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Brain Calcification v1.96 Zornitza Stark removed gene:GBA from the panel
Brain Calcification v1.95 GBA Clare van Eyk Deleted their review
Brain Calcification v1.95 GBA Clare van Eyk gene: GBA was added
gene: GBA was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBA were set to PMID: 38693247
Phenotypes for gene: GBA were set to Gaucher disease, MIM#231000
Review for gene: GBA was set to RED
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Gaucher disease can be associated with ataxia, dystonia and spasticity with variable age of onset.
Sources: Literature
Brain Calcification v1.95 NAA60 Zornitza Stark Phenotypes for gene: NAA60 were changed from Basal ganglia calcification, MONDO:0008947, NAA60-related to Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786
Brain Calcification v1.94 NAA60 Zornitza Stark reviewed gene: NAA60: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.94 NAA60 Zornitza Stark Marked gene: NAA60 as ready
Brain Calcification v1.94 NAA60 Zornitza Stark Gene: naa60 has been classified as Green List (High Evidence).
Brain Calcification v1.94 NAA60 Zornitza Stark Phenotypes for gene: NAA60 were changed from Basal ganglia calcification to Basal ganglia calcification, MONDO:0008947, NAA60-related
Brain Calcification v1.93 NAA60 Chirag Patel Classified gene: NAA60 as Green List (high evidence)
Brain Calcification v1.93 NAA60 Chirag Patel Gene: naa60 has been classified as Green List (High Evidence).
Brain Calcification v1.93 NAA60 Chirag Patel Classified gene: NAA60 as Green List (high evidence)
Brain Calcification v1.93 NAA60 Chirag Patel Gene: naa60 has been classified as Green List (High Evidence).
Brain Calcification v1.92 NAA60 Chirag Patel reviewed gene: NAA60: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary familial brain calcification; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Brain Calcification v1.92 NAA60 Chirag Patel Deleted their review
Brain Calcification v1.92 NAA60 Chirag Patel gene: NAA60 was added
gene: NAA60 was added to Brain Calcification. Sources: Other
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NAA60 were set to Basal ganglia calcification
Review for gene: NAA60 was set to GREEN
gene: NAA60 was marked as current diagnostic
Added comment: ESHG 2023:
10 individuals from 7 families with biallelic variants in NAA60 (missense and framshift).
All with primary brain calcification - 4/10 childhood onset (DD, ID), 6/10 adult onset (cerebellar and pyramidal dysfunction, dystonia, parkinsonism, cognitive impairment, psychiatric manifestations).

NAA60 catalyses N-terminal acetylation of transmembrane proteins and localises to Golgi apparatus. In vitro assay of variants showed reduced capacity of Nt acetylation. Fibroblast studies showed significantly reduced levels of phosphate importer (SLC20A2). Loss of function variants in SLC20A2 (~50% of PFBC cases) lead to increased extracellular phosphate (which is thought to lead to calcium deposits in brain).
Sources: Other
Brain Calcification v1.91 ESAM Zornitza Stark Phenotypes for gene: ESAM were changed from Neurodevelopmental disorder (MONDO#0700092), ESAM-related to Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371
Brain Calcification v1.90 ESAM Zornitza Stark reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.90 ZBTB20 Zornitza Stark Marked gene: ZBTB20 as ready
Brain Calcification v1.90 ZBTB20 Zornitza Stark Gene: zbtb20 has been classified as Green List (High Evidence).
Brain Calcification v1.90 ZBTB20 Zornitza Stark Classified gene: ZBTB20 as Green List (high evidence)
Brain Calcification v1.90 ZBTB20 Zornitza Stark Gene: zbtb20 has been classified as Green List (High Evidence).
Brain Calcification v1.89 ZBTB20 Yetong Chen gene: ZBTB20 was added
gene: ZBTB20 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: ZBTB20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB20 were set to 32734340; 25017102
Phenotypes for gene: ZBTB20 were set to Primrose syndrome, MIM# 259050
Review for gene: ZBTB20 was set to GREEN
Added comment: PMID 32266967 reports 4 patients (1, 2, 22 and 24) with different ZBTB20 variants (p.Gln209Arg, p.Cys580Tyr, p.His624Pro, and p.Met625Val) who had brain calcifications.
PMID reports 3 patients (11D5135, 12D6966 and PRS_02) with different ZBTB20 variants (p.T601I, p.G602A and p.V626M) who had intracranial calcification.
Sources: Expert list
Brain Calcification v1.89 XPR1 Zornitza Stark Publications for gene: XPR1 were set to 25938945
Brain Calcification v1.88 WDR45 Zornitza Stark Classified gene: WDR45 as Amber List (moderate evidence)
Brain Calcification v1.88 WDR45 Zornitza Stark Gene: wdr45 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.87 VARS2 Zornitza Stark Marked gene: VARS2 as ready
Brain Calcification v1.87 VARS2 Zornitza Stark Gene: vars2 has been classified as Red List (Low Evidence).
Brain Calcification v1.87 VARS2 Zornitza Stark Classified gene: VARS2 as Red List (low evidence)
Brain Calcification v1.87 VARS2 Zornitza Stark Gene: vars2 has been classified as Red List (Low Evidence).
Brain Calcification v1.86 TYROBP Zornitza Stark Publications for gene: TYROBP were set to 30242731
Brain Calcification v1.85 TSC2 Zornitza Stark Publications for gene: TSC2 were set to
Brain Calcification v1.84 TBCE Zornitza Stark Marked gene: TBCE as ready
Brain Calcification v1.84 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Brain Calcification v1.84 TBCE Zornitza Stark Classified gene: TBCE as Green List (high evidence)
Brain Calcification v1.84 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Brain Calcification v1.83 TBCE Zornitza Stark reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypoparathyroidism-retardation-dysmorphism syndrome, MIM# 241410; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.83 XPR1 Yetong Chen reviewed gene: XPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27230854, 29955172, 33433330; Phenotypes: Basal ganglia calcification, idiopathic, 6, MIM# 616413; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.83 WDR45 Yetong Chen gene: WDR45 was added
gene: WDR45 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: WDR45 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: WDR45 were set to 26859818; 25301227
Phenotypes for gene: WDR45 were set to Neurodegeneration with brain iron accumulation 5, MIM# 300894
Review for gene: WDR45 was set to AMBER
Added comment: PMID 26859818 reports a patient with a heterozygous WDR45 variant (c.400G > A) who had symmetrical calcification of the medial globus pallidi.
