the next major review.
Ataxia and cerebellar anomalies - narrow panel v4.20 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.19 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DAGLA.
Ataxia and cerebellar anomalies - narrow panel v4.19 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v4.18 DAGLA Achchuthan Shanmugasundram edited their review of gene: DAGLA: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v4.18 DAGLA Achchuthan Shanmugasundram gene: DAGLA was added
gene: DAGLA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to 35737950
Phenotypes for gene: DAGLA were set to Ataxia, HP:0001251
Review for gene: DAGLA was set to GREEN
Added comment: There are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All nine children had ataxia and the age of these children ranged between 4 and 15 years of age. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v4.17 DMXL2 Arina Puzriakova Mode of inheritance for gene: DMXL2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.16 DMXL2 Arina Puzriakova Classified gene: DMXL2 as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v4.16 DMXL2 Arina Puzriakova Added comment: Comment on list classification: Downgraded from Amber to Red. Ataxia (onset in adolescence) has only been reported in one consanguineous family to date (PMID: 25248098) and this finding has not since been replicated. Therefore demoting the gene rating, inline with review by Dmitrijs Rots.
Ataxia and cerebellar anomalies - narrow panel v4.16 DMXL2 Arina Puzriakova Gene: dmxl2 has been classified as Red List (Low Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.15 DMXL2 Arina Puzriakova Publications for gene: DMXL2 were set to 25248098; 22875945; 27657680
Ataxia and cerebellar anomalies - narrow panel v4.14 DMXL2 Arina Puzriakova Phenotypes for gene: DMXL2 were changed from Sensorineural Hearing Loss; ORPHA90636; OMIM:612186 to ?Polyendocrine-polyneuropathy syndrome, OMIM:616113
Ataxia and cerebellar anomalies - narrow panel v4.13 FEM1C Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: FEM1C.
Ataxia and cerebellar anomalies - narrow panel v4.13 FEM1C Achchuthan Shanmugasundram Classified gene: FEM1C as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.13 FEM1C Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases (one in literature and another from Diagnostic Discovery initiative) and functional evidence from animal models in support of the association of this gene to ataxia. Hence, this gene can be rated Green at the next major update.
Ataxia and cerebellar anomalies - narrow panel v4.13 FEM1C Achchuthan Shanmugasundram Gene: fem1c has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.12 FEM1C Achchuthan Shanmugasundram commented on gene: FEM1C: PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. The introduction of the equivalent variant in C. elegans resulted in disabled locomotion caused by synaptic abnormalities and not by muscle dysfunction.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Ataxia and cerebellar anomalies - narrow panel v4.12 FEM1C Achchuthan Shanmugasundram gene: FEM1C was added
gene: FEM1C was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: FEM1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEM1C were set to 36336956
Phenotypes for gene: FEM1C were set to Ataxia, HP:0001251
Review for gene: FEM1C was set to GREEN
Added comment: Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v4.11 INTS11 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.151
Ataxia and cerebellar anomalies - narrow panel v4.11 INTS11 Arina Puzriakova gene: INTS11 was added
gene: INTS11 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: INTS11.
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to 37054711
Phenotypes for gene: INTS11 were set to Complex neurodevelopmental disorder, MONDO:0100038
Ataxia and cerebellar anomalies - narrow panel v4.10 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290; Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Ataxia and cerebellar anomalies - narrow panel v4.9 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis to Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Ataxia and cerebellar anomalies - narrow panel v4.8 COASY Sarah Leigh Publications for gene: COASY were set to 24360804; 30089828
Ataxia and cerebellar anomalies - narrow panel v4.7 SUFU Arina Puzriakova Tag Q4_22_expert_review tag was added to gene: SUFU.
Ataxia and cerebellar anomalies - narrow panel v4.7 PRDX3 Achchuthan Shanmugasundram changed review comment from: Comment on publications: PMID:35766882 reports a case of infantile-onset cerebellar ataxia that started ate 19 months old and presented with severe cerebellar atrophy and peripheral neuropathy early in the course of disease. This patient was identified with the homozygous variant p.Asp163Glu in PRDX3 gene.; to: Comment on publications: PMID:35766882 reports a case of infantile-onset cerebellar ataxia that started at the age of 19 months and presented with severe cerebellar atrophy and peripheral neuropathy early in the course of disease. This patient was identified with the homozygous variant p.Asp163Glu in PRDX3 gene.
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh commented on gene: SPG7: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form).; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form).
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh edited their review of gene: SPG7: Changed publications to: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be both monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh Tag Q2_23_MOI tag was added to gene: SPG7.
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh reviewed gene: SPG7: Rating: ; Mode of pathogenicity: None; Publications: 9635427, 16534102, 17646629, 18200586, 20186691, 22571692; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.7 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447; 32893728; 33774748; 32161564; 31068484; 23065789; 9635427; 16534102; 17646629; 18200586, 20186691; 22571692
Ataxia and cerebellar anomalies - narrow panel v4.6 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 25681447; 32893728
Ataxia and cerebellar anomalies - narrow panel v4.5 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, OMIM:607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Classified gene: NFASC as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v4.4 NFASC Sarah Leigh Gene: nfasc has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Tag Q2_23_promote_green tag was added to gene: NFASC.
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Classified gene: NFASC as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v4.3 NFASC Sarah Leigh Gene: nfasc has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.2 NFASC Sarah Leigh Entity copied from Hereditary ataxia v1.317
Ataxia and cerebellar anomalies - narrow panel v4.2 NFASC Sarah Leigh gene: NFASC was added
gene: NFASC was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature,Expert Review Green
Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFASC were set to 30850329; 31608123; 31501903
Phenotypes for gene: NFASC were set to Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356; neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:0032698
Penetrance for gene: NFASC were set to Complete
Ataxia and cerebellar anomalies - narrow panel v4.1 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor & sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor/ sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.
Ataxia and cerebellar anomalies - narrow panel v4.1 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor > sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor & sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.
Ataxia and cerebellar anomalies - narrow panel v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Ataxia and cerebellar anomalies - narrow panel v4.0 Arina Puzriakova promoted panel to version 4.0
Ataxia and cerebellar anomalies - narrow panel v3.41 PRDX3 Achchuthan Shanmugasundram changed review comment from: Comment on publications: PMID:35766882 reports a case of infantile-onset cerebellar ataxia that started ate 19 months old and presented with severe cerebellar atrophy and peripheral neuropathy early in the course of disease. This patient was identified with a homozygous variant in PRDX3 gene (p.Asp163Glu).; to: Comment on publications: PMID:35766882 reports a case of infantile-onset cerebellar ataxia that started ate 19 months old and presented with severe cerebellar atrophy and peripheral neuropathy early in the course of disease. This patient was identified with the homozygous variant p.Asp163Glu in PRDX3 gene.
Ataxia and cerebellar anomalies - narrow panel v3.41 PRDX3 Achchuthan Shanmugasundram Phenotypes for gene: PRDX3 were changed from Cerebellar ataxia (early onset, mild to moderate, progressive) to Spinocerebellar ataxia, autosomal recessive 32, OMIM:619862
Ataxia and cerebellar anomalies - narrow panel v3.40 PRDX3 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:35766882 reports a case of infantile-onset cerebellar ataxia that started ate 19 months old and presented with severe cerebellar atrophy and peripheral neuropathy early in the course of disease. This patient was identified with a homozygous variant in PRDX3 gene (p.Asp163Glu).
Ataxia and cerebellar anomalies - narrow panel v3.40 PRDX3 Achchuthan Shanmugasundram Publications for gene: PRDX3 were set to 33889951
Ataxia and cerebellar anomalies - narrow panel v3.39 MAG Arina Puzriakova Entity copied from Hereditary spastic paraplegia - childhood onset v3.18
Ataxia and cerebellar anomalies - narrow panel v3.39 MAG Arina Puzriakova gene: MAG was added
gene: MAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Yorkshire and North East GLH,London North GLH,Literature,Expert Review Amber,NHS GMS
Q1_23_promote_green tags were added to gene: MAG.
Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAG were set to 24482476; 26179919; 31402626; 32629324; 32340215
Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, OMIM:616680
Ataxia and cerebellar anomalies - narrow panel v3.38 MTCL1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MTCL1.
Ataxia and cerebellar anomalies - narrow panel v3.38 NPTX1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: NPTX1.
Ataxia and cerebellar anomalies - narrow panel v3.38 NPTX1 Achchuthan Shanmugasundram Phenotypes for gene: NPTX1 were changed from Ataxia to Spinocerebellar ataxia 50, OMIM:620158
Ataxia and cerebellar anomalies - narrow panel v3.37 NPTX1 Achchuthan Shanmugasundram Publications for gene: NPTX1 were set to 34788392; 35285082; 35560436
Ataxia and cerebellar anomalies - narrow panel v3.36 NPTX1 Achchuthan Shanmugasundram Classified gene: NPTX1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.36 NPTX1 Achchuthan Shanmugasundram Gene: nptx1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.35 NPTX1 Achchuthan Shanmugasundram reviewed gene: NPTX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34788392, 35285082, 35288776, 35560436; Phenotypes: Spinocerebellar ataxia 50, OMIM:620158; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v3.35 SPTAN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with ataxia and was also supported by functional studies including results from mouse model.

One patient each was identified with SPTAN1 variants and was reported with ataxia from PMID:29050398 and PMID:30548380. Out of three patients identified with SPTAN1 variants and reported with Developmental and epileptic encephalopathy 5 in PMID:34590414, one patient had ataxia and another had mild ataxia. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, four unrelated patients displaying p.Lys2083del variant were reported with cerebellar ataxia, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum.

In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, 3 were presented with complex HA/HSP and two were presented with pure HA.

A 33-year old Korean woman identified with SPTAN1 variant was reported with cerebellar ataxia in PMID:36408834, being the first reported case of SPTAN1-related cerebellar ataxia.

In addition, a strain of C57BL/6J mice harbouring a single point mutation in Sptan1 (c.3293G > A/ p.Arg1098Gln) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis was reported in PMID:33790315. Homozygotes are embryonically lethal and heterozygotes develop a progressive ataxia.; to: Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with ataxia and was also supported by functional studies including results from mouse model.

One patient each was identified with SPTAN1 variants and was reported with ataxia from PMID:29050398 and PMID:30548380. Out of three patients identified with SPTAN1 variants and reported with Developmental and epileptic encephalopathy 5 in PMID:34590414, one patient had ataxia and another had mild ataxia. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, four unrelated patients displaying p.Lys2083del variant were reported with cerebellar ataxia, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum.

In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, five (from three families) were presented with complex HA/HSP and two were presented with pure HA.

A 33-year old Korean woman identified with SPTAN1 variant was reported with cerebellar ataxia in PMID:36408834, being the first reported case of SPTAN1-related cerebellar ataxia.

In addition, a strain of C57BL/6J mice harbouring a single point mutation in Sptan1 (c.3293G > A/ p.Arg1098Gln) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis was reported in PMID:33790315. Homozygotes are embryonically lethal and heterozygotes develop a progressive ataxia.
Ataxia and cerebellar anomalies - narrow panel v3.35 SPTAN1 Achchuthan Shanmugasundram Phenotypes for gene: SPTAN1 were changed from Ataxia; hereditary spastic paraplegia to Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064
Ataxia and cerebellar anomalies - narrow panel v3.34 SPTAN1 Achchuthan Shanmugasundram Publications for gene: SPTAN1 were set to 36331550; 35150594
Ataxia and cerebellar anomalies - narrow panel v3.33 SPTAN1 Achchuthan Shanmugasundram edited their review of gene: SPTAN1: Changed phenotypes to: Developmental and epileptic encephalopathy 5, OMIM:613477, Cerebellar ataxia, MONDO:0000437, Hereditary spastic paraplegia, MONDO:0019064
Ataxia and cerebellar anomalies - narrow panel v3.33 SPTAN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: SPTAN1.
Ataxia and cerebellar anomalies - narrow panel v3.33 SPTAN1 Achchuthan Shanmugasundram Classified gene: SPTAN1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.33 SPTAN1 Achchuthan Shanmugasundram Gene: sptan1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.32 SPTAN1 Achchuthan Shanmugasundram reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29050398, 30548380, 33790315, 34590414, 35150594, 36331550, 36408834; Phenotypes: Developmental and epileptic encephalopathy 5, OMIM:613477, Cerebellar ataxia, MONDO:0000437; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v3.32 CAPRIN1 Achchuthan Shanmugasundram Phenotypes for gene: CAPRIN1 were changed from Infantile-onset ataxia to Cerebellar ataxia, MONDO:0000437; Early-onset ataxia
Ataxia and cerebellar anomalies - narrow panel v3.31 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.31 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.30 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor > sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green.

PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor > sensory axonal neuropathy) as the other two patients.

In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics.

These functional evidences also suggest a gain-of-function mechanism for P512L variant.
Ataxia and cerebellar anomalies - narrow panel v3.30 CAPRIN1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: CAPRIN1.
Ataxia and cerebellar anomalies - narrow panel v3.30 CAPRIN1 Achchuthan Shanmugasundram reviewed gene: CAPRIN1: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 36136249; Phenotypes: Cerebellar ataxia, MONDO:0000437, Early-onset ataxia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v3.30 TGM6 Eleanor Williams Tag Q2_21_rating was removed from gene: TGM6.
Tag Q2_21_expert_review was removed from gene: TGM6.
Ataxia and cerebellar anomalies - narrow panel v3.30 SPG7 Eleanor Williams Tag Q3_22_rating was removed from gene: SPG7.
Tag Q3_22_expert_review was removed from gene: SPG7.
Ataxia and cerebellar anomalies - narrow panel v3.30 XRCC1 Eleanor Williams Tag Q2_21_rating was removed from gene: XRCC1.
Ataxia and cerebellar anomalies - narrow panel v3.30 UCHL1 Eleanor Williams Tag Q2_21_rating was removed from gene: UCHL1.
Ataxia and cerebellar anomalies - narrow panel v3.30 UBTF Eleanor Williams Tag Q2_21_rating was removed from gene: UBTF.
Ataxia and cerebellar anomalies - narrow panel v3.30 TDP2 Eleanor Williams Tag Q2_21_rating was removed from gene: TDP2.
Ataxia and cerebellar anomalies - narrow panel v3.30 TBC1D23 Eleanor Williams Tag Q2_21_rating was removed from gene: TBC1D23.
Ataxia and cerebellar anomalies - narrow panel v3.30 SQSTM1 Eleanor Williams Tag Q2_21_rating was removed from gene: SQSTM1.
Ataxia and cerebellar anomalies - narrow panel v3.30 SPR Eleanor Williams Tag Q2_21_rating was removed from gene: SPR.
Ataxia and cerebellar anomalies - narrow panel v3.30 SNX14 Eleanor Williams Tag Q3_21_MOI was removed from gene: SNX14.
Ataxia and cerebellar anomalies - narrow panel v3.30 SNAP25 Eleanor Williams Tag Q2_21_rating was removed from gene: SNAP25.
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC9A1 Eleanor Williams Tag Q2_21_rating was removed from gene: SLC9A1.
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC44A1 Eleanor Williams Tag Q2_21_rating was removed from gene: SLC44A1.
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC17A5 Eleanor Williams Tag Q2_21_rating was removed from gene: SLC17A5.
Ataxia and cerebellar anomalies - narrow panel v3.30 SCYL1 Eleanor Williams Tag Q2_21_rating was removed from gene: SCYL1.
Ataxia and cerebellar anomalies - narrow panel v3.30 SCN8A Eleanor Williams Tag Q2_21_rating was removed from gene: SCN8A.
Ataxia and cerebellar anomalies - narrow panel v3.30 SCN1A Eleanor Williams Tag Q2_21_rating was removed from gene: SCN1A.
Ataxia and cerebellar anomalies - narrow panel v3.30 SAR1B Eleanor Williams Tag Q2_21_rating was removed from gene: SAR1B.
Ataxia and cerebellar anomalies - narrow panel v3.30 RORA Eleanor Williams Tag Q2_21_rating was removed from gene: RORA.
Ataxia and cerebellar anomalies - narrow panel v3.30 RNF220 Eleanor Williams Tag Q4_21_rating was removed from gene: RNF220.
Ataxia and cerebellar anomalies - narrow panel v3.30 PRDX3 Eleanor Williams Tag Q1_22_rating was removed from gene: PRDX3.
Ataxia and cerebellar anomalies - narrow panel v3.30 POU4F1 Eleanor Williams Tag Q2_21_rating was removed from gene: POU4F1.
Ataxia and cerebellar anomalies - narrow panel v3.30 POLR3B Eleanor Williams Tag Q2_21_rating was removed from gene: POLR3B.
Ataxia and cerebellar anomalies - narrow panel v3.30 PMPCB Eleanor Williams Tag Q2_21_rating was removed from gene: PMPCB.
Ataxia and cerebellar anomalies - narrow panel v3.30 PITRM1 Eleanor Williams Tag Q2_21_rating was removed from gene: PITRM1.
Ataxia and cerebellar anomalies - narrow panel v3.30 PI4KA Eleanor Williams Tag Q3_21_rating was removed from gene: PI4KA.
Ataxia and cerebellar anomalies - narrow panel v3.30 PEX6 Eleanor Williams Tag Q2_22_rating was removed from gene: PEX6.
Ataxia and cerebellar anomalies - narrow panel v3.30 OPA1 Eleanor Williams Tag Q2_21_rating was removed from gene: OPA1.
Ataxia and cerebellar anomalies - narrow panel v3.30 NKX2-1 Eleanor Williams Tag Q2_21_rating was removed from gene: NKX2-1.
Ataxia and cerebellar anomalies - narrow panel v3.30 NAXE Eleanor Williams Tag Q2_21_rating was removed from gene: NAXE.
Ataxia and cerebellar anomalies - narrow panel v3.30 MVK Eleanor Williams Tag Q2_21_rating was removed from gene: MVK.
Ataxia and cerebellar anomalies - narrow panel v3.30 MTFMT Eleanor Williams Tag Q2_21_rating was removed from gene: MTFMT.
Ataxia and cerebellar anomalies - narrow panel v3.30 MTCL1 Eleanor Williams Tag Q2_21_rating was removed from gene: MTCL1.
Ataxia and cerebellar anomalies - narrow panel v3.30 MSTO1 Eleanor Williams Tag Q2_21_rating was removed from gene: MSTO1.
Ataxia and cerebellar anomalies - narrow panel v3.30 MINPP1 Eleanor Williams Tag Q2_21_rating was removed from gene: MINPP1.
Ataxia and cerebellar anomalies - narrow panel v3.30 MAPK8IP3 Eleanor Williams Tag Q4_21_rating was removed from gene: MAPK8IP3.
Ataxia and cerebellar anomalies - narrow panel v3.30 LAMA1 Eleanor Williams Tag Q2_21_rating was removed from gene: LAMA1.
Ataxia and cerebellar anomalies - narrow panel v3.30 KIF1A Eleanor Williams Tag Q3_21_rating was removed from gene: KIF1A.
Ataxia and cerebellar anomalies - narrow panel v3.30 KCNN2 Eleanor Williams Tag Q2_21_rating was removed from gene: KCNN2.
Ataxia and cerebellar anomalies - narrow panel v3.30 KCNA2 Eleanor Williams Tag Q2_21_rating was removed from gene: KCNA2.
Ataxia and cerebellar anomalies - narrow panel v3.30 IRF2BPL Eleanor Williams Tag Q2_21_rating was removed from gene: IRF2BPL.
Ataxia and cerebellar anomalies - narrow panel v3.30 GEMIN5 Eleanor Williams Tag Q2_21_rating was removed from gene: GEMIN5.
Ataxia and cerebellar anomalies - narrow panel v3.30 FBXL4 Eleanor Williams Tag Q2_21_rating was removed from gene: FBXL4.
Ataxia and cerebellar anomalies - narrow panel v3.30 FA2H Eleanor Williams Tag Q2_21_rating was removed from gene: FA2H.
Ataxia and cerebellar anomalies - narrow panel v3.30 EBF3 Eleanor Williams Tag Q2_21_rating was removed from gene: EBF3.
Ataxia and cerebellar anomalies - narrow panel v3.30 DPYSL5 Eleanor Williams Tag Q3_21_rating was removed from gene: DPYSL5.
Ataxia and cerebellar anomalies - narrow panel v3.30 DOCK3 Eleanor Williams Tag Q2_21_rating was removed from gene: DOCK3.
Ataxia and cerebellar anomalies - narrow panel v3.30 DHDDS Eleanor Williams Tag Q4_21_rating was removed from gene: DHDDS.
Ataxia and cerebellar anomalies - narrow panel v3.30 CSTB Eleanor Williams Tag Q2_21_rating was removed from gene: CSTB.
Ataxia and cerebellar anomalies - narrow panel v3.30 COA7 Eleanor Williams Tag Q2_21_rating was removed from gene: COA7.
Ataxia and cerebellar anomalies - narrow panel v3.30 CLP1 Eleanor Williams Tag Q2_21_rating was removed from gene: CLP1.
Ataxia and cerebellar anomalies - narrow panel v3.30 CLN5 Eleanor Williams Tag Q2_21_rating was removed from gene: CLN5.
Ataxia and cerebellar anomalies - narrow panel v3.30 CLCN2 Eleanor Williams Tag Q4_21_MOI was removed from gene: CLCN2.
Ataxia and cerebellar anomalies - narrow panel v3.30 CAD Eleanor Williams Tag Q2_21_rating was removed from gene: CAD.
Ataxia and cerebellar anomalies - narrow panel v3.30 BBS1 Eleanor Williams Tag Q2_21_rating was removed from gene: BBS1.
Ataxia and cerebellar anomalies - narrow panel v3.30 B4GAT1 Eleanor Williams Tag Q3_21_rating was removed from gene: B4GAT1.
Ataxia and cerebellar anomalies - narrow panel v3.30 ATP8A2 Eleanor Williams Tag Q2_21_rating was removed from gene: ATP8A2.
Ataxia and cerebellar anomalies - narrow panel v3.30 ATAD3A Eleanor Williams Tag Q2_21_rating was removed from gene: ATAD3A.
Ataxia and cerebellar anomalies - narrow panel v3.30 ALDH5A1 Eleanor Williams Tag Q3_21_rating was removed from gene: ALDH5A1.
Ataxia and cerebellar anomalies - narrow panel v3.30 ADPRHL2 Eleanor Williams Tag Q2_21_rating was removed from gene: ADPRHL2.
Ataxia and cerebellar anomalies - narrow panel v3.30 ACO2 Eleanor Williams Tag Q2_21_rating was removed from gene: ACO2.
Tag Q2_22_MOI was removed from gene: ACO2.
Ataxia and cerebellar anomalies - narrow panel v3.30 ABCB7 Eleanor Williams Tag Q3_21_MOI was removed from gene: ABCB7.
Ataxia and cerebellar anomalies - narrow panel v3.30 STUB1 Eleanor Williams Tag Q3_22_MOI was removed from gene: STUB1.
Ataxia and cerebellar anomalies - narrow panel v3.30 PRDM13 Eleanor Williams Tag Q3_22_rating was removed from gene: PRDM13.
Ataxia and cerebellar anomalies - narrow panel v3.30 OGDHL Eleanor Williams Tag Q3_22_rating was removed from gene: OGDHL.
Ataxia and cerebellar anomalies - narrow panel v3.30 CYP2U1 Eleanor Williams Tag Q3_22_rating was removed from gene: CYP2U1.
Tag Q3_22_expert_review was removed from gene: CYP2U1.
Ataxia and cerebellar anomalies - narrow panel v3.30 CACNA1A Eleanor Williams Tag Q3_22_MOI was removed from gene: CACNA1A.
Tag Q3_22_NHS_review was removed from gene: CACNA1A.
Ataxia and cerebellar anomalies - narrow panel v3.30 ATP6V0A1 Eleanor Williams Tag Q3_22_rating was removed from gene: ATP6V0A1.
Ataxia and cerebellar anomalies - narrow panel v3.30 ATG7 Eleanor Williams Tag Q3_22_rating was removed from gene: ATG7.
Ataxia and cerebellar anomalies - narrow panel v3.30 TGM6 Eleanor Williams reviewed gene: TGM6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SPG7 Eleanor Williams edited their review of gene: SPG7: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains green. The reviewers note that the age of onset includes under 16. Gene should be included in a diagnostic test for ataxia. At least 2 patients with age of onset of 15 years in 30588500; further 2 patients with onset 11 and 14 in 14985266.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v3.30 SAR1B Eleanor Williams commented on gene: SAR1B: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v3.30 CYP2U1 Eleanor Williams edited their review of gene: CYP2U1: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Ataxia and cerebellar anomalies - narrow panel v3.30 XRCC1 Eleanor Williams reviewed gene: XRCC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 UCHL1 Eleanor Williams reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 UBTF Eleanor Williams reviewed gene: UBTF: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 TDP2 Eleanor Williams reviewed gene: TDP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 TBC1D23 Eleanor Williams reviewed gene: TBC1D23: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SQSTM1 Eleanor Williams reviewed gene: SQSTM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SPR Eleanor Williams reviewed gene: SPR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SNAP25 Eleanor Williams reviewed gene: SNAP25: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC9A1 Eleanor Williams reviewed gene: SLC9A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC44A1 Eleanor Williams reviewed gene: SLC44A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SLC17A5 Eleanor Williams reviewed gene: SLC17A5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SCYL1 Eleanor Williams reviewed gene: SCYL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SCN8A Eleanor Williams reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 SCN1A Eleanor Williams reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 RORA Eleanor Williams reviewed gene: RORA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 RNF220 Eleanor Williams reviewed gene: RNF220: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PRDX3 Eleanor Williams reviewed gene: PRDX3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 POU4F1 Eleanor Williams reviewed gene: POU4F1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 POLR3B Eleanor Williams reviewed gene: POLR3B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PMPCB Eleanor Williams reviewed gene: PMPCB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PITRM1 Eleanor Williams reviewed gene: PITRM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PI4KA Eleanor Williams reviewed gene: PI4KA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 OPA1 Eleanor Williams reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 NKX2-1 Eleanor Williams reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 NAXE Eleanor Williams reviewed gene: NAXE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MVK Eleanor Williams reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MTFMT Eleanor Williams reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MTCL1 Eleanor Williams reviewed gene: MTCL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MSTO1 Eleanor Williams reviewed gene: MSTO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MINPP1 Eleanor Williams reviewed gene: MINPP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 MAPK8IP3 Eleanor Williams edited their review of gene: MAPK8IP3: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v3.30 LAMA1 Eleanor Williams reviewed gene: LAMA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 KIF1A Eleanor Williams reviewed gene: KIF1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 KCNN2 Eleanor Williams reviewed gene: KCNN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 KCNA2 Eleanor Williams reviewed gene: KCNA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 IRF2BPL Eleanor Williams reviewed gene: IRF2BPL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 GEMIN5 Eleanor Williams reviewed gene: GEMIN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 FBXL4 Eleanor Williams reviewed gene: FBXL4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 FA2H Eleanor Williams reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 EBF3 Eleanor Williams reviewed gene: EBF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 DPYSL5 Eleanor Williams reviewed gene: DPYSL5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 DOCK3 Eleanor Williams reviewed gene: DOCK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 DHDDS Eleanor Williams reviewed gene: DHDDS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 CSTB Eleanor Williams reviewed gene: CSTB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 COA7 Eleanor Williams reviewed gene: COA7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 CLP1 Eleanor Williams reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 CLN5 Eleanor Williams reviewed gene: CLN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 CAD Eleanor Williams reviewed gene: CAD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 BBS1 Eleanor Williams reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 B4GAT1 Eleanor Williams reviewed gene: B4GAT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ATP8A2 Eleanor Williams reviewed gene: ATP8A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ATAD3A Eleanor Williams reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ALDH5A1 Eleanor Williams reviewed gene: ALDH5A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ADPRHL2 Eleanor Williams reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ATP6V0A1 Eleanor Williams reviewed gene: ATP6V0A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PEX6 Eleanor Williams reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ACO2 Eleanor Williams reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 PRDM13 Eleanor Williams reviewed gene: PRDM13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 OGDHL Eleanor Williams reviewed gene: OGDHL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ATG7 Eleanor Williams reviewed gene: ATG7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v3.30 ABCB7 Eleanor Williams commented on gene: ABCB7
Ataxia and cerebellar anomalies - narrow panel v3.30 STUB1 Eleanor Williams commented on gene: STUB1
Ataxia and cerebellar anomalies - narrow panel v3.30 CACNA1A Eleanor Williams commented on gene: CACNA1A
Ataxia and cerebellar anomalies - narrow panel v3.30 SNX14 Eleanor Williams commented on gene: SNX14
Ataxia and cerebellar anomalies - narrow panel v3.30 CLCN2 Eleanor Williams commented on gene: CLCN2
Ataxia and cerebellar anomalies - narrow panel v3.29 TGM6 Eleanor Williams Source NHS GMS was added to TGM6.
Source Expert Review Amber was added to TGM6.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 XRCC1 Eleanor Williams Source Expert Review Green was added to XRCC1.
Source NHS GMS was added to XRCC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 UCHL1 Eleanor Williams Source Expert Review Green was added to UCHL1.
Source NHS GMS was added to UCHL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 UBTF Eleanor Williams Source Expert Review Green was added to UBTF.
Source NHS GMS was added to UBTF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 TDP2 Eleanor Williams Source Expert Review Green was added to TDP2.
Source NHS GMS was added to TDP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 TBC1D23 Eleanor Williams Source Expert Review Green was added to TBC1D23.
Source NHS GMS was added to TBC1D23.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 STUB1 Eleanor Williams Source NHS GMS was added to STUB1.
Mode of inheritance for gene STUB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.29 SQSTM1 Eleanor Williams Source Expert Review Green was added to SQSTM1.
Source NHS GMS was added to SQSTM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SPR Eleanor Williams Source Expert Review Green was added to SPR.
Source NHS GMS was added to SPR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SNX14 Eleanor Williams Source NHS GMS was added to SNX14.
Mode of inheritance for gene SNX14 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.29 SNAP25 Eleanor Williams Source Expert Review Green was added to SNAP25.
Source NHS GMS was added to SNAP25.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SLC9A1 Eleanor Williams Source Expert Review Green was added to SLC9A1.
Source NHS GMS was added to SLC9A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SLC44A1 Eleanor Williams Source Expert Review Green was added to SLC44A1.
Source NHS GMS was added to SLC44A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SLC17A5 Eleanor Williams Source Expert Review Green was added to SLC17A5.
Source NHS GMS was added to SLC17A5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SCYL1 Eleanor Williams Source Expert Review Green was added to SCYL1.
Source NHS GMS was added to SCYL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SCN8A Eleanor Williams Source Expert Review Green was added to SCN8A.
Source NHS GMS was added to SCN8A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SCN1A Eleanor Williams Source Expert Review Green was added to SCN1A.
Source NHS GMS was added to SCN1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 SAR1B Eleanor Williams Source Expert Review Red was added to SAR1B.
Source NHS GMS was added to SAR1B.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 RORA Eleanor Williams Source Expert Review Green was added to RORA.
Source NHS GMS was added to RORA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 RNF220 Eleanor Williams Source Expert Review Green was added to RNF220.
Source NHS GMS was added to RNF220.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PRDX3 Eleanor Williams Source Expert Review Green was added to PRDX3.
Source NHS GMS was added to PRDX3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PRDM13 Eleanor Williams Source Expert Review Green was added to PRDM13.
Source NHS GMS was added to PRDM13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 POU4F1 Eleanor Williams Source Expert Review Green was added to POU4F1.
Source NHS GMS was added to POU4F1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 POLR3B Eleanor Williams Source Expert Review Green was added to POLR3B.
Source NHS GMS was added to POLR3B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PMPCB Eleanor Williams Source Expert Review Green was added to PMPCB.
Source NHS GMS was added to PMPCB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PITRM1 Eleanor Williams Source Expert Review Green was added to PITRM1.
Source NHS GMS was added to PITRM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PI4KA Eleanor Williams Source Expert Review Green was added to PI4KA.
Source NHS GMS was added to PI4KA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 PEX6 Eleanor Williams Source Expert Review Green was added to PEX6.
Source NHS GMS was added to PEX6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 OPA1 Eleanor Williams Source Expert Review Green was added to OPA1.
Source NHS GMS was added to OPA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 OGDHL Eleanor Williams Source Expert Review Green was added to OGDHL.
Source NHS GMS was added to OGDHL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 NKX2-1 Eleanor Williams Source Expert Review Green was added to NKX2-1.
Source NHS GMS was added to NKX2-1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 NAXE Eleanor Williams Source Expert Review Green was added to NAXE.
Source NHS GMS was added to NAXE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MVK Eleanor Williams Source Expert Review Green was added to MVK.
Source NHS GMS was added to MVK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MTFMT Eleanor Williams Source Expert Review Green was added to MTFMT.
Source NHS GMS was added to MTFMT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MTCL1 Eleanor Williams Source Expert Review Green was added to MTCL1.
Source NHS GMS was added to MTCL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MSTO1 Eleanor Williams Source Expert Review Green was added to MSTO1.
Source NHS GMS was added to MSTO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MINPP1 Eleanor Williams Source Expert Review Green was added to MINPP1.
Source NHS GMS was added to MINPP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 MAPK8IP3 Eleanor Williams Source Expert Review Green was added to MAPK8IP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 LAMA1 Eleanor Williams Source Expert Review Green was added to LAMA1.
Source NHS GMS was added to LAMA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 KIF1A Eleanor Williams Source Expert Review Green was added to KIF1A.
Source NHS GMS was added to KIF1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 KCNN2 Eleanor Williams Source Expert Review Green was added to KCNN2.
Source NHS GMS was added to KCNN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 KCNA2 Eleanor Williams Source Expert Review Green was added to KCNA2.
Source NHS GMS was added to KCNA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 IRF2BPL Eleanor Williams Source Expert Review Green was added to IRF2BPL.
Source NHS GMS was added to IRF2BPL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 GEMIN5 Eleanor Williams Source Expert Review Green was added to GEMIN5.
Source NHS GMS was added to GEMIN5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 FBXL4 Eleanor Williams Source Expert Review Green was added to FBXL4.
Source NHS GMS was added to FBXL4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 FA2H Eleanor Williams Source Expert Review Green was added to FA2H.
Source NHS GMS was added to FA2H.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 EBF3 Eleanor Williams Source Expert Review Green was added to EBF3.
Source NHS GMS was added to EBF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 DPYSL5 Eleanor Williams Source Expert Review Green was added to DPYSL5.
Source NHS GMS was added to DPYSL5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 DOCK3 Eleanor Williams Source Expert Review Green was added to DOCK3.
Source NHS GMS was added to DOCK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 DHDDS Eleanor Williams Source Expert Review Green was added to DHDDS.
Source NHS GMS was added to DHDDS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CYP2U1 Eleanor Williams Source Expert Review Red was added to CYP2U1.
Source NHS GMS was added to CYP2U1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CSTB Eleanor Williams Source Expert Review Green was added to CSTB.
Source NHS GMS was added to CSTB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 COA7 Eleanor Williams Source Expert Review Green was added to COA7.
Source NHS GMS was added to COA7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CLP1 Eleanor Williams Source Expert Review Green was added to CLP1.
Source NHS GMS was added to CLP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CLN5 Eleanor Williams Source Expert Review Green was added to CLN5.
Source NHS GMS was added to CLN5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CLCN2 Eleanor Williams Source NHS GMS was added to CLCN2.
Mode of inheritance for gene CLCN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.29 CAD Eleanor Williams Source Expert Review Green was added to CAD.
Source NHS GMS was added to CAD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 CACNA1A Eleanor Williams Source NHS GMS was added to CACNA1A.
Mode of inheritance for gene CACNA1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.29 BBS1 Eleanor Williams Source Expert Review Green was added to BBS1.
Source NHS GMS was added to BBS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 B4GAT1 Eleanor Williams Source Expert Review Green was added to B4GAT1.
Source NHS GMS was added to B4GAT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ATP8A2 Eleanor Williams Source Expert Review Green was added to ATP8A2.
Source NHS GMS was added to ATP8A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ATP6V0A1 Eleanor Williams Source Expert Review Green was added to ATP6V0A1.
Source NHS GMS was added to ATP6V0A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ATG7 Eleanor Williams Source Expert Review Green was added to ATG7.
Source NHS GMS was added to ATG7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ATAD3A Eleanor Williams Source Expert Review Green was added to ATAD3A.
Source NHS GMS was added to ATAD3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ALDH5A1 Eleanor Williams Source Expert Review Green was added to ALDH5A1.
Source NHS GMS was added to ALDH5A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ADPRHL2 Eleanor Williams Source Expert Review Green was added to ADPRHL2.
Source NHS GMS was added to ADPRHL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ACO2 Eleanor Williams Source Expert Review Green was added to ACO2.
Source NHS GMS was added to ACO2.
Mode of inheritance for gene ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v3.29 ABCB7 Eleanor Williams Source NHS GMS was added to ABCB7.
Mode of inheritance for gene ABCB7 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia and cerebellar anomalies - narrow panel v3.28 ISCA-46553-Loss Arina Puzriakova reviewed Region: ISCA-46553-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v3.28 ISCA-46553-Loss Arina Puzriakova Region: ISCA-46553-Loss was added
Region: ISCA-46553-Loss was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46553-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46553-Loss were set to 21204220; 15338008; 22067867; 21471554; 28503614
Ataxia and cerebellar anomalies - narrow panel v3.27 TECPR2 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: TECPR2.
Ataxia and cerebellar anomalies - narrow panel v3.27 TECPR2 Mafalda Gomes Phenotypes for gene: TECPR2 were changed from to Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, OMIM:615031
Ataxia and cerebellar anomalies - narrow panel v3.26 TECPR2 Mafalda Gomes Publications for gene: TECPR2 were set to
Ataxia and cerebellar anomalies - narrow panel v3.25 TECPR2 Mafalda Gomes changed review comment from: Neuser et al. (2021) report 17 unrelated cases with biallelic pathogenic variants in TECPR2. The study also includes 11 previously reported patients. The core manifestations in these individuals are global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea. Peripheral neuropathy was present in two-thirds of all individuals. The majority of the pathogenic variants identified are truncating variants; however, missense variants were also found, predominantly located in the N-terminal and C-terminal regions. The TECPR2 gene is implicated in the autophagy pathway, which is critical to the development and function of the central nervous system. Loss?of?function variants in several genes of the autophagy pathway lead to both neurodevelopmental and neurodegenerative diseases. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.; to: Neuser et al. (2021) report 17 unrelated cases with biallelic pathogenic variants in TECPR2. The study also includes 11 previously reported patients. The core manifestations in these individuals are global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea. Peripheral neuropathy was present in two-thirds of all individuals. The majority of the pathogenic variants identified are truncating variants; however, missense variants were also found, predominantly located in the N-terminal and C-terminal regions. The TECPR2 gene is implicated in the autophagy pathway, which is critical to the development and function of the central nervous system. Loss of function variants in several genes of the autophagy pathway lead to both neurodevelopmental and neurodegenerative diseases. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.
Ataxia and cerebellar anomalies - narrow panel v3.25 TECPR2 Mafalda Gomes reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: 33847017; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, OMIM:615031; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.24 TECPR2 Mafalda Gomes gene: TECPR2 was added
gene: TECPR2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.23 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209
Ataxia and cerebellar anomalies - narrow panel v3.22 UCHL1 Sarah Leigh reviewed gene: UCHL1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.22 UCHL1 Sarah Leigh Publications for gene: UCHL1 were set to 23359680; 28007905; 29735986; 32656641; 11555633; 33159930
Ataxia and cerebellar anomalies - narrow panel v3.21 DMXL2 Dmitrijs Rots reviewed gene: DMXL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v3.21 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from complex cortical dysplasia with other brain malformations-7 , 610031 to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Ataxia and cerebellar anomalies - narrow panel v3.20 CASK Arina Puzriakova Publications for gene: CASK were set to 35149592
Ataxia and cerebellar anomalies - narrow panel v3.19 CASK Arina Puzriakova Publications for gene: CASK were set to
Ataxia and cerebellar anomalies - narrow panel v3.18 SPTAN1 Dmitrijs Rots gene: SPTAN1 was added
gene: SPTAN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTAN1 were set to 36331550; 35150594
Phenotypes for gene: SPTAN1 were set to Ataxia; hereditary spastic paraplegia
Review for gene: SPTAN1 was set to GREEN
Added comment: Two large cohorts (36331550; 35150594) described >30 cases with hereditary ataxia and a variant in SPTAN1.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v3.18 FRMD5 Arina Puzriakova Classified gene: FRMD5 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.18 FRMD5 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 7 unrelated cases with ataxia plus supportive fly model.
Ataxia and cerebellar anomalies - narrow panel v3.18 FRMD5 Arina Puzriakova Gene: frmd5 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.17 FRMD5 Arina Puzriakova gene: FRMD5 was added
gene: FRMD5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q4_22_promote_green tags were added to gene: FRMD5.
Mode of inheritance for gene: FRMD5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FRMD5 were set to 36206744
Phenotypes for gene: FRMD5 were set to Neurodevelopmental disorder with eye movement abnormalities and ataxia, OMIM:620094
Review for gene: FRMD5 was set to GREEN
Added comment: Lu et al. 2022 (PMID: 36206744) report 8 unrelated individuals with de novo missense FRMD5 variants who presented with developmental delay (8/8), intellectual disability (7/7), ataxia (7/8), seizures (5/8), and abnormalities of eye movement (8/8). LOF mutant flies exhibited motor impairment, defective responses to light and heat-induced seizures. Fly phenotypes were rescued by expression of the wildtype gene but not by two of the patient missense mutants.