PMID 25301227 reports a patient with a heterozygous WDR45 variant (c.488del C p.Pro163Argfs*34) who had bilateral dense calcification of the globus pallidus.
Sources: Expert list
Brain Calcification v1.83 VARS2 Yetong Chen gene: VARS2 was added
gene: VARS2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: VARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VARS2 were set to 29314548
Phenotypes for gene: VARS2 were set to Combined oxidative phosphorylation deficiency 20, MIM# 615917
Review for gene: VARS2 was set to RED
Added comment: Limited evidence supports the causal role of the VARS2 gene in brain calcification.
PMID 29314548 reports a patient (Patient 5) with compound heterozygous VARS2 variants (c.1135G > A, p.Ala379Thr and c.1877C > A, p.Ala626Asp) who had symmetrical bilateral basal ganglia calcification.
Sources: Expert list
Brain Calcification v1.83 TYROBP Yetong Chen reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 11402114; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, MIM# 221770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.83 TSC2 Yetong Chen reviewed gene: TSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21175459, 30628968, 19258292, 28786492; Phenotypes: Tuberous sclerosis-2, MIM# 613254; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.83 TBCE Yetong Chen gene: TBCE was added
gene: TBCE was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to 28138323; 35935360
Phenotypes for gene: TBCE were set to Hypoparathyroidism-retardation-dysmorphism syndrome, MIM# 241410
Review for gene: TBCE was set to AMBER
Added comment: PMID 35935360 reports a total of 63 patients with hypoparathyroidism-retardation-dysmorphism (HRD) Syndrome, of which 32 had brain calcifications. Although the paper states that 25 of 63 patients had genetic diagnoses, the number of patients with brain calcification carrying TBCE variants is unclear.
Sources: Expert list
Brain Calcification v1.83 MT-ATP6 Zornitza Stark Marked gene: MT-ATP6 as ready
Brain Calcification v1.83 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Red List (Low Evidence).
Brain Calcification v1.83 MT-ATP6 Zornitza Stark Phenotypes for gene: MT-ATP6 were changed from Leigh syndrome, MIM# 256000 to Leigh syndrome, MONDO:0009723
Brain Calcification v1.82 MT-ATP6 Zornitza Stark Classified gene: MT-ATP6 as Red List (low evidence)
Brain Calcification v1.82 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Red List (Low Evidence).
Brain Calcification v1.81 MT-ATP6 Zornitza Stark reviewed gene: MT-ATP6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Leigh syndrome, MONDO:0009723; Mode of inheritance: MITOCHONDRIAL
Brain Calcification v1.81 GNAS Zornitza Stark Marked gene: GNAS as ready
Brain Calcification v1.81 GNAS Zornitza Stark Gene: gnas has been classified as Green List (High Evidence).
Brain Calcification v1.81 GNAS Zornitza Stark Classified gene: GNAS as Green List (high evidence)
Brain Calcification v1.81 GNAS Zornitza Stark Gene: gnas has been classified as Green List (High Evidence).
Brain Calcification v1.80 MOCS1 Zornitza Stark Marked gene: MOCS1 as ready
Brain Calcification v1.80 MOCS1 Zornitza Stark Gene: mocs1 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.80 MOCS1 Zornitza Stark Classified gene: MOCS1 as Amber List (moderate evidence)
Brain Calcification v1.80 MOCS1 Zornitza Stark Gene: mocs1 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.79 MOCS1 Zornitza Stark reviewed gene: MOCS1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Molybdenum cofactor deficiency A, MIM# 252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.79 ISG15 Zornitza Stark Marked gene: ISG15 as ready
Brain Calcification v1.79 ISG15 Zornitza Stark Gene: isg15 has been classified as Green List (High Evidence).
Brain Calcification v1.79 ISG15 Zornitza Stark Classified gene: ISG15 as Green List (high evidence)
Brain Calcification v1.79 ISG15 Zornitza Stark Gene: isg15 has been classified as Green List (High Evidence).
Brain Calcification v1.78 PLXNA1 Zornitza Stark Marked gene: PLXNA1 as ready
Brain Calcification v1.78 PLXNA1 Zornitza Stark Gene: plxna1 has been classified as Red List (Low Evidence).
Brain Calcification v1.78 PLXNA1 Zornitza Stark Classified gene: PLXNA1 as Red List (low evidence)
Brain Calcification v1.78 PLXNA1 Zornitza Stark Gene: plxna1 has been classified as Red List (Low Evidence).
Brain Calcification v1.77 TRPM6 Zornitza Stark Marked gene: TRPM6 as ready
Brain Calcification v1.77 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Red List (Low Evidence).
Brain Calcification v1.77 TRPM6 Zornitza Stark Classified gene: TRPM6 as Red List (low evidence)
Brain Calcification v1.77 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Red List (Low Evidence).
Brain Calcification v1.76 TRPM6 Yetong Chen gene: TRPM6 was added
gene: TRPM6 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: TRPM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPM6 were set to 22982920
Phenotypes for gene: TRPM6 were set to Hypomagnesemia 1, intestinal, MIM# 602014
Review for gene: TRPM6 was set to RED
Added comment: Insufficient evidence supports the gene-disease association.
PMID 22982920 reports a patient with a novel homozygous variant (ins 2999T) of the TRPM6 gene who had bilateral basal ganglia calci­fication. The authors state that brain calcification has never been reported in hypomagnesemia patients before.
Sources: Expert list
Brain Calcification v1.76 TREX1 Yetong Chen reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34949589, 26581299, 29386495; Phenotypes: Aicardi-Goutieres syndrome 1, dominant and recessive, MIM# 225750; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v1.76 TREM2 Yetong Chen reviewed gene: TREM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33969597, 35705056; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.76 TINF2 Yetong Chen reviewed gene: TINF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33734615, 32966588, 28095086; Phenotypes: Dyskeratosis congenita, autosomal dominant 3, MIM# 613990; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.76 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Brain Calcification v1.76 PANK2 Zornitza Stark Gene: pank2 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.76 PANK2 Zornitza Stark Classified gene: PANK2 as Amber List (moderate evidence)
Brain Calcification v1.76 PANK2 Zornitza Stark Gene: pank2 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.75 PANK2 Zornitza Stark reviewed gene: PANK2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 1, MIM# 234200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.75 PANK2 Zornitza Stark Classified gene: PANK2 as Red List (low evidence)
Brain Calcification v1.75 PANK2 Zornitza Stark Gene: pank2 has been classified as Red List (Low Evidence).
Brain Calcification v1.74 PCDH12 Zornitza Stark Marked gene: PCDH12 as ready
Brain Calcification v1.74 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Brain Calcification v1.74 PCDH12 Zornitza Stark Classified gene: PCDH12 as Green List (high evidence)
Brain Calcification v1.74 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Brain Calcification v1.73 PSMB8 Zornitza Stark Marked gene: PSMB8 as ready
Brain Calcification v1.73 PSMB8 Zornitza Stark Gene: psmb8 has been classified as Red List (Low Evidence).
Brain Calcification v1.73 PSMB8 Zornitza Stark Classified gene: PSMB8 as Red List (low evidence)
Brain Calcification v1.73 PSMB8 Zornitza Stark Gene: psmb8 has been classified as Red List (Low Evidence).
Brain Calcification v1.72 PSMG2 Zornitza Stark Classified gene: PSMG2 as Red List (low evidence)
Brain Calcification v1.72 PSMG2 Zornitza Stark Gene: psmg2 has been classified as Red List (Low Evidence).
Brain Calcification v1.71 PTH Zornitza Stark Marked gene: PTH as ready
Brain Calcification v1.71 PTH Zornitza Stark Gene: pth has been classified as Red List (Low Evidence).
Brain Calcification v1.71 PTH Zornitza Stark Classified gene: PTH as Red List (low evidence)
Brain Calcification v1.71 PTH Zornitza Stark Gene: pth has been classified as Red List (Low Evidence).
Brain Calcification v1.71 PTS Zornitza Stark Marked gene: PTS as ready
Brain Calcification v1.71 PTS Zornitza Stark Gene: pts has been classified as Red List (Low Evidence).
Brain Calcification v1.71 PTS Zornitza Stark Classified gene: PTS as Red List (low evidence)
Brain Calcification v1.71 PTS Zornitza Stark Gene: pts has been classified as Red List (Low Evidence).
Brain Calcification v1.70 QDPR Zornitza Stark Marked gene: QDPR as ready
Brain Calcification v1.70 QDPR Zornitza Stark Gene: qdpr has been classified as Red List (Low Evidence).
Brain Calcification v1.70 QDPR Zornitza Stark Classified gene: QDPR as Red List (low evidence)
Brain Calcification v1.70 QDPR Zornitza Stark Gene: qdpr has been classified as Red List (Low Evidence).
Brain Calcification v1.69 GNA11 Zornitza Stark Marked gene: GNA11 as ready
Brain Calcification v1.69 GNA11 Zornitza Stark Gene: gna11 has been classified as Red List (Low Evidence).
Brain Calcification v1.69 GNA11 Zornitza Stark Classified gene: GNA11 as Red List (low evidence)
Brain Calcification v1.69 GNA11 Zornitza Stark Gene: gna11 has been classified as Red List (Low Evidence).
Brain Calcification v1.68 GLA Zornitza Stark Marked gene: GLA as ready
Brain Calcification v1.68 GLA Zornitza Stark Gene: gla has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.68 GLA Zornitza Stark Classified gene: GLA as Amber List (moderate evidence)
Brain Calcification v1.68 GLA Zornitza Stark Gene: gla has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.67 GCM2 Zornitza Stark Marked gene: GCM2 as ready
Brain Calcification v1.67 GCM2 Zornitza Stark Gene: gcm2 has been classified as Green List (High Evidence).
Brain Calcification v1.67 GCM2 Zornitza Stark Classified gene: GCM2 as Green List (high evidence)
Brain Calcification v1.67 GCM2 Zornitza Stark Gene: gcm2 has been classified as Green List (High Evidence).
Brain Calcification v1.66 FOLR1 Zornitza Stark Marked gene: FOLR1 as ready
Brain Calcification v1.66 FOLR1 Zornitza Stark Gene: folr1 has been classified as Red List (Low Evidence).
Brain Calcification v1.66 GATA3 Zornitza Stark Marked gene: GATA3 as ready
Brain Calcification v1.66 GATA3 Zornitza Stark Gene: gata3 has been classified as Green List (High Evidence).
Brain Calcification v1.66 GATA3 Zornitza Stark Classified gene: GATA3 as Green List (high evidence)
Brain Calcification v1.66 GATA3 Zornitza Stark Gene: gata3 has been classified as Green List (High Evidence).
Brain Calcification v1.65 FOLR1 Zornitza Stark Phenotypes for gene: FOLR1 were changed from to Neurodegeneration due to cerebral folate transport deficiency, MIM# 613068
Brain Calcification v1.64 FAM20C Zornitza Stark Marked gene: FAM20C as ready
Brain Calcification v1.64 FAM20C Zornitza Stark Gene: fam20c has been classified as Green List (High Evidence).
Brain Calcification v1.64 FAM20C Zornitza Stark Publications for gene: FAM20C were set to 27862258; 20825432; 36914045; 34259997; 32299476; 29341424
Brain Calcification v1.63 FAM20C Zornitza Stark Publications for gene: FAM20C were set to 27862258; 20825432
Brain Calcification v1.63 FOLR1 Zornitza Stark Classified gene: FOLR1 as Red List (low evidence)
Brain Calcification v1.63 FOLR1 Zornitza Stark Gene: folr1 has been classified as Red List (Low Evidence).