FRMD5 is associated with a relevant phenotype in OMIM (MIM# 620094) but is not yet listed in G2P.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v3.16 CAPRIN1 Dmitrijs Rots gene: CAPRIN1 was added
gene: CAPRIN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAPRIN1 were set to 36136249
Phenotypes for gene: CAPRIN1 were set to Infantile-onset ataxia
Penetrance for gene: CAPRIN1 were set to Complete
Mode of pathogenicity for gene: CAPRIN1 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: CAPRIN1 was set to GREEN
Added comment: CAPRIN1 is reported in two indepedent cases with infantile-onset ataxia and cognitive decline (reported 2 de novo in two cases + functional evidence, so enough evidence for green rating).
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v3.16 NPTX1 Dmitrijs Rots gene: NPTX1 was added
gene: NPTX1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: NPTX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPTX1 were set to 34788392; 35285082; 35560436
Phenotypes for gene: NPTX1 were set to Ataxia
Penetrance for gene: NPTX1 were set to unknown
Mode of pathogenicity for gene: NPTX1 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: NPTX1 was set to GREEN
Added comment: Multiple individiuals with de novo or inherited (segregating with the phenotype) NPTX1 reported in the literature with both late and infantile-onset ataxia. Enough evidence for green.

The phenotype is described in 34788392 as:
"The NPTX1-associated phenotype consists of a late-onset, slowly progressive, cerebellar ataxia, with downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging."
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v3.16 TPR Achchuthan Shanmugasundram edited their review of gene: TPR: Changed rating: RED
Ataxia and cerebellar anomalies - narrow panel v3.16 TPR Achchuthan Shanmugasundram gene: TPR was added
gene: TPR was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: TPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPR were set to 34494102
Phenotypes for gene: TPR were set to Cerebellar ataxia, MONDO:0000437
Added comment: Comment on classification of this gene: This gene should be added with a RED rating as the association of TPR to ataxia is based on biallelic variants identified from a report of two siblings.

Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability.

Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v3.15 SUFU Arina Puzriakova Entity copied from Neurological ciliopathies v2.4
Ataxia and cerebellar anomalies - narrow panel v3.15 SUFU Arina Puzriakova gene: SUFU was added
gene: SUFU was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list,Expert Review Amber
watchlist_moi, Q4_22_MOI, Q4_22_promote_green tags were added to gene: SUFU.
Mode of inheritance for gene: SUFU was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SUFU were set to 21289193; 28965847; 33024317; 34675124
Phenotypes for gene: SUFU were set to Joubert syndrome 32, OMIM:617757
Ataxia and cerebellar anomalies - narrow panel v3.14 SLC52A2 Achchuthan Shanmugasundram Tag treatable tag was added to gene: SLC52A2.
Tag Q4_22_promote_green tag was added to gene: SLC52A2.
Ataxia and cerebellar anomalies - narrow panel v3.14 SLC52A2 Achchuthan Shanmugasundram Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2, MIM# 614707 to Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867; Cerebellar ataxia, MONDO:0000437
Ataxia and cerebellar anomalies - narrow panel v3.13 SLC52A2 Achchuthan Shanmugasundram Publications for gene: SLC52A2 were set to 30377535
Ataxia and cerebellar anomalies - narrow panel v3.12 SLC52A2 Achchuthan Shanmugasundram Classified gene: SLC52A2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.12 SLC52A2 Achchuthan Shanmugasundram Gene: slc52a2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.11 SLC52A2 Achchuthan Shanmugasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740598, 22864630, 23243084, 24253200, 30343981, 30377535, 31868069, 32909658, 35608644, 36186484; Phenotypes: Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867, Cerebellar ataxia, MONDO:0000437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.11 SLC25A46 Achchuthan Shanmugasundram changed review comment from: Comment on classification of this gene: The rating for this gene should be GREEN, as this gene has been implicated in ataxia, as identified from biallelic loss-of-function variants from at least 8 unrelated individuals/ families from multiple ethnicities and supported by results from animal models.

Two brothers of consanguineous parents of Pakistani origin were identified with homozygous variant in SLC25A46 (c.413T>G./ p.Leu138Arg). The younger of the two brothers was presented with balancing difficulties in infancy, prominent myoclonus, cerebellar ataxia, profound visual loss, rod cone dysfunction, exotropia, difficulty initiating saccades, mild spasticity, and axonal sensory-motor neuropathy leading to trophic changes. He also developed scoliosis and had cerebellar atrophy as well as T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities and cavitations in the cerebellum. The older brother was mildly affected with similar clinical manifestations (PMID:27430653).

A study on patients from three North African families (Two siblings from Tunisian family and two unrelated Algerians) showed that the previously reported variant c.1018C>T/ p.Arg340Cys (displayed in Tunisian siblings and one Algerian patient) was associated with childhood onset, optic atrophy, gait and speech difficulties and wasting of the lower limbs, and the Algerian patient with the novel variant p.Trp160Ser did not present with optic atrophy, while all patients were presented with ataxia (PMID:28558379). Similarly, ataxia was also observed in Sardinian (p.Arg340Cys) and Palestinian (c.1005A>T/ p.Glu335Asp) patients from Abrams et al, 2015 (PMID:26168012).

A six year old boy with homozygous missense variant c.770G>A (p.Arg257Gln) was reported with optic atrophy, peripheral neuropathy, ataxia, but not cerebellar atrophy (PMID:30178502). p.Arg340Cys variant was also identified in the eleven year old male patient and in other unaffected family members, and the patient was presented with insidious onset, progressive vision loss and swaying since 8 years of age. The other presentations were gait ataxia, torticollis to left and tilt to right, head tremors and myoclonus (PMID:33816684).

Mouse models with loss-of-function mutation or lacking SLC25A46 gene manifest the main clinical features identified in patients such as ataxia, optic atrophy, cerebellar hypoplasia and peripheral neuropathy which were completely rescued by expression of human ortholog (PMID:28376086; PMID:28934388). The results suggest that the gene loss causes degeneration in neurons by affecting mitochondrial dynamics and energy production.

Loss-of-function in cultured cells and in zebrafish also led to increased mitochondrial connectivity, while severely affecting the development and maintenance of neurons in the zebrafish (PMID:26168012).

SLC25A46 has been associated with neuropathy, hereditary motor and sensory, type VIB in OMIM and Gene2Phenotype and with pontocerebellar hypoplasia, type 1E in OMIM.; to: Comment on classification of this gene:

The rating for this gene should be GREEN, as this gene has been identified to be implicated in cerebellar ataxia (MONDO:0000437) from biallelic loss-of-function variants from at least 8 unrelated individuals/ families and in pontocerebellar hypoplasia, type 1E (MIM# 619303) from biallelic loss-of-function variants from at least 6 unrelated individuals/ families. These cases were from multiple ethnicities and were supported by results from animal models.

In addition, this gene has also been identified to be implicated in cerebellar hypoplasia from monoallelic loss-of-function variants from a family of three siblings. As we currently do not have three unrelated cases for monoallelic inheritance, this gene is assigned only to biallelic MOI.

Cerebellar ataxia:

Two brothers of consanguineous parents of Pakistani origin were identified with homozygous variant in SLC25A46 (c.413T>G./ p.Leu138Arg). The younger of the two brothers was presented with balancing difficulties in infancy, prominent myoclonus, cerebellar ataxia, profound visual loss, rod cone dysfunction, exotropia, difficulty initiating saccades, mild spasticity, and axonal sensory-motor neuropathy leading to trophic changes. He also developed scoliosis and had cerebellar atrophy as well as T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities and cavitations in the cerebellum. The older brother was mildly affected with similar clinical manifestations (PMID:27430653).

A study on patients from three North African families (Two siblings from Tunisian family and two unrelated Algerians) showed that the previously reported variant c.1018C>T/ p.Arg340Cys (displayed in Tunisian siblings and one Algerian patient) was associated with childhood onset, optic atrophy, gait and speech difficulties and wasting of the lower limbs, and the Algerian patient with the novel variant p.Trp160Ser did not present with optic atrophy, while all patients were presented with ataxia (PMID:28558379). Similarly, ataxia was also observed in Sardinian (p.Arg340Cys) and Palestinian (c.1005A>T/ p.Glu335Asp) patients from Abrams et al, 2015 (PMID:26168012).

A six year old boy with homozygous missense variant c.770G>A (p.Arg257Gln) was reported with optic atrophy, peripheral neuropathy, ataxia, but not cerebellar atrophy (PMID:30178502). p.Arg340Cys variant was also identified in the eleven year old male patient and in other unaffected family members, and the patient was presented with insidious onset, progressive vision loss and swaying since 8 years of age. The other presentations were gait ataxia, torticollis to left and tilt to right, head tremors and myoclonus (PMID:33816684).

Cerebellar hypoplasia:

Four infants from two different families with homozygous variants (family 1: c.1022T>C/ p.Leu341Pro; family 2: deletion of exon 1) were reported to have died soon after birth with a profound neurodevelopmental disorder associated with congenital pontocerebellar hypoplasia (PMID:27543974). The phenotypes are similar to a female infant from the United States with pontocerebellar atrophy who died at age 15 weeks. This infant reported by Abram et al (2015) exhibited compound heterozygous variants (c.882_885dupTTAC/ p.Asn296fs*297 & c.998C>T/ p.Pro333Leu) (PMID:26168012).

Four infants from two unrelated families of German and Italian descent were reported with PCH1E. All died in the first days or weeks of life. The German infants were identified with homozygous variant c.736A>T (p.Arg246Ter) and the Italian infants were identified with compound heterozygous variants c.42C>G (p.Tyr14Ter) & 462+ 1G>A (PMID:28653766).

Two siblings with bi-allelic compound heterozygous variants (a splicing variant - c.385-1G > A and a deletion) had a fulminant neonatal course. The mother of these siblings exhibited a heterozygous c.385-1G > A allele and the father had an 80-kb deletion spanning SLC25A46 and TMEM232 genes. Pontocerebellar hypoplasia was reported by postmortem brain CT imaging in one of the siblings (PMID:35012485).

Barth (1993) reported a Dutch family in which three siblings died within the first day of life due to lack of spontaneous respiration and profound muscle weakness (PMID:8147499). Although these infants displayed similarities to the clinical indications described by Wan et al, 2016 (PMID:27543974), they were identified to possess heterozygous variant leading to a premature stop codon (c.691C>T/ p.Arg231Ter) in exon 8 of the SLC25A46 gene (PMID:28637197).

Functional studies:

Mouse models with loss-of-function mutation or lacking SLC25A46 gene manifest the main clinical features identified in patients such as ataxia, optic atrophy, cerebellar hypoplasia and peripheral neuropathy which were completely rescued by expression of human ortholog (PMID:28376086; PMID:28934388). The results suggest that the gene loss causes degeneration in neurons by affecting mitochondrial dynamics and energy production.

Loss-of-function in cultured cells and in zebrafish also led to increased mitochondrial connectivity, while severely affecting the development and maintenance of neurons in the zebrafish (PMID:26168012).

SLC25A46 has been associated with neuropathy, hereditary motor and sensory, type VIB in OMIM and Gene2Phenotype and with pontocerebellar hypoplasia, type 1E in OMIM.
Ataxia and cerebellar anomalies - narrow panel v3.11 SLC25A46 Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: SLC25A46.
Ataxia and cerebellar anomalies - narrow panel v3.11 SLC25A46 Achchuthan Shanmugasundram Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505 to Cerebellar ataxia, MONDO:0000437; Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260; Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505
Ataxia and cerebellar anomalies - narrow panel v3.10 SLC25A46 Achchuthan Shanmugasundram Classified gene: SLC25A46 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.10 SLC25A46 Achchuthan Shanmugasundram Gene: slc25a46 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.9 SLC25A46 Achchuthan Shanmugasundram reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: None; Publications: 26168012, 27430653, 28376086, 28558379, 28934388, 30178502, 33816684; Phenotypes: Cerebellar ataxia, MONDO:0000437, Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260, Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.9 SCN2A Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: SCN2A.
Ataxia and cerebellar anomalies - narrow panel v3.9 SCN2A Achchuthan Shanmugasundram Phenotypes for gene: SCN2A were changed from Epileptic encephalopathy, early infantile, 11, MIM# 613721 to Episodic ataxia, type 9, MIM# 618924, MONDO:0030064; Developmental and epileptic encephalopathy 11, MIM# 613721, MONDO:0013388
Ataxia and cerebellar anomalies - narrow panel v3.8 SCN2A Achchuthan Shanmugasundram Publications for gene: SCN2A were set to 31924505; 32893078; 31904126
Ataxia and cerebellar anomalies - narrow panel v3.7 SCN2A Achchuthan Shanmugasundram Mode of pathogenicity for gene: SCN2A was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v3.6 SCN2A Achchuthan Shanmugasundram Classified gene: SCN2A as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.6 SCN2A Achchuthan Shanmugasundram Gene: scn2a has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.5 SCN2A Achchuthan Shanmugasundram reviewed gene: SCN2A: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 20956790, 26291284, 26645390, 27159988, 27328862, 28065826, 30165711, 30741786, 30813219, 30928199, 32893078, 35219921; Phenotypes: Episodic ataxia, type 9, MIM# 618924, MONDO:0030064, Developmental and epileptic encephalopathy 11, MIM# 613721, MONDO:0013388; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v3.5 COQ4 Achchuthan Shanmugasundram Tag treatable tag was added to gene: COQ4.
Tag Q4_22_promote_green tag was added to gene: COQ4.
Ataxia and cerebellar anomalies - narrow panel v3.5 COQ4 Achchuthan Shanmugasundram Phenotypes for gene: COQ4 were changed from Childhood onset ataxia to Childhood-onset spinocerebellar ataxia; Adult-onset ataxia-spasticity spectrum disease; Hereditary spastic paraparesis, MONDO:0019064; Cerebellar ataxia, MONDO:0000437
Ataxia and cerebellar anomalies - narrow panel v3.4 COQ4 Achchuthan Shanmugasundram Publications for gene: COQ4 were set to PMID: 30225196; 33704555; 30847826
Ataxia and cerebellar anomalies - narrow panel v3.3 COQ4 Achchuthan Shanmugasundram Classified gene: COQ4 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.3 COQ4 Achchuthan Shanmugasundram Gene: coq4 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.2 COQ4 Achchuthan Shanmugasundram reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30225196, 30847826, 33215859, 33704555, 36047608; Phenotypes: Childhood-onset spinocerebellar ataxia, Adult-onset ataxia-spasticity spectrum disease, Hereditary spastic paraparesis, MONDO:0019064, Cerebellar ataxia, MONDO:0000437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.2 COG5 Arina Puzriakova Mode of inheritance for gene: COG5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.1 COG5 Arina Puzriakova Tag watchlist_moi tag was added to gene: COG5.
Ataxia and cerebellar anomalies - narrow panel v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Ataxia and cerebellar anomalies - narrow panel v3.0 Arina Puzriakova promoted panel to version 3.0
Ataxia and cerebellar anomalies - narrow panel v2.318 COG5 Arina Puzriakova Mode of inheritance for gene: COG5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.317 COG5 Arina Puzriakova Added comment: Comment on mode of inheritance: All cases reported to date have been associated with recessive inheritance with the exception of one family with "one potential heterozygous mutation" reported in 2017 (PMID: 28960046). As no further monoallelic cases have been reported since, updating the MOI from 'both mono- and biallelic' to 'biallelic' only until further evidence emerges supporting pathogenicity of heterozygous variants in this gene.
Ataxia and cerebellar anomalies - narrow panel v2.317 COG5 Arina Puzriakova Mode of inheritance for gene: COG5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.316 PITRM1 Eleanor Williams Tag gene-checked tag was added to gene: PITRM1.
Ataxia and cerebellar anomalies - narrow panel v2.316 TERT Arina Puzriakova changed review comment from: Cerebellar hypoplasia (without ataxia) has been identified in 2/5 unrelated AR cases who displayed a phenotype of Hoyeraal-Hreidarsson syndrome, a severe variant of DKC (PMIDs: 17785587; 34890115).

There is no link with AD form and given the various other non-relevant phenotypes linked to heterozygous variants, AR inheritance is appropriate for this panel.; to: Cerebellar hypoplasia (without ataxia) has been identified in 2/5 unrelated AR cases to date, who displayed a phenotype of Hoyeraal-Hreidarsson syndrome, a severe variant of DKC (PMIDs: 17785587; 34890115).

There is no link with AD form and given the various other non-relevant phenotypes linked to heterozygous variants, AR inheritance is appropriate for this panel.
Ataxia and cerebellar anomalies - narrow panel v2.316 TERT Arina Puzriakova changed review comment from: Cerebellar hypoplasia (without ataxia) has been identified in 2/5 unrelated AR cases displaying a phenotype of Hoyeraal-Hreidarsson syndrome, a severe variant of DKC (PMIDs: 17785587; 34890115).

There is no link with AD form and given the various other non-relevant phenotypes linked to heterozygous variants, AR inheritance is appropriate for this panel.; to: Cerebellar hypoplasia (without ataxia) has been identified in 2/5 unrelated AR cases who displayed a phenotype of Hoyeraal-Hreidarsson syndrome, a severe variant of DKC (PMIDs: 17785587; 34890115).

There is no link with AD form and given the various other non-relevant phenotypes linked to heterozygous variants, AR inheritance is appropriate for this panel.
Ataxia and cerebellar anomalies - narrow panel v2.316 TERT Arina Puzriakova Tag watchlist tag was added to gene: TERT.
Ataxia and cerebellar anomalies - narrow panel v2.316 TERT Arina Puzriakova Classified gene: TERT as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.316 TERT Arina Puzriakova Gene: tert has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.315 TERT Arina Puzriakova reviewed gene: TERT: Rating: AMBER; Mode of pathogenicity: None; Publications: 17785587, 34890115; Phenotypes: Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.315 TERT Arina Puzriakova Deleted their review
Ataxia and cerebellar anomalies - narrow panel v2.315 TERT Arina Puzriakova Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v2.315 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989 to Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Ataxia and cerebellar anomalies - narrow panel v2.314 TERT Arina Puzriakova Mode of inheritance for gene: TERT was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.313 TERT Arina Puzriakova Classified gene: TERT as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v2.313 TERT Arina Puzriakova Added comment: Comment on list classification: Couldn't find any evidence linking TERT with ataxia and therefore demoting from Amber to Red.
Ataxia and cerebellar anomalies - narrow panel v2.313 TERT Arina Puzriakova Gene: tert has been classified as Red List (Low Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.312 TERT Arina Puzriakova Mode of inheritance for gene: TERT was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.311 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from dyskeratosis congenita-2 to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Ataxia and cerebellar anomalies - narrow panel v2.310 FMR1 Arina Puzriakova Classified gene: FMR1 as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v2.310 FMR1 Arina Puzriakova Added comment: Comment on list classification: FMR1 should be demoted from Green to Red at the next GMS panel update as the disease mechanism for FXTAS (includes ataxia) is repeat expansions and SNVs are not relevant. Furthermore, the FMR1_CGG STR entity will not be added as FXTAS is a late-onset condition and this panel feeds into the childhood-onset ataxia super panel (R55). The STR is already Green on the R45 Hereditary ataxia - adult onset (v2.13) panel.
Ataxia and cerebellar anomalies - narrow panel v2.310 FMR1 Arina Puzriakova Gene: fmr1 has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.309 FMR1 Arina Puzriakova Tag Q4_22_demote_red tag was added to gene: FMR1.
Ataxia and cerebellar anomalies - narrow panel v2.309 GRN Arina Puzriakova changed review comment from: Comment on list classification: This gene should be promoted to Green at the next GMS panel update.; to: Comment on list classification: This gene should be promoted to Green at the next GMS panel update. Multiple cases reported with variable ages of onset. Cerebellar ataxia with cerebellar atrophy on brain MRI is a prominent feature detected in almost all cases with homozygous pathogenic variants in this gene.
Ataxia and cerebellar anomalies - narrow panel v2.309 GRN Arina Puzriakova Entity copied from Neuronal ceroid lipofuscinosis v1.25
Ataxia and cerebellar anomalies - narrow panel v2.309 GRN Arina Puzriakova gene: GRN was added
gene: GRN was added to Ataxia and cerebellar anomalies - narrow panel. Sources: London North GLH,NHS GMS,Expert Review Amber
Q4_22_promote_green tags were added to gene: GRN.
Mode of inheritance for gene: GRN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRN were set to 22608501; 27021778; 28000352; 28404863; 30922528; 31855245
Phenotypes for gene: GRN were set to Ceroid lipofuscinosis, neuronal, 11 OMIM:614706; neuronal ceroid lipofuscinosis 11 MONDO:0013866
Ataxia and cerebellar anomalies - narrow panel v2.308 GRM1 Arina Puzriakova commented on gene: GRM1
Ataxia and cerebellar anomalies - narrow panel v2.308 GRM1 Arina Puzriakova Tag watchlist_moi tag was added to gene: GRM1.
Ataxia and cerebellar anomalies - narrow panel v2.308 GRM1 Arina Puzriakova Phenotypes for gene: GRM1 were changed from Spinocerebellar ataxia, autosomal recessive 13 to Spinocerebellar ataxia 44, OMIM:617691; Spinocerebellar ataxia, autosomal recessive 13, OMIM:614831
Ataxia and cerebellar anomalies - narrow panel v2.307 GRM1 Arina Puzriakova Publications for gene: GRM1 were set to
Ataxia and cerebellar anomalies - narrow panel v2.306 SPG7 Eleanor Williams Tag Q2_21_expert_review was removed from gene: SPG7.
Tag Q3_22_rating tag was added to gene: SPG7.
Tag Q3_22_expert_review tag was added to gene: SPG7.
Ataxia and cerebellar anomalies - narrow panel v2.306 SPG7 Eleanor Williams commented on gene: SPG7
Ataxia and cerebellar anomalies - narrow panel v2.306 CYP2U1 Eleanor Williams commented on gene: CYP2U1
Ataxia and cerebellar anomalies - narrow panel v2.306 CYP2U1 Eleanor Williams Tag Q2_21_expert_review was removed from gene: CYP2U1.
Tag Q3_22_rating tag was added to gene: CYP2U1.
Tag Q3_22_expert_review tag was added to gene: CYP2U1.
Ataxia and cerebellar anomalies - narrow panel v2.306 CACNA1A Sarah Leigh Phenotypes for gene: CACNA1A were changed from Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500 to Developmental and epileptic encephalopathy 42, OMIM:617106; developmental and epileptic encephalopathy, 42, MONDO:0014917; Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Ataxia and cerebellar anomalies - narrow panel v2.305 CACNA1A Sarah Leigh Tag Q3_22_MOI tag was added to gene: CACNA1A.
Tag Q3_22_NHS_review tag was added to gene: CACNA1A.
Ataxia and cerebellar anomalies - narrow panel v2.305 CACNA1A Sarah Leigh reviewed gene: CACNA1A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.305 STUB1 Sarah Leigh Tag Q3_22_MOI tag was added to gene: STUB1.
Ataxia and cerebellar anomalies - narrow panel v2.305 STUB1 Sarah Leigh reviewed gene: STUB1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.305 TBP_CAG Sarah Leigh Publications for STR: TBP_CAG were set to 20301611
Ataxia and cerebellar anomalies - narrow panel v2.304 STUB1 Sarah Leigh Phenotypes for gene: STUB1 were changed from Spinocerebellar ataxia, autosomal recessive 16; Spinocerebellar ataxia, autosomal recessive 16 615768 to Autosomal recessive spinocerebellar ataxia type 16, OMIM:615768; autosomal recessive spinocerebellar ataxia 16, MONDO:0014339; Spinocerebellar ataxia 48, OMIM:618093; spinocerebellar ataxia 48, MONDO:0032526
Ataxia and cerebellar anomalies - narrow panel v2.303 STUB1 Sarah Leigh Publications for gene: STUB1 were set to 24312598
Ataxia and cerebellar anomalies - narrow panel v2.302 PRDM13 Arina Puzriakova Classified gene: PRDM13 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.302 PRDM13 Arina Puzriakova Added comment: Comment on list classification: This gene should be promoted to Green at the next GMS panel update.
Ataxia and cerebellar anomalies - narrow panel v2.302 PRDM13 Arina Puzriakova Gene: prdm13 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.301 PRDM13 Arina Puzriakova Tag Q3_22_rating tag was added to gene: PRDM13.
Ataxia and cerebellar anomalies - narrow panel v2.301 PRDM13 Arina Puzriakova Entity copied from Cerebellar hypoplasia v1.64
Ataxia and cerebellar anomalies - narrow panel v2.301 PRDM13 Arina Puzriakova gene: PRDM13 was added
gene: PRDM13 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PRDM13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM13 were set to 35390279; 34730112
Phenotypes for gene: PRDM13 were set to Pontocerebellar hypoplasia, type 17, OMIM:619909; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, OMIM:619761
Ataxia and cerebellar anomalies - narrow panel v2.300 OGDHL Arina Puzriakova Entity copied from Intellectual disability v3.1644
Ataxia and cerebellar anomalies - narrow panel v2.300 OGDHL Arina Puzriakova gene: OGDHL was added
gene: OGDHL was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Q3_22_rating tags were added to gene: OGDHL.
Mode of inheritance for gene: OGDHL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OGDHL were set to 28017472; 34800363
Phenotypes for gene: OGDHL were set to Yoon-Bellen neurodevelopmental syndrome, OMIM:619701
Ataxia and cerebellar anomalies - narrow panel v2.299 RFXANK Arina Puzriakova Phenotypes for gene: RFXANK were changed from Progressive Ataxia and Neurologic Regression; MHC class II deficiency, complementation group B MIM#209920 to MHC class II deficiency, complementation group B, OMIM:209920; Progressive Ataxia and Neurologic Regression
Ataxia and cerebellar anomalies - narrow panel v2.298 ATG7 Arina Puzriakova Tag Q3_22_rating tag was added to gene: ATG7.
Ataxia and cerebellar anomalies - narrow panel v2.298 ATG7 Arina Puzriakova Classified gene: ATG7 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.298 ATG7 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark and based on the evidence provided this gene should be promoted to Green at the next GMS panel update. ATG7 is associated with a relevant phenotype in OMIM (MIM# 34161705) and has a 'strong' disease confidence classification for this phenotype in G2P.