Brain Calcification v1.62 FAM20C Zornitza Stark Classified gene: FAM20C as Green List (high evidence)
Brain Calcification v1.62 FAM20C Zornitza Stark Gene: fam20c has been classified as Green List (High Evidence).
Brain Calcification v1.61 SUOX Zornitza Stark Marked gene: SUOX as ready
Brain Calcification v1.61 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Brain Calcification v1.61 FAM20C Zornitza Stark reviewed gene: FAM20C: Rating: GREEN; Mode of pathogenicity: None; Publications: 36914045, 34259997, 32299476, 29341424; Phenotypes: Raine syndrome, MIM# 259775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.61 SUOX Zornitza Stark Classified gene: SUOX as Green List (high evidence)
Brain Calcification v1.61 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Brain Calcification v1.60 TBC1D20 Zornitza Stark Marked gene: TBC1D20 as ready
Brain Calcification v1.60 TBC1D20 Zornitza Stark Gene: tbc1d20 has been classified as Red List (Low Evidence).
Brain Calcification v1.60 TBC1D20 Zornitza Stark Phenotypes for gene: TBC1D20 were changed from Cerebroretinal microangiopathy with calcifications and cysts 2, MIM# 617341 to Warburg micro syndrome 4, MIM# 615663
Brain Calcification v1.59 TBC1D20 Zornitza Stark Classified gene: TBC1D20 as Red List (low evidence)
Brain Calcification v1.59 TBC1D20 Zornitza Stark Gene: tbc1d20 has been classified as Red List (Low Evidence).
Brain Calcification v1.58 TBC1D20 Zornitza Stark reviewed gene: TBC1D20: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Warburg micro syndrome 4, MIM# 615663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.58 STN1 Zornitza Stark Publications for gene: STN1 were set to 27432940; 32627942
Brain Calcification v1.57 SNORD118 Zornitza Stark Publications for gene: SNORD118 were set to 27571260
Brain Calcification v1.56 SLC46A1 Zornitza Stark Marked gene: SLC46A1 as ready
Brain Calcification v1.56 SLC46A1 Zornitza Stark Gene: slc46a1 has been classified as Green List (High Evidence).
Brain Calcification v1.56 SLC46A1 Zornitza Stark Classified gene: SLC46A1 as Green List (high evidence)
Brain Calcification v1.56 SLC46A1 Zornitza Stark Gene: slc46a1 has been classified as Green List (High Evidence).
Brain Calcification v1.55 SUOX Yetong Chen gene: SUOX was added
gene: SUOX was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUOX were set to 27289259; 23250141; 24384336
Phenotypes for gene: SUOX were set to Sulfite oxidase deficiency, MIM# 272300
Review for gene: SUOX was set to GREEN
Added comment: PMID 27289259 reports 2 unrelated patients with different homozygous SUOX variants (c.713G > A(p.G238Q*) and c.884G > A (p.G295E)) who had thalami calcifications.
PMID 23250141 reports a patient with homozygous SUOX variant (c.1232-1233 delTG) who had faint calcification in the thalami.
PMID 24384336 reports a patient (patient 2) with homozygous SUOX variant (c.1232-1233delT) who had faint calcification in both thalami.
Sources: Expert list
Brain Calcification v1.55 TBC1D20 Yetong Chen gene: TBC1D20 was added
gene: TBC1D20 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: TBC1D20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D20 were set to 32740904
Phenotypes for gene: TBC1D20 were set to Cerebroretinal microangiopathy with calcifications and cysts 2, MIM# 617341
Review for gene: TBC1D20 was set to RED
Added comment: Limited evidence supports the causal role of TBC1D20 in brain calcification.
PMID 32740904 reports one patient (case 34) with homozygous TBC1D20 variant (c.199C>T (p.Arg67*)) who developed bilateral faint calcification in basal ganglia.
Sources: Expert list
Brain Calcification v1.55 STN1 Yetong Chen reviewed gene: STN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34110109; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts 2, MIM# 617341; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.55 SNORD118 Yetong Chen reviewed gene: SNORD118: Rating: GREEN; Mode of pathogenicity: None; Publications: 34220662, 28177126, 34986804; Phenotypes: Leukoencephalopathy, brain calcifications, and cysts, MIM# 614561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.55 SLC46A1 Yetong Chen gene: SLC46A1 was added
gene: SLC46A1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: SLC46A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC46A1 were set to 33146883; 28685492; 24534056; 27938595
Phenotypes for gene: SLC46A1 were set to Folate malabsorption, hereditary, MIM# 229050
Review for gene: SLC46A1 was set to GREEN
Added comment: PMID 33146883 reports a patient with homozygous SLC46A1 variant (c.620dupG (p.Y208Lfs *25)) who had calcifications in bilateral basal ganglia, thalamus, and subcortical white matter.
PMID 28685492 reports a patient (case 2) with homozygous SLC46A1 variant (c.198C>A (p.Cys66*)) who developed basal ganglia calcification.
PMID 24534056 reports a patient with compound heterozygous SLC46A1 variants (c.1A>T (MIL) and c.194-195insG (p.Cys66LeufsX99)) who developed calcifications in bilateral frontal, temporal, parietal and occipital lobes, and basal ganglia.
PMID 27938595 reports 2 patients harbouring SLC46A1 variants who had progressive bilateral symmetrical calcification. Both patients had compound heterozygous variants. Patient 1 had c. 1238T>C (L413P) and c. 194-195insG (p.Cys66LeufsX99) while patient 2 had c. 1A>T (M1L) and c. 194-195insG (p.Cys66LeufsX99). It should be noted that this publication is written in Chinese and only the abstract is available in English, so details about the calcifications are not available.
Sources: Expert list
Brain Calcification v1.55 RAB39B Bryony Thompson Marked gene: RAB39B as ready
Brain Calcification v1.55 RAB39B Bryony Thompson Gene: rab39b has been classified as Red List (Low Evidence).
Brain Calcification v1.55 RAB39B Bryony Thompson Classified gene: RAB39B as Red List (low evidence)
Brain Calcification v1.55 RAB39B Bryony Thompson Gene: rab39b has been classified as Red List (Low Evidence).
Brain Calcification v1.54 GJA1 Bryony Thompson Classified gene: GJA1 as Green List (high evidence)
Brain Calcification v1.54 GJA1 Bryony Thompson Added comment: Comment on list classification: Brain calcification appears to be a variable feature of the ODDD phenotype
Brain Calcification v1.54 GJA1 Bryony Thompson Gene: gja1 has been classified as Green List (High Evidence).
Brain Calcification v1.53 GJA1 Bryony Thompson Marked gene: GJA1 as ready
Brain Calcification v1.53 GJA1 Bryony Thompson Gene: gja1 has been classified as Green List (High Evidence).
Brain Calcification v1.53 GJA1 Bryony Thompson Deleted their comment
Brain Calcification v1.53 GJA1 Bryony Thompson Added comment: Comment on mode of inheritance: Brain calcification appears to be a variable feature of the ODDD phenotype
Brain Calcification v1.53 GJA1 Bryony Thompson Mode of inheritance for gene: GJA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v1.52 GJA1 Bryony Thompson Classified gene: GJA1 as Green List (high evidence)
Brain Calcification v1.52 GJA1 Bryony Thompson Gene: gja1 has been classified as Green List (High Evidence).
Brain Calcification v1.51 SLC20A2 Yetong Chen reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28162874, 31267306, 35850697, 34025715; Phenotypes: Basal ganglia calcification, idiopathic, 1, MIM# 213600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.51 SAMHD1 Yetong Chen reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35418820, 36405817; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 RNASEH2C Yetong Chen reviewed gene: RNASEH2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 33681774, 27411419; Phenotypes: Aicardi-Goutieres syndrome 3, MIM# 610329; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 RNASEH2B Yetong Chen reviewed gene: RNASEH2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 33482855, 30826161, 26581299; Phenotypes: Aicardi-Goutieres syndrome 2, MIM# 610181; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 MT-ATP6 Yetong Chen edited their review of gene: MT-ATP6: Changed phenotypes: Leigh syndrome, MIM* 516060
Brain Calcification v1.51 QDPR Yetong Chen changed review comment from: There is insufficient evidence supporting the causal role of the QDPR gene in brain calcification.
Sources: Expert list; to: There is insufficient evidence supporting the causal role of the QDPR gene in brain calcification.
The suggested literature (PMID 2135679) is not accessible in PubMed. A similar paper, PMID 2785251, reports intracranial calcification in a patient with dihydropteridine reductase deficiency. DNA sequencing was not available when the case was reported.
Sources: Expert list
Brain Calcification v1.51 QDPR Yetong Chen gene: QDPR was added
gene: QDPR was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: QDPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QDPR were set to 2135679
Phenotypes for gene: QDPR were set to Dihydropteridine Reductase (DHPR) Deficiency, MIM* 612676
Review for gene: QDPR was set to RED
Added comment: There is insufficient evidence supporting the causal role of the QDPR gene in brain calcification.
Sources: Expert list
Brain Calcification v1.51 RAB39B Yetong Chen gene: RAB39B was added
gene: RAB39B was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: RAB39B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RAB39B were set to 27943471
Phenotypes for gene: RAB39B were set to Intellectual developmental disorder, X-linked 72, MIM# 300271
Review for gene: RAB39B was set to RED
Added comment: Only one 2 cases from the same family are reported, insufficient evidence supports the causal role of the RAB39B gene in brain calcification.
PMID 27943471 reports 2 patients (II-2 and III-1) from the same family harbouring a RAB39B variant (c.536dupA, p.E179fsX48) who developed brain calcification.
Sources: Expert list
Brain Calcification v1.51 PTS Yetong Chen gene: PTS was added
gene: PTS was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PTS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTS were set to 16601879; 32734340
Phenotypes for gene: PTS were set to Hyperphenylalaninemia, BH4-deficient, A, MIM# 261640
Review for gene: PTS was set to RED
Added comment: Although brain calcification might be seen in patients with BH4 deficiency, none of the papers mentions PTS variants found in the affected patients.
Further, there are multiple genes that can cause BH4 deficiency, of which PTS is one of them.
The suggested literature, PMID 16601879, reports a BH4 deficiency patient with brain calcification (No.544). However, the mutation analysis was not done for this patient.
Insufficient evidence suggests the causal role of the PTS gene in brain calcification.
Sources: Expert list
Brain Calcification v1.51 PTH Yetong Chen gene: PTH was added
gene: PTH was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PTH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PTH were set to 29383229
Phenotypes for gene: PTH were set to Hypoparathyroidism, familial isolated 1, MIM# 146200
Review for gene: PTH was set to RED
Added comment: Several publications report brain calcifications found in patients with hyperparathyroidism (e.g. PMID 29383229); however, none of them reports the genetic profiles of the patients.
In addition, less than 10% of hyperparathyroidism cases are due to genetic causes.
Thus, limited evidence suggests a causal role of the PTH gene in brain calcification.
Sources: Expert list
Brain Calcification v1.51 PSMB8 Yetong Chen gene: PSMB8 was added
gene: PSMB8 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PSMB8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB8 were set to 28895430; 23768303
Phenotypes for gene: PSMB8 were set to Proteasome-associated autoinflammatory syndrome 1 and digenic forms, MIM# 256040
Review for gene: PSMB8 was set to RED
Added comment: Insufficient evidence supports the causal role of the PSMB8 gene in brain calcification.
PMID 28895430 report a patient with homozygous PSMB8 variants (p.A92T) who developed basal ganglia calcification.
PMID 23768303 reports a patient with heterozygous PSMB8 variants (p.A92T/p.T75M) who had brain calcification.
Sources: Expert list
Brain Calcification v1.51 PSMG2 Yetong Chen gene: PSMG2 was added
gene: PSMG2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PSMG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMG2 were set to 30664889
Phenotypes for gene: PSMG2 were set to Proteasome-associated autoinflammatory syndrome 4, MIM# 619183
Review for gene: PSMG2 was set to RED
Added comment: There is limited evidence supporting the causal role of PSMG2 in brain calcification.