Collier et al. 2021 (PMID: 34161705) identified 5 unrelated families with distinct ATG7 variants and a neurodevelopmental disorder which mainly comprised cerebellar ataxia (11/11), mild-to-severe ID (12/12), optic atrophy (7/11), among other features.
Ataxia and cerebellar anomalies - narrow panel v2.298 ATG7 Arina Puzriakova Gene: atg7 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.297 ATG7 Arina Puzriakova Phenotypes for gene: ATG7 were changed from Spinocerebellar ataxia, SCAR31, MIM#619422 to Spinocerebellar ataxia, autosomal recessive 31, OMIM:619422
Ataxia and cerebellar anomalies - narrow panel v2.296 ATP6V0A1 Sarah Leigh Tag Q3_22_MOI was removed from gene: ATP6V0A1.
Tag Q3_22_NHS_review was removed from gene: ATP6V0A1.
Ataxia and cerebellar anomalies - narrow panel v2.296 ATP6V0A1 Sarah Leigh edited their review of gene: ATP6V0A1: Added comment: Only 2/4 biallelic cases reported by PMID: 34909687, exhibited ataxia, as a result of this biallelic mode of inheritance has not been included for ATP6V0A1 on the Ataxia and cerebellar anomalies - narrow panel.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v2.296 ATP6V0A1 Sarah Leigh Entity copied from Genetic epilepsy syndromes v2.539
Ataxia and cerebellar anomalies - narrow panel v2.296 ATP6V0A1 Sarah Leigh gene: ATP6V0A1 was added
gene: ATP6V0A1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature,Expert Review Amber
Q3_22_rating, Q3_22_MOI, Q3_22_NHS_review tags were added to gene: ATP6V0A1.
Mode of inheritance for gene: ATP6V0A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0A1 were set to 30842224; 33057194; 34909687; 33833240
Phenotypes for gene: ATP6V0A1 were set to ATP6V0A1-related developmental disorder (monoallelic)
Ataxia and cerebellar anomalies - narrow panel v2.295 PEX6 Sarah Leigh changed review comment from: Comment on mode of inheritance: The mode of inheritance for PEX6 has been set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.; to: Comment on mode of inheritance: The mode of inheritance for PEX6 has been set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted for this gene, in order to highlight that unaffected parents may also carry rs61753230.
Ataxia and cerebellar anomalies - narrow panel v2.295 TBP_CAG Eleanor Williams Tag for-review was removed from STR: TBP_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.295 PPP2R2B_CAG Eleanor Williams Tag for-review was removed from STR: PPP2R2B_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.295 NOP56_GGCCTG Eleanor Williams Tag for-review was removed from STR: NOP56_GGCCTG.
Ataxia and cerebellar anomalies - narrow panel v2.295 GLS_GCA Eleanor Williams Tag for-review was removed from STR: GLS_GCA.
Ataxia and cerebellar anomalies - narrow panel v2.295 CACNA1A_CAG Eleanor Williams Tag for-review was removed from STR: CACNA1A_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.295 ATXN3_CAG Eleanor Williams Tag for-review was removed from STR: ATXN3_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.295 ATXN10_ATTCT Eleanor Williams Tag for-review was removed from STR: ATXN10_ATTCT.
Ataxia and cerebellar anomalies - narrow panel v2.295 ATXN1_CAG Eleanor Williams Tag for-review was removed from STR: ATXN1_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.295 ATN1_CAG Eleanor Williams Tag for-review was removed from STR: ATN1_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.295 ACO2 Sarah Leigh commented on gene: ACO2: PMID: 34056600 reports 61 cases of genetically unsolved inherited optic neuropathies who were harbouring variants in ACO2, of which 50 carried dominant variants (the remaining 11 cases were biallelic). The authors state that this is the first report of monoallelic pathogenic ACO2 variants resulting in dominant optic atrophy.
Ataxia and cerebellar anomalies - narrow panel v2.295 ACO2 Sarah Leigh reviewed gene: ACO2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.295 ACO2 Sarah Leigh Tag Q2_22_MOI tag was added to gene: ACO2.
Ataxia and cerebellar anomalies - narrow panel v2.295 MT-ATP6 Eleanor Williams Tag gene-checked tag was added to gene: MT-ATP6.
Ataxia and cerebellar anomalies - narrow panel v2.295 FMR1 Dmitrijs Rots reviewed gene: FMR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.295 SETX Sarah Leigh Phenotypes for gene: SETX were changed from Ataxia-ocular apraxia-2; ataxia with oculomotor apraxia type 2 (AOA2), juvenile amyotrophic lateral sclerosis (ALS4) and autosomal dominant ataxia to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, OMIM:606002
Ataxia and cerebellar anomalies - narrow panel v2.294 SETX Sarah Leigh reviewed gene: SETX: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.294 AFG3L2 Arina Puzriakova Phenotypes for gene: AFG3L2 were changed from Spinocerebellar ataxia 28; Spinocerebellar Ataxia, Dominant; Ataxia, spastic, 5, autosomal recessive to Spinocerebellar ataxia 28, OMIM:610246; Spastic ataxia 5, autosomal recessive, OMIM:614487
Ataxia and cerebellar anomalies - narrow panel v2.293 OPA1 Arina Puzriakova Phenotypes for gene: OPA1 were changed from Optic atrophy plus syndrome OMIM:125250; optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy MONDO:0007429; Behr syndrome OMIM:210000; Behr syndrome MONDO:0008858 to Optic atrophy 1, OMIM:165500; Optic atrophy plus syndrome, OMIM:125250; Behr syndrome, OMIM:210000
Ataxia and cerebellar anomalies - narrow panel v2.292 PEX6 Sarah Leigh Tag Q2_22_MOI was removed from gene: PEX6.
Tag Q2_22_rating tag was added to gene: PEX6.
Ataxia and cerebellar anomalies - narrow panel v2.292 PEX6 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for PEX6 has been set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
Ataxia and cerebellar anomalies - narrow panel v2.292 PEX6 Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.291 PEX6 Sarah Leigh Classified gene: PEX6 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.291 PEX6 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for PEX6 to be green on this panel.
Ataxia and cerebellar anomalies - narrow panel v2.291 PEX6 Sarah Leigh Gene: pex6 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.290 PEX6 Sarah Leigh gene: PEX6 was added
gene: PEX6 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q2_22_MOI tags were added to gene: PEX6.
Mode of inheritance for gene: PEX6 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PEX6 were set to 25655951; 29220678
Phenotypes for gene: PEX6 were set to Peroxisome biogenesis disorder 4B, OMIM:614863
Penetrance for gene: PEX6 were set to Incomplete
Mode of pathogenicity for gene: PEX6 was set to Other
Review for gene: PEX6 was set to GREEN
Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.289 CACNA1A_CAG Louise Daugherty reviewed STR: CACNA1A_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.289 ATXN10_ATTCT Louise Daugherty reviewed STR: ATXN10_ATTCT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.289 GLS Eleanor Williams commented on gene: GLS
Ataxia and cerebellar anomalies - narrow panel v2.289 GLS Eleanor Williams Tag for-review was removed from gene: GLS.
Tag watchlist tag was added to gene: GLS.
Ataxia and cerebellar anomalies - narrow panel v2.289 ISCA-37478-Loss Eleanor Williams commented on Region: ISCA-37478-Loss
Ataxia and cerebellar anomalies - narrow panel v2.289 ISCA-37478-Gain Eleanor Williams commented on Region: ISCA-37478-Gain
Ataxia and cerebellar anomalies - narrow panel v2.289 ISCA-37404-Loss Arina Puzriakova commented on Region: ISCA-37404-Loss
Ataxia and cerebellar anomalies - narrow panel v2.289 ISCA-37478-Loss Arina Puzriakova GRCh38 position for ISCA-37478-Loss was changed from 23513243-28312040 to 23465365-28134728.
Required Overlap Percentage for ISCA-37478-Loss was changed from 80 to 60.
Ataxia and cerebellar anomalies - narrow panel v2.289 ISCA-37478-Gain Arina Puzriakova GRCh38 position for ISCA-37478-Gain was changed from 23513243-28312040 to 23465365-28134728.
Required Overlap Percentage for ISCA-37478-Gain was changed from 80 to 60.
Ataxia and cerebellar anomalies - narrow panel v2.289 ISCA-37404-Loss Arina Puzriakova GRCh38 position for ISCA-37404-Loss was changed from 22782170-28134729 to 22782170-28134728.
Required Overlap Percentage for ISCA-37404-Loss was changed from 80 to 60.
Ataxia and cerebellar anomalies - narrow panel v2.288 HTT_CAG Arina Puzriakova commented on STR: HTT_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
Ataxia and cerebellar anomalies - narrow panel v2.288 TBP_CAG Arina Puzriakova commented on STR: TBP_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
Ataxia and cerebellar anomalies - narrow panel v2.288 PPP2R2B_CAG Arina Puzriakova commented on STR: PPP2R2B_CAG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
Ataxia and cerebellar anomalies - narrow panel v2.288 NOP56_GGCCTG Arina Puzriakova commented on STR: NOP56_GGCCTG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
Ataxia and cerebellar anomalies - narrow panel v2.288 FXN_GAA Sarah Leigh commented on STR: FXN_GAA
Ataxia and cerebellar anomalies - narrow panel v2.288 CSTB_CCCCGCCCCGCG Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG: STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
Ataxia and cerebellar anomalies - narrow panel v2.288 CACNA1A_CAG Eleanor Williams commented on STR: CACNA1A_CAG
Ataxia and cerebellar anomalies - narrow panel v2.288 ATXN7_CAG Eleanor Williams commented on STR: ATXN7_CAG
Ataxia and cerebellar anomalies - narrow panel v2.288 ATXN3_CAG Eleanor Williams commented on STR: ATXN3_CAG
Ataxia and cerebellar anomalies - narrow panel v2.288 ATXN2_CAG Ivone Leong commented on STR: ATXN2_CAG
Ataxia and cerebellar anomalies - narrow panel v2.288 ATXN10_ATTCT Ivone Leong commented on STR: ATXN10_ATTCT
Ataxia and cerebellar anomalies - narrow panel v2.288 ATXN1_CAG Ivone Leong commented on STR: ATXN1_CAG
Ataxia and cerebellar anomalies - narrow panel v2.288 ATN1_CAG Ivone Leong commented on STR: ATN1_CAG
Ataxia and cerebellar anomalies - narrow panel v2.288 VPS41 Ivone Leong Tag Q2_21_rating was removed from gene: VPS41.
Tag Q2_21_NHS_review was removed from gene: VPS41.
Ataxia and cerebellar anomalies - narrow panel v2.288 VPS41 Sarah Leigh commented on gene: VPS41
Ataxia and cerebellar anomalies - narrow panel v2.287 VPS41 Ivone Leong Source Expert Review Green was added to VPS41.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v2.284 HTT_CAG Arina Puzriakova Normal Number of Repeats for HTT_CAG was changed from 40 to 36.
Source NHS GMS was added to STR: HTT_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.284 TBP_CAG Arina Puzriakova Source NHS GMS was added to STR: TBP_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.284 PPP2R2B_CAG Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33.
Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43.
Source NHS GMS was added to STR: PPP2R2B_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.284 NOP56_GGCCTG Arina Puzriakova Source NHS GMS was added to STR: NOP56_GGCCTG.
Ataxia and cerebellar anomalies - narrow panel v2.284 FXN_GAA Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA.
Ataxia and cerebellar anomalies - narrow panel v2.284 CSTB_CCCCGCCCCGCG Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18.
Source NHS GMS was added to STR: CSTB_CCCCGCCCCGCG.
Ataxia and cerebellar anomalies - narrow panel v2.284 CACNA1A_CAG Arina Puzriakova Normal Number of Repeats for CACNA1A_CAG was changed from 18 to 19.
Source NHS GMS was added to STR: CACNA1A_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.284 ATXN7_CAG Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28.
Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37.
Source NHS GMS was added to STR: ATXN7_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.284 ATXN3_CAG Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45.
Source NHS GMS was added to STR: ATXN3_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.284 ATXN2_CAG Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32.
Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35.
Source NHS GMS was added to STR: ATXN2_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.284 ATXN10_ATTCT Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33.
Source NHS GMS was added to STR: ATXN10_ATTCT.
Ataxia and cerebellar anomalies - narrow panel v2.284 ATXN1_CAG Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36.
Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45.
Source NHS GMS was added to STR: ATXN1_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.284 ATN1_CAG Arina Puzriakova Normal Number of Repeats for ATN1_CAG was changed from 35 to 36.
Source NHS GMS was added to STR: ATN1_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.283 LARS2 Sarah Leigh Tag for-review was removed from gene: LARS2.
Ataxia and cerebellar anomalies - narrow panel v2.283 LARS2 Sarah Leigh Source Expert Review Green was added to LARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v2.282 LARS2 Sarah Leigh commented on gene: LARS2: The rating of this gene has been updated following NHS Genomic Medicine Service approval
Ataxia and cerebellar anomalies - narrow panel v2.281 MVK Arina Puzriakova Phenotypes for gene: MVK were changed from Mevalonic aciduria OMIM:610377; mevalonic aciduria MONDO:0012481 to Mevalonic aciduria, OMIM:610377
Ataxia and cerebellar anomalies - narrow panel v2.280 PRDX3 Arina Puzriakova Entity copied from Hereditary ataxia - adult onset v2.138
Ataxia and cerebellar anomalies - narrow panel v2.280 PRDX3 Arina Puzriakova gene: PRDX3 was added
gene: PRDX3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Q1_22_rating tags were added to gene: PRDX3.
Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDX3 were set to 33889951
Phenotypes for gene: PRDX3 were set to Cerebellar ataxia (early onset, mild to moderate, progressive)
Ataxia and cerebellar anomalies - narrow panel v2.279 ALDH5A1 Ivone Leong Tag Q3_21_rating tag was added to gene: ALDH5A1.
Ataxia and cerebellar anomalies - narrow panel v2.279 VPS41 Arina Puzriakova Tag Q2_21_NHS_review tag was added to gene: VPS41.
Ataxia and cerebellar anomalies - narrow panel v2.279 HEXB Arina Puzriakova Phenotypes for gene: HEXB were changed from Sandhoff disease, infantile, juvenile, and adult forms, 268800 to Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800
Ataxia and cerebellar anomalies - narrow panel v2.278 COQ4 Dmitrijs Rots gene: COQ4 was added
gene: COQ4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ4 were set to PMID: 30225196; 33704555; 30847826
Phenotypes for gene: COQ4 were set to Childhood onset ataxia
Penetrance for gene: COQ4 were set to Complete
Review for gene: COQ4 was set to GREEN
Added comment: The phenotype of COQ4 deficiency is very broad. In the three publications, at 6 individuals from 4 families are reported as having childhood onset ataxia.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.278 MAPK8IP3 Arina Puzriakova Classified gene: MAPK8IP3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.278 MAPK8IP3 Arina Puzriakova Added comment: Comment on list classification: 18 individuals from 17 families reported with de novo variants in this gene (PMIDs: 30612693; 30945334) of which 3 subjects displayed cerebellar atrophy on brain MRI and 2 had ataxia. Onset in childhood. Overall there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Ataxia and cerebellar anomalies - narrow panel v2.278 MAPK8IP3 Arina Puzriakova Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.277 MAPK8IP3 Arina Puzriakova Entity copied from Hereditary ataxia - adult onset v2.129
Ataxia and cerebellar anomalies - narrow panel v2.277 MAPK8IP3 Arina Puzriakova gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Wessex and West Midlands GLH,Expert Review Green,NHS GMS
Q4_21_rating tags were added to gene: MAPK8IP3.
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK8IP3 were set to 30612693; 30945334
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443
Ataxia and cerebellar anomalies - narrow panel v2.276 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia, type 1B, 614678; Pontocerebellar Hypoplasia type 1B to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Ataxia and cerebellar anomalies - narrow panel v2.275 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Ataxia and cerebellar anomalies - narrow panel v2.275 GLS_GCA Arina Puzriakova Phenotypes for STR: GLS_GCA were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
Ataxia and cerebellar anomalies - narrow panel v2.274 GLS Arina Puzriakova Phenotypes for gene: GLS were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
Ataxia and cerebellar anomalies - narrow panel v2.273 NOP56_GGCCTG Arina Puzriakova Phenotypes for STR: NOP56_GGCCTG were changed from Spinocerebellar ataxia 36 614153 to Spinocerebellar ataxia 36, OMIM:614153
Ataxia and cerebellar anomalies - narrow panel v2.272 NOP56_GGCCTG Arina Puzriakova Tag watchlist tag was added to STR: NOP56_GGCCTG.
Ataxia and cerebellar anomalies - narrow panel v2.272 NOP56 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: NOP56.
Tag currently-ngs-unreportable tag was added to gene: NOP56.
Ataxia and cerebellar anomalies - narrow panel v2.272 NOP56 Arina Puzriakova Phenotypes for gene: NOP56 were changed from Spinocerebellarataxia36,614153 to Spinocerebellar ataxia 36, OMIM:614153
Ataxia and cerebellar anomalies - narrow panel v2.271 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.271 PPP2R2B Arina Puzriakova Mode of inheritance for gene: PPP2R2B was changed from Unknown to Other
Ataxia and cerebellar anomalies - narrow panel v2.270 PPP2R2B Arina Puzriakova Phenotypes for gene: PPP2R2B were changed from Spinocerebellarataxia12,604326 to Spinocerebellar ataxia 12, OMIM:604326
Ataxia and cerebellar anomalies - narrow panel v2.269 PPP2R2B Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: PPP2R2B.
Tag currently-ngs-unreportable tag was added to gene: PPP2R2B.
Ataxia and cerebellar anomalies - narrow panel v2.269 PPP2R2B_CAG Arina Puzriakova Phenotypes for STR: PPP2R2B_CAG were changed from Spinocerebellar ataxia 12 604326 to Spinocerebellar ataxia 12, OMIM:604326
Ataxia and cerebellar anomalies - narrow panel v2.268 PPP2R2B_CAG Arina Puzriakova Tag watchlist tag was added to STR: PPP2R2B_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.268 TBP_CAG Arina Puzriakova Phenotypes for STR: TBP_CAG were changed from Spinocerebellar ataxia 17 607136 to Spinocerebellar ataxia 17, OMIM:607136
Ataxia and cerebellar anomalies - narrow panel v2.267 TBP_CAG Arina Puzriakova Tag watchlist tag was added to STR: TBP_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.267 TBP Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.267 TBP Arina Puzriakova Mode of inheritance for gene: TBP was changed from Unknown to Other
Ataxia and cerebellar anomalies - narrow panel v2.266 TBP Arina Puzriakova Phenotypes for gene: TBP were changed from Spinocerebellarataxia17,607136{Parkinsondisease,susceptibilityto},168600 to Spinocerebellar ataxia 17, OMIM:607136
Ataxia and cerebellar anomalies - narrow panel v2.265 TBP Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: TBP.
Tag currently-ngs-unreportable tag was added to gene: TBP.
Ataxia and cerebellar anomalies - narrow panel v2.265 HTT_CAG Arina Puzriakova Phenotypes for STR: HTT_CAG were changed from Huntington disease 143100 to Huntington disease, OMIM:143100
Ataxia and cerebellar anomalies - narrow panel v2.264 FMR1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FMR1.
Ataxia and cerebellar anomalies - narrow panel v2.264 FMR1 Arina Puzriakova Phenotypes for gene: FMR1 were changed from FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related premature ovarian insufficiency (POI); males with a tremor phenotype; FragileXtremor/ataxiasyndrome,300623 to Fragile X tremor/ataxia syndrome, OMIM:300623
Ataxia and cerebellar anomalies - narrow panel v2.263 ATXN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.263 ATXN1 Arina Puzriakova Mode of inheritance for gene: ATXN1 was changed from Unknown to Other
Ataxia and cerebellar anomalies - narrow panel v2.262 ATXN1 Arina Puzriakova Phenotypes for gene: ATXN1 were changed from Spinocerebellarataxia1,164400 to Spinocerebellar ataxia 1, OMIM:164400
Ataxia and cerebellar anomalies - narrow panel v2.261 ATXN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN1.
Tag currently-ngs-unreportable tag was added to gene: ATXN1.
Ataxia and cerebellar anomalies - narrow panel v2.261 ATXN1_CAG Arina Puzriakova Phenotypes for STR: ATXN1_CAG were changed from Spinocerebellar ataxia 1 164400 to Spinocerebellar ataxia 1, OMIM:164400
Ataxia and cerebellar anomalies - narrow panel v2.260 ATXN1_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN1_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.260 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Ataxia and cerebellar anomalies - narrow panel v2.260 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Spinocerebellar ataxia 6; Episodic ataxia, type 2 to Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Ataxia and cerebellar anomalies - narrow panel v2.259 CACNA1A_CAG Arina Puzriakova Phenotypes for STR: CACNA1A_CAG were changed from Spinocerebellar ataxia 6 183086 to Spinocerebellar ataxia 6, OMIM:183086
Ataxia and cerebellar anomalies - narrow panel v2.258 CACNA1A_CAG Arina Puzriakova Tag watchlist tag was added to STR: CACNA1A_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.258 ATXN7_CAG Arina Puzriakova Phenotypes for STR: ATXN7_CAG were changed from Spinocerebellar ataxia 7 164500 to Spinocerebellar ataxia 7, OMIM:164500
Ataxia and cerebellar anomalies - narrow panel v2.257 ATXN7 Arina Puzriakova Phenotypes for gene: ATXN7 were changed from Spinocerebellarataxia7,164500 to Spinocerebellar ataxia 7, OMIM:164500
Ataxia and cerebellar anomalies - narrow panel v2.256 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.256 ATXN7 Arina Puzriakova Mode of inheritance for gene: ATXN7 was changed from Unknown to Other
Ataxia and cerebellar anomalies - narrow panel v2.255 ATXN7 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN7.
Tag currently-ngs-unreportable tag was added to gene: ATXN7.
Ataxia and cerebellar anomalies - narrow panel v2.255 ATXN3_CAG Arina Puzriakova Phenotypes for STR: ATXN3_CAG were changed from Machado-Joseph disease 109150 to Machado-Joseph disease, OMIM:109150
Ataxia and cerebellar anomalies - narrow panel v2.254 ATXN3_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATXN3_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.254 ATXN3 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.254 ATXN3 Arina Puzriakova Mode of inheritance for gene: ATXN3 was changed from Unknown to Other
Ataxia and cerebellar anomalies - narrow panel v2.253 ATXN3 Arina Puzriakova Phenotypes for gene: ATXN3 were changed from to Machado-Joseph disease, OMIM:109150
Ataxia and cerebellar anomalies - narrow panel v2.252 ATXN3 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN3.
Tag currently-ngs-unreportable tag was added to gene: ATXN3.
Ataxia and cerebellar anomalies - narrow panel v2.252 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2 183090 to Spinocerebellar ataxia 2, OMIM:183090
Ataxia and cerebellar anomalies - narrow panel v2.251 ATXN2 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.251 ATXN2 Arina Puzriakova Mode of inheritance for gene: ATXN2 was changed from Unknown to Other
Ataxia and cerebellar anomalies - narrow panel v2.250 ATXN2 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN2.
Tag currently-ngs-unreportable tag was added to gene: ATXN2.
Ataxia and cerebellar anomalies - narrow panel v2.250 ATXN2 Arina Puzriakova Phenotypes for gene: ATXN2 were changed from Spinocerebellarataxia2,183090{Amyotrophiclateralsclerosis,susceptibilityto,13},183090 to Spinocerebellar ataxia 2, OMIM:183090
Ataxia and cerebellar anomalies - narrow panel v2.249 ATXN10_ATTCT Arina Puzriakova Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 10 603516 to Spinocerebellar ataxia 10, OMIM:603516
Ataxia and cerebellar anomalies - narrow panel v2.248 ATXN10_ATTCT Arina Puzriakova Tag watchlist tag was added to STR: ATXN10_ATTCT.
Ataxia and cerebellar anomalies - narrow panel v2.248 ATXN10 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN10.
Tag currently-ngs-unreportable tag was added to gene: ATXN10.
Ataxia and cerebellar anomalies - narrow panel v2.248 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.248 ATXN10 Arina Puzriakova Mode of inheritance for gene: ATXN10 was changed from Unknown to Other
Ataxia and cerebellar anomalies - narrow panel v2.247 ATXN10 Arina Puzriakova Phenotypes for gene: ATXN10 were changed from Spinocerebellarataxia10,603516 to Spinocerebellar ataxia 10, OMIM:603516
Ataxia and cerebellar anomalies - narrow panel v2.246 ATN1_CAG Arina Puzriakova Tag watchlist tag was added to STR: ATN1_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.246 ATN1_CAG Arina Puzriakova Phenotypes for STR: ATN1_CAG were changed from Dentatorubro-pallidoluysian atrophy 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Ataxia and cerebellar anomalies - narrow panel v2.245 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Ataxia and cerebellar anomalies - narrow panel v2.244 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Ataxia and cerebellar anomalies - narrow panel v2.244 ATN1 Arina Puzriakova Mode of inheritance for gene: ATN1 was changed from Other - please specifiy in evaluation comments to Other
Ataxia and cerebellar anomalies - narrow panel v2.243 ATN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATN1.
Tag currently-ngs-unreportable tag was added to gene: ATN1.
Ataxia and cerebellar anomalies - narrow panel v2.243 DHDDS Arina Puzriakova Classified gene: DHDDS as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.243 DHDDS Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Ataxia and cerebellar anomalies - narrow panel v2.243 DHDDS Arina Puzriakova Gene: dhdds has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.242 DHDDS Arina Puzriakova gene: DHDDS was added
gene: DHDDS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q4_21_rating tags were added to gene: DHDDS.
Mode of inheritance for gene: DHDDS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DHDDS were set to 29100083; 33798445; 34182312; 34382076
Phenotypes for gene: DHDDS were set to Developmental delay and seizures with or without movement abnormalities, OMIM:617836
Review for gene: DHDDS was set to GREEN
Added comment: Monoallelic variants are associated with a neurodevelopmental disorder comprising infantile or childhood-onset DD/ID, epilepsy and a variable movement phenotype which typically initially manifests as action myoclonus/cortical tremor and in some cases ataxia - at least 11 unrelated cases of ataxia reported in literature.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.241 B4GAT1 Ivone Leong reviewed gene: B4GAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.241 B4GAT1 Ivone Leong Publications for gene: B4GAT1 were set to 23359570
Ataxia and cerebellar anomalies - narrow panel v2.240 B4GAT1 Ivone Leong Tag Q3_21_rating tag was added to gene: B4GAT1.
Ataxia and cerebellar anomalies - narrow panel v2.240 AP1S2 Arina Puzriakova Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic 5, 304340 to Pettigrew syndrome, OMIM:304340
Ataxia and cerebellar anomalies - narrow panel v2.239 CLCN2 Arina Puzriakova Publications for gene: CLCN2 were set to 19191339; 23707145
Ataxia and cerebellar anomalies - narrow panel v2.238 CLCN2 Arina Puzriakova Tag Q4_21_MOI tag was added to gene: CLCN2.
Ataxia and cerebellar anomalies - narrow panel v2.238 CLCN2 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be changed from 'Both mono- and biallelic' to 'Biallelic' only. Ataxia is a frequent feature of CLCN2-related Leukoencephalopathy (MIM# 615651) which is caused by biallelic variants. Autosomal dominant pathogenic variants are also associated with hyperaldosteronism (MIM# 605635) and susceptibility to idiopathic epilepsy (MIM# 607628) but neither of these phenotypes include ataxia.
Ataxia and cerebellar anomalies - narrow panel v2.238 CLCN2 Arina Puzriakova Mode of inheritance for gene: CLCN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.237 CLCN2 Arina Puzriakova Phenotypes for gene: CLCN2 were changed from {Epilepsy, juvenile absence, susceptibility to, 2}, 607628; {Epilepsy, idiopathic generalized, susceptibility to, 11}, 607628; {Epilepsy, juvenile myoclonic, susceptibility to, 8}, 607628; Leukoencephalopathy with ataxia, 615651 to Leukoencephalopathy with ataxia, OMIM:615651
Ataxia and cerebellar anomalies - narrow panel v2.236 RFXANK Zornitza Stark gene: RFXANK was added
gene: RFXANK was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: RFXANK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFXANK were set to 33855173; 23314770; 28676232
Phenotypes for gene: RFXANK were set to Progressive Ataxia and Neurologic Regression; MHC class II deficiency, complementation group B MIM#209920
Review for gene: RFXANK was set to AMBER
Added comment: PMID: 33855173 - 1 family (2 affecteds, 3rd not sequenced) with a homozygous c.271+1G>C splice variant, late-onset immunodeficiency and subacute progressive neurodegenerative disease, including cognition, motor, visual and cerebellar features. MRI demonstrated global cerebral and cerebellar atrophy.

PMID: 23314770 - 1/34 MHCII deficient patients with biallelic variants reported with ataxia. Majority of patients (including patient with ataxia) share a founder variant (c.338-25_338del26).

PMID: 28676232 - single 30 month old patient with ataxic gait and dysarthria and a homozygous PTC.

Summary: 3 patients but uncommon feature of an established immunological disorder, variable expressivity
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.236 DAB1 Zornitza Stark reviewed gene: DAB1: Rating: RED; Mode of pathogenicity: None; Publications: 33928188; Phenotypes: Ataxia, Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.236 TRIP4 Zornitza Stark gene: TRIP4 was added
gene: TRIP4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: TRIP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIP4 were set to 34075209
Phenotypes for gene: TRIP4 were set to cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures.
Review for gene: TRIP4 was set to AMBER
Added comment: PMID: 34075209:
One patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures, hom PTV. The same PTV had been previously reported in 3 patients from 2 families with prenatal spinal muscular atrophy and congenital bone fractures (PMID: 26924529).

Possible phenotype expansion.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.236 RNF220 Ivone Leong Phenotypes for gene: RNF220 were changed from Intellectual disability, MONDO:0001071 to Ataxia, HP:0001251
Ataxia and cerebellar anomalies - narrow panel v2.235 RNF220 Ivone Leong Tag Q4_21_rating tag was added to gene: RNF220.
Ataxia and cerebellar anomalies - narrow panel v2.235 RNF220 Ivone Leong changed review comment from: Comment on list classification: New gene added by Konstantinos Varvagiannis. This gene is currently not associated with a phenotype in OMIM or Gene2Phenotype. There are >3 cases for this gene; however, 3 of the cases described in PMID:33964137 are of Roma descent and haplotype analysis has shown that the variant found in these families are due to a founder effect (c.1094G>A, p.Arg365Gly). A separate Roma family also has the same variant (c.1094G>A, p.Arg365Gly). An Italian family with similar phenotypes has a different variant (c.1088G>A, p.Arg363Gly). The authors also report on in vitro and in vivo studies.

There is enough evidence to support a gene-disease association; however, the ID severity in these patients do not meet the criteria (moderate to severe) for this panel (patients show mild (mostly) to moderate severity). Therefore, this gene has been given an Amber rating.; to: Comment on list classification: New gene added by Konstantinos Varvagiannis. This gene is currently not associated with a phenotype in OMIM or Gene2Phenotype. There are >3 cases for this gene; however, 3 of the cases described in PMID:33964137 are of Roma descent and haplotype analysis has shown that the variant found in these families are due to a founder effect (c.1094G>A, p.Arg365Gly). A separate Roma family also has the same variant (c.1094G>A, p.Arg365Gly). An Italian family with similar phenotypes has a different variant (c.1088G>A, p.Arg363Gly). The authors also report on in vitro and in vivo studies.

There is enough evidence to support a gene-disease association. Therefore, this gene should be Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.235 RNF220 Ivone Leong Entity copied from Intellectual disability v3.1329
Ataxia and cerebellar anomalies - narrow panel v2.235 RNF220 Ivone Leong gene: RNF220 was added
gene: RNF220 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature,Expert Review Amber,Other
Mode of inheritance for gene: RNF220 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF220 were set to 33964137; 10881263
Phenotypes for gene: RNF220 were set to Intellectual disability, MONDO:0001071
Penetrance for gene: RNF220 were set to Complete
Ataxia and cerebellar anomalies - narrow panel v2.234 GMPPB Sarah Leigh Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 OMIM:615350; muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 MONDO:0014140
Ataxia and cerebellar anomalies - narrow panel v2.233 PI4KA Ivone Leong Tag Q3_21_rating tag was added to gene: PI4KA.
Ataxia and cerebellar anomalies - narrow panel v2.233 PI4KA Ivone Leong Phenotypes for gene: PI4KA were changed from Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis , 616531 to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, OMIM:616531
Ataxia and cerebellar anomalies - narrow panel v2.232 PI4KA Ivone Leong Publications for gene: PI4KA were set to 25855803
Ataxia and cerebellar anomalies - narrow panel v2.231 PI4KA Ivone Leong Classified gene: PI4KA as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.231 PI4KA Ivone Leong Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.230 PI4KA Ivone Leong reviewed gene: PI4KA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25855803, 34415322, 34415310; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.230 CHP1 Arina Puzriakova Entity copied from Hereditary ataxia v1.241
Ataxia and cerebellar anomalies - narrow panel v2.230 CHP1 Arina Puzriakova gene: CHP1 was added
gene: CHP1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: CHP1.
Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHP1 were set to 23904602; 29379881; 32787936
Phenotypes for gene: CHP1 were set to Spastic ataxia 9, autosomal recessive, OMIM:618438
Ataxia and cerebellar anomalies - narrow panel v2.229 NKX6-2 Arina Puzriakova Phenotypes for gene: NKX6-2 were changed from Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, OMIM:617560
Ataxia and cerebellar anomalies - narrow panel v2.228 KIF1C Arina Puzriakova Publications for gene: KIF1C were set to
Ataxia and cerebellar anomalies - narrow panel v2.227 KIF1C Arina Puzriakova Phenotypes for gene: KIF1C were changed from Spastic ataxia 2,autosomal recessive to Spastic ataxia 2, autosomal recessive, OMIM:611302
Ataxia and cerebellar anomalies - narrow panel v2.226 SNX14 Ivone Leong Tag Q3_21_MOI tag was added to gene: SNX14.
Ataxia and cerebellar anomalies - narrow panel v2.226 SNX14 Ivone Leong reviewed gene: SNX14: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.226 ATG7 Zornitza Stark gene: ATG7 was added
gene: ATG7 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG7 were set to 34161705
Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, SCAR31, MIM#619422
Review for gene: ATG7 was set to GREEN
Added comment: 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.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.226 KIF1A Arina Puzriakova Classified gene: KIF1A as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.226 KIF1A Arina Puzriakova Added comment: Comment on list classification: There are sufficient cases (>3) with monoallelic KIF1A variants and cerebellar atrophy and/or ataxia to rate as Green on this panel.
Ataxia and cerebellar anomalies - narrow panel v2.226 KIF1A Arina Puzriakova Gene: kif1a has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.225 KIF1A Arina Puzriakova Added comment: Comment on mode of inheritance: Cerebellar anomalies associated with recessive KIF1A-related HSP are significantly milder than those observed in individuals with dominant HSP or NESCAV syndrome. There are also only 2 families with biallelic variants who presented with the relevant features, which does not reach the threshold for inclusion under this MOI at this time.

For this reason, the MOI has been set to 'monoallelic' only with the 'watchlist_MOI' tag to monitor future evidence linking biallelic variants with cerebellar ataxia.
Ataxia and cerebellar anomalies - narrow panel v2.225 KIF1A Arina Puzriakova Mode of inheritance for gene: KIF1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v2.224 KIF1A Arina Puzriakova gene: KIF1A was added
gene: KIF1A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q3_21_rating, watchlist_moi tags were added to gene: KIF1A.
Mode of inheritance for gene: KIF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF1A were set to 22258533; 28332297; 25265257; 26125038; 26354034; 31805580; 32096284; 32737135; 32746806; 34121983; https://doi.org/10.1016/j.ejpn.2017.04.926
Phenotypes for gene: KIF1A were set to Spastic paraplegia 30, autosomal dominant, OMIM:610357; Spastic paraplegia 30, autosomal recessive, OMIM:610357; NESCAV syndrome, OMIM:614255
Review for gene: KIF1A was set to GREEN
Added comment: KIF1A is associated HSP type 30 (MIM# 610357) which can be inherited recessively or dominantly, as well as NESCAV syndrome (MIM# 614255) caused by heterozygous variants in this gene.

Cerebellar signs including: ataxia; dysmetria; and saccadic ocular pursuit, associated with mild cerebellar atrophy, were reported in 2/4 families with recessive HSP (PMID: 21487076; 22258533; 28332297).

Variable ataxic features, cerebellar signs and cerebellar atrophy have been described in multiple cases with the complex forms of dominant KIF1A-related HSP (PMID: 31805580; 32737135), but these features are even more prominent in individuals with NESCAV syndrome (PMID: 25265257; 26125038; 26354034; 32096284; 34121983).

Of note, at least 11 heterozygous cases have been described in which congenital or early onset ataxia with cerebellar signs was the presenting clinical feature (PMID: 26354034; 32737135; 32746806; https://doi.org/10.1016/j.ejpn.2017.04.926)
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.223 DPYSL5 Ivone Leong Entity copied from Intellectual disability v3.1214
Ataxia and cerebellar anomalies - narrow panel v2.223 DPYSL5 Ivone Leong gene: DPYSL5 was added
gene: DPYSL5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Q3_21_rating tags were added to gene: DPYSL5.
Mode of inheritance for gene: DPYSL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DPYSL5 were set to 33894126
Phenotypes for gene: DPYSL5 were set to Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Ataxia and cerebellar anomalies - narrow panel v2.222 ABCB7 Ivone Leong Tag Q3_21_MOI tag was added to gene: ABCB7.
Ataxia and cerebellar anomalies - narrow panel v2.222 ABCB7 Ivone Leong reviewed gene: ABCB7: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia and cerebellar anomalies - narrow panel v2.222 ATM Arina Puzriakova Phenotypes for gene: ATM were changed from Ataxia-telangiectasia,; Ataxia-Telangiectasia to Ataxia-telangiectasia, OMIM:208900
Ataxia and cerebellar anomalies - narrow panel v2.221 HEATR5B Ivone Leong Entity copied from Intellectual disability v3.1188
Ataxia and cerebellar anomalies - narrow panel v2.221 HEATR5B Ivone Leong gene: HEATR5B was added
gene: HEATR5B was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: HEATR5B.
Mode of inheritance for gene: HEATR5B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR5B were set to 33824466
Phenotypes for gene: HEATR5B were set to pontocerebellar hypoplasia, MONDO:0020135; intellectual disability, MONDO:0001071; seizures
Ataxia and cerebellar anomalies - narrow panel v2.220 ABCB7 Ivone Leong Phenotypes for gene: ABCB7 were changed from Anemia, sideroblastic, with ataxia,; Sideroblastic Anemia and Ataxia to Anemia, sideroblastic, with ataxia, OMIM:301310
Ataxia and cerebellar anomalies - narrow panel v2.219 ATAD3A Arina Puzriakova changed review comment from: Comment on mode of inheritance: Changed MOI from 'Both mono- and biallelic' to 'Biallelic' only.

ATAD3A is associated with Harel-Yoon syndrome (MIM# 617183) with both dominant and recessive patterns of inheritance. However, only families with the biallelic form displayed cerebellar atrophy (PMID: 27640307; 32607449; 33845882). Brain MRI results have been normal in heterozygous cases to date.

Furthermore, biallelic variants in ATAD3A are also associated with another phenotype comprising neonatal lethal pontocerebellar hypoplasia (MIM# 618810) - at least 13 unrelated families in literature, including 2 families with SNVs (PMID: 29053797; 31727539) and 11 families with deletions affecting ATAD3A (PMID: 27640307; 28549128; 29053797; 33845882); to: ATAD3A is associated with Harel-Yoon syndrome (MIM# 617183) with both dominant and recessive patterns of inheritance. However, only families with the biallelic form displayed cerebellar atrophy (PMID: 27640307; 32607449; 33845882). Brain MRI results have been normal in heterozygous cases to date (MOI set to 'Biallelic' only).

Furthermore, biallelic variants in ATAD3A are also associated with another phenotype comprising neonatal lethal pontocerebellar hypoplasia (MIM# 618810) - at least 13 unrelated families in literature, including 2 families with SNVs (PMID: 29053797; 31727539) and 11 families with deletions affecting ATAD3A (PMID: 27640307; 28549128; 29053797; 33845882)
Ataxia and cerebellar anomalies - narrow panel v2.219 ATAD3A Arina Puzriakova changed review comment from: Comment on list classification: Upgraded from Amber to Green, as the number of unrelated families (at least 7) with cerebellar/pontocerebellar hypoplasia and biallelic SNVs in ATAD3A reaches the threshold for inclusion on this panel.; to: Comment on list classification: There is enough evidence to promote this gene to Green at the next GMS panel update - the number of unrelated families (at least 7) with cerebellar/pontocerebellar hypoplasia and biallelic SNVs in ATAD3A reaches the threshold for inclusion on this panel.
Ataxia and cerebellar anomalies - narrow panel v2.219 ATAD3A Arina Puzriakova Tag Q2_21_rating tag was added to gene: ATAD3A.
Ataxia and cerebellar anomalies - narrow panel v2.219 ATAD3A Arina Puzriakova Classified gene: ATAD3A as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.219 ATAD3A Arina Puzriakova Gene: atad3a has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.218 ATAD3A Arina Puzriakova Entity copied from Cerebellar hypoplasia v1.52
Ataxia and cerebellar anomalies - narrow panel v2.218 ATAD3A Arina Puzriakova gene: ATAD3A was added
gene: ATAD3A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: ATAD3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATAD3A were set to 27640307; 28549128; 29053797; 31727539; 32607449; 33845882
Phenotypes for gene: ATAD3A were set to Harel-Yoon syndrome, OMIM:617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810
Ataxia and cerebellar anomalies - narrow panel v2.217 SAR1B Eleanor Williams Phenotypes for gene: SAR1B were changed from Chylomicron retention disease to Chylomicron retention disease, OMIM:246700
Ataxia and cerebellar anomalies - narrow panel v2.216 SAR1B Eleanor Williams Publications for gene: SAR1B were set to
Ataxia and cerebellar anomalies - narrow panel v2.215 SAR1B Eleanor Williams Classified gene: SAR1B as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v2.215 SAR1B Eleanor Williams Added comment: Comment on list classification: Leaving rating as green, but with recommendation of a red rating following GMS review. Ataxia rarely reported and as the expert reviewer notes this is secondary to malabsorption.
Ataxia and cerebellar anomalies - narrow panel v2.215 SAR1B Eleanor Williams Gene: sar1b has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.214 SAR1B Eleanor Williams Tag Q2_21_rating tag was added to gene: SAR1B.
Ataxia and cerebellar anomalies - narrow panel v2.214 SAR1B Eleanor Williams reviewed gene: SAR1B: Rating: RED; Mode of pathogenicity: None; Publications: 12692552, 3792776, 7601203, 2426307, 10521380, 10665502, 17945526; Phenotypes: Chylomicron retention disease, OMIM:246700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.214 XRCC1 Arina Puzriakova edited their review of gene: XRCC1: Changed rating: GREEN; Changed publications to: 28002403, 29472272; Changed phenotypes to: Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.214 XRCC1 Arina Puzriakova changed review comment from: Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team) it was agreed that there is enough evidence to promote this gene to Green at the next GMS panel update (see details below).
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Three individuals from unrelated families all from South Asian descent with cerebellar ataxia and peripheral neuropathy and a recurrent variant (c.1293G>C, 2 homozygotes and a comp het) in the XRCC1 gene. Homozygosity mapping in 2 families confirmed a shared haplotype and the recurrent variant is found in a heterozygous state in an unaffected sib and 4 individuals of South Asian descent in ExAC - indicating that this is a founder variant that is pathogenic when biallelic. There is some strong functional evidence that supports pathogenicity, including an animal model that recapitulated human phenotypes such as cerebellar ataxia.; to: Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team) it was agreed that there is enough evidence to promote this gene to Green at the next GMS panel update (see details below).
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Three individuals from unrelated families all from South Asian descent with cerebellar ataxia and peripheral neuropathy and a recurrent variant (c.1293G>C, 2 homozygotes and a comp het) in the XRCC1 gene. Homozygosity mapping in 2 families confirmed a shared haplotype and the recurrent variant is found in a heterozygous state in an unaffected sib and 4 individuals of South Asian descent in ExAC - indicating that this is a founder variant that is pathogenic when when in trans with a second variant. There is some strong functional evidence that supports pathogenicity, including an animal model that recapitulated human phenotypes such as cerebellar ataxia.
Ataxia and cerebellar anomalies - narrow panel v2.214 XRCC1 Arina Puzriakova Tag founder-effect tag was added to gene: XRCC1.
Tag Q2_21_rating tag was added to gene: XRCC1.
Ataxia and cerebellar anomalies - narrow panel v2.214 XRCC1 Arina Puzriakova Classified gene: XRCC1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.214 XRCC1 Arina Puzriakova Added comment: Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team) it was agreed that there is enough evidence to promote this gene to Green at the next GMS panel update (see details below).
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Three individuals from unrelated families all from South Asian descent with cerebellar ataxia and peripheral neuropathy and a recurrent variant (c.1293G>C, 2 homozygotes and a comp het) in the XRCC1 gene. Homozygosity mapping in 2 families confirmed a shared haplotype and the recurrent variant is found in a heterozygous state in an unaffected sib and 4 individuals of South Asian descent in ExAC - indicating that this is a founder variant that is pathogenic when biallelic. There is some strong functional evidence that supports pathogenicity, including an animal model that recapitulated human phenotypes such as cerebellar ataxia.
Ataxia and cerebellar anomalies - narrow panel v2.214 XRCC1 Arina Puzriakova Gene: xrcc1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.213 XRCC1 Arina Puzriakova Publications for gene: XRCC1 were set to 28002403
Ataxia and cerebellar anomalies - narrow panel v2.212 XRCC1 Arina Puzriakova Phenotypes for gene: XRCC1 were changed from ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia to Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633
Ataxia and cerebellar anomalies - narrow panel v2.211 GEMIN5 Arina Puzriakova Entity copied from Intellectual disability v3.1145
Ataxia and cerebellar anomalies - narrow panel v2.211 GEMIN5 Arina Puzriakova gene: GEMIN5 was added
gene: GEMIN5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Q2_21_rating tags were added to gene: GEMIN5.
Mode of inheritance for gene: GEMIN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GEMIN5 were set to 33963192
Phenotypes for gene: GEMIN5 were set to Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, OMIM:619333
Ataxia and cerebellar anomalies - narrow panel v2.210 POU4F1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: POU4F1.
Ataxia and cerebellar anomalies - narrow panel v2.210 POU4F1 Arina Puzriakova Classified gene: POU4F1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.210 POU4F1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is sufficient evidence to promote this gene to Green at the next GMS panel update - sufficient number of unrelated cases (>3), supported by an animal model (see details below)
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Webb et al. 2021 (PMID:33783914) identified four unrelated individuals with different de novo POU4F1 variants. All presented with ataxia, hypotonia, and intention tremor. 3/4 also had strabismus and a history of paroxysmal tonic upgaze. Pou4f1−/− mice are known to have uncoordinated movements consistent with the ataxia phenotype seen in this patient cohort.

POU4F1 is associated with a relevant phenotype in OMIM (Ataxia, intention tremor, and hypotonia syndrome, childhood-onset, MIM# 619352) but is not yet listed in G2P.
Ataxia and cerebellar anomalies - narrow panel v2.210 POU4F1 Arina Puzriakova Gene: pou4f1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.209 POU4F1 Arina Puzriakova Phenotypes for gene: POU4F1 were changed from Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) , MIM#619352 to Ataxia, intention tremor, and hypotonia syndrome, childhood-onset, OMIM:619352
Ataxia and cerebellar anomalies - narrow panel v2.208 Arina Puzriakova removed gene:POU1F1 from the panel
Ataxia and cerebellar anomalies - narrow panel v2.207 SLC17A5 Arina Puzriakova Tag Q2_21_rating tag was added to gene: SLC17A5.
Ataxia and cerebellar anomalies - narrow panel v2.207 SLC17A5 Arina Puzriakova Publications for gene: SLC17A5 were set to 26171070
Ataxia and cerebellar anomalies - narrow panel v2.206 SLC17A5 Arina Puzriakova Phenotypes for gene: SLC17A5 were changed from Sialic acid storage disorder, infantile, MIM# 269920 to Salla disease, OMIM:604369; Sialic acid storage disorder, infantile, OMIM:269920
Ataxia and cerebellar anomalies - narrow panel v2.205 SLC17A5 Arina Puzriakova Classified gene: SLC17A5 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.205 SLC17A5 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Zornitza Stark (Australian Genomics). There is enough evidence to promote this gene to Green at the next GMS panel update.

Associated with relevant phenotypes in OMIM and has a 'confirmed' disease confidence rating in G2P. At least 6 variants reported in at least 6 cases of Sialic acid storage disorder, infantile (MIM# 269920) and at least 2 variants reported in at least 5 cases of Salla disease (MIM# 604369). Cerebellar ataxia is a main presenting feature of this disorder, typically arising within the first year of life.
Ataxia and cerebellar anomalies - narrow panel v2.205 SLC17A5 Arina Puzriakova Gene: slc17a5 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.204 SCN8A Arina Puzriakova changed review comment from: SCN8A is associated with a range of phenotypes including epilepsy, neurodevelopmental defects, and movement disorders. Some individuals with deleterious SCN8A variants develop ataxia - at least 14 individuals with ataxia reported in literature (see publications list). Variable age of onset including both childhood-onset and adult-onset cases.

Several patients with the other phenotypes (although not including ataxia) have been reported as having cerebellar abnormalities. Mouse Scn8a mutants exhibit movement disorders including ataxia, tremor and dystonia.; to: SCN8A is associated with a range of phenotypes including epilepsy, neurodevelopmental defects, and movement disorders. Some individuals with deleterious SCN8A variants develop ataxia - at least 14 individuals with ataxia reported in literature (see publications list). Variable age of onset - mostly during childhood but adult-onset cases have also been described.

Several patients with the other phenotypes (although not including ataxia) have been reported as having cerebellar abnormalities. Mouse Scn8a mutants exhibit movement disorders including ataxia, tremor and dystonia.
Ataxia and cerebellar anomalies - narrow panel v2.204 SCN8A Arina Puzriakova Classified gene: SCN8A as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.204 SCN8A Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but there is enough evidence to rate this gene as Green at the next GMS panel update.
Ataxia and cerebellar anomalies - narrow panel v2.204 SCN8A Arina Puzriakova Gene: scn8a has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.203 SCN8A Arina Puzriakova Tag Q2_21_rating tag was added to gene: SCN8A.
Ataxia and cerebellar anomalies - narrow panel v2.203 SCN8A Arina Puzriakova Publications for gene: SCN8A were set to
Ataxia and cerebellar anomalies - narrow panel v2.202 SCN8A Arina Puzriakova reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 16236810, 22365152, 25725044, 28702509, 31675620, 31887642; Phenotypes: Cognitive impairment with or without cerebellar ataxia, OMIM:614306, Developmental and epileptic encephalopathy 13, OMIM:614558; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ataxia and cerebellar anomalies - narrow panel v2.202 SCN8A Arina Puzriakova Phenotypes for gene: SCN8A were changed from Cognitive impairment with or without cerebellar ataxia, 614306 to Cognitive impairment with or without cerebellar ataxia, OMIM:614306; Developmental and epileptic encephalopathy 13, OMIM:614558
Ataxia and cerebellar anomalies - narrow panel v2.201 RUBCN Arina Puzriakova Publications for gene: RUBCN were set to PMID: 20826435
Ataxia and cerebellar anomalies - narrow panel v2.200 RUBCN Arina Puzriakova Classified gene: RUBCN as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v2.200 RUBCN Arina Puzriakova Added comment: Comment on list classification: Gene was reassessed following a Green review by Zornitza Stark. Five individuals from two consanguineous Saudi families have been identified (PMID: 20826435; 32450808) who presented with early-onset ataxia, dysarthria, and developmental delay. All harboured the same c.2624delC variant, which was confirmed to be a founder variant by autozygosity mapping. Limited functional data showing the variant results in mislocalisation of the mutant protein from the late endosome and lysosomes to diffuse cytosolic distribution.

*Note the third publication identified by Zornitza (PMID:30237576) refers to the same sib pair as in PMID:32450808. The variants appeared distinct as the two papers refer to different reference sequences (NM_014687 vs NM_001145642.2) but the variant/case are in fact the same.
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Overall as there is only a single variant in a single population with only limited in vitro functional support, maintaining Red rating on this panel until further evidence on the gene/variants emerges.
Ataxia and cerebellar anomalies - narrow panel v2.200 RUBCN Arina Puzriakova Gene: rubcn has been classified as Red List (Low Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.199 RUBCN Arina Puzriakova Tag founder-effect tag was added to gene: RUBCN.
Ataxia and cerebellar anomalies - narrow panel v2.199 RUBCN Arina Puzriakova Phenotypes for gene: RUBCN were changed from to Spinocerebellar ataxia, autosomal recessive 15, OMIM:615705
Ataxia and cerebellar anomalies - narrow panel v2.198 POLR3B Arina Puzriakova Phenotypes for gene: POLR3B were changed from Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381 to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381; POLR3B-related neurodevelopmental disorder; Ataxia, spasticity, and demyelinating neuropathy
Ataxia and cerebellar anomalies - narrow panel v2.197 POLR3B Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Progressive childhood-onset cerebellar ataxia is a feature in a subset of cases with biallelic variants in this gene. There are sufficient unrelated families in literature to warrant a Green rating on this panel (>10 individuals reported with ataxia)

Recently, heterozygous variants were also linked to ataxia, with different de novo POLR3B variants identified in 6 unrelated individuals presenting (PMID:33417887). All had had a variable degree of gait dysfunction - 5/6 had truncal and/or appendicular ataxia with wide-based ataxic gait, inability to perform tandem gait, or gait instability. Protein modelling and proteomic analysis shows variants caused aberrant association of individual enzyme subunits rather than affecting overall enzyme assembly or stability.


Comment on mode of inheritance: Both biallelic and monoallelic variants have been linked to ataxia - enough evidence for a Green rating for both allelic requirements; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Progressive childhood-onset cerebellar ataxia is a feature in a subset of cases with biallelic variants in this gene. There are sufficient unrelated families in literature to warrant a Green rating on this panel (>10 individuals reported with ataxia)

Recently, heterozygous variants were also linked to ataxia, with different de novo POLR3B variants identified in 6 unrelated individuals (PMID:33417887). All had had a variable degree of gait dysfunction - 5/6 had truncal and/or appendicular ataxia with wide-based ataxic gait, inability to perform tandem gait, or gait instability. Protein modelling and proteomic analysis shows variants caused aberrant association of individual enzyme subunits rather than affecting overall enzyme assembly or stability.