PMID 30664889 reports a patient with heterozygous PSMG2 variants (c.666_667delGT, p.Y223Sfs*2 and c.675 T>G, p.N225K) who had bilateral basal ganglia calcifications.
Sources: Expert list
Brain Calcification v1.51 PLXNA1 Yetong Chen gene: PLXNA1 was added
gene: PLXNA1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PLXNA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PLXNA1 were set to 34054129
Phenotypes for gene: PLXNA1 were set to Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Review for gene: PLXNA1 was set to RED
Added comment: There is limited evidence supporting the causal role of the PLXNA1 gene in brain calcification.
PMID 34054129 reports a patient (H:II-1) with a PLXNA1 variant (c.5242C>T) who developed basal ganglia calcifications.
Sources: Expert list
Brain Calcification v1.51 PDGFRB Yetong Chen reviewed gene: PDGFRB: Rating: ; Mode of pathogenicity: None; Publications: 29955172, 23255827; Phenotypes: Basal ganglia calcification, idiopathic, 4, MIM# 615007; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.51 PDGFB Yetong Chen reviewed gene: PDGFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27433546, 35747618, 25211641, 29955172, 31267306, 28162874; Phenotypes: Basal ganglia calcification, idiopathic, 5, MIM# 615483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.51 PCDH12 Yetong Chen gene: PCDH12 was added
gene: PCDH12 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PCDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDH12 were set to 28804758; 34773825; 30178464
Phenotypes for gene: PCDH12 were set to Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280
Review for gene: PCDH12 was set to GREEN
Added comment: PMID 28804758 reports a patient with a homozygous PCDH12 nonsense variant who developed brain calcification. The authors also screen the PCDH12 gene in 79 patients with unknown causes of brain calcification and detected 4 rare PCDH12 variants in 4 unrelated patients. This finding confirms the association between PCDH12 and brain calcification, supported by very low frequencies in the ExAC database, functional studies of the variants, studies of patient cells, and segregation studies.
PMID 34773825 reports a patient with a homozygous truncating variant (c.1176G>A; p.Trp392*) in PCDH12 who developed brain calcification.
PMID 30178464 described 14 affected individuals from 8 families who carried PCDH12 variants. The authors report 6 patients with PCDH12 variants who developed subtle brain calcifications; however, the relationship between these patients is unclear and the results of CT studies of these 6 patients are not shown in the article.
Sources: Expert list
Brain Calcification v1.51 PANK2 Yetong Chen gene: PANK2 was added
gene: PANK2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PANK2 were set to 23968566; 29642163; 28024710
Phenotypes for gene: PANK2 were set to Neurodegeneration with brain iron accumulation 1, MIM# 234200
Review for gene: PANK2 was set to RED
Added comment: The 3 cases were reported within 5 years (2013-2018); however, no more new cases are reported after 2018. Hence, limited evidence supports the causal role of the MOCS1 gene in brain calcification.
PMID 23968566 reports a patient with heterozygous PANK2 variants (p.G521R and p.T528M) who exhibited basal ganglia calcifications.
PMID 29642163 reports a patient with heterozygous PANK2 variants (p.D217G and p.D447E) who developed basal ganglia calcifications.
PMID 28024710 reports a patient with 2 homozygous PANK2 variants (p.Asp403Val) who developed bilateral calcification of globus pallidus.
Sources: Expert list
Brain Calcification v1.51 MT-ATP6 Yetong Chen gene: MT-ATP6 was added
gene: MT-ATP6 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene gene: MT-ATP6 was set to MITOCHONDRIAL
Publications for gene: MT-ATP6 were set to 32042910; 29929013
Phenotypes for gene: MT-ATP6 were set to Leigh syndrome, MIM# 256000
Review for gene: MT-ATP6 was set to RED
Added comment: Limited evidence supports the causal role of the MT-ATP6 gene in brain calcification.
PMID 32042910 reports a patient (patient P2) with the m.8782G>A: p.(Gly86*) variant in MT-ATP6 who developed basal ganglia calcification.
PMID PMID: 29929013 reports a patient with the m.8936T > A variant in MT-ATP6 who developed brain calcification.
Sources: Expert list
Brain Calcification v1.51 MOCS1 Yetong Chen gene: MOCS1 was added
gene: MOCS1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: MOCS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOCS1 were set to 27289259
Phenotypes for gene: MOCS1 were set to Molybdenum cofactor deficiency A, MIM# 252150
Review for gene: MOCS1 was set to RED
Added comment: Limited evidence supports the causal role of the MOCS1 gene in brain calcification.
PMID reports 2 patients (patients 1 and 5) with different homozygous MOCS1 variants (c.253C > T (p.Q85*) and c.722_722delT (p.L241Rfs*6)) who developed brain calcification.
Sources: Expert list
Brain Calcification v1.51 JAM2 Yetong Chen reviewed gene: JAM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32142645; Phenotypes: Basal ganglia calcification, idiopathic, 8, autosomal recessive, MIM# 618824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 ISG15 Yetong Chen gene: ISG15 was added
gene: ISG15 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: ISG15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISG15 were set to 25307056; 32944031
Phenotypes for gene: ISG15 were set to Immunodeficiency 38 with BG calcification, MIM# 616126
Review for gene: ISG15 was set to GREEN
Added comment: Brain calcification is consistently observed in patients with biallelic pathogenic variants in ISG15.
PMID 25307056 reports 5 patients (patients P1-3, P5 and P6) from 3 unrelated families who had ISG15 variants and developed brain calcification. In this paper, patient P4 was from the same family as patients P5 and P6; however, P4 only had inferred genotype so she is not counted here.
PMID 32944031 reports a patient with compound heterozygous ISG15 variants who developed brain calcification.