Comment on mode of inheritance: Both biallelic and monoallelic variants have been linked to ataxia - enough evidence for a Green rating for both allelic requirements
Ataxia and cerebellar anomalies - narrow panel v2.197 POLR3B Arina Puzriakova edited their review of gene: POLR3B: Changed rating: GREEN; Changed publications to: 22036171, 18851904, 22036172, 24190003, 25339210, 26204956, 27159321, 32319736, 33417887; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.197 POLR3B Arina Puzriakova Tag Q2_21_rating tag was added to gene: POLR3B.
Ataxia and cerebellar anomalies - narrow panel v2.197 POLR3B Arina Puzriakova Publications for gene: POLR3B were set to 22036171; 22036172
Ataxia and cerebellar anomalies - narrow panel v2.196 POLR3B Arina Puzriakova Mode of inheritance for gene: POLR3B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.195 POLR3B Arina Puzriakova Classified gene: POLR3B as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.195 POLR3B Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Progressive childhood-onset cerebellar ataxia is a feature in a subset of cases with biallelic variants in this gene. There are sufficient unrelated families in literature to warrant a Green rating on this panel (>10 individuals reported with ataxia)

Recently, heterozygous variants were also linked to ataxia, with different de novo POLR3B variants identified in 6 unrelated individuals presenting (PMID:33417887). All had had a variable degree of gait dysfunction - 5/6 had truncal and/or appendicular ataxia with wide-based ataxic gait, inability to perform tandem gait, or gait instability. Protein modelling and proteomic analysis shows variants caused aberrant association of individual enzyme subunits rather than affecting overall enzyme assembly or stability.


Comment on mode of inheritance: Both biallelic and monoallelic variants have been linked to ataxia - enough evidence for a Green rating for both allelic requirements
Ataxia and cerebellar anomalies - narrow panel v2.195 POLR3B Arina Puzriakova Gene: polr3b has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.194 POLR3B Arina Puzriakova Phenotypes for gene: POLR3B were changed from Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381 to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381
Ataxia and cerebellar anomalies - narrow panel v2.193 PITRM1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: PITRM1.
Ataxia and cerebellar anomalies - narrow panel v2.193 PITRM1 Arina Puzriakova Classified gene: PITRM1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.193 PITRM1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence for PITRM1 to be classified as Green at the next GMS panel update. Three unrelated families including 2 consanguineous Palestinian families each with 2 affected boys (PMID: 29764912) and a consanguineous Norwegian family also with 2 affected sibs (PMID: 26697887). Phenotypes include ataxia although severity is variable. Supported by functional work and mouse model also exhibiting progressive ataxia.
Ataxia and cerebellar anomalies - narrow panel v2.193 PITRM1 Arina Puzriakova Gene: pitrm1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.192 VPS41 Arina Puzriakova Publications for gene: VPS41 were set to 32808683; 33764426
Ataxia and cerebellar anomalies - narrow panel v2.191 VPS41 Arina Puzriakova Classified gene: VPS41 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.191 VPS41 Arina Puzriakova Added comment: Comment on list classification: New gene added by James Polke (North Thames GLH). There is sufficient evidence to promote this gene to Green at the next GSM panel update - cerebellar ataxia was evident in 9/11 patients reported to date.
Ataxia and cerebellar anomalies - narrow panel v2.191 VPS41 Arina Puzriakova Gene: vps41 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.190 VPS41 Arina Puzriakova Tag Q2_21_rating tag was added to gene: VPS41.
Ataxia and cerebellar anomalies - narrow panel v2.190 VPS41 Arina Puzriakova reviewed gene: VPS41: Rating: GREEN; Mode of pathogenicity: None; Publications: 32808683, 33764426, 33851776; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.190 POU4F1 Zornitza Stark gene: POU4F1 was added
gene: POU4F1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: POU4F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU4F1 were set to 33783914; 8876243
Phenotypes for gene: POU4F1 were set to Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) , MIM#619352
Review for gene: POU4F1 was set to GREEN
gene: POU4F1 was marked as current diagnostic
Added comment: 4 unrelated probands presenting with paediatric onset ataxia, intention tremor, and hypotonia, with de novo loss of function variants, and supporting null mouse model.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.190 POU1F1 Zornitza Stark Deleted their review
Ataxia and cerebellar anomalies - narrow panel v2.190 POU1F1 Zornitza Stark gene: POU1F1 was added
gene: POU1F1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: POU1F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU1F1 were set to 33783914; 8876243
Phenotypes for gene: POU1F1 were set to Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) , MIM#619352
Review for gene: POU1F1 was set to GREEN
gene: POU1F1 was marked as current diagnostic
Added comment: 4 unrelated probands presenting with paediatric onset ataxia, intention tremor, and hypotonia, with de novo loss of function variants, and supporting null mouse model.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.190 VPS41 James Polke gene: VPS41 was added
gene: VPS41 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: NHS GMS
Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS41 were set to 32808683; 33764426
Phenotypes for gene: VPS41 were set to Generalised Neurodevelopmental disorder; Ataxia; Dystonia
Review for gene: VPS41 was set to GREEN
Added comment: 32808683: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders.

PMID 33764426: Additional 9 individuals from 5 unrelated families reported.
Sources: NHS GMS
Ataxia and cerebellar anomalies - narrow panel v2.190 SLC9A1 Sarah Leigh Tag Q2_21_rating tag was added to gene: SLC9A1.
Ataxia and cerebellar anomalies - narrow panel v2.190 SLC9A1 Sarah Leigh reviewed gene: SLC9A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.190 SLC9A1 Sarah Leigh Classified gene: SLC9A1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.190 SLC9A1 Sarah Leigh Gene: slc9a1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.189 SLC9A1 Sarah Leigh Phenotypes for gene: SLC9A1 were changed from Lichtenstein-Knorr syndrome, MIM# 616291 to Lichtenstein-Knorr syndrome OMIM:616291; Lichtenstein-Knorr syndrome MONDO:0014572
Ataxia and cerebellar anomalies - narrow panel v2.188 NAXE Arina Puzriakova changed review comment from: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.; to: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. Added to this panel as acute/early-onset ataxia is described in several cases as one of the first symptoms of disease and inclusion may allow for earlier detection. Other cerebellar signs such as nystagmus and dysarthria also reported.
Ataxia and cerebellar anomalies - narrow panel v2.188 NAXE Arina Puzriakova Entity copied from White matter disorders and cerebral calcification - narrow panel v1.108
Ataxia and cerebellar anomalies - narrow panel v2.188 NAXE Arina Puzriakova gene: NAXE was added
gene: NAXE was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Q2_21_rating tags were added to gene: NAXE.
Mode of inheritance for gene: NAXE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXE were set to 27616477; 27122014; 27290639; 30022751; 31758406; 31745726
Phenotypes for gene: NAXE were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, OMIM:617186
Ataxia and cerebellar anomalies - narrow panel v2.187 SCYL1 Sarah Leigh Tag Q2_21_rating tag was added to gene: SCYL1.
Ataxia and cerebellar anomalies - narrow panel v2.187 SCYL1 Sarah Leigh edited their review of gene: SCYL1: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least nine variants reported in at least seven cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.187 SCYL1 Sarah Leigh Classified gene: SCYL1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.187 SCYL1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.187 SCYL1 Sarah Leigh Gene: scyl1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.186 SCYL1 Sarah Leigh Phenotypes for gene: SCYL1 were changed from Spinocerebellar ataxia, autosomal recessive 21, MIM# 616719 to Spinocerebellar ataxia, autosomal recessive 21 OMIM:616719; acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome MONDO:0014744
Ataxia and cerebellar anomalies - narrow panel v2.185 RORA Sarah Leigh Tag Q2_21_rating tag was added to gene: RORA.
Ataxia and cerebellar anomalies - narrow panel v2.185 RORA Sarah Leigh edited their review of gene: RORA: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least four variants reported in at least four cases with ataxia (PMID 29656859).; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.185 RORA Sarah Leigh Classified gene: RORA as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.185 RORA Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.185 RORA Sarah Leigh Gene: rora has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.184 RORA Sarah Leigh Phenotypes for gene: RORA were changed from Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, MIM# 618060 to Intellectual developmental disorder with or without epilepsy or cerebellar ataxia OMIM:618060; intellectual developmental disorder with or without epilepsy or cerebellar ataxia MONDO:0060745
Ataxia and cerebellar anomalies - narrow panel v2.183 LIG3 Ivone Leong Tag watchlist tag was added to gene: LIG3.
Ataxia and cerebellar anomalies - narrow panel v2.183 LIG3 Ivone Leong edited their review of gene: LIG3: Added comment: As only 1 family has signs of ataxia and the knockout mouse model recapitulated this phenotype this gene has been given an Amber rating on this panel.; Changed rating: AMBER
Ataxia and cerebellar anomalies - narrow panel v2.183 LIG3 Ivone Leong Tag Q2_21_rating was removed from gene: LIG3.
Ataxia and cerebellar anomalies - narrow panel v2.183 LIG3 Ivone Leong Entity copied from White matter disorders and cerebral calcification - narrow panel v1.100
Ataxia and cerebellar anomalies - narrow panel v2.183 LIG3 Ivone Leong gene: LIG3 was added
gene: LIG3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature
Q2_21_rating tags were added to gene: LIG3.
Mode of inheritance for gene: LIG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG3 were set to 33855352
Phenotypes for gene: LIG3 were set to gut dysmotility; spasticity; ataxia; repetitive behaviours; neurogenic bladder; macular degeneration; leukoencephalopathy; cerebellar atrophy; mitochondrial DNA depletion
Ataxia and cerebellar anomalies - narrow panel v2.182 TSEN54 Arina Puzriakova Publications for gene: TSEN54 were set to PMID: 20956791; PMID: 18711368; PMID: 20952379; PMID: 21368912
Ataxia and cerebellar anomalies - narrow panel v2.181 TSEN54 Arina Puzriakova Phenotypes for gene: TSEN54 were changed from Pontocerebellar Hypoplasia type 2A; Pontocerebellar hypoplasia 2A (#277470) and 4 (#225753); Pontocerebellar hypoplasia type 2A, 277470; Pontocerebellar Hypoplasia type 4; Pontocerebellar hypoplasia type 4, 225753; Pontocerebellar Hypoplasia; Pontocerebellar Hypoplasia type 5 to ?Pontocerebellar hypoplasia type 5, OMIM:610204; Pontocerebellar hypoplasia type 2A, OMIM:277470; Pontocerebellar hypoplasia type 4, OMIM:225753
Ataxia and cerebellar anomalies - narrow panel v2.180 POLR3K Ivone Leong Entity copied from White matter disorders and cerebral calcification - narrow panel v1.98
Ataxia and cerebellar anomalies - narrow panel v2.180 POLR3K Ivone Leong gene: POLR3K was added
gene: POLR3K was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature,Expert Review Amber
watchlist, founder-effect tags were added to gene: POLR3K.
Mode of inheritance for gene: POLR3K was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3K were set to 30584594; 33659930
Phenotypes for gene: POLR3K were set to Leukodystrophy, hypomyelinating, 21, OMIM:619310
Ataxia and cerebellar anomalies - narrow panel v2.179 TSEN15 Arina Puzriakova Tag watchlist tag was added to gene: TSEN15.
Ataxia and cerebellar anomalies - narrow panel v2.179 TSEN15 Arina Puzriakova Classified gene: TSEN15 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.179 TSEN15 Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber - PMID:27392077 report on 2 families with PCH and biallelic variants in this gene (brain MRI was not available in third family). Additional cases required prior to inclusion as diagnostic-grade (added watchlist tag)
Ataxia and cerebellar anomalies - narrow panel v2.179 TSEN15 Arina Puzriakova Gene: tsen15 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.178 TSEN15 Arina Puzriakova Phenotypes for gene: TSEN15 were changed from Pontocerebellar hypoplasia, type 2F 617026 to Pontocerebellar hypoplasia, type 2F, OMIM:617026
Ataxia and cerebellar anomalies - narrow panel v2.177 TSEN15 Arina Puzriakova reviewed gene: TSEN15: Rating: ; Mode of pathogenicity: None; Publications: 27392077; Phenotypes: Pontocerebellar hypoplasia, type 2F, OMIM:617026; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.177 VRK1 Arina Puzriakova Phenotypes for gene: VRK1 were changed from Pontocerebellar Hypoplasia type 1A; Pontocerebellar Hypoplasia with infantile SMA; Pontocerebellar Hypoplasia with anterior horn cell disease; Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 1A (#607596); Pontocerebellar hypoplasia type 1A,607596 to Pontocerebellar hypoplasia type 1A, OMIM:607596
Ataxia and cerebellar anomalies - narrow panel v2.176 SPTBN2 Arina Puzriakova Phenotypes for gene: SPTBN2 were changed from Spinocerebellar ataxia 5 (AD); Spinocerebellar ataxia, autosomal recessive 14; SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 14; Spinocerebellar Ataxia, Dominant; Spinocerebellar ataxia, autosomal recessive 14 (AR); Spinocerebellar ataxia 5; SPINOCEREBELLAR ATAXIA 5 (autosomal dominant) to Spinocerebellar ataxia 5, OMIM:600224; Spinocerebellar ataxia, autosomal recessive 14, OMIM:615386
Ataxia and cerebellar anomalies - narrow panel v2.175 MTCL1 Arina Puzriakova Classified gene: MTCL1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.175 MTCL1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote this gene to Green at the next GMS panel update - two unrelated individuals with different LoF variants in this gene. Ataxia with cerebellar atrophy was the predominant presentation in both cases (PMIDs: 30548255; 32961396). Knockout animal model recapitulates human phenotypes and provides functional support.
Ataxia and cerebellar anomalies - narrow panel v2.175 MTCL1 Arina Puzriakova Gene: mtcl1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.174 MTCL1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: MTCL1.
Ataxia and cerebellar anomalies - narrow panel v2.174 MTCL1 Arina Puzriakova reviewed gene: MTCL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30548255, 32961396; Phenotypes: Cerebellar ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.174 MINPP1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: MINPP1.
Ataxia and cerebellar anomalies - narrow panel v2.174 MINPP1 Arina Puzriakova Publications for gene: MINPP1 were set to 33257696
Ataxia and cerebellar anomalies - narrow panel v2.173 MINPP1 Arina Puzriakova Classified gene: MINPP1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.173 MINPP1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green status at the next GMS panel update.

To date, at least 16 individuals from 10 unrelated families reported, all with different biallelic variants in MINPP1 (5 truncating, 6 missense). Main clinical characteristics included mild to severe PCH on brain MRI (16/16), moderate to severe DD/ID (16/16), microcephaly (14/16), and seizures (12/16). Supported by some functional data (PMIDs: 33257696; 33168985)
Ataxia and cerebellar anomalies - narrow panel v2.173 MINPP1 Arina Puzriakova Gene: minpp1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.172 PMPCB Sarah Leigh Tag Q2_21_rating tag was added to gene: PMPCB.
Ataxia and cerebellar anomalies - narrow panel v2.172 PMPCB Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least five variants reported in three unrelated cases, together with supportive functional studies (PMID 29576218).; to: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for Neurodegeneration in Early Childhood. At least five variants reported in three unrelated cases, together with supportive functional studies (PMID 29576218).
Ataxia and cerebellar anomalies - narrow panel v2.172 PMPCB Sarah Leigh edited their review of gene: PMPCB: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least five variants reported in three unrelated cases, together with supportive functional studies (PMID 29576218).; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.172 PMPCB Sarah Leigh Classified gene: PMPCB as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.172 PMPCB Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.172 PMPCB Sarah Leigh Gene: pmpcb has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.171 PMPCB Sarah Leigh Phenotypes for gene: PMPCB were changed from Multiple mitochondrial dysfunctions syndrome 6, MIM# 617954 to Multiple mitochondrial dysfunctions syndrome 6 OMIM:617954; multiple mitochondrial dysfunctions syndrome 6 MONDO:0054785
Ataxia and cerebellar anomalies - narrow panel v2.170 FXN_GAA Sarah Leigh Phenotypes for STR: FXN_GAA were changed from Friedreich ataxia OMIM:229300; Friedreich ataxia with retained reflexes OMIM:229300; Friedreich ataxia 1 MONDO:0100340 to Friedreich ataxia OMIM:229300; Friedreich ataxia with retained reflexes OMIM:229300; Friedreich ataxia 1 MONDO:0100340
Ataxia and cerebellar anomalies - narrow panel v2.169 FXN_GAA Sarah Leigh Phenotypes for STR: FXN_GAA were changed from Friedreich ataxia 229300 to Friedreich ataxia OMIM:229300; Friedreich ataxia with retained reflexes OMIM:229300; Friedreich ataxia 1 MONDO:0100340
Ataxia and cerebellar anomalies - narrow panel v2.168 FXN Sarah Leigh Phenotypes for gene: FXN were changed from Friedreichataxia,229300Friedreichataxiawithretainedreflexes,229300 to Friedreich ataxia OMIM:229300; Friedreich ataxia with retained reflexes OMIM:229300; Friedreich ataxia 1 MONDO:0100340
Ataxia and cerebellar anomalies - narrow panel v2.167 CAD Arina Puzriakova Publications for gene: CAD were set to 32820246
Ataxia and cerebellar anomalies - narrow panel v2.166 CAD Arina Puzriakova Classified gene: CAD as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.166 CAD Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. There are sufficient cases with ataxia and biallelic variants in this gene to rate as Green on this panel, but note that not all cases present this feature (ataxia reported in 8/18 individuals to date - PMID: 32820246)
Ataxia and cerebellar anomalies - narrow panel v2.166 CAD Arina Puzriakova Gene: cad has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.165 CAD Arina Puzriakova Tag Q2_21_rating tag was added to gene: CAD.
Ataxia and cerebellar anomalies - narrow panel v2.165 CAD Arina Puzriakova Phenotypes for gene: CAD were changed from Epileptic encephalopathy, early infantile, 50; OMIM # 616457 to Developmental and epileptic encephalopathy 50, OMIM:616457
Ataxia and cerebellar anomalies - narrow panel v2.164 UCHL1 Arina Puzriakova Phenotypes for gene: UCHL1 were changed from Early onset ataxia and optic neuropathy to Spastic paraplegia 79, autosomal recessive, OMIM:615491
Ataxia and cerebellar anomalies - narrow panel v2.163 UCHL1 Arina Puzriakova Publications for gene: UCHL1 were set to PMID: 23359680
Ataxia and cerebellar anomalies - narrow panel v2.162 UCHL1 Arina Puzriakova Classified gene: UCHL1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.162 UCHL1 Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update - ataxia and other cerebellar signs are a feature of this UCHL1-related neurodegenerative disorder. At least 4 unrelated families reported (PMIDs: 23359680; 28007905; 29735986; 32656641) with biallelic variants, supported by functional and animal model data.
Ataxia and cerebellar anomalies - narrow panel v2.162 UCHL1 Arina Puzriakova Gene: uchl1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.161 UCHL1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: UCHL1.
Ataxia and cerebellar anomalies - narrow panel v2.161 UCHL1 Arina Puzriakova reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23359680, 28007905, 29735986, 32656641, 11555633, 33159930; Phenotypes: Spastic paraplegia 79, autosomal recessive, OMIM:615491; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.161 UBTF Arina Puzriakova Publications for gene: UBTF were set to 29300972
Ataxia and cerebellar anomalies - narrow panel v2.160 UBTF Arina Puzriakova Mode of pathogenicity for gene: UBTF was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v2.159 UBTF Arina Puzriakova Classified gene: UBTF as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.159 UBTF Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 9 unrelated individuals from different ethnic backgrounds in literature with neuroregression including ataxia as an early feature due to a recurrent variant in this gene (PMIDs: 28777933; 29300972; 30517966; 31931739)
Ataxia and cerebellar anomalies - narrow panel v2.159 UBTF Arina Puzriakova Gene: ubtf has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.158 UBTF Arina Puzriakova Tag Q2_21_rating tag was added to gene: UBTF.
Ataxia and cerebellar anomalies - narrow panel v2.158 UBTF Arina Puzriakova reviewed gene: UBTF: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 28777933, 29300972, 30517966, 31931739; Phenotypes: Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v2.158 UBTF Arina Puzriakova Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset, with brain atrophy MIM#617672 to Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672
Ataxia and cerebellar anomalies - narrow panel v2.157 WFS1 Eleanor Williams Phenotypes for gene: WFS1 were changed from Wolfram syndrome 1, 222300 to Wolfram syndrome 1, OMIM:222300
Ataxia and cerebellar anomalies - narrow panel v2.156 WFS1 Eleanor Williams reviewed gene: WFS1: Rating: ; Mode of pathogenicity: None; Publications: 33693650; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.156 SCN1A Sarah Leigh edited their review of gene: SCN1A: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.156 SCN1A Sarah Leigh Tag Q2_21_rating tag was added to gene: SCN1A.
Ataxia and cerebellar anomalies - narrow panel v2.156 SCN1A Sarah Leigh Publications for gene: SCN1A were set to 27264139; 27817982; 28732259
Ataxia and cerebellar anomalies - narrow panel v2.155 SCN1A Sarah Leigh Classified gene: SCN1A as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.155 SCN1A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.155 SCN1A Sarah Leigh Gene: scn1a has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.154 SCN1A Sarah Leigh Phenotypes for gene: SCN1A were changed from Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208 to Dravet syndrome OMIM:607208; developmental and epileptic encephalopathy, 6 MONDO:0100079
Ataxia and cerebellar anomalies - narrow panel v2.153 TGM6 Ivone Leong commented on gene: TGM6
Ataxia and cerebellar anomalies - narrow panel v2.153 TGM6 Ivone Leong Tag Q2_21_rating tag was added to gene: TGM6.
Ataxia and cerebellar anomalies - narrow panel v2.153 TGM6 Ivone Leong Tag Q2_21_expert_review tag was added to gene: TGM6.
Ataxia and cerebellar anomalies - narrow panel v2.153 TGM6 Ivone Leong Phenotypes for gene: TGM6 were changed from Spinocerebellar ataxia 35, 613908 to Spinocerebellar ataxia 35, OMIM:613908
Ataxia and cerebellar anomalies - narrow panel v2.152 TGM6 Ivone Leong Publications for gene: TGM6 were set to 32426513; 30670339
Ataxia and cerebellar anomalies - narrow panel v2.151 TGM6 Ivone Leong Publications for gene: TGM6 were set to
Ataxia and cerebellar anomalies - narrow panel v2.150 TDP2 Ivone Leong Tag Q2_21_rating tag was added to gene: TDP2.
Ataxia and cerebellar anomalies - narrow panel v2.150 TDP2 Ivone Leong Classified gene: TDP2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.150 TDP2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.150 TDP2 Ivone Leong Gene: tdp2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.149 SPG7 Ivone Leong Tag Q2_21_expert_review tag was added to gene: SPG7.
Ataxia and cerebellar anomalies - narrow panel v2.149 SPG7 Ivone Leong edited their review of gene: SPG7: Added comment: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype.

PMID:33774748. Age of onset reported ranged from 12-61 yo (mean age = 39.1). 25 unrelated families of Irish descent.
PMID:32161564. Age of onset 25 - 45 yo.
PMID:31068484. Age of onset 35.5 +/- 14.3 years (mean age = 50.4). 241 patients were part of the study.
PMID:23065789. Age of onset 10 - 45 yo. 137 patients were part of the study.

As the age of onset is quite a wide range this gene will remain Green to ensure edge cases are identified. This gene has been tagged for GMS expert review on whether this gene's rating needs to be changed.; Changed publications: 33774748, 32161564, 31068484, 23065789
Ataxia and cerebellar anomalies - narrow panel v2.149 OPA1 Sarah Leigh edited their review of gene: OPA1: Added comment: Associated with relevant phenotypes in OMIM and as confirmed Gen2Phen gene for Optic atrophy plus syndrome OMIM:125250 and a probable gene for Behr syndrome OMIM:210000. At least biallelic 11 variants reported in at least 10 unrelated cases (summarized in PMID 28494813, additional file 7).; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.149 OPA1 Sarah Leigh Tag Q2_21_rating tag was added to gene: OPA1.
Ataxia and cerebellar anomalies - narrow panel v2.149 OPA1 Sarah Leigh Classified gene: OPA1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.149 OPA1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.149 OPA1 Sarah Leigh Gene: opa1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.148 OPA1 Sarah Leigh Phenotypes for gene: OPA1 were changed from Optic atrophy plus syndrome, MIM# 125250 to Optic atrophy plus syndrome OMIM:125250; optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy MONDO:0007429; Behr syndrome OMIM:210000; Behr syndrome MONDO:0008858
Ataxia and cerebellar anomalies - narrow panel v2.147 OPA1 Sarah Leigh Publications for gene: OPA1 were set to 28494813; 27150940; 24970096; 11017079; 11017080; 17722006; 25012220
Ataxia and cerebellar anomalies - narrow panel v2.146 OPA1 Sarah Leigh Publications for gene: OPA1 were set to 28494813
Ataxia and cerebellar anomalies - narrow panel v2.145 OPA1 Sarah Leigh Mode of inheritance for gene: OPA1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.144 OPA1 Sarah Leigh Mode of inheritance for gene: OPA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.143 NKX2-1 Sarah Leigh edited their review of gene: NKX2-1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in unrelated cases of Choreoathetosis, hypothyroidism, and neonatal respiratory distress OMIM:610978.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.143 NKX2-1 Sarah Leigh Tag Q2_21_rating tag was added to gene: NKX2-1.
Ataxia and cerebellar anomalies - narrow panel v2.143 NKX2-1 Sarah Leigh Classified gene: NKX2-1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.143 NKX2-1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.143 NKX2-1 Sarah Leigh Gene: nkx2-1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.142 NKX2-1 Sarah Leigh Phenotypes for gene: NKX2-1 were changed from Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700 to Choreoathetosis, hypothyroidism, and neonatal respiratory distress OMIM; hereditary progressive chorea without dementia MONDO:0021011:610978; brain-lung-thyroid syndrome MONDO:0012593; Chorea, hereditary benign OMIM:118700
Ataxia and cerebellar anomalies - narrow panel v2.141 MVK Sarah Leigh edited their review of gene: MVK: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Mevalonic aciduria OMIM:610377. At least nine variants reported at least seven unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.141 MVK Sarah Leigh Tag Q2_21_rating tag was added to gene: MVK.
Ataxia and cerebellar anomalies - narrow panel v2.141 MVK Sarah Leigh Publications for gene: MVK were set to 24896178; 26503795
Ataxia and cerebellar anomalies - narrow panel v2.140 MVK Sarah Leigh Added comment: Comment on phenotypes: Variants are associated with Hyper-IgD syndrome OMIM:260920 (biallelic) & Porokeratosis 3, multiple types OMIM:175900 (monoallelic).
Ataxia and cerebellar anomalies - narrow panel v2.140 MVK Sarah Leigh Phenotypes for gene: MVK were changed from Mevalonic aciduria 610377 to Mevalonic aciduria OMIM:610377; mevalonic aciduria MONDO:0012481
Ataxia and cerebellar anomalies - narrow panel v2.139 MTFMT Sarah Leigh edited their review of gene: MTFMT: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least eight variants reported in at least eight unrelated cases of Combined oxidative phosphorylation deficiency 15 OMIM:614947.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.139 MTFMT Sarah Leigh Tag Q2_21_rating tag was added to gene: MTFMT.
Ataxia and cerebellar anomalies - narrow panel v2.139 MTFMT Sarah Leigh Classified gene: MTFMT as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.139 MTFMT Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.139 MTFMT Sarah Leigh Gene: mtfmt has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.138 MTFMT Sarah Leigh Publications for gene: MTFMT were set to 26060307; 24461907
Ataxia and cerebellar anomalies - narrow panel v2.137 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15 MIM#614947; Mitochondrial complex I deficiency, nuclear type 27 MIM#618248 to Combined oxidative phosphorylation deficiency 15 OMIM:614947; combined oxidative phosphorylation defect type 15 MONDO:0013987; Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248; mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631
Ataxia and cerebellar anomalies - narrow panel v2.136 ADPRHL2 Sarah Leigh Tag Q2_21_rating tag was added to gene: ADPRHL2.
Ataxia and cerebellar anomalies - narrow panel v2.136 EEF2 Eleanor Williams Classified gene: EEF2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.136 EEF2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber on advice of Genomics England clinical team. Amber rating selected pending further cases and delineation of the phenotype
Ataxia and cerebellar anomalies - narrow panel v2.136 EEF2 Eleanor Williams Gene: eef2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.135 EEF2 Eleanor Williams gene: EEF2 was added
gene: EEF2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: EEF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EEF2 were set to 23001565; 33355653
Phenotypes for gene: EEF2 were set to Spinocerebellar ataxia 26 OMIM:609306
Review for gene: EEF2 was set to AMBER
Added comment: Provisionally associated with ?Spinocerebellar ataxia 26 #609306 (AD) in OMIM based on Hekman et al 2012 case.

PMID: 23001565 - Hekman et al 2012 - report a six-generation kindred of Norwegian ancestry with a late-onset pure cerebellar ataxia in which a heterozygous P596H substitution in eEF2 was found to segregate with the disease phenotype in 24 individuals and two currently asymptomatic individuals. Functional studies in yeast showed that the variant (P580H in the EFT2 gene in yeast) affected translational fidelity.

PMID: 33355653 - Nabais Sá et al 2021 - identified de novo EEF2 missense variants in 3 unrelated children (3, 6 and 9 years of age) with a mild phenotype comprising motor delay and relative macrocephaly associated with ventriculomegaly.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.134 CYP2U1 Sarah Leigh changed review comment from: Comment on phenotypes: Autosomal recessive spastic paraplegia 56 (#615030) complex form of disorder, ataxia not yet identified in affected patients.; to: Comment on phenotypes: Autosomal recessive spastic paraplegia 56 (#615030) is a complex form of disorder, ataxia not yet identified in affected patients (Table 1 in PMID: 27292318 provides a review of cases reported so far).
Ataxia and cerebellar anomalies - narrow panel v2.134 CYP2U1 Sarah Leigh Tag Q2_21_expert_review tag was added to gene: CYP2U1.
Ataxia and cerebellar anomalies - narrow panel v2.134 LAMA1 Sarah Leigh edited their review of gene: LAMA1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in at least three unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.134 LAMA1 Sarah Leigh Tag Q2_21_rating tag was added to gene: LAMA1.
Ataxia and cerebellar anomalies - narrow panel v2.134 LAMA1 Sarah Leigh Phenotypes for gene: LAMA1 were changed from Cerebellar ataxia, intellectual disability, oculomotor apraxia, cerebellar cysts; Poretti Boltshauser syndrome MIM#615960 to Poretti-Boltshauser syndrome OMIM:615960; ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome MONDO:0014419
Ataxia and cerebellar anomalies - narrow panel v2.133 LAMA1 Sarah Leigh Classified gene: LAMA1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.133 LAMA1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.133 LAMA1 Sarah Leigh Gene: lama1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.132 KCNA2 Sarah Leigh edited their review of gene: KCNA2: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least four variants reported in numberous cases, together with supportive functional studies, demonstrating GOF and LOF mechanisms.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.132 KCNA2 Sarah Leigh Classified gene: KCNA2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.132 KCNA2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.132 KCNA2 Sarah Leigh Gene: kcna2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.131 KCNA2 Sarah Leigh Tag Q2_21_rating tag was added to gene: KCNA2.
Ataxia and cerebellar anomalies - narrow panel v2.131 KCNA2 Sarah Leigh Mode of pathogenicity for gene: KCNA2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v2.130 KCNA2 Sarah Leigh Phenotypes for gene: KCNA2 were changed from Early infantile encephalopathy 32, MIM#616366 to Developmental and epileptic encephalopathy 32 OMIM:616366; developmental and epileptic encephalopathy, 32 MONDO:0014607
Ataxia and cerebellar anomalies - narrow panel v2.129 KCNA2 Sarah Leigh Added comment: Comment on mode of pathogenicity: Both dominant negative variants that result in LOF effect (RCV000170511, rs786205231) and GOF variants (rs786205231, rs786205232) have been associated with Developmental and epileptic encephalopathy 32 OMIM:616366
Ataxia and cerebellar anomalies - narrow panel v2.129 KCNA2 Sarah Leigh Mode of pathogenicity for gene: KCNA2 was changed from None to None
Ataxia and cerebellar anomalies - narrow panel v2.128 KCNA2 Sarah Leigh Publications for gene: KCNA2 were set to 29050392
Ataxia and cerebellar anomalies - narrow panel v2.127 EXOSC1 Sarah Leigh Added comment: Comment on phenotypes: No phenotype in OMIM or in MONDO (21/04/2021)
Ataxia and cerebellar anomalies - narrow panel v2.127 EXOSC1 Sarah Leigh Phenotypes for gene: EXOSC1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia
Ataxia and cerebellar anomalies - narrow panel v2.126 EXOSC1 Sarah Leigh Classified gene: EXOSC1 as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v2.126 EXOSC1 Sarah Leigh Added comment: Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic variant reported.
Ataxia and cerebellar anomalies - narrow panel v2.126 EXOSC1 Sarah Leigh Gene: exosc1 has been classified as Red List (Low Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.125 EXOSC1 Sarah Leigh Added comment: Comment on phenotypes: No phenotype listed in OMIM or in MONDO (21/04/2021)
Ataxia and cerebellar anomalies - narrow panel v2.125 EXOSC1 Sarah Leigh Phenotypes for gene: EXOSC1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia
Ataxia and cerebellar anomalies - narrow panel v2.124 EXOSC1 Sarah Leigh Classified gene: EXOSC1 as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v2.124 EXOSC1 Sarah Leigh Added comment: Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic variant reported (PMID 33463720).
Ataxia and cerebellar anomalies - narrow panel v2.124 EXOSC1 Sarah Leigh Gene: exosc1 has been classified as Red List (Low Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.123 TDP2 Ivone Leong Phenotypes for gene: TDP2 were changed from Spinocerebellar ataxia, autosomal recessive 23, 616949 to Spinocerebellar ataxia, autosomal recessive 23, OMIM:616949
Ataxia and cerebellar anomalies - narrow panel v2.122 TBC1D23 Ivone Leong Phenotypes for gene: TBC1D23 were changed from Pontocerebellar hypoplasia, type 11, MIM# 617695 to Pontocerebellar hypoplasia, type 11, OMIM:617695
Ataxia and cerebellar anomalies - narrow panel v2.121 TBC1D23 Ivone Leong Classified gene: TBC1D23 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.121 TBC1D23 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.121 TBC1D23 Ivone Leong Gene: tbc1d23 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.120 TBC1D23 Ivone Leong Tag Q2_21_rating tag was added to gene: TBC1D23.
Ataxia and cerebellar anomalies - narrow panel v2.120 TBC1D23 Ivone Leong Added comment: Comment on publications: PMID:28823707. 2 of 3 unrelated families (4 of 7 affected individuals) had ataxia. 1 family (3 affected individuals) had coloboma and strabismus. 1 family (1 individual) had hyperopia and strabismus.

PMID:28823706. 2 of 4 unrelated families (4 of 6 affected individuals) had ataxia. 2 of 6 individuals with eye phenotype (strabismus or esotropia of the left eye).