Sources: Expert list
Brain Calcification v1.51 IFIH1 Yetong Chen reviewed gene: IFIH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 31898846, 29782060; Phenotypes: Aicardi-Goutieres syndrome 7, MIM# 615846; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.51 GNAS Yetong Chen gene: GNAS was added
gene: GNAS was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: GNAS were set to 28296742; 35600030; 20444925
Phenotypes for gene: GNAS were set to Pseudohypoparathyroidism Ib, MIM# 603233
Review for gene: GNAS was set to GREEN
Added comment: The imprinting of GNAS is complex. While GNAS is primarily expressed from the maternal allele, only the paternal allele is expressed in some tissues.
Although the number of cases is limited, patients are reported by different authors across the years.
PMID 28296742 reports 2 patients from the same family, who had the same GNAS variant (p.P115S, p.V340M), and developed brain calcification.
PMID 35600030 reports a patient with a rare GNAS variant who developed bilateral basal ganglia calcification.
PMID 20444925 reports 2 patients from the same family who developed brain calcification. The patients had broad epigenetic defects at the GNAS gene and a deletion that exclusively affects exons encoding the antisense transcript (delAS3-4). The deletion is suspected to partially influence the imprinting of some GNAS loci.
Sources: Expert list
Brain Calcification v1.51 GNA11 Yetong Chen gene: GNA11 was added
gene: GNA11 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: GNA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNA11 were set to 27334330
Phenotypes for gene: GNA11 were set to Hypocalcemia, autosomal dominant 2, MIM# 615361
Review for gene: GNA11 was set to RED
Added comment: PMID 27334330 reports 4 patients with the same GNA11 variant (c.1018G>A), who are from the same family, developed intracranial calcifications.
Sources: Expert list
Brain Calcification v1.51 GLA Yetong Chen gene: GLA was added
gene: GLA was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: GLA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GLA were set to 32734340; 24372060; 30532363
Phenotypes for gene: GLA were set to Fabry disease, MIM# 301500
Review for gene: GLA was set to AMBER
Added comment: PMID 17224688 suggests Fabry disease should not be considered an X-linked recessive disorder since women carrying heterozygous GLA variants may experience significant life-threatening conditions.
The association between brain calcification and Fabry disease is well-established. However, no cases with GLA variants that developed brain calcification are reported in the literature.
Sources: Expert list
Brain Calcification v1.51 GJA1 Yetong Chen edited their review of gene: GJA1: Changed rating: GREEN
Brain Calcification v1.51 GJA1 Yetong Chen gene: GJA1 was added
gene: GJA1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: GJA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GJA1 were set to 26444782; 31023660; 31240666
Phenotypes for gene: GJA1 were set to Oculodentodigital dysplasia, MIM# 164200
Review for gene: GJA1 was set to RED
Added comment: PMID 26444782 reports a patient with a heterozygous missense GJA1 variant who developed bilateral calcifications of the basal ganglia and mild hydrocephalus.
PMID 31023660 reports 2 patients with missense GJA1 variants who developed brain calcifications. Patients 4 and 7 had unilateral and bilateral calcifications, respectively.
PMID 31240666 reports a patient with a homozygous GJA1 variant who developed bilateral calcification of the basal ganglia, thalamus and deep white matter.
Sources: Expert list
Brain Calcification v1.51 GCM2 Yetong Chen gene: GCM2 was added
gene: GCM2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: GCM2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GCM2 were set to 32642802; 19940031; 36405867; 18583467
Phenotypes for gene: GCM2 were set to Hypoparathyroidism, familial isolated 2, MIM# 618883
Review for gene: GCM2 was set to GREEN
Added comment: PMID 19940031 reports 11 patients with GCM2 variants who developed basal ganglia calcification. In the pedigrees of 5 families, some individuals with an R110W variant were affected while some with an R110W variant were nonaffected.
PMID 36405867 reports a patient with a GCM2 variant who developed bilateral basal ganglia calcification.
PMID 18583467 reports 2 patients from the same family who had the same GCM2 variant and developed basal ganglia calcification.
Sources: Expert list
Brain Calcification v1.51 GATA3 Yetong Chen gene: GATA3 was added
gene: GATA3 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: GATA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATA3 were set to 32642802; 19248180; 26268891; 16912130; 15337474
Phenotypes for gene: GATA3 were set to Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255
Review for gene: GATA3 was set to GREEN
Added comment: PMID 19248180 reports a patient with a GATA3 variant who developed basal ganglia calcification.
PMID 26268891 reports a patient with a GATA3 variant who developed multiple intracranial calcifications.
PMID 16912130 reports a patient with a GATA3 variant who developed basal ganglia calcification.
PMID 15337474 reports a patient with a chromosome 10p deletion, where the GATA3 gene is located, who developed basal ganglia calcification.
Sources: Expert list
Brain Calcification v1.51 GALC Yetong Chen reviewed gene: GALC: Rating: GREEN; Mode of pathogenicity: None; Publications: 22150413, 20135576; Phenotypes: Krabbe disease, MIM# 245200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 FARSB Yetong Chen reviewed gene: FARSB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29979980, 19161147, 30014610; Phenotypes: Rajab interstitial lung disease with brain calcifications 1, MIM# 613658; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 FARSA Yetong Chen changed review comment from: PMID 31355908 reports a patient with compound heterozygous variants of FARSA who developed brain calcification.
PMID 30014610 reports 5 patients with homozygous variants of FARSA who developed brain calcification. The 5 individuals are from a large consanguineous family. Co-segregation of phenotype and FARSA variant is confirmed. 3 deceased individuals were affected by brain calcification; however, their genotypes are not indicated in the pedigree while the author state that all affected individuals carried the same FARSA variant. The genotypes of the 3 individuals are unsure, so they are not counted.; to: An additional case is reported.
PMID 31355908 reports a patient with compound heterozygous variants of FARSA who developed brain calcification.
Brain Calcification v1.51 FOLR1 Yetong Chen gene: FOLR1 was added
gene: FOLR1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: FOLR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOLR1 were set to 24556562; 27378809
Review for gene: FOLR1 was set to RED
Added comment: Limited evidence supports the causal role of the FOLR1 gene in brain calcification since there are only 2 patients reported.