PMID: 32360255. 1 case with ataxia. No eye phenotype reported.
Ataxia and cerebellar anomalies - narrow panel v2.120 TBC1D23 Ivone Leong Publications for gene: TBC1D23 were set to 28823707; 28823706
Ataxia and cerebellar anomalies - narrow panel v2.119 SQSTM1 Ivone Leong Classified gene: SQSTM1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.119 SQSTM1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.119 SQSTM1 Ivone Leong Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.118 SQSTM1 Ivone Leong Tag Q2_21_rating tag was added to gene: SQSTM1.
Ataxia and cerebellar anomalies - narrow panel v2.118 SQSTM1 Ivone Leong Publications for gene: SQSTM1 were set to 27545679
Ataxia and cerebellar anomalies - narrow panel v2.117 SQSTM1 Ivone Leong Phenotypes for gene: SQSTM1 were changed from Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, MIM# 617145 to Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, OMIM:617145
Ataxia and cerebellar anomalies - narrow panel v2.116 SPR Ivone Leong Classified gene: SPR as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.116 SPR Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.116 SPR Ivone Leong Gene: spr has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.115 SPR Ivone Leong Tag Q2_21_rating tag was added to gene: SPR.
Ataxia and cerebellar anomalies - narrow panel v2.115 SPR Ivone Leong Phenotypes for gene: SPR were changed from Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716 to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Ataxia and cerebellar anomalies - narrow panel v2.114 SPG7 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia
Ataxia and cerebellar anomalies - narrow panel v2.114 SPG7 Ivone Leong Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia to Spastic paraplegia 7, autosomal recessive, OMIM:607259
Ataxia and cerebellar anomalies - narrow panel v2.113 SPG7 Ivone Leong Publications for gene: SPG7 were set to PMID: 25681447
Ataxia and cerebellar anomalies - narrow panel v2.112 SNAP25 Ivone Leong Classified gene: SNAP25 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.112 SNAP25 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.112 SNAP25 Ivone Leong Gene: snap25 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.111 SNAP25 Ivone Leong Tag Q2_21_rating tag was added to gene: SNAP25.
Ataxia and cerebellar anomalies - narrow panel v2.111 SNAP25 Ivone Leong Phenotypes for gene: SNAP25 were changed from Myasthenic syndrome, congenital, 18, 616330; cerebellar ataxia and seizures to ?Myasthenic syndrome, congenital, 18, OMIM:616330; cerebellar ataxia, MONDO:0000437; seizures, HP:0001250
Ataxia and cerebellar anomalies - narrow panel v2.110 EXOSC1 Zornitza Stark gene: EXOSC1 was added
gene: EXOSC1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: EXOSC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC1 were set to 33463720
Phenotypes for gene: EXOSC1 were set to Pontocerebellar hypoplasia
Review for gene: EXOSC1 was set to RED
Added comment: An 8‐months‐old male with developmental delay, microcephaly, subtle dysmorphism, hypotonia, pontocerebellar hypoplasia and delayed myelination. Similarly affected elder sibling succumbed at the age of 4‐years 6‐months. Exome sequencing revealed a homozygous missense variant (c.104C >T, p.Ser35Leu) in EXOSC1. In silico mutagenesis revealed loss of a polar contact with neighbouring Leu37 residue. Quantitative real‐time PCR indicated no appreciable differences in EXOSC1 transcript levels. Immunoblotting and blue native PAGE revealed reduction in the EXOSC1 protein levels and EXO9 complex in the proband, respectively. Of note, bi‐allelic variants in other exosome subunits EXOSC3, EXOSC8 and EXOSC9 have been reported to cause pontocerebellar hypoplasia type 1B, type 1C and type 1D, respectively.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.110 MSTO1 Sarah Leigh Tag Q2_21_rating tag was added to gene: MSTO1.
Ataxia and cerebellar anomalies - narrow panel v2.110 MSTO1 Sarah Leigh edited their review of gene: MSTO1: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least eight variants reported in five unrelated cases of recessive Myopathy, mitochondrial, and ataxia and one variant reported in dominant Myopathy, mitochondrial, and ataxia in one family, together with supportive functional studies (PMID 28554942).; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.110 MSTO1 Sarah Leigh Classified gene: MSTO1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.110 MSTO1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.110 MSTO1 Sarah Leigh Gene: msto1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.109 MSTO1 Sarah Leigh Phenotypes for gene: MSTO1 were changed from Myopathy, mitochondrial, and ataxia, MIM# 617675 to Myopathy, mitochondrial, and ataxia OMIM:617675; mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714
Ataxia and cerebellar anomalies - narrow panel v2.108 IRF2BPL Sarah Leigh Classified gene: IRF2BPL as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.108 IRF2BPL Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.108 IRF2BPL Sarah Leigh Gene: irf2bpl has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.107 IRF2BPL Sarah Leigh Publications for gene: IRF2BPL were set to 30057031; 30166628
Ataxia and cerebellar anomalies - narrow panel v2.106 IRF2BPL Sarah Leigh Publications for gene: IRF2BPL were set to 30057031
Ataxia and cerebellar anomalies - narrow panel v2.105 IRF2BPL Sarah Leigh reviewed gene: IRF2BPL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.105 IRF2BPL Sarah Leigh Phenotypes for gene: IRF2BPL were changed from Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, MIM# 618088 to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures OMIM:618088; neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MONDO:0060759
Ataxia and cerebellar anomalies - narrow panel v2.104 IRF2BPL Sarah Leigh Tag Q2_21_rating tag was added to gene: IRF2BPL.
Ataxia and cerebellar anomalies - narrow panel v2.104 FBXL4 Sarah Leigh edited their review of gene: FBXL4: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in five unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.104 FBXL4 Sarah Leigh Tag Q2_21_rating tag was added to gene: FBXL4.
Ataxia and cerebellar anomalies - narrow panel v2.104 FBXL4 Sarah Leigh Classified gene: FBXL4 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.104 FBXL4 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.104 FBXL4 Sarah Leigh Gene: fbxl4 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.103 FBXL4 Sarah Leigh Phenotypes for gene: FBXL4 were changed from Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), MIM# 615471 to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) OMIM:615471; mitochondrial DNA depletion syndrome 13 MONDO:0014198
Ataxia and cerebellar anomalies - narrow panel v2.102 FA2H Sarah Leigh Publications for gene: FA2H were set to 31135052
Ataxia and cerebellar anomalies - narrow panel v2.101 FA2H Sarah Leigh Tag Q2_21_rating tag was added to gene: FA2H.
Ataxia and cerebellar anomalies - narrow panel v2.101 FA2H Sarah Leigh edited their review of gene: FA2H: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least eight variants reported in seven unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.101 FA2H Sarah Leigh Classified gene: FA2H as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.101 FA2H Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.101 FA2H Sarah Leigh Gene: fa2h has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.100 FA2H Sarah Leigh Phenotypes for gene: FA2H were changed from Spastic paraplegia 35, autosomal recessive MIM#612319 to Spastic paraplegia 35, autosomal recessive OMIM:612319; hereditary spastic paraplegia 35 MONDO:0012866
Ataxia and cerebellar anomalies - narrow panel v2.99 EBF3 Sarah Leigh edited their review of gene: EBF3: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 10 variants reported in at least 11 unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.99 EBF3 Sarah Leigh Phenotypes for gene: EBF3 were changed from Hypotonia, ataxia, and delayed development syndrome, MIM# 617330 to Hypotonia, ataxia, and delayed development syndrome OMIM:617330; hypotonia, ataxia, and delayed development syndrome MONDO:0015021
Ataxia and cerebellar anomalies - narrow panel v2.98 EBF3 Sarah Leigh Classified gene: EBF3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.98 EBF3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.98 EBF3 Sarah Leigh Gene: ebf3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.97 EBF3 Sarah Leigh Tag Q2_21_rating tag was added to gene: EBF3.
Ataxia and cerebellar anomalies - narrow panel v2.97 DOCK3 Sarah Leigh edited their review of gene: DOCK3: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least seven variants reported in at least five unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.97 DOCK3 Sarah Leigh Phenotypes for gene: DOCK3 were changed from Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, MIM#618292 to Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia OMIM:618292; neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia MONDO:0032661
Ataxia and cerebellar anomalies - narrow panel v2.96 DOCK3 Sarah Leigh Tag Q2_21_rating tag was added to gene: DOCK3.
Ataxia and cerebellar anomalies - narrow panel v2.96 DOCK3 Sarah Leigh Classified gene: DOCK3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.96 DOCK3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.96 DOCK3 Sarah Leigh Gene: dock3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.95 DKC1 Sarah Leigh reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.95 DKC1 Sarah Leigh Publications for gene: DKC1 were set to 9590285; 9886310; 10921354; 33734615; 10583221
Ataxia and cerebellar anomalies - narrow panel v2.94 DKC1 Sarah Leigh Publications for gene: DKC1 were set to 9590285; 9886310; 10921354
Ataxia and cerebellar anomalies - narrow panel v2.93 DKC1 Sarah Leigh Phenotypes for gene: DKC1 were changed from X-linked dyskeratosis congenita to Dyskeratosis congenita, X-linked OMIM:305000; dyskeratosis congenita, X-linked MONDO:0010584
Ataxia and cerebellar anomalies - narrow panel v2.92 DKC1 Sarah Leigh Publications for gene: DKC1 were set to 9590285; 9886310
Ataxia and cerebellar anomalies - narrow panel v2.91 CYP2U1 Sarah Leigh Added comment: Comment on phenotypes: Autosomal recessive spastic paraplegia 56 (#615030) complex form of disorder, ataxia not yet identified in affected patients.
Ataxia and cerebellar anomalies - narrow panel v2.91 CYP2U1 Sarah Leigh Phenotypes for gene: CYP2U1 were changed from Autosomal recessive spastic paraplegia 56 (#615030) complex form of disorder, ataxia not yet identified in affected patients. to Spastic paraplegia 56, autosomal recessive OMIM:615030; hereditary spastic paraplegia 56 MONDO:0014015
Ataxia and cerebellar anomalies - narrow panel v2.90 CYP2U1 Sarah Leigh Publications for gene: CYP2U1 were set to
Ataxia and cerebellar anomalies - narrow panel v2.89 CSTB Sarah Leigh Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) OMIM:254800; Unverricht-Lundborg syndrome MONDO:0009698
Ataxia and cerebellar anomalies - narrow panel v2.88 CSTB_CCCCGCCCCGCG Sarah Leigh Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) OMIM:254800; Unverricht-Lundborg syndrome MONDO:0009698
Ataxia and cerebellar anomalies - narrow panel v2.87 CSTB_CCCCGCCCCGCG Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
Ataxia and cerebellar anomalies - narrow panel v2.87 CSTB Sarah Leigh edited their review of gene: CSTB: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in at least four unrelated cases. Some cases are compound heterozygous with STR: CSTB_CCCCGCCCCGCG; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.87 CSTB_CCCCGCCCCGCG Sarah Leigh Publications for STR: CSTB_CCCCGCCCCGCG were set to
Ataxia and cerebellar anomalies - narrow panel v2.86 CSTB Sarah Leigh Publications for gene: CSTB were set to
Ataxia and cerebellar anomalies - narrow panel v2.85 CSTB Sarah Leigh Classified gene: CSTB as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.85 CSTB Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.85 CSTB Sarah Leigh Gene: cstb has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.84 CSTB Sarah Leigh Tag Q2_21_rating tag was added to gene: CSTB.
Ataxia and cerebellar anomalies - narrow panel v2.84 COA7 Sarah Leigh edited their review of gene: COA7: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least five variants reported in at least five unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.84 COA7 Sarah Leigh Tag Q2_21_rating tag was added to gene: COA7.
Ataxia and cerebellar anomalies - narrow panel v2.84 COA7 Sarah Leigh Classified gene: COA7 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.84 COA7 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.84 COA7 Sarah Leigh Gene: coa7 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.83 COA7 Sarah Leigh Publications for gene: COA7 were set to 29718187; 27683825
Ataxia and cerebellar anomalies - narrow panel v2.82 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, MIM#618387 to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Ataxia and cerebellar anomalies - narrow panel v2.81 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from Perrault syndrome 4, MIM# 615300; Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021; Leukodystrophy to Perrault syndrome 4, OMIM:615300
Ataxia and cerebellar anomalies - narrow panel v2.80 CLPP Sarah Leigh reviewed gene: CLPP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.80 CLPP Sarah Leigh Publications for gene: CLPP were set to 25254289
Ataxia and cerebellar anomalies - narrow panel v2.79 CLPP Sarah Leigh Phenotypes for gene: CLPP were changed from Perrault syndrome 3 OMIM:614129; Perrault syndrome 3 MONDO:0013588 to Perrault syndrome 3 OMIM:614129; Perrault syndrome 3 MONDO:0013588
Ataxia and cerebellar anomalies - narrow panel v2.78 CLPP Sarah Leigh Classified gene: CLPP as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.78 CLPP Sarah Leigh Gene: clpp has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.77 CLPP Sarah Leigh Classified gene: CLPP as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.77 CLPP Sarah Leigh Gene: clpp has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.76 CLPP Sarah Leigh Publications for gene: CLPP were set to 25254289
Ataxia and cerebellar anomalies - narrow panel v2.75 CLPP Sarah Leigh Phenotypes for gene: CLPP were changed from Perrault syndrome 3, MIM# 614129 to Perrault syndrome 3 OMIM:614129; Perrault syndrome 3 MONDO:0013588
Ataxia and cerebellar anomalies - narrow panel v2.74 CLN5 Sarah Leigh edited their review of gene: CLN5: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least ten variants reported in at least nine unrelated cases.
Ataxia is a feature of Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.74 CLN5 Sarah Leigh Tag Q2_21_rating tag was added to gene: CLN5.
Ataxia and cerebellar anomalies - narrow panel v2.74 CLN5 Sarah Leigh Classified gene: CLN5 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.74 CLN5 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.74 CLN5 Sarah Leigh Gene: cln5 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.73 CLN5 Sarah Leigh Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5, MIM# 256731 to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745
Ataxia and cerebellar anomalies - narrow panel v2.72 BBS1 Sarah Leigh Tag Q2_21_rating tag was added to gene: BBS1.
Ataxia and cerebellar anomalies - narrow panel v2.72 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Bardet-Biedl syndrome 1, MIM#209900 to Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Ataxia and cerebellar anomalies - narrow panel v2.71 BBS1 Sarah Leigh edited their review of gene: BBS1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in numerous unrelated cases.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.71 BBS1 Sarah Leigh Classified gene: BBS1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.71 BBS1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.71 BBS1 Sarah Leigh Gene: bbs1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.70 ATP8A2 Sarah Leigh edited their review of gene: ATP8A2: Added comment: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 21 variants reported in 17 unrelated cases with varying degrees of severity, together with supportive expression and functional studies (PMID 31612321).; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.70 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 29531481; 30012219; 31612321; 27679995
Ataxia and cerebellar anomalies - narrow panel v2.69 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 29531481; 30012219; 31612321
Ataxia and cerebellar anomalies - narrow panel v2.68 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 30012219; 31612321
Ataxia and cerebellar anomalies - narrow panel v2.67 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 31612321
Ataxia and cerebellar anomalies - narrow panel v2.66 ATP8A2 Sarah Leigh Tag Q2_21_rating tag was added to gene: ATP8A2.
Ataxia and cerebellar anomalies - narrow panel v2.66 ATP8A2 Sarah Leigh Classified gene: ATP8A2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.66 ATP8A2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.66 ATP8A2 Sarah Leigh Gene: atp8a2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.65 ATP8A2 Sarah Leigh Phenotypes for gene: ATP8A2 were changed from Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 615268 to ?Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 OMIM:615268; cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 MONDO:0014104
Ataxia and cerebellar anomalies - narrow panel v2.64 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to PMID: 22892528
Ataxia and cerebellar anomalies - narrow panel v2.63 ATCAY Sarah Leigh reviewed gene: ATCAY: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.63 ATCAY Sarah Leigh Publications for gene: ATCAY were set to 29449188; 14556008; 23226316
Ataxia and cerebellar anomalies - narrow panel v2.62 ATCAY Sarah Leigh Publications for gene: ATCAY were set to 29449188; 14556008
Ataxia and cerebellar anomalies - narrow panel v2.61 ATCAY Sarah Leigh Phenotypes for gene: ATCAY were changed from Ataxia, cerebellar, Cayman type; Cerebellar Ataxia, Cayman type to Ataxia, cerebellar, Cayman type OMIM:601238; Cayman type cerebellar ataxia MONDO:0011025
Ataxia and cerebellar anomalies - narrow panel v2.60 ATCAY Sarah Leigh Publications for gene: ATCAY were set to
Ataxia and cerebellar anomalies - narrow panel v2.59 ALDH5A1 Sarah Leigh edited their review of gene: ALDH5A1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in numerous cases, together with supportive functional evidence and mouse model.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.59 ALDH5A1 Sarah Leigh Classified gene: ALDH5A1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.59 ALDH5A1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.59 ALDH5A1 Sarah Leigh Gene: aldh5a1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.58 ALDH5A1 Sarah Leigh Publications for gene: ALDH5A1 were set to 14635103
Ataxia and cerebellar anomalies - narrow panel v2.57 ADPRHL2 Sarah Leigh Classified gene: ADPRHL2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.57 ADPRHL2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.57 ADPRHL2 Sarah Leigh Gene: adprhl2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.56 ADPRHL2 Sarah Leigh edited their review of gene: ADPRHL2: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 8 variants reported in 8 unrelated cases, together with supportive fuctional studies and a Drosophila paralog where a loss of Parg resulted in lethality on oxidative challenge that was rescued by human ADPRHL2.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.56 ADPRHL2 Sarah Leigh commented on gene: ADPRHL2
Ataxia and cerebellar anomalies - narrow panel v2.56 ADPRHL2 Sarah Leigh Tag new-gene-name tag was added to gene: ADPRHL2.
Ataxia and cerebellar anomalies - narrow panel v2.56 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures MONDO:0100095
Ataxia and cerebellar anomalies - narrow panel v2.55 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170 to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170
Ataxia and cerebellar anomalies - narrow panel v2.54 ACO2 Arina Puzriakova Phenotypes for gene: ACO2 were changed from Infantile cerebellar-retinal degeneration, MIM#614559 to Infantile cerebellar-retinal degeneration, OMIM:614559; Infantile cerebellar-retinal degeneration, MONDO:0013802
Ataxia and cerebellar anomalies - narrow panel v2.53 ACO2 Arina Puzriakova Publications for gene: ACO2 were set to 32519519
Ataxia and cerebellar anomalies - narrow panel v2.52 ACO2 Arina Puzriakova Tag Q2_21_rating tag was added to gene: ACO2.
Ataxia and cerebellar anomalies - narrow panel v2.52 ACO2 Arina Puzriakova Classified gene: ACO2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.52 ACO2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. This gene should be promoted to Green at the next GMS panel update.

Sufficient unrelated cases to ascertain causation (see publications list). Childhood-onset ataxia often reported as a core feature of the disease presentation, particularly in milder cases. Both episodic and classic forms have been described.
Ataxia and cerebellar anomalies - narrow panel v2.52 ACO2 Arina Puzriakova Gene: aco2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.51 THG1L Arina Puzriakova Tag watchlist tag was added to gene: THG1L.
Ataxia and cerebellar anomalies - narrow panel v2.51 THG1L Arina Puzriakova Phenotypes for gene: THG1L were changed from Cerebellar ataxia to Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800; Spinocerebellar ataxia, autosomal recessive 28, MONDO:0032923
Ataxia and cerebellar anomalies - narrow panel v2.50 THG1L Arina Puzriakova Classified gene: THG1L as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.50 THG1L Arina Puzriakova Added comment: Comment on list classification: Ataxia only reported in 3 Ashkenazi Jewish families with the same p.V55A founder variant. Unclear whether the fourth case with a different variant (p.L294P) displayed ataxia. Therefore, additional cases or functional analysis of the p.V55A variant are required prior to upgrading this gene to Green.
Ataxia and cerebellar anomalies - narrow panel v2.50 THG1L Arina Puzriakova Gene: thg1l has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.49 THG1L Arina Puzriakova reviewed gene: THG1L: Rating: AMBER; Mode of pathogenicity: None; Publications: 27307223, 31168944, 30214071; Phenotypes: Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.49 SLC44A1 Arina Puzriakova changed review comment from: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update.; to: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update - at least 3 unrelated families reported with distinct SLC44A1 variants and this neurodegenerative disorder, including progressive cerebellar ataxia (PMID: 31855247)
Ataxia and cerebellar anomalies - narrow panel v2.49 SLC44A1 Arina Puzriakova Classified gene: SLC44A1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.49 SLC44A1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update.
Ataxia and cerebellar anomalies - narrow panel v2.49 SLC44A1 Arina Puzriakova Gene: slc44a1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.48 SLC44A1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: SLC44A1.
Ataxia and cerebellar anomalies - narrow panel v2.48 SLC44A1 Arina Puzriakova reviewed gene: SLC44A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31855247; Phenotypes: Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, OMIM:618868, Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, MONDO:0030028; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.48 HTT_CAG Arina Puzriakova Tag curated_removed tag was added to STR: HTT_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.48 CLP1 Sarah Leigh edited their review of gene: CLP1: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. A single variant was reported in Turkish families who shared an 11.5 Mb haplotype in the CLP1 region, this did not suggest a recent ancestory amongst seemingly unrelated families (PMID 24766809). Supportive functional studies and a mouse model were also reported.; Changed rating: GREEN; Changed publications: 24766810
Ataxia and cerebellar anomalies - narrow panel v2.48 CLP1 Sarah Leigh Tag Q2_21_rating tag was added to gene: CLP1.
Ataxia and cerebellar anomalies - narrow panel v2.48 CLP1 Sarah Leigh Classified gene: CLP1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.48 CLP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.48 CLP1 Sarah Leigh Gene: clp1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.47 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349 to Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349
Ataxia and cerebellar anomalies - narrow panel v2.46 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 10 OMIM:615803 to Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349
Ataxia and cerebellar anomalies - narrow panel v2.45 CLP1 Sarah Leigh Tag founder-effect tag was added to gene: CLP1.
Ataxia and cerebellar anomalies - narrow panel v2.45 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 10 (#615803); Pontocerebellar Hypoplasia type 10 to Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 10 OMIM:615803
Ataxia and cerebellar anomalies - narrow panel v2.44 CLP1 Sarah Leigh Publications for gene: CLP1 were set to PMID: 24766810
Ataxia and cerebellar anomalies - narrow panel v2.43 CLP1 Zornitza Stark reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24766809, 29307788; Phenotypes: Pontocerebellar hypoplasia, type 10, MIM# 615803; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.43 SLC44A1 Arina Puzriakova Phenotypes for gene: SLC44A1 were changed from progressive ataxia; tremor; cognitive decline; dysphagia; optic atrophy; dysarthria to Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, OMIM:618868; Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, MONDO:0030028
Ataxia and cerebellar anomalies - narrow panel v2.42 KCNN2 Arina Puzriakova Classified gene: KCNN2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.42 KCNN2 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to promote this gene to Green at the next GMS panel update - cerebellar ataxia, with an early onset from childhood to adolescence, was reported in 4/10 individuals with distinct KCNN2 variants. Pathogenicity of variants was supported by functional data.
Ataxia and cerebellar anomalies - narrow panel v2.42 KCNN2 Arina Puzriakova Gene: kcnn2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.41 KCNN2 Arina Puzriakova gene: KCNN2 was added
gene: KCNN2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q2_21_rating tags were added to gene: KCNN2.
Mode of inheritance for gene: KCNN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNN2 were set to 33242881
Phenotypes for gene: KCNN2 were set to Intellectual disability; seizures; movement disorder
Review for gene: KCNN2 was set to GREEN
Added comment: - PMID: 33242881 (2020) - 10 patients with de novo KCNN2 variants and one individual with a heterozygous missense variant inherited from an affected parent, detected by WES. Patch-clamp functional studies showed that all but one variant (p.Glu30Gln) tested, which was reclassified VUS, led to to a loss-of-function of SK2 channels.

Excluding the case with the VUS, one patient displayed DD, 4 patients exhibited mild ID, 3 patients had moderate ID, and 2 had severe ID. Other clinical characteristics include a movement disorder (6/10) including tremor (5), cerebellar ataxia (4), and extrapyramidal symptoms (4); epilepsy (2/10); white matter abnormalities (3/6). Authors note that the 4 individuals without a movement disorder were under the age of 16 years at the time of the study and there is a possibility that this manifestation may arise later in life.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.40 SYNE1 Arina Puzriakova Phenotypes for gene: SYNE1 were changed from Cerebellar Ataxia; Spinocerebellar ataxia, autosomal recessive 8 to Spinocerebellar ataxia, autosomal recessive 8, OMIM:610743; Autosomal recessive ataxia, Beauce type, MONDO:0012549
Ataxia and cerebellar anomalies - narrow panel v2.39 LAMA1 John Sayer reviewed gene: LAMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://www.ncbi.nlm.nih.gov/pubmed/25105227; Phenotypes: cerebellar dysplasia, cerebellar vermis atrophy, myopia, cerebellar cysts, abnormal eye movements; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.39 GLS Arina Puzriakova Classified gene: GLS as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.39 GLS Arina Puzriakova Added comment: Comment on list classification: Progressive ataxia is the main feature of the disease presentation (childhood-onset), and there are sufficient unrelated cases for inclusion as diagnostic-grade.

However, detection of the 5' UTR triplet expansion must first be validated within the Genomics England pipeline. In the meantime, rating Amber but will raise the STR for validation with the Rare Disease team.
Ataxia and cerebellar anomalies - narrow panel v2.39 GLS Arina Puzriakova Gene: gls has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.38 GLS Arina Puzriakova gene: GLS was added
gene: GLS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
STR, for-review tags were added to gene: GLS.
Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLS were set to 30970188
Phenotypes for gene: GLS were set to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733
Review for gene: GLS was set to GREEN
Added comment: GLS is associated with relevant phenotype in OMIM, but currently is not in Gene2Phenoype.
----------

- PMID: 30970188 (2019) - Three unrelated cases who presented with an early-onset global developmental delay, progressive ataxia, and elevated levels of glutamine (MIM# 618412). One patient also showed cerebellar atrophy.

All 3 individuals harboured a large trinucleotide (GCA) repeat expansion in the 5' UTR (length: 680-1,500-copy repeats). The repeat expansion was found in homozygosity in 1 case, and occurred in compound heterozygosity with an SNV in the other two cases (missense and frameshift variant, respectively). Functional analysis showed the repeat expansion results in reduced expression and glutaminase deficiency.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.37 GLS_GCA Arina Puzriakova Classified STR: GLS_GCA as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v2.37 GLS_GCA Arina Puzriakova Added comment: Comment on list classification: Progressive ataxia is the main feature of the disease presentation (childhood-onset), and there are sufficient unrelated cases for inclusion as diagnostic-grade.

However, detection of this 5' UTR triplet expansion must first be validated within the Genomics England pipeline. In the meantime, rating Red but will raise the STR for validation with the Rare Disease team.
Ataxia and cerebellar anomalies - narrow panel v2.37 GLS_GCA Arina Puzriakova Str: gls_gca has been classified as Red List (Low Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.36 GLS_GCA Arina Puzriakova STR: GLS_GCA was added
STR: GLS_GCA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
STR, NGS Not Validated, for-review tags were added to STR: GLS_GCA.
Mode of inheritance for STR: GLS_GCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: GLS_GCA were set to 30970188
Phenotypes for STR: GLS_GCA were set to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733
Review for STR: GLS_GCA was set to GREEN
Added comment: GLS is associated with relevant phenotypes in OMIM, but currently is not in Gene2Phenoype.
----------

- PMID: 30970188 (2019) - Three unrelated cases who presented with an early-onset global developmental delay, progressive ataxia, and elevated levels of glutamine (MIM# 618412). One patient also showed cerebellar atrophy.

All 3 individuals harboured a large trinucleotide (GCA) repeat expansion in the 5' UTR (length: 680-1,500-copy repeats). The repeat expansion was found in homozygosity in 1 case, and occurred in compound heterozygosity with an SNV in the other two cases (missense and frameshift variant, respectively). Functional analysis showed the repeat expansion results in reduced expression and glutaminase deficiency.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.35 AARS Arina Puzriakova Phenotypes for gene: AARS were changed from to Charcot-Marie-Tooth disease, axonal, type 2N, OMIM:613287; Charcot-Marie-Tooth disease axonal type 2N, MONDO:0013212
Ataxia and cerebellar anomalies - narrow panel v2.34 AAAS Arina Puzriakova Phenotypes for gene: AAAS were changed from Achalasia-addisonianism-alacrimia syndrome, 231550 to Achalasia-addisonianism-alacrimia syndrome, OMIM:231550; Triple-A syndrome, MONDO:0009279
Ataxia and cerebellar anomalies - narrow panel v2.33 MINPP1 Zornitza Stark gene: MINPP1 was added
gene: MINPP1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MINPP1 were set to 33257696
Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia
Review for gene: MINPP1 was set to GREEN
Added comment: 8 individuals from 6 unrelated families reported with bi-allelic LOF variants. All presented with almost complete absence of motor and cognitive development, progressive or congenital microcephaly, spastic tetraplegia or dystonia, and vision impairments. For most, the first symptoms included neonatal severe axial hypotonia and epilepsy that started during the first months or years of life. Prenatal symptoms of microcephaly associated with increased thalami echogenicity were detected in one, while the seven other individuals presented with progressive microcephaly. Some exhibited rapidly progressive phenotype and the affected children died in their infancy or middle-childhood. Strikingly, all the affected children had a unique brain MRI showing a mild to severe PCH, fluid-filled posterior fossa, with dilated lateral ventricles. In addition, severe atrophy at the level of the basal ganglia or thalami often associated with typical T2 hypersignal were identified in all the patients MRI.

Supportive functional data showing accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.33 MTCL1 Zornitza Stark gene: MTCL1 was added
gene: MTCL1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: MTCL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTCL1 were set to 30548255; 28283581; 32961396
Phenotypes for gene: MTCL1 were set to slowly progressive cerebellar ataxia; mild intellectual disability; seizures; episodic pain; spinocerebellar ataxia
Review for gene: MTCL1 was set to GREEN
Added comment: Two families reported with bi-allelic LOF variants, early onset ataxia and a supportive null mouse model.
Single family with mono-allelic variant in two individuals and adult-onset ataxia (not pertinent to this panel, and less compelling).
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.33 SVBP Arina Puzriakova Classified gene: SVBP as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.33 SVBP Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). SVBP is associated with a relevant phenotype in OMIM. 12 individuals from 5 independent families (PMIDs: 31363758 and 30607023) reported at present with biallelic variants.

Rating Amber as phenotypes include ataxia in only 2 families (remaining cases present spasticity rather than ataxia).
Ataxia and cerebellar anomalies - narrow panel v2.33 SVBP Arina Puzriakova Gene: svbp has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.32 SVBP Arina Puzriakova Phenotypes for gene: SVBP were changed from Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, OMIM #618569 to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, OMIM:618569; Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, MONDO:0032816
Ataxia and cerebellar anomalies - narrow panel v2.31 ABCA2 Arina Puzriakova Phenotypes for gene: ABCA2 were changed from Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM: 618808 to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM:618808; Intellectual developmental disorder with poor growth and with or without seizures or ataxia, MONDO:0032930
Ataxia and cerebellar anomalies - narrow panel v2.30 ABCA2 Arina Puzriakova Classified gene: ABCA2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.30 ABCA2 Arina Puzriakova Added comment: Comment on list classification: Rating Amber as only 2 unrelated families with ataxia and ABCA2 variants reported at present.
Ataxia and cerebellar anomalies - narrow panel v2.30 ABCA2 Arina Puzriakova Gene: abca2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.29 ABCA2 Arina Puzriakova gene: ABCA2 was added
gene: ABCA2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799
Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM: 618808
Added comment: Associated with relevant phenotype in OMIM, but currently not in Gene2Phenotype.

At least 7 individuals from 4 unrelated families reported at present with different biallelic variants in the ABCA2 gene. Overlapping clinical features include psychomotor delay (6/7), microcephaly (3/7), ataxia (3/7), and epilepsy (2/7).

- Hu et al (PMID: 29302074) reported 3 sibs, of which one (III:2) was unable to walk and had ataxic gait.
- Aslam and Naz (PMID: 31047799) provided clinical details on 2 siblings, both of whom presented delayed ambulation, staggered gait ataxia, limb incoordination and dysarthria, but no abnormalities on brain MRI.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.28 TMEM106B Arina Puzriakova Phenotypes for gene: TMEM106B were changed from Leukodystrophy, hypomyelinating, 16, MIM# 617964 to Leukodystrophy, hypomyelinating, 16, OMIM:617964; Leukodystrophy, hypomyelinating, 16, MONDO:0054791
Ataxia and cerebellar anomalies - narrow panel v2.27 TMEM106B Arina Puzriakova Tag missense tag was added to gene: TMEM106B.
Ataxia and cerebellar anomalies - narrow panel v2.27 TMEM106B Arina Puzriakova Mode of pathogenicity for gene: TMEM106B was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v2.26 TMEM106B Arina Puzriakova Publications for gene: TMEM106B were set to 29186371; 29444210
Ataxia and cerebellar anomalies - narrow panel v2.25 TMEM106B Arina Puzriakova Classified gene: TMEM106B as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.25 TMEM106B Arina Puzriakova Added comment: Comment on list classification: Rating Amber as only 2/6 cases present ataxia, which is mild in one individual. Cases are more likely to be recognised for the leukodystrophy feature of this disease presentation; however, this may be reviewed if evidence emerges of a more prominent ataxic phenotype.
Ataxia and cerebellar anomalies - narrow panel v2.25 TMEM106B Arina Puzriakova Gene: tmem106b has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.24 TMEM106B Arina Puzriakova changed review comment from: Associated with relevant phenotype in OMIM, and is a 'probable' gene for 'TMEM106B related hypomyelinating leukodystrophy' in Gene2Phenotype.

Recurrent variant c.754G>A p.(Asp252Asn) identified in 6 unrelated families from different ethnicities. Clinical characteristics include hypomyelinating leukodystrophy (6/6), nystagmus (6/6), hypotonia (5/6), cognitive impairment (5/6), movement disorder (3/6) and seizures (2/6).

Only 2 individuals present gait ataxia and intention tremor (mild/minimal in one case), with no prominent cerebellar atrophy on brain MRI.; to: Associated with relevant phenotype in OMIM, and is a 'probable' gene for 'TMEM106B related hypomyelinating leukodystrophy' in Gene2Phenotype.

Recurrent variant c.754G>A p.(Asp252Asn) identified in 6 unrelated families from different ethnicities. Clinical characteristics include hypomyelinating leukodystrophy (6/6), nystagmus (6/6), hypotonia (5/6), cognitive impairment (5/6), movement disorder (3/6) and seizures (2/6).

Only 2 individuals present gait ataxia and intention tremor (mild/minimal in one case), with only mild cerebellar atrophy identified in one patient on brain MRI.
Ataxia and cerebellar anomalies - narrow panel v2.24 TMEM106B Arina Puzriakova reviewed gene: TMEM106B: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 29186371, 29444210, 30643851, 32595021; Phenotypes: Leukodystrophy, hypomyelinating, 16 OMIM:617964; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ataxia and cerebellar anomalies - narrow panel v2.24 Arina Puzriakova Panel version has been signed off
Ataxia and cerebellar anomalies - narrow panel v2.22 ATXN3_CAG Arina Puzriakova Classified STR: ATXN3_CAG as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.22 ATXN3_CAG Arina Puzriakova Added comment: Comment on list classification: Downgraded from Green to Amber as this STR was not listed on the recent GMS STRs document supplied by Jane Deller (NHS England) on behalf of GLHs for the GMS Neurology Test Group
Ataxia and cerebellar anomalies - narrow panel v2.22 ATXN3_CAG Arina Puzriakova Str: atxn3_cag has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.21 TBP_CAG Arina Puzriakova Classified STR: TBP_CAG as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.21 TBP_CAG Arina Puzriakova Added comment: Comment on list classification: Downgraded from Green to Amber as this STR was not listed on the recent GMS STRs document supplied by Jane Deller (NHS England) on behalf of GLHs for the GMS Neurology Test Group
Ataxia and cerebellar anomalies - narrow panel v2.21 TBP_CAG Arina Puzriakova Str: tbp_cag has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.20 TBP_CAG Arina Puzriakova Tag for-review tag was added to STR: TBP_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.20 PPP2R2B_CAG Arina Puzriakova Classified STR: PPP2R2B_CAG as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.20 PPP2R2B_CAG Arina Puzriakova Added comment: Comment on list classification: Downgraded from Green to Amber as this STR was not listed on the recent GMS STRs document supplied by Jane Deller (NHS England) on behalf of GLHs for the GMS Neurology Test Group
Ataxia and cerebellar anomalies - narrow panel v2.20 PPP2R2B_CAG Arina Puzriakova Str: ppp2r2b_cag has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.19 PPP2R2B_CAG Arina Puzriakova Tag for-review tag was added to STR: PPP2R2B_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.19 NOP56_GGCCTG Arina Puzriakova Classified STR: NOP56_GGCCTG as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.19 NOP56_GGCCTG Arina Puzriakova Added comment: Comment on list classification: Downgraded from Green to Amber as this STR was not listed on the recent GMS STRs document supplied by Jane Deller (NHS England) on behalf of GLHs for the GMS Neurology Test Group
Ataxia and cerebellar anomalies - narrow panel v2.19 NOP56_GGCCTG Arina Puzriakova Str: nop56_ggcctg has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.18 NOP56_GGCCTG Arina Puzriakova Tag for-review tag was added to STR: NOP56_GGCCTG.
Ataxia and cerebellar anomalies - narrow panel v2.18 CACNA1A_CAG Arina Puzriakova Classified STR: CACNA1A_CAG as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.18 CACNA1A_CAG Arina Puzriakova Added comment: Comment on list classification: Downgraded from Green to Amber as this STR was not listed on the recent GMS STRs document supplied by Jane Deller (NHS England) on behalf of GLHs for the GMS Neurology Test Group
Ataxia and cerebellar anomalies - narrow panel v2.18 CACNA1A_CAG Arina Puzriakova Str: cacna1a_cag has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.17 CACNA1A_CAG Arina Puzriakova Tag for-review tag was added to STR: CACNA1A_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.17 ATXN3_CAG Arina Puzriakova Tag for-review tag was added to STR: ATXN3_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.17 ATXN1_CAG Arina Puzriakova Classified STR: ATXN1_CAG as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.17 ATXN1_CAG Arina Puzriakova Added comment: Comment on list classification: Downgraded from Green to Amber as this STR was not listed on the recent STRs document supplied by Jane Deller (NHS England) on behalf of GLHs for the GMS Neurology Test Group
Ataxia and cerebellar anomalies - narrow panel v2.17 ATXN1_CAG Arina Puzriakova Str: atxn1_cag has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.16 ATXN1_CAG Arina Puzriakova Tag for-review tag was added to STR: ATXN1_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.16 ATXN10_ATTCT Arina Puzriakova Classified STR: ATXN10_ATTCT as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.16 ATXN10_ATTCT Arina Puzriakova Added comment: Comment on list classification: Downgraded from Green to Amber as this STR was not listed on the recent STRs document supplied by Jane Deller (NHS England) on behalf of GLHs for the GMS Neurology Test Group
Ataxia and cerebellar anomalies - narrow panel v2.16 ATXN10_ATTCT Arina Puzriakova Str: atxn10_attct has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.15 ATXN10_ATTCT Arina Puzriakova Tag for-review tag was added to STR: ATXN10_ATTCT.
Ataxia and cerebellar anomalies - narrow panel v2.15 ATN1_CAG Arina Puzriakova Classified STR: ATN1_CAG as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.15 ATN1_CAG Arina Puzriakova Added comment: Comment on list classification: Downgraded from Green to Amber as this STR was not listed on the recent GMS STRs document supplied by Jane Deller (NHS England) on behalf of GLHs for the GMS Neurology Test Group.
Ataxia and cerebellar anomalies - narrow panel v2.15 ATN1_CAG Arina Puzriakova Str: atn1_cag has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.14 ATN1_CAG Arina Puzriakova Tag for-review tag was added to STR: ATN1_CAG.
Ataxia and cerebellar anomalies - narrow panel v2.14 HTT_CAG Arina Puzriakova Classified STR: HTT_CAG as No list
Ataxia and cerebellar anomalies - narrow panel v2.14 HTT_CAG Arina Puzriakova Added comment: Comment on list classification: This STR has been removed at the request of GHLs for the GMS Neurology Specialist Test Group as it is available as a core test for R68 Huntington Disease. Inclusion on panels for other neurological CIs raises concerns regarding counselling, and so it has been agreed that HTT_CAG will be excluded from this panel.
Ataxia and cerebellar anomalies - narrow panel v2.14 HTT_CAG Arina Puzriakova Str: htt_cag has been removed from the panel.
Ataxia and cerebellar anomalies - narrow panel v2.13 CAD Zornitza Stark gene: CAD was added
gene: CAD was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAD were set to 32820246
Phenotypes for gene: CAD were set to Epileptic encephalopathy, early infantile, 50; OMIM # 616457
Review for gene: CAD was set to GREEN
Added comment: 2020 series: 6/20 patients reported had ataxia relating to cerebellar atrophy, which is an expansion to the phenotype.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.13 LARS2 Sarah Leigh Tag for-review tag was added to gene: LARS2.
Ataxia and cerebellar anomalies - narrow panel v2.13 LARS2 Sarah Leigh edited their review of gene: LARS2: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.13 LARS2 Sarah Leigh Classified gene: LARS2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.13 LARS2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for Perrault syndrome. At least 6 variants reported as compound heterozygotes in three unrelated cases whose varied phenotypes included ataxia (PMID 30737337).
Ataxia and cerebellar anomalies - narrow panel v2.13 LARS2 Sarah Leigh Gene: lars2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.12 XRCC1 Zornitza Stark reviewed gene: XRCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28002403, 29472272; Phenotypes: Spinocerebellar ataxia, autosomal recessive 26 MIM#617633; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Ataxia and cerebellar anomalies - narrow panel v2.12 UCHL1 Zornitza Stark reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28007905, 23359680, 11555633; Phenotypes: Spastic paraplegia 79, autosomal recessive, MIM#615491; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Ataxia and cerebellar anomalies - narrow panel v2.12 UBTF Zornitza Stark gene: UBTF was added
gene: UBTF was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBTF were set to 29300972
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672
Review for gene: UBTF was set to GREEN
gene: UBTF was marked as current diagnostic
Added comment: Paediatric ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 TMEM106B Zornitza Stark gene: TMEM106B was added
gene: TMEM106B was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM106B were set to 29186371; 29444210
Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16, MIM# 617964
Review for gene: TMEM106B was set to GREEN
gene: TMEM106B was marked as current diagnostic
Added comment: Cerebellar signs including ataxia prominent.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 TGM6 Zornitza Stark reviewed gene: TGM6: Rating: RED; Mode of pathogenicity: None; Publications: 32426513, 30670339; Phenotypes: Spinocerebellar ataxia 35, MIM# 613908; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v2.12 TDP2 Zornitza Stark gene: TDP2 was added
gene: TDP2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: TDP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDP2 were set to 24658003; 30109272; 31410782
Phenotypes for gene: TDP2 were set to Spinocerebellar ataxia, autosomal recessive 23, 616949
Review for gene: TDP2 was set to GREEN
gene: TDP2 was marked as current diagnostic
Added comment: At least 6 individuals from 4 unrelated families reported.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 TBC1D23 Zornitza Stark gene: TBC1D23 was added
gene: TBC1D23 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: TBC1D23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D23 were set to 28823707; 28823706
Phenotypes for gene: TBC1D23 were set to Pontocerebellar hypoplasia, type 11, MIM# 617695
Review for gene: TBC1D23 was set to GREEN
gene: TBC1D23 was marked as current diagnostic
Added comment: Seven unrelated families reported, ataxia is part of the phenotype.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SVBP Zornitza Stark gene: SVBP was added
gene: SVBP was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SVBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVBP were set to 31363758; 30607023
Phenotypes for gene: SVBP were set to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, OMIM #618569
Review for gene: SVBP was set to GREEN
gene: SVBP was marked as current diagnostic
Added comment: 5 families with homozygous mutations in SVBP; syndromic cause of paediatric ataxia. Some shared same founder variant, p.Q28*. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SQSTM1 Zornitza Stark gene: SQSTM1 was added
gene: SQSTM1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SQSTM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SQSTM1 were set to 27545679
Phenotypes for gene: SQSTM1 were set to Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, MIM# 617145
Review for gene: SQSTM1 was set to GREEN
gene: SQSTM1 was marked as current diagnostic
Added comment: Four unrelated families, presenting feature of this progressive neurological disorder was ataxia.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SPR Zornitza Stark gene: SPR was added
gene: SPR was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SPR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPR were set to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716
Review for gene: SPR was set to GREEN
gene: SPR was marked as current diagnostic
Added comment: Complex movement disorder, dystonia predominant, but ataxia described in some individuals. Most individuals have had bi-allelic variants identified, uncertain whether there is an association with mono-allelic variants.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SPG7 Zornitza Stark reviewed gene: SPG7: Rating: AMBER; Mode of pathogenicity: None; Publications: 32893728; Phenotypes: Spastic paraplegia 7, autosomal recessive, MIM# 607259; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.12 SNAP25 Zornitza Stark gene: SNAP25 was added
gene: SNAP25 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SNAP25 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SNAP25 were set to 29491473; 25381298; 17283335
Phenotypes for gene: SNAP25 were set to Myasthenic syndrome, congenital, 18, 616330; cerebellar ataxia and seizures
Review for gene: SNAP25 was set to GREEN
gene: SNAP25 was marked as current diagnostic
Added comment: Phenotype in 3 reported cases and mouse model includes ataxia as a feature.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SLC9A1 Zornitza Stark gene: SLC9A1 was added
gene: SLC9A1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SLC9A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC9A1 were set to 25205112; 30018422; 25760855
Phenotypes for gene: SLC9A1 were set to Lichtenstein-Knorr syndrome, MIM# 616291
Review for gene: SLC9A1 was set to AMBER
Added comment: Two families with bi-allelic variants in this gene reported and combination of deafness and ataxia.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SLC52A2 Zornitza Stark gene: SLC52A2 was added
gene: SLC52A2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SLC52A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC52A2 were set to 30377535
Phenotypes for gene: SLC52A2 were set to Brown-Vialetto-Van Laere syndrome 2, MIM# 614707
Review for gene: SLC52A2 was set to GREEN
gene: SLC52A2 was marked as current diagnostic
Added comment: Generally presents with a range of neuropathies but ataxia described. Treatable condition.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SLC25A46 Zornitza Stark gene: SLC25A46 was added
gene: SLC25A46 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SLC25A46 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A46 were set to 30178502; 26168012; 27543974; 27430653; 27390132; 28934388; 28558379
Phenotypes for gene: SLC25A46 were set to Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505
Review for gene: SLC25A46 was set to GREEN
gene: SLC25A46 was marked as current diagnostic
Added comment: Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they show abnormal movements, such as ataxia, dysmetria, and myoclonus.

At least 10 unrelated families reported, supportive functional data.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SLC17A5 Zornitza Stark gene: SLC17A5 was added
gene: SLC17A5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SLC17A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC17A5 were set to 26171070
Phenotypes for gene: SLC17A5 were set to Sialic acid storage disorder, infantile, MIM# 269920
Review for gene: SLC17A5 was set to GREEN
gene: SLC17A5 was marked as current diagnostic
Added comment: Ataxia is prominent in childhood.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SCYL1 Zornitza Stark gene: SCYL1 was added
gene: SCYL1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SCYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL1 were set to 29419818; 17571074; 26581903; 30531813
Phenotypes for gene: SCYL1 were set to Spinocerebellar ataxia, autosomal recessive 21, MIM# 616719
Review for gene: SCYL1 was set to GREEN
gene: SCYL1 was marked as current diagnostic
Added comment: Early-onset ataxia (<1 year) with recurrent episodes of liver failure, sensory-motor axonal neuropathy, cerebellar atrophy. At least 7 unrelated families reported.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SCN8A Zornitza Stark reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31904124, 31887642, 31675620; Phenotypes: Cognitive impairment with or without cerebellar ataxia, MIM# 614306, Epileptic encephalopathy, early infantile, 13, MIM# 614558; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Ataxia and cerebellar anomalies - narrow panel v2.12 SCN2A Zornitza Stark gene: SCN2A was added
gene: SCN2A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SCN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN2A were set to 31924505; 32893078; 31904126
Phenotypes for gene: SCN2A were set to Epileptic encephalopathy, early infantile, 11, MIM# 613721
Review for gene: SCN2A was set to GREEN
gene: SCN2A was marked as current diagnostic
Added comment: Classically presents with seizures and DD/ID although a range of other manifestations reported, including movement abnormalities, including ataxia, especially episodic ataxia.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SCN1A Zornitza Stark gene: SCN1A was added
gene: SCN1A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN1A were set to 27264139; 27817982; 28732259
Phenotypes for gene: SCN1A were set to Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208
Review for gene: SCN1A was set to GREEN
gene: SCN1A was marked as current diagnostic
Added comment: Ataxia is part of the phenotype.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 SAR1B Zornitza Stark reviewed gene: SAR1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Chylomicron retention disease, 246700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.12 RUBCN Zornitza Stark reviewed gene: RUBCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20826435, 30237576, 32450808; Phenotypes: Spinocerebellar ataxia, autosomal recessive 15, MIM#615705; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Ataxia and cerebellar anomalies - narrow panel v2.12 RORA Zornitza Stark gene: RORA was added
gene: RORA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: RORA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RORA were set to 29656859
Phenotypes for gene: RORA were set to Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, MIM# 618060
Review for gene: RORA was set to GREEN
gene: RORA was marked as current diagnostic
Added comment: 11 unrelated individuals with syndromic intellectual disability and de novo variants in this gene. Severity varied from mild borderline intellectual disability with mild speech delay or normal speech, through to severe cognitive impairment with poor or absent speech. Most had ataxia, hypotonia, poor coordination, and/or mild tremor, suggesting cerebellar dysfunction. Three individuals had documented cerebellar hypoplasia or pontocerebellar atrophy on brain imaging. Seven had seizures of variable types, including neonatal myoclonic, tonic-clonic, multifocal, generalized, and absence. Five were diagnosed with autism spectrum disorder. More variable features included strabismus, esotropia, nystagmus, and oculomotor apraxia. Postulated that some variants exert dominant-negative effect resulting in a more severe phenotype than the LoF variants.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 POLR3B Zornitza Stark gene: POLR3B was added
gene: POLR3B was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3B were set to 22036171; 22036172
Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381
Review for gene: POLR3B was set to GREEN
gene: POLR3B was marked as current diagnostic
Added comment: Ataxia is a presenting feature.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 PMPCB Zornitza Stark gene: PMPCB was added
gene: PMPCB was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: PMPCB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMPCB were set to 29576218
Phenotypes for gene: PMPCB were set to Multiple mitochondrial dysfunctions syndrome 6, MIM# 617954
Review for gene: PMPCB was set to GREEN
gene: PMPCB was marked as current diagnostic
Added comment: Progressive disorder, includes ataxia. Four unrelated families reported.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 PITRM1 Zornitza Stark gene: PITRM1 was added
gene: PITRM1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: PITRM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PITRM1 were set to 26697887; 29764912; 29383861
Phenotypes for gene: PITRM1 were set to Ataxia; Intellectual disability
Review for gene: PITRM1 was set to GREEN
gene: PITRM1 was marked as current diagnostic
Added comment: Three families with two unique variants and in vitro functional assays. Cases and mouse model have spinocerebellar ataxia as a prominent feature of the phenotype. No OMIM phenotype.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 OPA1 Zornitza Stark edited their review of gene: OPA1: Set current diagnostic: yes
Ataxia and cerebellar anomalies - narrow panel v2.12 OPA1 Zornitza Stark gene: OPA1 was added
gene: OPA1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: OPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OPA1 were set to 28494813
Phenotypes for gene: OPA1 were set to Optic atrophy plus syndrome, MIM# 125250
Review for gene: OPA1 was set to GREEN
Added comment: Syndromic optic atrophy, also known as DOA+ syndrome, is a neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia (PEO), muscle cramps, hyperreflexia, and ataxia. See PMID 28494813 for three unrelated children where ataxia was a prominent part of the phenotype.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 NKX2-1 Zornitza Stark gene: NKX2-1 was added
gene: NKX2-1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: NKX2-1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969
Phenotypes for gene: NKX2-1 were set to Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700
Review for gene: NKX2-1 was set to GREEN
gene: NKX2-1 was marked as current diagnostic
Added comment: Paediatric onset ataxia reported in greater than 3 families with the condition.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 MVK Zornitza Stark reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: None; Publications: 12563048, 10401001, 28095071; Phenotypes: Mevalonic aciduria MIM#610377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.12 MTFMT Zornitza Stark gene: MTFMT was added
gene: MTFMT was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: MTFMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTFMT were set to 26060307; 24461907
Phenotypes for gene: MTFMT were set to Combined oxidative phosphorylation deficiency 15 MIM#614947; Mitochondrial complex I deficiency, nuclear type 27 MIM#618248
Review for gene: MTFMT was set to GREEN
gene: MTFMT was marked as current diagnostic
Added comment: Five unrelated cases reported with paediatric onset ataxia as a prominent feature of the condition.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 MSTO1 Zornitza Stark gene: MSTO1 was added
gene: MSTO1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: MSTO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MSTO1 were set to 28554942; 28544275; 31604776; 31463572; 31130378; 30684668; 29339779
Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia, MIM# 617675
Review for gene: MSTO1 was set to GREEN
gene: MSTO1 was marked as current diagnostic
Added comment: Impaired mitochondrial fusion disorder. Multiple families reported with bi-allelic variants and childhood-onset muscular dystrophy, corticospinal tract dysfunction and early-onset non-progressive cerebellar atrophy and ataxia. One family reported with heterozygous variant in this gene, gene-disease association for mono allelic variants not well established.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 LARS2 Zornitza Stark gene: LARS2 was added
gene: LARS2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: LARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARS2 were set to 29205794; 32423379; 30737337
Phenotypes for gene: LARS2 were set to Perrault syndrome 4, MIM# 615300; Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021; Leukodystrophy
Review for gene: LARS2 was set to GREEN
gene: LARS2 was marked as current diagnostic
Added comment: Bi-allelic variants in LARS2 cause a range of phenotypes, with some individuals displaying neurological features, including at least three individuals reported with ataxia (reviewed in PMID 32423379)
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 LAMA1 Zornitza Stark gene: LAMA1 was added
gene: LAMA1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: LAMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA1 were set to 25105227
Phenotypes for gene: LAMA1 were set to Cerebellar ataxia, intellectual disability, oculomotor apraxia, cerebellar cysts; Poretti Boltshauser syndrome MIM#615960
Review for gene: LAMA1 was set to GREEN
gene: LAMA1 was marked as current diagnostic
Added comment: Five unrelated families reported.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 KCNA2 Zornitza Stark gene: KCNA2 was added
gene: KCNA2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: KCNA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNA2 were set to 29050392
Phenotypes for gene: KCNA2 were set to Early infantile encephalopathy 32, MIM#616366
Review for gene: KCNA2 was set to GREEN
gene: KCNA2 was marked as current diagnostic
Added comment: Ataxia is part of the phenotype.

Review of 23 affected individuals in PMID 29050392: some variants are LoF and others GoF, and some genotype-phenotype correlations made. The main differences were (i) predominant focal (loss-of-function) versus generalized (gain-of-function) seizures and corresponding epileptic discharges with prominent sleep activation in most cases with loss-of-function mutations; (ii) more severe epilepsy, developmental problems and ataxia, and atrophy of the cerebellum or even the whole brain in about half of the patients with gain-of-function mutations; and (iii) most severe early-onset phenotypes, occasionally with neonatal onset epilepsy and developmental impairment, as well as generalised and focal seizures and EEG abnormalities for patients with gain- and loss-of-function mutations.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 IRF2BPL Zornitza Stark gene: IRF2BPL was added
gene: IRF2BPL was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF2BPL were set to 30057031
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, MIM# 618088
Review for gene: IRF2BPL was set to GREEN
gene: IRF2BPL was marked as current diagnostic
Added comment: Progressive ataxia is a feature reported in the original cohort of 7 unrelated patients.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 FBXL4 Zornitza Stark gene: FBXL4 was added
gene: FBXL4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: FBXL4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXL4 were set to 28383868
Phenotypes for gene: FBXL4 were set to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), MIM# 615471
Review for gene: FBXL4 was set to GREEN
Added comment: Ataxia is a reported feature of this mitochondrial disorder.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 FA2H Zornitza Stark gene: FA2H was added
gene: FA2H was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FA2H were set to 31135052
Phenotypes for gene: FA2H were set to Spastic paraplegia 35, autosomal recessive MIM#612319
Review for gene: FA2H was set to GREEN
Added comment: Limb ataxia is reported as a feature of the condition in at least 13 cases with mainly paediatric onset.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 EBF3 Zornitza Stark gene: EBF3 was added
gene: EBF3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: EBF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EBF3 were set to 28017373; 28017372; 28017370; 32366537
Phenotypes for gene: EBF3 were set to Hypotonia, ataxia, and delayed development syndrome, MIM# 617330
Review for gene: EBF3 was set to GREEN
gene: EBF3 was marked as current diagnostic
Added comment: Twenty unrelated families reported with mono-allelic variants in this gene and HADDS, a neurodevelopmental syndrome characterised by congenital hypotonia, delayed psychomotor development, variable intellectual disability with speech delay, variable dysmorphic facial features, and ataxia, often associated with cerebellar hypoplasia.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 DOCK3 Zornitza Stark gene: DOCK3 was added
gene: DOCK3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: DOCK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOCK3 were set to 28195318; 29130632; 30976111
Phenotypes for gene: DOCK3 were set to Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, MIM#618292
Review for gene: DOCK3 was set to GREEN
gene: DOCK3 was marked as current diagnostic
Added comment: Five unrelated families reported.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 DKC1 Zornitza Stark reviewed gene: DKC1: Rating: RED; Mode of pathogenicity: None; Publications: 10921354; Phenotypes: Dyskeratosis congenita, X-linked, MIM# 305000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia and cerebellar anomalies - narrow panel v2.12 CYP2U1 Zornitza Stark reviewed gene: CYP2U1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 56, autosomal recessive, MIM#615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.12 CSTB Zornitza Stark reviewed gene: CSTB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), MIM# 254800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.12 COA7 Zornitza Stark gene: COA7 was added
gene: COA7 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: COA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COA7 were set to 29718187; 27683825
Phenotypes for gene: COA7 were set to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, MIM#618387
Review for gene: COA7 was set to GREEN
gene: COA7 was marked as current diagnostic
Added comment: Five unrelated individuals reported with bi-allelic variants in this gene. Slowly progressive condition with variable onset, but at least three individuals presented at <5 years of age.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 CLPP Zornitza Stark gene: CLPP was added
gene: CLPP was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: CLPP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLPP were set to 25254289
Phenotypes for gene: CLPP were set to Perrault syndrome 3, MIM# 614129
Review for gene: CLPP was set to GREEN
gene: CLPP was marked as current diagnostic
Added comment: Neurological abnormalities including cerebellar ataxia are present in some individuals with this condition.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 CLN5 Zornitza Stark edited their review of gene: CLN5: Set current diagnostic: yes
Ataxia and cerebellar anomalies - narrow panel v2.12 CLN5 Zornitza Stark gene: CLN5 was added
gene: CLN5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: CLN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLN5 were set to 25359263
Phenotypes for gene: CLN5 were set to Ceroid lipofuscinosis, neuronal, 5, MIM# 256731
Review for gene: CLN5 was set to GREEN
Added comment: Ataxia is part of the phenotype of this disorder, which is typically of paediatric onset. Please also note report of adult-onset ataxia in PMID 25359263.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 BBS1 Zornitza Stark gene: BBS1 was added
gene: BBS1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: BBS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BBS1 were set to 15637713
Phenotypes for gene: BBS1 were set to Bardet-Biedl syndrome 1, MIM#209900
Review for gene: BBS1 was set to GREEN
gene: BBS1 was marked as current diagnostic
Added comment: Ataxia is a common feature of the phenotype.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 ATP8A2 Zornitza Stark reviewed gene: ATP8A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22892528, 31612321; Phenotypes: Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4, MIM#615268; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.12 ATCAY Zornitza Stark reviewed gene: ATCAY: Rating: AMBER; Mode of pathogenicity: None; Publications: 14556008; Phenotypes: Ataxia, cerebellar, Cayman type, MIM# 601238; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.12 ALDH5A1 Zornitza Stark gene: ALDH5A1 was added
gene: ALDH5A1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: ALDH5A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH5A1 were set to 14635103
Phenotypes for gene: ALDH5A1 were set to Succinic semialdehyde dehydrogenase deficiency, MIM# 271980
Review for gene: ALDH5A1 was set to GREEN
gene: ALDH5A1 was marked as current diagnostic
Added comment: Over 50 unrelated families reported. Ataxia is part of the phenotype, which also includes developmental delay, hypotonia, intellectual disability, seizures, hyperkinetic behaviour, aggression, and sleep disturbances.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 ADPRHL2 Zornitza Stark gene: ADPRHL2 was added
gene: ADPRHL2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: ADPRHL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADPRHL2 were set to 30100084; 30401461
Phenotypes for gene: ADPRHL2 were set to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170
Review for gene: ADPRHL2 was set to GREEN
gene: ADPRHL2 was marked as current diagnostic
Added comment: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 ACO2 Zornitza Stark gene: ACO2 was added
gene: ACO2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: ACO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACO2 were set to 32519519
Phenotypes for gene: ACO2 were set to Infantile cerebellar-retinal degeneration, MIM#614559
Review for gene: ACO2 was set to GREEN
gene: ACO2 was marked as current diagnostic
Added comment: Ataxia is part of the phenotype, particularly in more mildly affected individuals, where it can be the presenting feature.
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v2.12 HARS Arina Puzriakova commented on gene: HARS: Added new-gene-name tag, new approved HGNC gene symbol for HARS is HARS1
Ataxia and cerebellar anomalies - narrow panel v2.12 HARS Arina Puzriakova Tag new-gene-name tag was added to gene: HARS.
Ataxia and cerebellar anomalies - narrow panel v2.12 HARS Arina Puzriakova Classified gene: HARS as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.12 HARS Arina Puzriakova Added comment: Comment on list classification: Relevant phenotype for this panel but additional cases required. Therefore, rating Amber in anticipation of further publications.
Ataxia and cerebellar anomalies - narrow panel v2.12 HARS Arina Puzriakova Gene: hars has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.11 HARS Arina Puzriakova gene: HARS was added
gene: HARS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: HARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS were set to 32333447
Phenotypes for gene: HARS were set to Multisystem ataxic syndrome; Intellectual disability
Review for gene: HARS was set to AMBER
Added comment: PMID: 32333447 (2020) - Three individuals from two unrelated families harbouring biallelic HARS variants. Manifestations included microcephaly, mild‐to severe ID, skeletal deformities, and ataxic broad base gait with clinical features affecting the cerebellar and pyramidal tract system. Some supportive functional analysis of the variants in skin fibroblasts and yeast.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.10 EXOSC5 Arina Puzriakova changed review comment from: - PMID: 32504085 (2020) - Five patients from four families with biallelic variants in EXCOSC5. Clinical features included short stature (3/5), developmental delays that affect motor skills (3/5), hypotonia (4/5), ataxia (3/4), cerebellar hypoplasia/atrophy (4/5). Cognitive function was generally preserved, but included mild speech delays in one patient.
Cerebellar ataxia was described in two sibs and one singleton - all of whom were compound heterozygous for the p.Thr114Ile variant, inherited in trans with a frameshift variant (p.His30Thrfs*35) or deletion involving exons 5–6 of EXOSC5, respectively.

A LoF zebrafish model resulted in a variety of morphological defects including shortened and curved tails/bodies, reduced eye/head size and oedema. Functional studies of the variants in budding yeast and cultured cells showed some defects in RNA exosome function and interactions, that could not be explained by decrease in the steady-state level of EXOSC5.

- PMID: 29302074 (2019) - Three sibs with a homozygous EXCOSC5 variant (p.Thr114Ile), associated with mild motor delays, cerebellar ataxia, nystagmus, dysarthria, and moderate ID. The family is also described in PMID: 30950035. No functional studies of the variant were undertaken.
Sources: Literature; to: - PMID: 32504085 (2020) - Five patients from four families with biallelic variants in EXOSC5. Clinical features included short stature (3/5), developmental delays that affect motor skills (3/5), hypotonia (4/5), ataxia (3/4), cerebellar hypoplasia/atrophy (4/5). Cognitive function was generally preserved, but included mild speech delays in one patient.
Cerebellar ataxia was described in two sibs and one singleton - all of whom were compound heterozygous for the p.Thr114Ile variant, inherited in trans with a frameshift variant (p.His30Thrfs*35) or deletion involving exons 5–6 of EXOSC5, respectively.

A LoF zebrafish model resulted in a variety of morphological defects including shortened and curved tails/bodies, reduced eye/head size and oedema. Functional studies of the variants in budding yeast and cultured cells showed some defects in RNA exosome function and interactions, that could not be explained by decrease in the steady-state level of EXOSC5.

- PMID: 29302074 (2019) - Three sibs with a homozygous EXOSC5 variant (p.Thr114Ile), associated with mild motor delays, cerebellar ataxia, nystagmus, dysarthria, and moderate ID. The family is also described in PMID: 30950035. No functional studies of the variant were undertaken.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.10 EXOSC5 Arina Puzriakova Classified gene: EXOSC5 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.10 EXOSC5 Arina Puzriakova Added comment: Comment on list classification: Three unrelated families presenting ataxia in association with cerebellar hypoplasia/atrophy. However, all harbour the same p.Thr114Ile variant, and thus it is unclear whether other EXOSC5 variants result in cerebellar ataxia.

Therefore, rating Amber in anticipation of additional publications/clinical evidence.
Ataxia and cerebellar anomalies - narrow panel v2.10 EXOSC5 Arina Puzriakova Gene: exosc5 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.9 EXOSC5 Arina Puzriakova Publications for gene: EXOSC5 were set to 32504085
Ataxia and cerebellar anomalies - narrow panel v2.8 EXOSC5 Arina Puzriakova edited their review of gene: EXOSC5: Changed publications: 32504085, 29302074
Ataxia and cerebellar anomalies - narrow panel v2.8 EXOSC5 Arina Puzriakova gene: EXOSC5 was added
gene: EXOSC5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: EXOSC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC5 were set to 32504085
Phenotypes for gene: EXOSC5 were set to Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia
Added comment: - PMID: 32504085 (2020) - Five patients from four families with biallelic variants in EXCOSC5. Clinical features included short stature (3/5), developmental delays that affect motor skills (3/5), hypotonia (4/5), ataxia (3/4), cerebellar hypoplasia/atrophy (4/5). Cognitive function was generally preserved, but included mild speech delays in one patient.
Cerebellar ataxia was described in two sibs and one singleton - all of whom were compound heterozygous for the p.Thr114Ile variant, inherited in trans with a frameshift variant (p.His30Thrfs*35) or deletion involving exons 5–6 of EXOSC5, respectively.

A LoF zebrafish model resulted in a variety of morphological defects including shortened and curved tails/bodies, reduced eye/head size and oedema. Functional studies of the variants in budding yeast and cultured cells showed some defects in RNA exosome function and interactions, that could not be explained by decrease in the steady-state level of EXOSC5.

- PMID: 29302074 (2019) - Three sibs with a homozygous EXCOSC5 variant (p.Thr114Ile), associated with mild motor delays, cerebellar ataxia, nystagmus, dysarthria, and moderate ID. The family is also described in PMID: 30950035. No functional studies of the variant were undertaken.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.7 DNMT1 Eleanor Williams Publications for gene: DNMT1 were set to
Ataxia and cerebellar anomalies - narrow panel v2.6 DNMT1 Eleanor Williams reviewed gene: DNMT1: Rating: ; Mode of pathogenicity: None; Publications: 31984424; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.6 ATXN8 Eleanor Williams commented on gene: ATXN8
Ataxia and cerebellar anomalies - narrow panel v2.6 ATXN8 Eleanor Williams Tag ensembl_ids_known_missing tag was added to gene: ATXN8.
Ataxia and cerebellar anomalies - narrow panel v2.6 THG1L Zornitza Stark gene: THG1L was added
gene: THG1L was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THG1L were set to 27307223; 30214071; 31168944
Phenotypes for gene: THG1L were set to Cerebellar ataxia
Review for gene: THG1L was set to GREEN
Added comment: Four Ashkenazi Jewish families reported, with same homozygous variant, p.V55A in affected individuals. Another individual from different ethnicity also reported. A carrier rate of 0.8%, but no THG1L V55A homozygotes, was found in a cohort of 3,232 unrelated Ashkenazi Jewish individuals, and no homozygotes found in Exac or gnomAD.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.6 SLC44A1 Zornitza Stark gene: SLC44A1 was added
gene: SLC44A1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: SLC44A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC44A1 were set to 31855247
Phenotypes for gene: SLC44A1 were set to progressive ataxia; tremor; cognitive decline; dysphagia; optic atrophy; dysarthria
Review for gene: SLC44A1 was set to GREEN
Added comment: Childhood neurodegenerative condition. Four affected individuals from three families with homozygous frameshift variants reported. Functional evidence points to impaired choline transporter function yet unchanged membrane phosphatidylcholine content. Choline treatments may be beneficial. Suggest adding to optic neuropathy and possibly other panels, including severe paediatric disorders.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.6 SCN8A Sarah Leigh Mode of inheritance for gene: SCN8A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v2.5 SCN8A Sarah Leigh Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v2.5 SCN8A Sarah Leigh Added comment: Comment on mode of inheritance: Based on report in PMID 31625145, reporting biallelic loss of function SCN8A variants in three cases in two families with severe developmental and epileptic encephalopathy. This differs from the previosly reported gain of function, monoallelic variants (PMID 24194747;22365152).
Ataxia and cerebellar anomalies - narrow panel v2.5 SCN8A Sarah Leigh Mode of inheritance for gene: SCN8A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.3 Catherine Snow Panel version has been signed off
Ataxia and cerebellar anomalies - narrow panel v2.2 Catherine Snow Panel types changed to GMS Rare Disease; Component Of Super Panel; GMS signed-off
Ataxia and cerebellar anomalies - narrow panel v2.0 PTRH2 Louise Daugherty reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.0 PTRH2 Ellen Thomas edited their review of gene: PTRH2: Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.0 PTRH2 Ellen Thomas gene: PTRH2 was added
gene: PTRH2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Other
Mode of inheritance for gene: PTRH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTRH2 were set to 25574476; 28328138
Phenotypes for gene: PTRH2 were set to Infantile-onset multisystem neurologic, endocrine, and pancreatic disease
Added comment: Currently on adult ataxia panel; more suitable for childhood onset panel
Sources: Other
Ataxia and cerebellar anomalies - narrow panel v2.0 Louise Daugherty promoted panel to version 2.0
Ataxia and cerebellar anomalies - narrow panel v1.9 Louise Daugherty Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Ataxia and cerebellar anomalies - narrow panel v1.8 Louise Daugherty Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel
Ataxia and cerebellar anomalies - narrow panel v1.7 NMNAT2 Louise Daugherty gene: NMNAT2 was added
gene: NMNAT2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review
Mode of inheritance for gene: NMNAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT2 were set to 31136762
Phenotypes for gene: NMNAT2 were set to hydrops fetalis; cystic hygroma; bilateral hypoplastic lungs; hydrocephalus; hypoplastic cerebellum; severely reduced skeletal muscle mass or absence; flexion contractures of all extremities; micrognathia; cleft palate; hydropic placenta
Review for gene: NMNAT2 was set to RED
Added comment: New gene added by external expert (Michael Coleman (University of Cambridge), 11 Sep 2019) on Cerebellar hypoplasia panel v 1.37 and reviewed by curation team: Although appropriate to include on the panel the gene has been rated Red until there is more information to support gene-disease association. The current information in the literature does not support a Green rating as suggested by external reviewer, there are not sufficient cases, only an animal model (PMID:31136762)
Sources: Expert Review
Ataxia and cerebellar anomalies - narrow panel v1.6 AARS Louise Daugherty Tag new-gene-name tag was added to gene: AARS.
Ataxia and cerebellar anomalies - narrow panel v1.6 AARS Louise Daugherty commented on gene: AARS
Ataxia and cerebellar anomalies - narrow panel v1.6 MORC2 Louise Daugherty Classified gene: MORC2 as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v1.6 MORC2 Louise Daugherty Gene: morc2 has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v1.5 MORC2 Louise Daugherty gene: MORC2 was added
gene: MORC2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
Mode of inheritance for gene: MORC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MORC2 were set to 28402445; 27794525
Phenotypes for gene: MORC2 were set to Axonal type CMT disease type 2Z, 616688
Review for gene: MORC2 was set to GREEN
Added comment: Thr362Arg variant has been reported as a de novo event in early onset cerebellar ataxia in two different families. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green on the childhood panel during the call discussing MORC2 on R52 Hereditary ataxia - adult onset https://panelapp.genomicsengland.co.uk/panels/466/ (where is was decided to rate as Amber)
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v1.4 CTBP1 Louise Daugherty changed review comment from: from review of gene on Intellectual disability (Version 2.981) panel, it was suggested by the Genomics England clinical team that the phenotype would also be suitable for the 'ataxia and cerebellar anomalies - narrow panel'

Comment on list classification: Gene added to panel and rated Green by Chris Buxton. Changed rating to Green after agreement from Genomics England clinical team- sufficient cases and relevant phenotype. Have added missense tag, because only one missense tag reported so far.
Rebecca Foulger (Genomics England curator), 25 Jul 2019

There are 12 individuals reported from 3 papers (2 papers from the same group). All 12 individuals have the same heterozygous missense variant (R331W in NM_001012614.1; R342W in NM_001328.2). It is a de novo variant in all cases except one where it's inherited from a somatic parent. The phenotype of all 12 is summarised in Table 1 of PMID:31041561. Global DD is a consistent feature (varying severity). ID is recorded in several patients. Developmental motor regression recorded in 4 patients (2 of which also had cognitive regression). Authors note that healthy individuals with heterozygous LOF alleles have been reported.
Rebecca Foulger (Genomics England curator), 25 Jul 2019

27094857 Beck 2016; 4 unrelated probands with denovo R342W missense with s syndromic disorder of developmental delay, intellectual disability, failure to thrive, hypotonia, ataxia, and tooth enamel defects. 31041561 Beck 2019: 7 additional unrelated probands with denovo R342W missense with a syndromic intellectual disability, ataxia, hypotonia, and tooth enamel defect disorder. Insilico modelling supports a conclusion of dysregulation of the normal apoptosis pathway via reduced chromatin/histone binding. Mechanism is proposed to be ?GoF via reduction of transcription repression.
Chris Buxton (North Bristol NHS Trust), 18 Jul 2019

12 individuals with a recurrent missense variant in CTBP1 have been reported, all summarized in the last article: - Beck et al. 2016 (PMID: 27094857) : 4 individuals - Sommerville et al. 2017 (PMID: 28955726) : 1 subject - Beck et al. 2019 (PMID: 31041561) : 7 further individuals Features included hypotonia, DD/ID, ataxia and tooth enamel defects. The degree of ID - when present - appeared to be highly variable based at least on the first two reports (3 individuals with severe ID, 1 with borderline-normal intellectual functioning, 1 did not exhibit ID) where this feature was further commented on. A recurrent missense variant was found in all 12 affected individuals [NM_001328.2:c.1024C>T - p.(Arg342Trp) or NM_001012614.1:c.991C>T - p.(Arg331Trp)]. De novo occurrence this SNV was shown for (almost) all individuals, although in one case maternal sequencing reads were compatible with low-level somatic mosaicism (4/75 reads) not detected by Sanger sequencing. The mother of this individual was phenotypically normal. The variant is absent from gnomAD. Several in silico predictions (SIFT, PolyPhen2, MutationTaster, etc) suggest a deleterious effect. Given recurrence of this specific variant, and presence of LoF ones in healthy individuals (pLI of 0.98 though in gnomAD) Beck et al. suggested a dominant negative or a gain-of-function effect rather than a loss of function mechanism. Exclusion of alternative causes: was mainly discussed for the subject reported by Sommerville et al., due to the primary suspicion of a mitochondrial disorder (sequencing and research for mtDNA rearrangements, additional analysis of nuclear genes for mitochondrial disorders). Expression: CTBP1 encodes C-terminal binding protein 1, with expression among others in brain and cerebellum (https://gtexportal.org/home/gene/CTBP1). Role and Functional studies: - The major nuclear isoform of CTBP1 (corresponding to NM_001328.2) and of its paralog CTBP2 function as transcriptional regulators (corepressors). The PLDLS(Pro-Leu-Asp-Leu-Ser)-binding cleft domain where this variant lies, acts as a high-affinity protein-binding interface to recruit DNA-binding repressors and chromatin modifying enzymes (PMID: 17967884). - In a human glioblastoma cell line interaction of various cofactors with (Flag-tagged) CTBP1 was studied by immunoprecitipation with the Flag antibody and subsequent proteomic (LC-MS) analysis. This demonstrated reduced interaction in the case of R342W (compared to wt) with Zn-finger transcription factors, histone deacetylases, histone methyltransferases, histone H3-K4 demethylase etc. Western blot analyses also revealed reduced interaction of the R342W with several CTBP cofactors. - RNA-seq analysis in glioblastoma cell line revealed similar overall transcriptional profiles between wt and R342W though multiple RNA species showed significant differences (eg. genes involved in the biological processes of mitotic nuclear division, DNA repair, transcription and regulation of transcription among those that were most upregulated and genes involved in brain development among the most downregulated). - Patient fibroblasts under conditions of glucose deprivation exhibited strikingly more cell death compared to control fibroblasts. Study of mRNA levels of pro-apoptotic genes by q-RT-PCR revealed that Noxa expression under glucose deprivation vs under normal glucose was 8 to 10-fold enhanced for control fibroblasts, but more than 30-fold enhanced in the case patient fibroblasts. Western blot analyses were also in line with this. - Mitochondrial dysfunction (probably secondary) with evidence of decreased complex I (and complex IV) activities in skeletal muscle was the case for 2 individuals among multiple patients who had muscle biopsies. Animal models: - Beck et al. discuss previously published mouse models where Ctbp1/2 both play overlapping transcriptional roles during development. Homozygous deletion of Ctbp2 is embryonically lethal (>E10.5). Homozygous deletion of Ctbp1 results in viable mice with reduced size and lifespan (Cited: Hildebrand et al. 2002 - PMID: 12101226) - As commented on by Sommerville et al., Ctbp1 knockout in mouse embryonic fibroblasts resulted in elongated mitochondria, abnormal mitochondrial cristae, diminished ATP and O2 consumption and mitochondrial membrane potential (Cited: Kim and Youn 2009 - PMID: 19136938). ---- CTBP1 is associated with Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (617915) in OMIM. It is not associated with any phenotype in G2P. Some diagnostic laboratories (eg. GeneDx participating in the first study and others) include this gene in panels for intellectual disability. ---- As a result, CTBP1 can be added in the current panel probably as green.
Konstantinos Varvagiannis (Other), 7 Jul 2019
Sources: Literature; to: from review of gene on Intellectual disability (Version 2.981) panel, it was suggested by the Genomics England clinical team that the phenotype would also be suitable for the 'ataxia and cerebellar anomalies - narrow panel'


Comment on list classification: Gene added to panel and rated Green by Chris Buxton. Changed rating to Green after agreement from Genomics England clinical team- sufficient cases and relevant phenotype. Have added missense tag, because only one missense tag reported so far.
Rebecca Foulger (Genomics England curator), 25 Jul 2019


There are 12 individuals reported from 3 papers (2 papers from the same group). All 12 individuals have the same heterozygous missense variant (R331W in NM_001012614.1; R342W in NM_001328.2). It is a de novo variant in all cases except one where it's inherited from a somatic parent. The phenotype of all 12 is summarised in Table 1 of PMID:31041561. Global DD is a consistent feature (varying severity). ID is recorded in several patients. Developmental motor regression recorded in 4 patients (2 of which also had cognitive regression). Authors note that healthy individuals with heterozygous LOF alleles have been reported.
Rebecca Foulger (Genomics England curator), 25 Jul 2019


27094857 Beck 2016; 4 unrelated probands with denovo R342W missense with s syndromic disorder of developmental delay, intellectual disability, failure to thrive, hypotonia, ataxia, and tooth enamel defects. 31041561 Beck 2019: 7 additional unrelated probands with denovo R342W missense with a syndromic intellectual disability, ataxia, hypotonia, and tooth enamel defect disorder. Insilico modelling supports a conclusion of dysregulation of the normal apoptosis pathway via reduced chromatin/histone binding. Mechanism is proposed to be ?GoF via reduction of transcription repression.
Chris Buxton (North Bristol NHS Trust), 18 Jul 2019


12 individuals with a recurrent missense variant in CTBP1 have been reported, all summarized in the last article: - Beck et al. 2016 (PMID: 27094857) : 4 individuals - Sommerville et al. 2017 (PMID: 28955726) : 1 subject - Beck et al. 2019 (PMID: 31041561) : 7 further individuals Features included hypotonia, DD/ID, ataxia and tooth enamel defects. The degree of ID - when present - appeared to be highly variable based at least on the first two reports (3 individuals with severe ID, 1 with borderline-normal intellectual functioning, 1 did not exhibit ID) where this feature was further commented on. A recurrent missense variant was found in all 12 affected individuals [NM_001328.2:c.1024C>T - p.(Arg342Trp) or NM_001012614.1:c.991C>T - p.(Arg331Trp)]. De novo occurrence this SNV was shown for (almost) all individuals, although in one case maternal sequencing reads were compatible with low-level somatic mosaicism (4/75 reads) not detected by Sanger sequencing. The mother of this individual was phenotypically normal. The variant is absent from gnomAD. Several in silico predictions (SIFT, PolyPhen2, MutationTaster, etc) suggest a deleterious effect. Given recurrence of this specific variant, and presence of LoF ones in healthy individuals (pLI of 0.98 though in gnomAD) Beck et al. suggested a dominant negative or a gain-of-function effect rather than a loss of function mechanism. Exclusion of alternative causes: was mainly discussed for the subject reported by Sommerville et al., due to the primary suspicion of a mitochondrial disorder (sequencing and research for mtDNA rearrangements, additional analysis of nuclear genes for mitochondrial disorders). Expression: CTBP1 encodes C-terminal binding protein 1, with expression among others in brain and cerebellum (https://gtexportal.org/home/gene/CTBP1). Role and Functional studies: - The major nuclear isoform of CTBP1 (corresponding to NM_001328.2) and of its paralog CTBP2 function as transcriptional regulators (corepressors). The PLDLS(Pro-Leu-Asp-Leu-Ser)-binding cleft domain where this variant lies, acts as a high-affinity protein-binding interface to recruit DNA-binding repressors and chromatin modifying enzymes (PMID: 17967884). - In a human glioblastoma cell line interaction of various cofactors with (Flag-tagged) CTBP1 was studied by immunoprecitipation with the Flag antibody and subsequent proteomic (LC-MS) analysis. This demonstrated reduced interaction in the case of R342W (compared to wt) with Zn-finger transcription factors, histone deacetylases, histone methyltransferases, histone H3-K4 demethylase etc. Western blot analyses also revealed reduced interaction of the R342W with several CTBP cofactors. - RNA-seq analysis in glioblastoma cell line revealed similar overall transcriptional profiles between wt and R342W though multiple RNA species showed significant differences (eg. genes involved in the biological processes of mitotic nuclear division, DNA repair, transcription and regulation of transcription among those that were most upregulated and genes involved in brain development among the most downregulated). - Patient fibroblasts under conditions of glucose deprivation exhibited strikingly more cell death compared to control fibroblasts. Study of mRNA levels of pro-apoptotic genes by q-RT-PCR revealed that Noxa expression under glucose deprivation vs under normal glucose was 8 to 10-fold enhanced for control fibroblasts, but more than 30-fold enhanced in the case patient fibroblasts. Western blot analyses were also in line with this. - Mitochondrial dysfunction (probably secondary) with evidence of decreased complex I (and complex IV) activities in skeletal muscle was the case for 2 individuals among multiple patients who had muscle biopsies. Animal models: - Beck et al. discuss previously published mouse models where Ctbp1/2 both play overlapping transcriptional roles during development. Homozygous deletion of Ctbp2 is embryonically lethal (>E10.5). Homozygous deletion of Ctbp1 results in viable mice with reduced size and lifespan (Cited: Hildebrand et al. 2002 - PMID: 12101226) - As commented on by Sommerville et al., Ctbp1 knockout in mouse embryonic fibroblasts resulted in elongated mitochondria, abnormal mitochondrial cristae, diminished ATP and O2 consumption and mitochondrial membrane potential (Cited: Kim and Youn 2009 - PMID: 19136938). ---- CTBP1 is associated with Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (617915) in OMIM. It is not associated with any phenotype in G2P. Some diagnostic laboratories (eg. GeneDx participating in the first study and others) include this gene in panels for intellectual disability. ---- As a result, CTBP1 can be added in the current panel probably as green.
Konstantinos Varvagiannis (Other), 7 Jul 2019
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v1.4 CTBP1 Louise Daugherty Classified gene: CTBP1 as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v1.4 CTBP1 Louise Daugherty Gene: ctbp1 has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v1.3 CTBP1 Louise Daugherty gene: CTBP1 was added
gene: CTBP1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
missense tags were added to gene: CTBP1.
Mode of inheritance for gene: CTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTBP1 were set to 27094857; 28955726; 31041561
Phenotypes for gene: CTBP1 were set to Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome, 617915
Mode of pathogenicity for gene: CTBP1 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: CTBP1 was set to GREEN
Added comment: from review of gene on Intellectual disability (Version 2.981) panel, it was suggested by the Genomics England clinical team that the phenotype would also be suitable for the 'ataxia and cerebellar anomalies - narrow panel'

Comment on list classification: Gene added to panel and rated Green by Chris Buxton. Changed rating to Green after agreement from Genomics England clinical team- sufficient cases and relevant phenotype. Have added missense tag, because only one missense tag reported so far.
Rebecca Foulger (Genomics England curator), 25 Jul 2019

There are 12 individuals reported from 3 papers (2 papers from the same group). All 12 individuals have the same heterozygous missense variant (R331W in NM_001012614.1; R342W in NM_001328.2). It is a de novo variant in all cases except one where it's inherited from a somatic parent. The phenotype of all 12 is summarised in Table 1 of PMID:31041561. Global DD is a consistent feature (varying severity). ID is recorded in several patients. Developmental motor regression recorded in 4 patients (2 of which also had cognitive regression). Authors note that healthy individuals with heterozygous LOF alleles have been reported.
Rebecca Foulger (Genomics England curator), 25 Jul 2019

27094857 Beck 2016; 4 unrelated probands with denovo R342W missense with s syndromic disorder of developmental delay, intellectual disability, failure to thrive, hypotonia, ataxia, and tooth enamel defects. 31041561 Beck 2019: 7 additional unrelated probands with denovo R342W missense with a syndromic intellectual disability, ataxia, hypotonia, and tooth enamel defect disorder. Insilico modelling supports a conclusion of dysregulation of the normal apoptosis pathway via reduced chromatin/histone binding. Mechanism is proposed to be ?GoF via reduction of transcription repression.
Chris Buxton (North Bristol NHS Trust), 18 Jul 2019

12 individuals with a recurrent missense variant in CTBP1 have been reported, all summarized in the last article: - Beck et al. 2016 (PMID: 27094857) : 4 individuals - Sommerville et al. 2017 (PMID: 28955726) : 1 subject - Beck et al. 2019 (PMID: 31041561) : 7 further individuals Features included hypotonia, DD/ID, ataxia and tooth enamel defects. The degree of ID - when present - appeared to be highly variable based at least on the first two reports (3 individuals with severe ID, 1 with borderline-normal intellectual functioning, 1 did not exhibit ID) where this feature was further commented on. A recurrent missense variant was found in all 12 affected individuals [NM_001328.2:c.1024C>T - p.(Arg342Trp) or NM_001012614.1:c.991C>T - p.(Arg331Trp)]. De novo occurrence this SNV was shown for (almost) all individuals, although in one case maternal sequencing reads were compatible with low-level somatic mosaicism (4/75 reads) not detected by Sanger sequencing. The mother of this individual was phenotypically normal. The variant is absent from gnomAD. Several in silico predictions (SIFT, PolyPhen2, MutationTaster, etc) suggest a deleterious effect. Given recurrence of this specific variant, and presence of LoF ones in healthy individuals (pLI of 0.98 though in gnomAD) Beck et al. suggested a dominant negative or a gain-of-function effect rather than a loss of function mechanism. Exclusion of alternative causes: was mainly discussed for the subject reported by Sommerville et al., due to the primary suspicion of a mitochondrial disorder (sequencing and research for mtDNA rearrangements, additional analysis of nuclear genes for mitochondrial disorders). Expression: CTBP1 encodes C-terminal binding protein 1, with expression among others in brain and cerebellum (https://gtexportal.org/home/gene/CTBP1). Role and Functional studies: - The major nuclear isoform of CTBP1 (corresponding to NM_001328.2) and of its paralog CTBP2 function as transcriptional regulators (corepressors). The PLDLS(Pro-Leu-Asp-Leu-Ser)-binding cleft domain where this variant lies, acts as a high-affinity protein-binding interface to recruit DNA-binding repressors and chromatin modifying enzymes (PMID: 17967884). - In a human glioblastoma cell line interaction of various cofactors with (Flag-tagged) CTBP1 was studied by immunoprecitipation with the Flag antibody and subsequent proteomic (LC-MS) analysis. This demonstrated reduced interaction in the case of R342W (compared to wt) with Zn-finger transcription factors, histone deacetylases, histone methyltransferases, histone H3-K4 demethylase etc. Western blot analyses also revealed reduced interaction of the R342W with several CTBP cofactors. - RNA-seq analysis in glioblastoma cell line revealed similar overall transcriptional profiles between wt and R342W though multiple RNA species showed significant differences (eg. genes involved in the biological processes of mitotic nuclear division, DNA repair, transcription and regulation of transcription among those that were most upregulated and genes involved in brain development among the most downregulated). - Patient fibroblasts under conditions of glucose deprivation exhibited strikingly more cell death compared to control fibroblasts. Study of mRNA levels of pro-apoptotic genes by q-RT-PCR revealed that Noxa expression under glucose deprivation vs under normal glucose was 8 to 10-fold enhanced for control fibroblasts, but more than 30-fold enhanced in the case patient fibroblasts. Western blot analyses were also in line with this. - Mitochondrial dysfunction (probably secondary) with evidence of decreased complex I (and complex IV) activities in skeletal muscle was the case for 2 individuals among multiple patients who had muscle biopsies. Animal models: - Beck et al. discuss previously published mouse models where Ctbp1/2 both play overlapping transcriptional roles during development. Homozygous deletion of Ctbp2 is embryonically lethal (>E10.5). Homozygous deletion of Ctbp1 results in viable mice with reduced size and lifespan (Cited: Hildebrand et al. 2002 - PMID: 12101226) - As commented on by Sommerville et al., Ctbp1 knockout in mouse embryonic fibroblasts resulted in elongated mitochondria, abnormal mitochondrial cristae, diminished ATP and O2 consumption and mitochondrial membrane potential (Cited: Kim and Youn 2009 - PMID: 19136938). ---- CTBP1 is associated with Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (617915) in OMIM. It is not associated with any phenotype in G2P. Some diagnostic laboratories (eg. GeneDx participating in the first study and others) include this gene in panels for intellectual disability. ---- As a result, CTBP1 can be added in the current panel probably as green.
Konstantinos Varvagiannis (Other), 7 Jul 2019
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v1.0 TMEM5 Louise Daugherty Tag new-gene-name tag was added to gene: TMEM5.
Ataxia and cerebellar anomalies - narrow panel v1.0 TMEM5 Louise Daugherty commented on gene: TMEM5
Ataxia and cerebellar anomalies - narrow panel v1.0 ISPD Louise Daugherty commented on gene: ISPD
Ataxia and cerebellar anomalies - narrow panel v1.0 ISPD Louise Daugherty Tag new-gene-name tag was added to gene: ISPD.
Ataxia and cerebellar anomalies - narrow panel v1.0 Louise Daugherty promoted panel to version 1.0
Ataxia and cerebellar anomalies - narrow panel v0.74 PRRT2 Louise Daugherty Phenotypes for gene: PRRT2 were changed from to Convulsions, familial infantile, with paroxysmal choreoathetosis, 602066; Episodic kinesigenic dyskinesia 1, 128200; Seizures, benign familial infantile, 2, 605751
Ataxia and cerebellar anomalies - narrow panel v0.73 SLC2A1 Louise Daugherty Phenotypes for gene: SLC2A1 were changed from to Dystonia 9, 601042; GLUT1 deficiency syndrome 1, infantile onset, severe, 606777; GLUT1 deficiency syndrome 2, childhood onset, 612126; Stomatin-deficient cryohydrocytosis with neurologic defects, 608885
Ataxia and cerebellar anomalies - narrow panel v0.72 NPC2 Louise Daugherty Phenotypes for gene: NPC2 were changed from Niemann-Pick disease type C2 (#607625) to Niemann-Pick disease type C2, 607625
Ataxia and cerebellar anomalies - narrow panel v0.71 AAAS Louise Daugherty Phenotypes for gene: AAAS were changed from to Achalasia-addisonianism-alacrimia syndrome, 231550
Ataxia and cerebellar anomalies - narrow panel v0.70 AP1S2 Louise Daugherty Phenotypes for gene: AP1S2 were changed from to Mental retardation, X-linked syndromic 5, 304340
Ataxia and cerebellar anomalies - narrow panel v0.69 CAMTA1 Louise Daugherty Phenotypes for gene: CAMTA1 were changed from Cerebellarataxia, nonprogressive, with mentalretardation, 614756 to Cerebellarataxia, nonprogressive, with mental retardation, 614756
Ataxia and cerebellar anomalies - narrow panel v0.68 CAMTA1 Louise Daugherty Phenotypes for gene: CAMTA1 were changed from Cerebellarataxia,nonprogressive,withmentalretardation,614756 3 to Cerebellarataxia, nonprogressive, with mentalretardation, 614756
Ataxia and cerebellar anomalies - narrow panel v0.67 CHMP1A Louise Daugherty Publications for gene: CHMP1A were set to PMID: 23023333
Ataxia and cerebellar anomalies - narrow panel v0.66 CHMP1A Louise Daugherty Phenotypes for gene: CHMP1A were changed from Pontocerebellar Hypoplasia; Pontocerebellar Hypoplasia type 8; Pontocerebellar hypoplasia,type 8,614961; Pontocerebellar hypoplasia 8 (#614961) to Pontocerebellar hypoplasia, type 8, 614961
Ataxia and cerebellar anomalies - narrow panel v0.65 CLN6 Louise Daugherty Phenotypes for gene: CLN6 were changed from Neuronal ceroid lipofuscinosis 6 (#601780) and adult onset form (#204300) to Ceroid lipofuscinosis, neuronal, 6, 601780; Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, 204300
Ataxia and cerebellar anomalies - narrow panel v0.64 COX20 Louise Daugherty Phenotypes for gene: COX20 were changed from to Mitochondrial complex IV deficiency, 220110
Ataxia and cerebellar anomalies - narrow panel v0.63 CP Louise Daugherty Phenotypes for gene: CP were changed from Cerebellar ataxia, to Cerebellar ataxia, 604290; Hemosiderosis, systemic, due to aceruloplasminemia, 604290
Ataxia and cerebellar anomalies - narrow panel v0.62 CYP27A1 Louise Daugherty Phenotypes for gene: CYP27A1 were changed from to Cerebrotendinous xanthomatosis, 213700
Ataxia and cerebellar anomalies - narrow panel v0.61 DARS2 Louise Daugherty Phenotypes for gene: DARS2 were changed from to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105
Ataxia and cerebellar anomalies - narrow panel v0.60 FOLR1 Louise Daugherty Phenotypes for gene: FOLR1 were changed from to Neurodegeneration due to cerebral folate transport deficiency, 613068
Ataxia and cerebellar anomalies - narrow panel v0.59 GBA2 Louise Daugherty Phenotypes for gene: GBA2 were changed from to Spastic paraplegia 46, autosomal recessive, 614409
Ataxia and cerebellar anomalies - narrow panel v0.58 GBA2 Louise Daugherty Publications for gene: GBA2 were set to
Ataxia and cerebellar anomalies - narrow panel v0.57 GRID2 Louise Daugherty Publications for gene: GRID2 were set to PMID: 25841024
Ataxia and cerebellar anomalies - narrow panel v0.56 GRID2 Louise Daugherty Phenotypes for gene: GRID2 were changed from Rare cases of autosomal dominant inheritance reported by Coutelier et al., 2015.; Autosomal recessive spinocerebellar ataxia 18 (#616204) to Spinocerebellar ataxia, autosomal recessive 18, 616204
Ataxia and cerebellar anomalies - narrow panel v0.55 HEXA Louise Daugherty Phenotypes for gene: HEXA were changed from to GM2-gangliosidosis, several forms, 272800; Tay-Sachs disease, 272800
Ataxia and cerebellar anomalies - narrow panel v0.54 HEXB Louise Daugherty Phenotypes for gene: HEXB were changed from to Sandhoff disease, infantile, juvenile, and adult forms, 268800
Ataxia and cerebellar anomalies - narrow panel v0.53 MMACHC Louise Daugherty Phenotypes for gene: MMACHC were changed from Ataxia and hypogonadism (AR), Also Methylmalonic aciduria and homocystinuria (AR) (OMIM #277400) to Ataxia and hypogonadism; Methylmalonic aciduria and homocystinuria, cblC type, 277400
Ataxia and cerebellar anomalies - narrow panel v0.52 MMACHC Louise Daugherty Publications for gene: MMACHC were set to PMID: 26283149
Ataxia and cerebellar anomalies - narrow panel v0.51 SIL1 Louise Daugherty Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome, 248800
Ataxia and cerebellar anomalies - narrow panel v0.50 SLC9A6 Louise Daugherty Phenotypes for gene: SLC9A6 were changed from to Mental retardation, X-linked syndromic, Christianson type, 300243
Ataxia and cerebellar anomalies - narrow panel v0.49 SRD5A3 Louise Daugherty Phenotypes for gene: SRD5A3 were changed from to Congenital disorder of glycosylation, type Iq, 612379; Kahrizi syndrome, 612713
Ataxia and cerebellar anomalies - narrow panel v0.48 TGM6 Louise Daugherty Phenotypes for gene: TGM6 were changed from Spinocerebellar ataxia 35 to Spinocerebellar ataxia 35, 613908
Ataxia and cerebellar anomalies - narrow panel v0.47 TMEM240 Louise Daugherty Phenotypes for gene: TMEM240 were changed from Spinocerebellar ataxia 21 (#616101) to Spinocerebellar ataxia 21, 607454
Ataxia and cerebellar anomalies - narrow panel v0.46 EIF2B2 Louise Daugherty Phenotypes for gene: EIF2B2 were changed from Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease to Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease; Leukoencephalopathy with vanishing white matter, 603896
Ataxia and cerebellar anomalies - narrow panel v0.45 TTC19 Louise Daugherty Phenotypes for gene: TTC19 were changed from Nuclear type mitochondrial complex III deficiency (#615157) to Mitochondrial complex III deficiency, nuclear type 2, 615157
Ataxia and cerebellar anomalies - narrow panel v0.44 TUBB4A Louise Daugherty Phenotypes for gene: TUBB4A were changed from Hypomyelinating leukodystrophy 6, 612438; Torsion dystonia 4 ,128101 to Leukodystrophy, hypomyelinating, 6, 612438; Dystonia 4, torsion, autosomal dominant, 128101
Ataxia and cerebellar anomalies - narrow panel v0.43 TUBB4A Louise Daugherty Publications for gene: TUBB4A were set to PMID: 25497598
Ataxia and cerebellar anomalies - narrow panel v0.42 TUBB4A Louise Daugherty Added comment: Comment on phenotypes: Implicated autosomal dominant variants in two families with ataxia; hypomyelinating leukodystrophy 6 (612438) - ataxia reported.; Torsion dystonia 4 (128101) - some individuals with ataxia
Ataxia and cerebellar anomalies - narrow panel v0.42 TUBB4A Louise Daugherty Phenotypes for gene: TUBB4A were changed from Implicated autosomal dominant variants in two families with ataxia; Torsion dystonia 4 (128101) - some individuals with ataxia; hypomyelinating leukodystrophy 6 (612438) - ataxia reported. to Hypomyelinating leukodystrophy 6, 612438; Torsion dystonia 4 ,128101
Ataxia and cerebellar anomalies - narrow panel v0.41 TWNK Louise Daugherty Phenotypes for gene: TWNK were changed from Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders (Dominant) to Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders, Dominant; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, 609286; Perrault syndrome 5, 616138; Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245
Ataxia and cerebellar anomalies - narrow panel v0.40 COQ8A Louise Daugherty Phenotypes for gene: COQ8A were changed from Coenzyme Q10 deficiency, Spinocerebellar Ataxia Type to Coenzyme Q10 deficiency, primary 4, 612016; Spinocerebellar Ataxia Type
Ataxia and cerebellar anomalies - narrow panel v0.39 VPS13D Louise Daugherty Phenotypes for gene: VPS13D were changed from spastic ataxia to Spinocerebellar ataxia, autosomal recessive 4, 607317
Ataxia and cerebellar anomalies - narrow panel v0.38 WDR73 Louise Daugherty Phenotypes for gene: WDR73 were changed from Galloway Mowat syndrome, when patients are ambulant ataxia is a recognisednfeature to Galloway Mowat syndrome, when patients are ambulant ataxia is a recognised feature; Galloway-Mowat syndrome 1, 251300
Ataxia and cerebellar anomalies - narrow panel v0.37 WFS1 Louise Daugherty Phenotypes for gene: WFS1 were changed from to Wolfram syndrome 1, 222300
Ataxia and cerebellar anomalies - narrow panel v0.36 WWOX Louise Daugherty Phenotypes for gene: WWOX were changed from Autosomal recessive spinocerebellar ataxia 12 (#614322) to Autosomal recessive spinocerebellar ataxia 12, 614322
Ataxia and cerebellar anomalies - narrow panel v0.35 TBP_CAG Louise Daugherty Classified STR: TBP_CAG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.35 TBP_CAG Louise Daugherty Str: tbp_cag has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.34 TBP_CAG Louise Daugherty STR: TBP_CAG was added
STR: TBP_CAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: TBP_CAG.
Mode of inheritance for STR: TBP_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: TBP_CAG were set to 20301611
Phenotypes for STR: TBP_CAG were set to Spinocerebellar ataxia 17 607136
Review for STR: TBP_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.33 PPP2R2B_CAG Louise Daugherty Classified STR: PPP2R2B_CAG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.33 PPP2R2B_CAG Louise Daugherty Str: ppp2r2b_cag has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.32 PPP2R2B_CAG Louise Daugherty STR: PPP2R2B_CAG was added
STR: PPP2R2B_CAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: PPP2R2B_CAG.
Mode of inheritance for STR: PPP2R2B_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: PPP2R2B_CAG were set to Spinocerebellar ataxia 12 604326
Review for STR: PPP2R2B_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.31 NOP56_GGCCTG Louise Daugherty Classified STR: NOP56_GGCCTG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.31 NOP56_GGCCTG Louise Daugherty Str: nop56_ggcctg has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.30 NOP56_GGCCTG Louise Daugherty STR: NOP56_GGCCTG was added
STR: NOP56_GGCCTG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: NOP56_GGCCTG.
Mode of inheritance for STR: NOP56_GGCCTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: NOP56_GGCCTG were set to Spinocerebellar ataxia 36 614153
Review for STR: NOP56_GGCCTG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.29 HTT_CAG Louise Daugherty Classified STR: HTT_CAG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.29 HTT_CAG Louise Daugherty Str: htt_cag has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.28 HTT_CAG Louise Daugherty STR: HTT_CAG was added
STR: HTT_CAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: HTT_CAG.
Mode of inheritance for STR: HTT_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: HTT_CAG were set to Huntington disease 143100
Review for STR: HTT_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.27 FXN_GAA Louise Daugherty Classified STR: FXN_GAA as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.27 FXN_GAA Louise Daugherty Str: fxn_gaa has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.26 FXN_GAA Louise Daugherty STR: FXN_GAA was added
STR: FXN_GAA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: FXN_GAA.
Mode of inheritance for STR: FXN_GAA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for STR: FXN_GAA were set to Friedreich ataxia 229300
Review for STR: FXN_GAA was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.25 CSTB_CCCCGCCCCGCG Louise Daugherty Classified STR: CSTB_CCCCGCCCCGCG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.25 CSTB_CCCCGCCCCGCG Louise Daugherty Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.24 CSTB_CCCCGCCCCGCG Louise Daugherty STR: CSTB_CCCCGCCCCGCG was added
STR: CSTB_CCCCGCCCCGCG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: CSTB_CCCCGCCCCGCG.
Mode of inheritance for STR: CSTB_CCCCGCCCCGCG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for STR: CSTB_CCCCGCCCCGCG were set to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800
Review for STR: CSTB_CCCCGCCCCGCG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.23 CACNA1A_CAG Louise Daugherty Classified STR: CACNA1A_CAG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.23 CACNA1A_CAG Louise Daugherty Str: cacna1a_cag has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.22 CACNA1A_CAG Louise Daugherty STR: CACNA1A_CAG was added
STR: CACNA1A_CAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: CACNA1A_CAG.
Mode of inheritance for STR: CACNA1A_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: CACNA1A_CAG were set to Spinocerebellar ataxia 6 183086
Review for STR: CACNA1A_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.21 ATXN7_CAG Louise Daugherty Classified STR: ATXN7_CAG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.21 ATXN7_CAG Louise Daugherty Str: atxn7_cag has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.20 ATXN7_CAG Louise Daugherty STR: ATXN7_CAG was added
STR: ATXN7_CAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: ATXN7_CAG.
Mode of inheritance for STR: ATXN7_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: ATXN7_CAG were set to Spinocerebellar ataxia 7 164500
Review for STR: ATXN7_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.19 ATXN3_CAG Louise Daugherty Classified STR: ATXN3_CAG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.19 ATXN3_CAG Louise Daugherty Str: atxn3_cag has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.18 ATXN3_CAG Louise Daugherty STR: ATXN3_CAG was added
STR: ATXN3_CAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: ATXN3_CAG.
Mode of inheritance for STR: ATXN3_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: ATXN3_CAG were set to Machado-Joseph disease 109150
Review for STR: ATXN3_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.17 ATXN2_CAG Louise Daugherty Classified STR: ATXN2_CAG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.17 ATXN2_CAG Louise Daugherty Str: atxn2_cag has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.16 ATXN2_CAG Louise Daugherty STR: ATXN2_CAG was added
STR: ATXN2_CAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: ATXN2_CAG.
Mode of inheritance for STR: ATXN2_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: ATXN2_CAG were set to Spinocerebellar ataxia 2 183090
Review for STR: ATXN2_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.14 ATXN10_ATTCT Louise Daugherty Classified STR: ATXN10_ATTCT as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.14 ATXN10_ATTCT Louise Daugherty Str: atxn10_attct has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.13 ATXN10_ATTCT Louise Daugherty STR: ATXN10_ATTCT was added
STR: ATXN10_ATTCT was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: ATXN10_ATTCT.
Mode of inheritance for STR: ATXN10_ATTCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: ATXN10_ATTCT were set to 12164725
Phenotypes for STR: ATXN10_ATTCT were set to Spinocerebellar ataxia 10 603516
Review for STR: ATXN10_ATTCT was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.12 ATXN1_CAG Louise Daugherty Classified STR: ATXN1_CAG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.12 ATXN1_CAG Louise Daugherty Str: atxn1_cag has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.11 ATXN1_CAG Louise Daugherty STR: ATXN1_CAG was added
STR: ATXN1_CAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: ATXN1_CAG.
Mode of inheritance for STR: ATXN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: ATXN1_CAG were set to Spinocerebellar ataxia 1 164400
Review for STR: ATXN1_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.10 ATN1_CAG Louise Daugherty Classified STR: ATN1_CAG as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.10 ATN1_CAG Louise Daugherty Str: atn1_cag has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.9 ATN1_CAG Louise Daugherty STR: ATN1_CAG was added
STR: ATN1_CAG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list
STR tags were added to STR: ATN1_CAG.
Mode of inheritance for STR: ATN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: ATN1_CAG were set to 20301664; 8136840; 20301664; 8136840; 8136826; 7614090
Phenotypes for STR: ATN1_CAG were set to Dentatorubro-pallidoluysian atrophy 125370
Review for STR: ATN1_CAG was set to GREEN
Added comment: Source PanelApp panels : Hereditary ataxia v1.150
Sources: Expert list
Ataxia and cerebellar anomalies - narrow panel v0.7 PMPCA Rebecca Foulger Classified gene: PMPCA as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v0.7 PMPCA Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green, to match Green rating on Hereditary ataxia v1.148 panel.
Ataxia and cerebellar anomalies - narrow panel v0.7 PMPCA Rebecca Foulger Gene: pmpca has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v0.5 DNAJC5 Ellen McDonagh gene: DNAJC5 was added
gene: DNAJC5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DNAJC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNAJC5 were set to 27604308; 21820099
Phenotypes for gene: DNAJC5 were set to Ceroid lipofuscinosis, neuronal, 4, Parry type
Ataxia and cerebellar anomalies - narrow panel v0.5 DAB1 Ellen McDonagh gene: DAB1 was added
gene: DAB1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: DAB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAB1 were set to 28686858
Phenotypes for gene: DAB1 were set to Spinocerebellar ataxia 37
Mode of pathogenicity for gene: DAB1 was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 ATXN8 Ellen McDonagh gene: ATXN8 was added
gene: ATXN8 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ATXN8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATXN8 were set to 10192387
Phenotypes for gene: ATXN8 were set to Spinocerebellar ataxia 8
Mode of pathogenicity for gene: ATXN8 was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 ELOVL4 Ellen McDonagh gene: ELOVL4 was added
gene: ELOVL4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ELOVL4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ELOVL4 were set to 24566826; 26010696
Phenotypes for gene: ELOVL4 were set to Spinocerebellar ataxia 34
Ataxia and cerebellar anomalies - narrow panel v0.5 COG5 Ellen McDonagh gene: COG5 was added
gene: COG5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: COG5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COG5 were set to 19690088; 28960046
Phenotypes for gene: COG5 were set to Congenital disorder of glycosylation, type IIi
Ataxia and cerebellar anomalies - narrow panel v0.5 SAR1B Ellen McDonagh gene: SAR1B was added
gene: SAR1B was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SAR1B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SAR1B were set to Chylomicron retention disease
Ataxia and cerebellar anomalies - narrow panel v0.5 ROBO3 Ellen McDonagh gene: ROBO3 was added
gene: ROBO3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ROBO3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROBO3 were set to 16525029; 15105459
Phenotypes for gene: ROBO3 were set to Gaze palsy, familial horizontal, with progressive scoliosis, 1
Ataxia and cerebellar anomalies - narrow panel v0.5 NKX6-2 Ellen McDonagh gene: NKX6-2 was added
gene: NKX6-2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NKX6-2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NKX6-2 were set to 15601927; 28575651
Phenotypes for gene: NKX6-2 were set to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy
Ataxia and cerebellar anomalies - narrow panel v0.5 NHLRC1 Ellen McDonagh gene: NHLRC1 was added
gene: NHLRC1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NHLRC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC1 were set to 12958597; 15781812
Phenotypes for gene: NHLRC1 were set to Epilepsy, progressive myoclonic 2B (Lafora)
Ataxia and cerebellar anomalies - narrow panel v0.5 EPM2A Ellen McDonagh gene: EPM2A was added
gene: EPM2A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EPM2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPM2A were set to 27604308; 10932264; 14722920
Phenotypes for gene: EPM2A were set to Epilepsy, progressive myoclonic 2A (Lafora)
Ataxia and cerebellar anomalies - narrow panel v0.5 DNAJC19 Ellen McDonagh gene: DNAJC19 was added
gene: DNAJC19 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DNAJC19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC19 were set to 16055927; 27604308; 27426421; 22797137; 27928778
Phenotypes for gene: DNAJC19 were set to 3-methylglutaconic aciduria, type V
Ataxia and cerebellar anomalies - narrow panel v0.5 TBP Ellen McDonagh gene: TBP was added
gene: TBP was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: TBP was set to Unknown
Phenotypes for gene: TBP were set to Spinocerebellarataxia17,607136{Parkinsondisease,susceptibilityto},168600
Mode of pathogenicity for gene: TBP was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 PPP2R2B Ellen McDonagh gene: PPP2R2B was added
gene: PPP2R2B was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: PPP2R2B was set to Unknown
Phenotypes for gene: PPP2R2B were set to Spinocerebellarataxia12,604326
Mode of pathogenicity for gene: PPP2R2B was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 PAX2 Ellen McDonagh gene: PAX2 was added
gene: PAX2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: PAX2 was set to Unknown
Phenotypes for gene: PAX2 were set to Ataxia,spastic2,autosomalrecessive(2)
Ataxia and cerebellar anomalies - narrow panel v0.5 EXOSC8 Ellen McDonagh gene: EXOSC8 was added
gene: EXOSC8 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: EXOSC8 was set to Unknown
Phenotypes for gene: EXOSC8 were set to Pontocerebellar hypoplasia,type 1C, 616081
Ataxia and cerebellar anomalies - narrow panel v0.5 DAG1 Ellen McDonagh gene: DAG1 was added
gene: DAG1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: DAG1 was set to Unknown
Phenotypes for gene: DAG1 were set to congenital muscular dystrophies
Ataxia and cerebellar anomalies - narrow panel v0.5 ATXN7 Ellen McDonagh gene: ATXN7 was added
gene: ATXN7 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ATXN7 was set to Unknown
Phenotypes for gene: ATXN7 were set to Spinocerebellarataxia7,164500
Mode of pathogenicity for gene: ATXN7 was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 ATXN3 Ellen McDonagh gene: ATXN3 was added
gene: ATXN3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ATXN3 was set to Unknown
Mode of pathogenicity for gene: ATXN3 was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 ATXN2 Ellen McDonagh gene: ATXN2 was added
gene: ATXN2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ATXN2 was set to Unknown
Phenotypes for gene: ATXN2 were set to Spinocerebellarataxia2,183090{Amyotrophiclateralsclerosis,susceptibilityto,13},183090
Mode of pathogenicity for gene: ATXN2 was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 ATXN10 Ellen McDonagh gene: ATXN10 was added
gene: ATXN10 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ATXN10 was set to Unknown
Phenotypes for gene: ATXN10 were set to Spinocerebellarataxia10,603516
Mode of pathogenicity for gene: ATXN10 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 ATXN1 Ellen McDonagh gene: ATXN1 was added
gene: ATXN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ATXN1 was set to Unknown
Phenotypes for gene: ATXN1 were set to Spinocerebellarataxia1,164400
Mode of pathogenicity for gene: ATXN1 was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 ATP2B3 Ellen McDonagh gene: ATP2B3 was added
gene: ATP2B3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ATP2B3 was set to Unknown
Phenotypes for gene: ATP2B3 were set to Spinocerebellar ataxia, X-linked 1
Ataxia and cerebellar anomalies - narrow panel v0.5 SLC9A6 Ellen McDonagh gene: SLC9A6 was added
gene: SLC9A6 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SLC9A6 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Ataxia and cerebellar anomalies - narrow panel v0.5 OPHN1 Ellen McDonagh gene: OPHN1 was added
gene: OPHN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: OPHN1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: OPHN1 were set to XLMR with Cerebellar Hypoplasia and Distinctive Facial Appearance; Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, 300486; Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance
Ataxia and cerebellar anomalies - narrow panel v0.5 FMR1 Ellen McDonagh gene: FMR1 was added
gene: FMR1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FMR1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: FMR1 were set to FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related premature ovarian insufficiency (POI); males with a tremor phenotype; FragileXtremor/ataxiasyndrome,300623
Ataxia and cerebellar anomalies - narrow panel v0.5 CASK Ellen McDonagh gene: CASK was added
gene: CASK was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CASK was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: CASK were set to FG syndrome 4, 300422; Mental retardation, with or without nystagmus; Mental retardation and microcephaly with pontine and cerebellar hypoplasia; Pontocerebellar Hypoplasia; FG syndrome 4; Mental retardation and microcephaly with pontine and cerebellar hypoplasia, 300749; Mental retardation, with or without nystagmus, 300422
Ataxia and cerebellar anomalies - narrow panel v0.5 AP1S2 Ellen McDonagh gene: AP1S2 was added
gene: AP1S2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: AP1S2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Ataxia and cerebellar anomalies - narrow panel v0.5 ALAS2 Ellen McDonagh gene: ALAS2 was added
gene: ALAS2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ALAS2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Ataxia and cerebellar anomalies - narrow panel v0.5 ABCB7 Ellen McDonagh gene: ABCB7 was added
gene: ABCB7 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ABCB7 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: ABCB7 were set to Anemia, sideroblastic, with ataxia,; Sideroblastic Anemia and Ataxia
Ataxia and cerebellar anomalies - narrow panel v0.5 DKC1 Ellen McDonagh gene: DKC1 was added
gene: DKC1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DKC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DKC1 were set to 9590285; 9886310
Phenotypes for gene: DKC1 were set to X-linked dyskeratosis congenita
Ataxia and cerebellar anomalies - narrow panel v0.5 NOP56 Ellen McDonagh gene: NOP56 was added
gene: NOP56 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: NOP56 was set to Other - please specifiy in evaluation comments
Phenotypes for gene: NOP56 were set to Spinocerebellarataxia36,614153
Mode of pathogenicity for gene: NOP56 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 ATN1 Ellen McDonagh gene: ATN1 was added
gene: ATN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ATN1 was set to Other - please specifiy in evaluation comments
Mode of pathogenicity for gene: ATN1 was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 TUBB3 Ellen McDonagh gene: TUBB3 was added
gene: TUBB3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB3 were set to 20829227
Phenotypes for gene: TUBB3 were set to Cortical dysplasia, complex, with other brain malformations 1 614039
Ataxia and cerebellar anomalies - narrow panel v0.5 TUBB2B Ellen McDonagh gene: TUBB2B was added
gene: TUBB2B was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TUBB2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB2B were set to 19465910
Phenotypes for gene: TUBB2B were set to complex cortical dysplasia with other brain malformations-7 , 610031
Ataxia and cerebellar anomalies - narrow panel v0.5 TUBB Ellen McDonagh gene: TUBB was added
gene: TUBB was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: TUBB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB were set to 23246003, 27010057
Phenotypes for gene: TUBB were set to Cortical dysplasia, complex, with other brain malformations 6, 615771
Ataxia and cerebellar anomalies - narrow panel v0.5 TUBA1A Ellen McDonagh gene: TUBA1A was added
gene: TUBA1A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TUBA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA1A were set to 17218254, 17584854
Phenotypes for gene: TUBA1A were set to Lissencephaly 3 6,1603
Ataxia and cerebellar anomalies - narrow panel v0.5 TINF2 Ellen McDonagh gene: TINF2 was added
gene: TINF2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TINF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TINF2 were set to 18979121; 18252230
Phenotypes for gene: TINF2 were set to Dyskeratosis congenita, autosomal dominant 3 613990
Ataxia and cerebellar anomalies - narrow panel v0.5 KCND3 Ellen McDonagh gene: KCND3 was added
gene: KCND3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: KCND3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCND3 were set to Spinocerebellarataxia19,607346
Ataxia and cerebellar anomalies - narrow panel v0.5 KCNC3 Ellen McDonagh Added phenotypes Spinocerebellar ataxia 13 for gene: KCNC3
Ataxia and cerebellar anomalies - narrow panel v0.5 KCNC3 Ellen McDonagh gene: KCNC3 was added
gene: KCNC3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: KCNC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCNC3 were set to Spinocerebellar ataxia 13
Ataxia and cerebellar anomalies - narrow panel v0.5 DNMT1 Ellen McDonagh gene: DNMT1 was added
gene: DNMT1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DNMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DNMT1 were set to Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant,
Ataxia and cerebellar anomalies - narrow panel v0.5 DMXL2 Ellen McDonagh gene: DMXL2 was added
gene: DMXL2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: DMXL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DMXL2 were set to 25248098; 22875945; 27657680
Phenotypes for gene: DMXL2 were set to Sensorineural Hearing Loss; ORPHA90636; OMIM:612186
Ataxia and cerebellar anomalies - narrow panel v0.5 CACNA1A Ellen McDonagh gene: CACNA1A was added
gene: CACNA1A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CACNA1A were set to Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Spinocerebellar ataxia 6; Episodic ataxia, type 2
Ataxia and cerebellar anomalies - narrow panel v0.5 ATP1A3 Ellen McDonagh gene: ATP1A3 was added
gene: ATP1A3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ATP1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATP1A3 were set to Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss (CAPOS, #601338); Alternating hemiplegia of childhood 2 (#614820) and Dystonia 12 (#128235)
Ataxia and cerebellar anomalies - narrow panel v0.5 VAMP1 Ellen McDonagh gene: VAMP1 was added
gene: VAMP1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: VAMP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: VAMP1 were set to Spastic ataxia 1, autosomal dominant, 108600
Ataxia and cerebellar anomalies - narrow panel v0.5 UBR4 Ellen McDonagh gene: UBR4 was added
gene: UBR4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: UBR4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UBR4 were set to PMID: 23982692
Phenotypes for gene: UBR4 were set to Episodic ataxia
Ataxia and cerebellar anomalies - narrow panel v0.5 TUBB4A Ellen McDonagh gene: TUBB4A was added
gene: TUBB4A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TUBB4A were set to PMID: 25497598
Phenotypes for gene: TUBB4A were set to Implicated autosomal dominant variants in two families with ataxia; Torsion dystonia 4 (128101) - some individuals with ataxia; hypomyelinating leukodystrophy 6 (612438) - ataxia reported.
Mode of pathogenicity for gene: TUBB4A was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 TTBK2 Ellen McDonagh gene: TTBK2 was added
gene: TTBK2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TTBK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TTBK2 were set to Spinocerebellar ataxia 11
Ataxia and cerebellar anomalies - narrow panel v0.5 TMEM240 Ellen McDonagh gene: TMEM240 was added
gene: TMEM240 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TMEM240 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TMEM240 were set to Spinocerebellar ataxia 21 (#616101)
Ataxia and cerebellar anomalies - narrow panel v0.5 TGM6 Ellen McDonagh gene: TGM6 was added
gene: TGM6 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TGM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TGM6 were set to Spinocerebellar ataxia 35
Ataxia and cerebellar anomalies - narrow panel v0.5 SLC1A3 Ellen McDonagh gene: SLC1A3 was added
gene: SLC1A3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SLC1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SLC1A3 were set to Episodic ataxia, type 6,
Ataxia and cerebellar anomalies - narrow panel v0.5 SCN8A Ellen McDonagh gene: SCN8A was added
gene: SCN8A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SCN8A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SCN8A were set to Cognitive impairment with or without cerebellar ataxia, 614306
Ataxia and cerebellar anomalies - narrow panel v0.5 RNF170 Ellen McDonagh gene: RNF170 was added
gene: RNF170 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: RNF170 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RNF170 were set to Ataxia, sensory, 1, autosomal dominant
Ataxia and cerebellar anomalies - narrow panel v0.5 PRRT2 Ellen McDonagh gene: PRRT2 was added
gene: PRRT2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PRRT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ataxia and cerebellar anomalies - narrow panel v0.5 PRNP Ellen McDonagh gene: PRNP was added
gene: PRNP was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PRNP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PRNP were set to Creutzfeldt-Jakob disease; Autosomal Dominant Ataxia; Gerstmann-Straussler disease; Huntington disease-like 1; Insomnia, fatal familial
Ataxia and cerebellar anomalies - narrow panel v0.5 PRKCG Ellen McDonagh gene: PRKCG was added
gene: PRKCG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PRKCG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PRKCG were set to Spinocerebellar ataxia 14
Ataxia and cerebellar anomalies - narrow panel v0.5 PDYN Ellen McDonagh gene: PDYN was added
gene: PDYN was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PDYN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PDYN were set to Spinocerebellar ataxia 23
Ataxia and cerebellar anomalies - narrow panel v0.5 KCNA1 Ellen McDonagh gene: KCNA1 was added
gene: KCNA1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: KCNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KCNA1 were set to Episodic ataxia/myokymia syndrome,
Ataxia and cerebellar anomalies - narrow panel v0.5 ISCA-37478-Loss Ellen McDonagh Region: ISCA-37478-Loss was added
Region: ISCA-37478-Loss was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for Region: ISCA-37478-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37478-Loss were set to 7611294; 22045295
Phenotypes for Region: ISCA-37478-Loss were set to microcephaly; Developmental delay, muscle weakness; 176270; Angelman syndrome; Prader-Willi syndrome; 105830; Mental retardation
Ataxia and cerebellar anomalies - narrow panel v0.5 ISCA-37478-Gain Ellen McDonagh Region: ISCA-37478-Gain was added
Region: ISCA-37478-Gain was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for Region: ISCA-37478-Gain was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37478-Gain were set to 16840569; 9106540; 18374305
Phenotypes for Region: ISCA-37478-Gain were set to autism, mental retardation, ataxia, seizures, developmental delays, and behavioral problems; hypotonia and motor delays, intellectual disability, autism spectrum disorder (ASD), and epilepsy including infantile spasms, 608636; chromosome 15q11-q13 duplication syndrome
Ataxia and cerebellar anomalies - narrow panel v0.5 ISCA-37404-Loss Ellen McDonagh Region: ISCA-37404-Loss was added
Region: ISCA-37404-Loss was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for Region: ISCA-37404-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37404-Loss were set to 7611294; 22045295
Phenotypes for Region: ISCA-37404-Loss were set to microcephaly; Developmental delay, muscle weakness; 176270; 105831; Angelman syndrome; Prader-Willi syndrome; Mental retardation
Ataxia and cerebellar anomalies - narrow panel v0.5 GFAP Ellen McDonagh gene: GFAP was added
gene: GFAP was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GFAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GFAP were set to Autosomal Dominant Ataxia; Alexander disease
Ataxia and cerebellar anomalies - narrow panel v0.5 FGF14 Ellen McDonagh gene: FGF14 was added
gene: FGF14 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FGF14 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FGF14 were set to Spinocerebellar ataxia 27
Ataxia and cerebellar anomalies - narrow panel v0.5 ELOVL5 Ellen McDonagh gene: ELOVL5 was added
gene: ELOVL5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ELOVL5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ELOVL5 were set to Spinocerebellar ataxia 36 (#615957)
Mode of pathogenicity for gene: ELOVL5 was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 DYNC1H1 Ellen McDonagh gene: DYNC1H1 was added
gene: DYNC1H1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: DYNC1H1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: DYNC1H1 were set to Charcot Marie Tooth, SMA, Intellectual disability
Ataxia and cerebellar anomalies - narrow panel v0.5 CCDC88C Ellen McDonagh gene: CCDC88C was added
gene: CCDC88C was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: CCDC88C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CCDC88C were set to PMID: 25062847
Phenotypes for gene: CCDC88C were set to autosomal dominant spinocerebellar ataxia
Mode of pathogenicity for gene: CCDC88C was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 CAMTA1 Ellen McDonagh gene: CAMTA1 was added
gene: CAMTA1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CAMTA1 were set to Cerebellarataxia,nonprogressive,withmentalretardation,614756 3
Ataxia and cerebellar anomalies - narrow panel v0.5 CACNB4 Ellen McDonagh gene: CACNB4 was added
gene: CACNB4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: CACNB4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNB4 were set to PMC1378014
Phenotypes for gene: CACNB4 were set to Episodic ataxia, type 5; Episodic Ataxia
Ataxia and cerebellar anomalies - narrow panel v0.5 CACNA1G Ellen McDonagh Mode of pathogenicity for gene CACNA1G was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added phenotypes Spinocerebellar ataxia 42 616795 for gene: CACNA1G
Publications for gene CACNA1G were changed from to 25558065; 29878067; 17397049; 28726809
Ataxia and cerebellar anomalies - narrow panel v0.5 CACNA1G Ellen McDonagh gene: CACNA1G was added
gene: CACNA1G was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CACNA1G was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mode of pathogenicity for gene: CACNA1G was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 BEAN1 Ellen McDonagh gene: BEAN1 was added
gene: BEAN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: BEAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BEAN1 were set to 19878914
Phenotypes for gene: BEAN1 were set to Spinocerebellar ataxia 31 117210
Ataxia and cerebellar anomalies - narrow panel v0.5 AARS Ellen McDonagh gene: AARS was added
gene: AARS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: AARS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ataxia and cerebellar anomalies - narrow panel v0.5 MT-ATP6 Ellen McDonagh gene: MT-ATP6 was added
gene: MT-ATP6 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene gene: MT-ATP6 was set to MITOCHONDRIAL
Phenotypes for gene: MT-ATP6 were set to Neuropathy, Ataxia, and Retinitis Pigmentosa
Ataxia and cerebellar anomalies - narrow panel v0.5 TWNK Ellen McDonagh gene: TWNK was added
gene: TWNK was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TWNK was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TWNK were set to Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders (Dominant)
Ataxia and cerebellar anomalies - narrow panel v0.5 SPTBN2 Ellen McDonagh Added phenotypes SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 14; Spinocerebellar Ataxia, Dominant; Spinocerebellar ataxia, autosomal recessive 14; SPINOCEREBELLAR ATAXIA 5 (autosomal dominant); Spinocerebellar ataxia 5 for gene: SPTBN2
Ataxia and cerebellar anomalies - narrow panel v0.5 SPTBN2 Ellen McDonagh gene: SPTBN2 was added
gene: SPTBN2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SPTBN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SPTBN2 were set to Spinocerebellar ataxia 5 (AD); Spinocerebellar ataxia, autosomal recessive 14 (AR)
Ataxia and cerebellar anomalies - narrow panel v0.5 SLC2A1 Ellen McDonagh gene: SLC2A1 was added
gene: SLC2A1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SLC2A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 POLG Ellen McDonagh gene: POLG was added
gene: POLG was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POLG was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: POLG were set to Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE)
Ataxia and cerebellar anomalies - narrow panel v0.5 NAGLU Ellen McDonagh gene: NAGLU was added
gene: NAGLU was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: NAGLU was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NAGLU were set to PMID: 25818867
Phenotypes for gene: NAGLU were set to Sensory neuropathy turning into a mild sensory ataxia (AD). Also Sanfilippo syndrome B (AR) (OMIM #252920)
Mode of pathogenicity for gene: NAGLU was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 CLCN2 Ellen McDonagh gene: CLCN2 was added
gene: CLCN2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CLCN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CLCN2 were set to 19191339; 23707145
Phenotypes for gene: CLCN2 were set to {Epilepsy, juvenile absence, susceptibility to, 2}, 607628; {Epilepsy, idiopathic generalized, susceptibility to, 11}, 607628; {Epilepsy, juvenile myoclonic, susceptibility to, 8}, 607628; Leukoencephalopathy with ataxia, 615651
Ataxia and cerebellar anomalies - narrow panel v0.5 AFG3L2 Ellen McDonagh gene: AFG3L2 was added
gene: AFG3L2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: AFG3L2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: AFG3L2 were set to Spinocerebellar ataxia 28; Spinocerebellar Ataxia, Dominant; Ataxia, spastic, 5, autosomal recessive
Mode of pathogenicity for gene: AFG3L2 was set to Other - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v0.5 SNX14 Ellen McDonagh Added phenotypes Spinocerebellar ataxia, autosomal recessive 20, 616354 for gene: SNX14
Publications for gene SNX14 were changed from to 25439728
Ataxia and cerebellar anomalies - narrow panel v0.5 SNX14 Ellen McDonagh gene: SNX14 was added
gene: SNX14 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SNX14 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: SNX14 were set to Autosomal recessive spinocerebellar ataxia (#616354)
Ataxia and cerebellar anomalies - narrow panel v0.5 ITPR1 Ellen McDonagh Mode of pathogenicity for gene ITPR1 was changed from to Other - please provide details in the comments
Added phenotypes Spinocerebellar ataxia 29; Spinocerebellar ataxia 15 for gene: ITPR1
Ataxia and cerebellar anomalies - narrow panel v0.5 ITPR1 Ellen McDonagh gene: ITPR1 was added
gene: ITPR1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ITPR1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: ITPR1 were set to Gillespie syndrome 206700; Spinocerebellar ataxia 15; Spinocerebellar ataxia 29, congenital nonprogressive
Ataxia and cerebellar anomalies - narrow panel v0.5 ZNF592 Ellen McDonagh gene: ZNF592 was added
gene: ZNF592 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ZNF592 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZNF592 were set to Spinocerebellar ataxia, autosomal recessive 5
Ataxia and cerebellar anomalies - narrow panel v0.5 ZFYVE26 Ellen McDonagh gene: ZFYVE26 was added
gene: ZFYVE26 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFYVE26 were set to PMID:25497598; 25842392
Phenotypes for gene: ZFYVE26 were set to Autosomal recessive spastic paraplegia 15 (#270700) complex form of the disease including ataxia. Pyle et al. (2015), Brain, 138, pp.276-283. Implicated in undiagnosed ataxia.
Ataxia and cerebellar anomalies - narrow panel v0.5 XRCC1 Ellen McDonagh gene: XRCC1 was added
gene: XRCC1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: XRCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XRCC1 were set to 28002403
Phenotypes for gene: XRCC1 were set to ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia
Ataxia and cerebellar anomalies - narrow panel v0.5 WWOX Ellen McDonagh gene: WWOX was added
gene: WWOX was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: WWOX was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WWOX were set to Autosomal recessive spinocerebellar ataxia 12 (#614322)
Ataxia and cerebellar anomalies - narrow panel v0.5 WFS1 Ellen McDonagh gene: WFS1 was added
gene: WFS1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: WFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 WDR81 Ellen McDonagh Added phenotypes Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2, 610185 for gene: WDR81
Publications for gene WDR81 were changed from to 21885617
Ataxia and cerebellar anomalies - narrow panel v0.5 WDR81 Ellen McDonagh gene: WDR81 was added
gene: WDR81 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: WDR81 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR81 were set to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2
Ataxia and cerebellar anomalies - narrow panel v0.5 WDR73 Ellen McDonagh gene: WDR73 was added
gene: WDR73 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: WDR73 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR73 were set to Galloway Mowat syndrome, when patients are ambulant ataxia is a recognisednfeature
Ataxia and cerebellar anomalies - narrow panel v0.5 VRK1 Ellen McDonagh Added phenotypes Pontocerebellar hypoplasia 1A (#607596) for gene: VRK1
Ataxia and cerebellar anomalies - narrow panel v0.5 VRK1 Ellen McDonagh gene: VRK1 was added
gene: VRK1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: VRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VRK1 were set to PMID: 21937992; PMID: 19646678; 24126608
Phenotypes for gene: VRK1 were set to Pontocerebellar Hypoplasia; Pontocerebellar Hypoplasia with anterior horn cell disease; Pontocerebellar hypoplasia type 1A,607596; Pontocerebellar Hypoplasia with infantile SMA; Pontocerebellar Hypoplasia type 1A
Ataxia and cerebellar anomalies - narrow panel v0.5 VPS53 Ellen McDonagh Added phenotypes Pontocerebellar hypoplasia 2E (#615851) for gene: VPS53
Publications for gene VPS53 were changed from PMID: 24577744 to 24577744
Ataxia and cerebellar anomalies - narrow panel v0.5 VPS53 Ellen McDonagh gene: VPS53 was added
gene: VPS53 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: VPS53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS53 were set to PMID: 24577744
Phenotypes for gene: VPS53 were set to Pontocerebellar Hypoplasia; Pontocerebellar Hypoplasia type 2E
Ataxia and cerebellar anomalies - narrow panel v0.5 VPS13D Ellen McDonagh gene: VPS13D was added
gene: VPS13D was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: VPS13D was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS13D were set to spastic ataxia
Ataxia and cerebellar anomalies - narrow panel v0.5 VLDLR Ellen McDonagh Added phenotypes Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, 224050; Cerebellar Hypoplasia for gene: VLDLR
Publications for gene VLDLR were changed from to 18364738; 16080122
Ataxia and cerebellar anomalies - narrow panel v0.5 VLDLR Ellen McDonagh gene: VLDLR was added
gene: VLDLR was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: VLDLR was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 UCHL1 Ellen McDonagh gene: UCHL1 was added
gene: UCHL1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: UCHL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UCHL1 were set to PMID: 23359680
Phenotypes for gene: UCHL1 were set to Early onset ataxia and optic neuropathy
Ataxia and cerebellar anomalies - narrow panel v0.5 TUBA8 Ellen McDonagh gene: TUBA8 was added
gene: TUBA8 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: TUBA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBA8 were set to 19896110, 27781032
Phenotypes for gene: TUBA8 were set to Polymicrogyria with optic nerve hypoplasia, 613180
Ataxia and cerebellar anomalies - narrow panel v0.5 TTPA Ellen McDonagh gene: TTPA was added
gene: TTPA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TTPA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTPA were set to Ataxia with isolated vitamin E deficiency; Ataxia with Vitamin E Deficiency
Ataxia and cerebellar anomalies - narrow panel v0.5 TTC19 Ellen McDonagh gene: TTC19 was added
gene: TTC19 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TTC19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC19 were set to Nuclear type mitochondrial complex III deficiency (#615157)
Ataxia and cerebellar anomalies - narrow panel v0.5 TSEN54 Ellen McDonagh Added phenotypes Pontocerebellar hypoplasia 2A (#277470) and 4 (#225753) for gene: TSEN54
Ataxia and cerebellar anomalies - narrow panel v0.5 TSEN54 Ellen McDonagh gene: TSEN54 was added
gene: TSEN54 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TSEN54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN54 were set to PMID: 20956791; PMID: 18711368; PMID: 20952379; PMID: 21368912
Phenotypes for gene: TSEN54 were set to Pontocerebellar Hypoplasia type 2A; Pontocerebellar hypoplasia type 2A, 277470; Pontocerebellar Hypoplasia type 4; Pontocerebellar hypoplasia type 4, 225753; Pontocerebellar Hypoplasia; Pontocerebellar Hypoplasia type 5
Ataxia and cerebellar anomalies - narrow panel v0.5 TSEN34 Ellen McDonagh Added phenotypes Pontocerebellar hypoplasia 2C (612390) for gene: TSEN34
Ataxia and cerebellar anomalies - narrow panel v0.5 TSEN34 Ellen McDonagh gene: TSEN34 was added
gene: TSEN34 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TSEN34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN34 were set to PMID: 18711368
Phenotypes for gene: TSEN34 were set to Pontocerebellar hypoplasia type 2C,612390; Pontocerebellar Hypoplasia type 2C; Pontocerebellar Hypoplasia
Ataxia and cerebellar anomalies - narrow panel v0.5 TSEN2 Ellen McDonagh Added phenotypes Pontocerebellar Hypoplasia; Pontocerebellar Hypoplasia type 2B; Pontocerebellar hypoplasia type 2B,612389 for gene: TSEN2
Publications for gene TSEN2 were changed from to PMID: 18711368; PMID: 23562994; PMID: 20952379
Ataxia and cerebellar anomalies - narrow panel v0.5 TSEN2 Ellen McDonagh gene: TSEN2 was added
gene: TSEN2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TSEN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSEN2 were set to Pontocerebellar hypoplasia 2B (612389)
Ataxia and cerebellar anomalies - narrow panel v0.5 TSEN15 Ellen McDonagh gene: TSEN15 was added
gene: TSEN15 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: TSEN15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN15 were set to 27392077
Phenotypes for gene: TSEN15 were set to Pontocerebellar hypoplasia, type 2F 617026
Ataxia and cerebellar anomalies - narrow panel v0.5 TPP1 Ellen McDonagh gene: TPP1 was added
gene: TPP1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPP1 were set to Autosomal recessive spinocerebellar ataxia 7 (#607998); Neuronal ceroid lipfuscinosis 7 (204500)
Ataxia and cerebellar anomalies - narrow panel v0.5 TOE1 Ellen McDonagh gene: TOE1 was added
gene: TOE1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TOE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOE1 were set to 28092684
Phenotypes for gene: TOE1 were set to Pontocerebellar hypoplasia, type 7 614969
Ataxia and cerebellar anomalies - narrow panel v0.5 TMEM5 Ellen McDonagh gene: TMEM5 was added
gene: TMEM5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TMEM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM5 were set to 23217329
Phenotypes for gene: TMEM5 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Ataxia and cerebellar anomalies - narrow panel v0.5 TERT Ellen McDonagh gene: TERT was added
gene: TERT was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: TERT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TERT were set to 17785587; 16247010
Phenotypes for gene: TERT were set to dyskeratosis congenita-2
Ataxia and cerebellar anomalies - narrow panel v0.5 TDP1 Ellen McDonagh gene: TDP1 was added
gene: TDP1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: TDP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TDP1 were set to Spinocerebellar ataxia, autosomal recessive with axonal neuropathy
Ataxia and cerebellar anomalies - narrow panel v0.5 SYT14 Ellen McDonagh gene: SYT14 was added
gene: SYT14 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SYT14 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SYT14 were set to Spinocerebellarataxia,autosomalrecessive11,614229
Ataxia and cerebellar anomalies - narrow panel v0.5 SYNE1 Ellen McDonagh gene: SYNE1 was added
gene: SYNE1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SYNE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SYNE1 were set to Cerebellar Ataxia; Spinocerebellar ataxia, autosomal recessive 8
Ataxia and cerebellar anomalies - narrow panel v0.5 STUB1 Ellen McDonagh Added phenotypes Spinocerebellar ataxia, autosomal recessive 16 615768 for gene: STUB1
Publications for gene STUB1 were changed from to 24312598
Ataxia and cerebellar anomalies - narrow panel v0.5 STUB1 Ellen McDonagh gene: STUB1 was added
gene: STUB1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: STUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STUB1 were set to Spinocerebellar ataxia, autosomal recessive 16
Ataxia and cerebellar anomalies - narrow panel v0.5 SRD5A3 Ellen McDonagh gene: SRD5A3 was added
gene: SRD5A3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SRD5A3 was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 SPG7 Ellen McDonagh gene: SPG7 was added
gene: SPG7 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SPG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG7 were set to PMID: 25681447
Phenotypes for gene: SPG7 were set to Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia
Ataxia and cerebellar anomalies - narrow panel v0.5 SMPD4 Ellen McDonagh gene: SMPD4 was added
gene: SMPD4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: SMPD4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMPD4 were set to cerebellar hypoplasia, hypomyelination, microcephaly, arthrogryposis, diabetes
Ataxia and cerebellar anomalies - narrow panel v0.5 SIL1 Ellen McDonagh gene: SIL1 was added
gene: SIL1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SIL1 was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 SETX Ellen McDonagh gene: SETX was added
gene: SETX was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SETX was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SETX were set to Ataxia-ocular apraxia-2; ataxia with oculomotor apraxia type 2 (AOA2), juvenile amyotrophic lateral sclerosis (ALS4) and autosomal dominant ataxia
Ataxia and cerebellar anomalies - narrow panel v0.5 SEPSECS Ellen McDonagh Added phenotypes Pontocerebellar hypoplasia type 2D (613811) for gene: SEPSECS
Ataxia and cerebellar anomalies - narrow panel v0.5 SEPSECS Ellen McDonagh gene: SEPSECS was added
gene: SEPSECS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SEPSECS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEPSECS were set to PMID: 12920088; PMID: 20920667
Phenotypes for gene: SEPSECS were set to Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia type 2D, 613811; Pontocerebellar Hypoplasia type 2D
Ataxia and cerebellar anomalies - narrow panel v0.5 SACS Ellen McDonagh gene: SACS was added
gene: SACS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type
Ataxia and cerebellar anomalies - narrow panel v0.5 RUBCN Ellen McDonagh gene: RUBCN was added
gene: RUBCN was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: RUBCN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RUBCN were set to PMID: 20826435
Ataxia and cerebellar anomalies - narrow panel v0.5 RNF216 Ellen McDonagh gene: RNF216 was added
gene: RNF216 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: RNF216 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RNF216 were set to Cerebellar ataxia and hypogonadotropic hypogonadism, 212840
Ataxia and cerebellar anomalies - narrow panel v0.5 RELN Ellen McDonagh gene: RELN was added
gene: RELN was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: RELN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RELN were set to 10973257
Phenotypes for gene: RELN were set to Lissencephaly 2, 257320
Ataxia and cerebellar anomalies - narrow panel v0.5 RARS2 Ellen McDonagh Added phenotypes epilepsy; Pontocerebellar hypoplasia for gene: RARS2
Ataxia and cerebellar anomalies - narrow panel v0.5 RARS2 Ellen McDonagh gene: RARS2 was added
gene: RARS2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: RARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RARS2 were set to PMID: 25809939; PMID: 17847012; PMID: 20635367
Phenotypes for gene: RARS2 were set to Pontocerebellar hypoplasia, type 6, 611523; Pontocerebellar Hypoplasia; Pontocerebellar Hypoplasia type 6
Ataxia and cerebellar anomalies - narrow panel v0.5 PTF1A Ellen McDonagh gene: PTF1A was added
gene: PTF1A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PTF1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTF1A were set to 15543146
Phenotypes for gene: PTF1A were set to Pancreatic and cerebellar agenesis, 609069
Ataxia and cerebellar anomalies - narrow panel v0.5 PRICKLE1 Ellen McDonagh gene: PRICKLE1 was added
gene: PRICKLE1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: PRICKLE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PRICKLE1 were set to Progressive Myoclonus Epilepsy with Ataxia
Ataxia and cerebellar anomalies - narrow panel v0.5 POMT2 Ellen McDonagh gene: POMT2 was added
gene: POMT2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMT2 were set to 15894594
Phenotypes for gene: POMT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Ataxia and cerebellar anomalies - narrow panel v0.5 POMT1 Ellen McDonagh gene: POMT1 was added
gene: POMT1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMT1 were set to 12369018
Phenotypes for gene: POMT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670
Ataxia and cerebellar anomalies - narrow panel v0.5 POMK Ellen McDonagh gene: POMK was added
gene: POMK was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: POMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMK were set to 24925318
Phenotypes for gene: POMK were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 615249
Ataxia and cerebellar anomalies - narrow panel v0.5 POMGNT2 Ellen McDonagh gene: POMGNT2 was added
gene: POMGNT2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POMGNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMGNT2 were set to 22958903
Phenotypes for gene: POMGNT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies type
Ataxia and cerebellar anomalies - narrow panel v0.5 POMGNT1 Ellen McDonagh gene: POMGNT1 was added
gene: POMGNT1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POMGNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMGNT1 were set to 11709191, 15236414
Phenotypes for gene: POMGNT1 were set to Congenital Muscular Dystrophy, alpha-dystroglycan related; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Ataxia and cerebellar anomalies - narrow panel v0.5 POLR3A Ellen McDonagh gene: POLR3A was added
gene: POLR3A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to 25655951; 21855841
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism; Autosomal Recessive Ataxia
Ataxia and cerebellar anomalies - narrow panel v0.5 PNPLA6 Ellen McDonagh gene: PNPLA6 was added
gene: PNPLA6 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PNPLA6 were set to Spinocerebellar ataxia, hypogonadotropic hypogonadism and chorioretinal dystrophy (Boucher-Neuhauser syndrome, #215470); Oliver-McFarlane syndrome (#603197); Autosomal recessive spastic paraplegia 39 (#612020), ataxia seen in some patients
Ataxia and cerebellar anomalies - narrow panel v0.5 PNKP Ellen McDonagh gene: PNKP was added
gene: PNKP was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PNKP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PNKP were set to Ataxia with oculomotor apraxia 4 (#616267)
Ataxia and cerebellar anomalies - narrow panel v0.5 PMPCA Ellen McDonagh Source Expert Review Red was added to PMPCA.
Added phenotypes Spinocerebellar ataxia, autosomal recessive 2 213200 AR for gene: PMPCA
Publications for gene PMPCA were changed from PMID:25808372 to PubMed: 10528257, 25808372
Rating Changed from Green List (high evidence) to Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v0.5 PMPCA Ellen McDonagh gene: PMPCA was added
gene: PMPCA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PMPCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMPCA were set to PMID:25808372
Phenotypes for gene: PMPCA were set to Non-progressive cerebellar ataxia recessive variants identified in 17 patients from four different families.
Ataxia and cerebellar anomalies - narrow panel v0.5 PLA2G6 Ellen McDonagh gene: PLA2G6 was added
gene: PLA2G6 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PLA2G6 were set to Infantile neuroaxonal dystrophy 1 (#256600); Parkinson disease 14 (#612953); Neurodegeneration with brain iron accumulation 2B (#610217)
Ataxia and cerebellar anomalies - narrow panel v0.5 PIK3R5 Ellen McDonagh gene: PIK3R5 was added
gene: PIK3R5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: PIK3R5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIK3R5 were set to Ataxia-oculomotor apraxia 3
Ataxia and cerebellar anomalies - narrow panel v0.5 PI4KA Ellen McDonagh gene: PI4KA was added
gene: PI4KA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: PI4KA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4KA were set to 25855803
Phenotypes for gene: PI4KA were set to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis , 616531
Ataxia and cerebellar anomalies - narrow panel v0.5 PHGDH Ellen McDonagh gene: PHGDH was added
gene: PHGDH was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: PHGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHGDH were set to 24836451
Phenotypes for gene: PHGDH were set to Neu-Laxova syndrome 1, 256520
Ataxia and cerebellar anomalies - narrow panel v0.5 PEX16 Ellen McDonagh gene: PEX16 was added
gene: PEX16 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX16 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX16 were set to Zellweger syndrome (614876); Peroxisome biogenesis disorder 8B (#614877) infantile progressive ataxia and spastic paresis
Ataxia and cerebellar anomalies - narrow panel v0.5 PCLO Ellen McDonagh Added phenotypes Pontocerebellar Hypoplasia type 3 for gene: PCLO
Ataxia and cerebellar anomalies - narrow panel v0.5 PCLO Ellen McDonagh gene: PCLO was added
gene: PCLO was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: PCLO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCLO were set to PMID: 25832664
Phenotypes for gene: PCLO were set to Pontocerebellar hypoplasia 3 homozygous non-sense variant identified in the affected individuals of a single pedigree.
Ataxia and cerebellar anomalies - narrow panel v0.5 PAX6 Ellen McDonagh gene: PAX6 was added
gene: PAX6 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PAX6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PAX6 were set to Aniridia, Cerebellar Ataxia, And Mental Retardation
Ataxia and cerebellar anomalies - narrow panel v0.5 OPA3 Ellen McDonagh gene: OPA3 was added
gene: OPA3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: OPA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OPA3 were set to 25201222; 25657044; 11668429; 20301646; 24944951
Phenotypes for gene: OPA3 were set to Costeff syndrome; 3-methylglutaconic aciduria, type III, 258501
Ataxia and cerebellar anomalies - narrow panel v0.5 NPC2 Ellen McDonagh gene: NPC2 was added
gene: NPC2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPC2 were set to Niemann-Pick disease type C2 (#607625)
Ataxia and cerebellar anomalies - narrow panel v0.5 NPC1 Ellen McDonagh gene: NPC1 was added
gene: NPC1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPC1 were set to Niemann-Pick disease types C1 and D (#257220)
Ataxia and cerebellar anomalies - narrow panel v0.5 MVK Ellen McDonagh gene: MVK was added
gene: MVK was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: MVK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MVK were set to 24896178; 26503795
Phenotypes for gene: MVK were set to Mevalonic aciduria 610377
Ataxia and cerebellar anomalies - narrow panel v0.5 MTTP Ellen McDonagh gene: MTTP was added
gene: MTTP was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: MTTP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTTP were set to Abetalipoproteinemia, 200100
Ataxia and cerebellar anomalies - narrow panel v0.5 MTPAP Ellen McDonagh gene: MTPAP was added
gene: MTPAP was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: MTPAP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTPAP were set to Ataxia, spastic, 4,
Ataxia and cerebellar anomalies - narrow panel v0.5 MRE11 Ellen McDonagh gene: MRE11 was added
gene: MRE11 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: MRE11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MRE11 were set to Ataxia-telangiectasia-like disorder; Ataxia-Telangiectasia-Like Disorder
Ataxia and cerebellar anomalies - narrow panel v0.5 MMACHC Ellen McDonagh gene: MMACHC was added
gene: MMACHC was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to PMID: 26283149
Phenotypes for gene: MMACHC were set to Ataxia and hypogonadism (AR), Also Methylmalonic aciduria and homocystinuria (AR) (OMIM #277400)
Ataxia and cerebellar anomalies - narrow panel v0.5 MARS2 Ellen McDonagh gene: MARS2 was added
gene: MARS2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: MARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS2 were set to PubMed: 22448145
Phenotypes for gene: MARS2 were set to Spastic ataxia 3, autosomal recessive
Ataxia and cerebellar anomalies - narrow panel v0.5 LARGE1 Ellen McDonagh gene: LARGE1 was added
gene: LARGE1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: LARGE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARGE1 were set to 17436019, 24709677
Phenotypes for gene: LARGE1 were set to Congenital Muscular Dystrophy, alpha-dystroglycan related; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Ataxia and cerebellar anomalies - narrow panel v0.5 KIF1C Ellen McDonagh gene: KIF1C was added
gene: KIF1C was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: KIF1C was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KIF1C were set to Spastic ataxia 2,autosomal recessive
Ataxia and cerebellar anomalies - narrow panel v0.5 KCNJ10 Ellen McDonagh gene: KCNJ10 was added
gene: KCNJ10 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: KCNJ10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KCNJ10 were set to Seizures, Sensorineural Deafness, Ataxia, Mental Retardation, and Electrolyte Imbalance Syndrome
Ataxia and cerebellar anomalies - narrow panel v0.5 ISPD Ellen McDonagh gene: ISPD was added
gene: ISPD was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ISPD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISPD were set to 22522420
Phenotypes for gene: ISPD were set to Congenital Muscular Dystrophy, alpha-dystroglycan related; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Ataxia and cerebellar anomalies - narrow panel v0.5 HEXB Ellen McDonagh gene: HEXB was added
gene: HEXB was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: HEXB was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 HEXA Ellen McDonagh gene: HEXA was added
gene: HEXA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 GRM1 Ellen McDonagh gene: GRM1 was added
gene: GRM1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GRM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GRM1 were set to Spinocerebellar ataxia, autosomal recessive 13
Ataxia and cerebellar anomalies - narrow panel v0.5 GRID2 Ellen McDonagh gene: GRID2 was added
gene: GRID2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GRID2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRID2 were set to PMID: 25841024
Phenotypes for gene: GRID2 were set to Rare cases of autosomal dominant inheritance reported by Coutelier et al., 2015.; Autosomal recessive spinocerebellar ataxia 18 (#616204)
Ataxia and cerebellar anomalies - narrow panel v0.5 GPAA1 Ellen McDonagh gene: GPAA1 was added
gene: GPAA1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GPAA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPAA1 were set to 29100095; 24896178
Phenotypes for gene: GPAA1 were set to Glycosylphosphatidylinositol biosynthesis defect 15, 617810
Ataxia and cerebellar anomalies - narrow panel v0.5 GOSR2 Ellen McDonagh gene: GOSR2 was added
gene: GOSR2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GOSR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOSR2 were set to 24285620; 21549339; 20301317
Phenotypes for gene: GOSR2 were set to Epilepsy, progressive myoclonic 6, 614018
Ataxia and cerebellar anomalies - narrow panel v0.5 GMPPB Ellen McDonagh gene: GMPPB was added
gene: GMPPB was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GMPPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMPPB were set to 23768512
Phenotypes for gene: GMPPB were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Ataxia and cerebellar anomalies - narrow panel v0.5 GJC2 Ellen McDonagh gene: GJC2 was added
gene: GJC2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GJC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GJC2 were set to Leukodystrophy, hypomyelinating, 2; Autosomal Recessive Ataxia
Ataxia and cerebellar anomalies - narrow panel v0.5 GBA2 Ellen McDonagh gene: GBA2 was added
gene: GBA2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GBA2 was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 FXN Ellen McDonagh gene: FXN was added
gene: FXN was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FXN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FXN were set to Friedreichataxia,229300Friedreichataxiawithretainedreflexes,229300
Ataxia and cerebellar anomalies - narrow panel v0.5 FRMD4A Ellen McDonagh gene: FRMD4A was added
gene: FRMD4A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: FRMD4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRMD4A were set to 25388005
Phenotypes for gene: FRMD4A were set to Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia, 616819
Ataxia and cerebellar anomalies - narrow panel v0.5 FOLR1 Ellen McDonagh gene: FOLR1 was added
gene: FOLR1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FOLR1 was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 FLVCR1 Ellen McDonagh gene: FLVCR1 was added
gene: FLVCR1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FLVCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FLVCR1 were set to Posterior Column Ataxia with Retinitis Pigmentosa; Ataxia, posterior column, with retinitis pigmentosa,
Ataxia and cerebellar anomalies - narrow panel v0.5 FKTN Ellen McDonagh gene: FKTN was added
gene: FKTN was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FKTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKTN were set to 9690476; 10545611
Phenotypes for gene: FKTN were set to Fukuyama Congenital Muscular Dystrophy; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type; Fukuyama congenital muscular dystrophy
Ataxia and cerebellar anomalies - narrow panel v0.5 FKRP Ellen McDonagh gene: FKRP was added
gene: FKRP was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FKRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKRP were set to 15121789
Phenotypes for gene: FKRP were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Ataxia and cerebellar anomalies - narrow panel v0.5 EXOSC3 Ellen McDonagh Added phenotypes Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia, type 1B, 614678; Pontocerebellar Hypoplasia type 1B for gene: EXOSC3
Publications for gene EXOSC3 were changed from to PMID: 24524299; PMID: 23284067; PMID: 22544365; PMID: 23564332
Ataxia and cerebellar anomalies - narrow panel v0.5 EXOSC3 Ellen McDonagh gene: EXOSC3 was added
gene: EXOSC3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EXOSC3 was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 EIF2B5 Ellen McDonagh gene: EIF2B5 was added
gene: EIF2B5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EIF2B5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B5 were set to Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease
Ataxia and cerebellar anomalies - narrow panel v0.5 EIF2B4 Ellen McDonagh gene: EIF2B4 was added
gene: EIF2B4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EIF2B4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B4 were set to Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease
Ataxia and cerebellar anomalies - narrow panel v0.5 EIF2B3 Ellen McDonagh gene: EIF2B3 was added
gene: EIF2B3 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EIF2B3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B3 were set to Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease
Ataxia and cerebellar anomalies - narrow panel v0.5 EIF2B2 Ellen McDonagh gene: EIF2B2 was added
gene: EIF2B2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EIF2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B2 were set to Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease
Ataxia and cerebellar anomalies - narrow panel v0.5 EIF2B1 Ellen McDonagh gene: EIF2B1 was added
gene: EIF2B1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EIF2B1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B1 were set to Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease; Childhood Ataxia with Central Nervous System Hypomyelination/Vanishing White Matter
Ataxia and cerebellar anomalies - narrow panel v0.5 DDHD2 Ellen McDonagh gene: DDHD2 was added
gene: DDHD2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DDHD2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DDHD2 were set to Autosomal recessive paraplegia 54 (#615033). Complex form of disease ataxia reported amongst the phenotypic features in Citterio et al. (2014), Journal of Neurology, 261, pp.373-381 and Doi et al. (2014), Scientific Reports, 4, 7132.
Ataxia and cerebellar anomalies - narrow panel v0.5 DCC Ellen McDonagh gene: DCC was added
gene: DCC was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: DCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCC were set to 28250456
Phenotypes for gene: DCC were set to Gaze palsy, familial horizontal, with progressive scoliosis 2, 617542
Ataxia and cerebellar anomalies - narrow panel v0.5 DARS2 Ellen McDonagh gene: DARS2 was added
gene: DARS2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 CYP2U1 Ellen McDonagh gene: CYP2U1 was added
gene: CYP2U1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CYP2U1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP2U1 were set to Autosomal recessive spastic paraplegia 56 (#615030) complex form of disorder, ataxia not yet identified in affected patients.
Ataxia and cerebellar anomalies - narrow panel v0.5 CYP27A1 Ellen McDonagh gene: CYP27A1 was added
gene: CYP27A1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 CWF19L1 Ellen McDonagh gene: CWF19L1 was added
gene: CWF19L1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CWF19L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CWF19L1 were set to 26197978, 25361784, 27016154
Phenotypes for gene: CWF19L1 were set to Spinocerebellar ataxia, autosomal recessive 17, 616127
Ataxia and cerebellar anomalies - narrow panel v0.5 CSTB Ellen McDonagh gene: CSTB was added
gene: CSTB was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: CSTB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CSTB were set to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800
Ataxia and cerebellar anomalies - narrow panel v0.5 CP Ellen McDonagh gene: CP was added
gene: CP was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CP were set to Cerebellar ataxia,
Ataxia and cerebellar anomalies - narrow panel v0.5 COX20 Ellen McDonagh gene: COX20 was added
gene: COX20 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: COX20 was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.5 COQ8A Ellen McDonagh gene: COQ8A was added
gene: COQ8A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, Spinocerebellar Ataxia Type
Ataxia and cerebellar anomalies - narrow panel v0.5 COASY Ellen McDonagh gene: COASY was added
gene: COASY was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 24360804; 30089828
Phenotypes for gene: COASY were set to Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis
Ataxia and cerebellar anomalies - narrow panel v0.5 CLP1 Ellen McDonagh Source Expert Review Red was added to CLP1.
Added phenotypes Pontocerebellar hypoplasia 10 (#615803) for gene: CLP1
Rating Changed from Green List (high evidence) to Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v0.5 CLP1 Ellen McDonagh gene: CLP1 was added
gene: CLP1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CLP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLP1 were set to PMID: 24766810
Phenotypes for gene: CLP1 were set to Pontocerebellar Hypoplasia; Pontocerebellar Hypoplasia type 10
Ataxia and cerebellar anomalies - narrow panel v0.5 CLN6 Ellen McDonagh gene: CLN6 was added
gene: CLN6 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CLN6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLN6 were set to Neuronal ceroid lipofuscinosis 6 (#601780) and adult onset form (#204300)
Ataxia and cerebellar anomalies - narrow panel v0.5 CHMP1A Ellen McDonagh Added phenotypes Pontocerebellar Hypoplasia; Pontocerebellar Hypoplasia type 8; Pontocerebellar hypoplasia,type 8,614961 for gene: CHMP1A
Publications for gene CHMP1A were changed from to PMID: 23023333
Ataxia and cerebellar anomalies - narrow panel v0.5 CHMP1A Ellen McDonagh gene: CHMP1A was added
gene: CHMP1A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CHMP1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHMP1A were set to Pontocerebellar hypoplasia 8 (#614961)
Ataxia and cerebellar anomalies - narrow panel v0.5 CDK5 Ellen McDonagh gene: CDK5 was added
gene: CDK5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: CDK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5 were set to 25560765, 15067135
Phenotypes for gene: CDK5 were set to Lissencephaly 7 with cerebellar hypoplasia 616342
Ataxia and cerebellar anomalies - narrow panel v0.5 CA8 Ellen McDonagh Added phenotypes Cerebellar ataxia and mental retardation with or without quadrupedal locomotion 3 613227 for gene: CA8
Publications for gene CA8 were changed from to 21885617
Ataxia and cerebellar anomalies - narrow panel v0.5 CA8 Ellen McDonagh gene: CA8 was added
gene: CA8 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CA8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CA8 were set to Cerebellar ataxia and mental retardation with or without quadrupedal locomotion 3
Ataxia and cerebellar anomalies - narrow panel v0.5 BRF1 Ellen McDonagh gene: BRF1 was added
gene: BRF1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: BRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRF1 were set to 25561519
Phenotypes for gene: BRF1 were set to Cerebellofaciodental syndrome 616202
Ataxia and cerebellar anomalies - narrow panel v0.5 B4GAT1 Ellen McDonagh gene: B4GAT1 was added
gene: B4GAT1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: B4GAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GAT1 were set to 23359570
Phenotypes for gene: B4GAT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13, 615287; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), typeA, 13, 615287
Ataxia and cerebellar anomalies - narrow panel v0.5 B3GALNT2 Ellen McDonagh gene: B3GALNT2 was added
gene: B3GALNT2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: B3GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GALNT2 were set to 23453667
Phenotypes for gene: B3GALNT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies typeA 11; congenital muscular dystrophies
Ataxia and cerebellar anomalies - narrow panel v0.5 ATP8A2 Ellen McDonagh Publications for gene ATP8A2 were changed from 22892528 to PMID: 22892528
Ataxia and cerebellar anomalies - narrow panel v0.5 ATP8A2 Ellen McDonagh gene: ATP8A2 was added
gene: ATP8A2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: ATP8A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP8A2 were set to 22892528
Phenotypes for gene: ATP8A2 were set to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 615268
Ataxia and cerebellar anomalies - narrow panel v0.5 ATM Ellen McDonagh gene: ATM was added
gene: ATM was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATM were set to Ataxia-telangiectasia,; Ataxia-Telangiectasia
Ataxia and cerebellar anomalies - narrow panel v0.5 ATCAY Ellen McDonagh gene: ATCAY was added
gene: ATCAY was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ATCAY was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATCAY were set to Ataxia, cerebellar, Cayman type; Cerebellar Ataxia, Cayman type
Ataxia and cerebellar anomalies - narrow panel v0.5 ARSA Ellen McDonagh gene: ARSA was added
gene: ARSA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ARSA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARSA were set to Metachromatic leukodystrophy (#250100)
Ataxia and cerebellar anomalies - narrow panel v0.5 APTX Ellen McDonagh gene: APTX was added
gene: APTX was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: APTX was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: APTX were set to Ataxia with Oculomotor Apraxia; Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
Ataxia and cerebellar anomalies - narrow panel v0.5 ANO10 Ellen McDonagh gene: ANO10 was added
gene: ANO10 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ANO10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ANO10 were set to Spinocerebellar ataxia, autosomal recessive 10,
Ataxia and cerebellar anomalies - narrow panel v0.5 AMPD2 Ellen McDonagh Added phenotypes Spastic paraplegia homozygous frameshift reported in single family (Novarino et al, 2014).; Pontocerebellar hypoplasia 9 (#615809) for gene: AMPD2
Publications for gene AMPD2 were changed from Akizu, N., Cantagrel, V., Schroth, J., Cai, N., Vaux, K., McCloskey, D., Naviaux, R. K., Van Vleet, J., Fenstermaker, A. G., Silhavy, J. L., Scheliga, J. S., Toyama, K., and 16 others. AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder. Cell 154: 505-517, 2013. http://www.omim.org/clinicalSynopsis/615809; 27066553; 23911318 to PMID: 24482476
Ataxia and cerebellar anomalies - narrow panel v0.5 AMPD2 Ellen McDonagh gene: AMPD2 was added
gene: AMPD2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: AMPD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMPD2 were set to Akizu, N., Cantagrel, V., Schroth, J., Cai, N., Vaux, K., McCloskey, D., Naviaux, R. K., Van Vleet, J., Fenstermaker, A. G., Silhavy, J. L., Scheliga, J. S., Toyama, K., and 16 others. AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder. Cell 154: 505-517, 2013. http://www.omim.org/clinicalSynopsis/615809; 27066553; 23911318
Phenotypes for gene: AMPD2 were set to pontocerebellar hypoplasia type 9, 615809
Ataxia and cerebellar anomalies - narrow panel v0.5 ADGRG1 Ellen McDonagh gene: ADGRG1 was added
gene: ADGRG1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ADGRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADGRG1 were set to 15044805
Phenotypes for gene: ADGRG1 were set to Polymicrogyria, bilateral frontoparietal 606854
Ataxia and cerebellar anomalies - narrow panel v0.5 ABHD12 Ellen McDonagh gene: ABHD12 was added
gene: ABHD12 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ABHD12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ABHD12 were set to Polyneuropathy, Hearing Loss, Ataxia, Retinitis Pigmentosa and Cataract (PHARC); Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract
Ataxia and cerebellar anomalies - narrow panel v0.5 AAAS Ellen McDonagh gene: AAAS was added
gene: AAAS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: AAAS was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v0.4 Louise Daugherty Panel types changed to GMS Rare Disease; Component Of Super Panel
Ataxia and cerebellar anomalies - narrow panel v0.2 Ellen McDonagh Panel types changed to GMS Rare Disease
Ataxia and cerebellar anomalies - narrow panel v0.0 Ellen McDonagh Added Panel Ataxia and cerebellar anomalies - narrow panel
Set panel types to: GMS Rare Disease Virtual