PMID 24556562 reports a patient with a homozygous variant of FOLR1 (c.610C>T, p.Arg204) who had bilateral calcification within the basal ganglia.
PMID 27378809 reports a patient with a homozygous variant of FOLR1 (c.562C.G, p.Leu188Val) who had brain calcification.
Sources: Expert list
Brain Calcification v1.51 FAM20C Yetong Chen gene: FAM20C was added
gene: FAM20C was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: FAM20C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM20C were set to 27862258; 20825432
Phenotypes for gene: FAM20C were set to Raine syndrome, MIM# 259775
Review for gene: FAM20C was set to RED
Added comment: PMID 27862258 reports 2 patients with compounded FAM20C variants, who were from the same family, developed brain calcification. Co-segregation of brain calcification and the genotype of compounded FAM20C variants is reported.
PMID 20825432 reports 2 patients with a homozygous FAM20C variant, who were from the same family, developed brain calcification. Co-segregation of brain calcification and the genotype of homozygous FAM20C variants is reported.
Although co-segregation of phenotypes and genotypes is seen, the 4 individuals are related so more evidence is required.
Sources: Expert list
Brain Calcification v1.51 FARSA Yetong Chen reviewed gene: FARSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31355908, 30014610; Phenotypes: Rajab interstitial lung disease with brain calcifications 2, MIM# 619013; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.51 ESAM Seb Lunke Marked gene: ESAM as ready
Brain Calcification v1.51 ESAM Seb Lunke Gene: esam has been classified as Green List (High Evidence).
Brain Calcification v1.51 ESAM Seb Lunke Classified gene: ESAM as Green List (high evidence)
Brain Calcification v1.51 ESAM Seb Lunke Gene: esam has been classified as Green List (High Evidence).
Brain Calcification v1.50 ESAM Chern Lim gene: ESAM was added
gene: ESAM was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESAM were set to 36996813
Phenotypes for gene: ESAM were set to Neurodevelopmental disorder (MONDO#0700092), ESAM-related
Review for gene: ESAM was set to GREEN
gene: ESAM was marked as current diagnostic
Added comment: PMID 36996813
- Thirteen affected individuals, including four fetuses, from eight unrelated families, with homozygous loss-of-function-type variants in ESAM – 2 of the variants are frameshifts, 1x nonsense, 1x canonical splice.
- Affected individuals have profound global developmental delay/unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/cerebral calcifications, the latter being also observed in the fetuses.
- One of the frameshift variant c.115del (p.Arg39Glyfs*33), was detected in six individuals from four unrelated families from the same geographic region in Turkey (southeastern Anatolia), suggesting a founder effect.
- The c.451+1G>A variant was detected in three individuals from two independent families with the same ethnic origin (Arab Bedouin)
Sources: Literature
Brain Calcification v1.50 FAM111A Zornitza Stark Marked gene: FAM111A as ready
Brain Calcification v1.50 FAM111A Zornitza Stark Gene: fam111a has been classified as Green List (High Evidence).
Brain Calcification v1.50 FAM111A Zornitza Stark Classified gene: FAM111A as Green List (high evidence)
Brain Calcification v1.50 FAM111A Zornitza Stark Gene: fam111a has been classified as Green List (High Evidence).
Brain Calcification v1.49 ERCC8 Zornitza Stark Publications for gene: ERCC8 were set to 26204423
Brain Calcification v1.48 ERCC6 Zornitza Stark Publications for gene: ERCC6 were set to
Brain Calcification v1.47 ERCC5 Zornitza Stark Marked gene: ERCC5 as ready
Brain Calcification v1.47 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Red List (Low Evidence).
Brain Calcification v1.47 ERCC5 Zornitza Stark Classified gene: ERCC5 as Red List (low evidence)
Brain Calcification v1.47 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Red List (Low Evidence).
Brain Calcification v1.46 ERCC3 Zornitza Stark Marked gene: ERCC3 as ready
Brain Calcification v1.46 ERCC3 Zornitza Stark Gene: ercc3 has been classified as Red List (Low Evidence).
Brain Calcification v1.46 ERCC3 Zornitza Stark Phenotypes for gene: ERCC3 were changed from to Xeroderma pigmentosum, group B, MIM# 610651
Brain Calcification v1.45 ECM1 Zornitza Stark Marked gene: ECM1 as ready
Brain Calcification v1.45 ECM1 Zornitza Stark Gene: ecm1 has been classified as Green List (High Evidence).
Brain Calcification v1.45 ERCC3 Zornitza Stark Classified gene: ERCC3 as Red List (low evidence)
Brain Calcification v1.45 ERCC3 Zornitza Stark Gene: ercc3 has been classified as Red List (Low Evidence).
Brain Calcification v1.44 ECM1 Zornitza Stark Classified gene: ECM1 as Green List (high evidence)
Brain Calcification v1.44 ECM1 Zornitza Stark Gene: ecm1 has been classified as Green List (High Evidence).
Brain Calcification v1.43 FAM111A Yetong Chen gene: FAM111A was added
gene: FAM111A was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: FAM111A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FAM111A were set to 32734340; 23996431; 35205306
Phenotypes for gene: FAM111A were set to Kenny-Caffey syndrome, type 2, MIM# 127000
Review for gene: FAM111A was set to GREEN
Added comment: PMID 32734340 reports 3 unrelated patients with FAM111A variants who developed calcification in the basal ganglia. Co-segregation is supported by pedigrees that contain parents and unaffected siblings.
PMID 35205306 reports a patient with a novel FAM111A variant who developed calcification in the basal ganglia and the thalamic region. The FAM111A variant caused Osteocraniostenosis (OCS, OMIM #602361), which is an allelic disorder sharing some common features with Kenny-Caffey syndrome.
Sources: Expert list
Brain Calcification v1.43 ERCC8 Yetong Chen reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17092472, 20522568; Phenotypes: Cockayne syndrome, type A, MIM# 216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.43 ERCC6 Yetong Chen reviewed gene: ERCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 17092472, 20522568; Phenotypes: Cockayne syndrome, type B, MIM# 133540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.43 ERCC5 Yetong Chen gene: ERCC5 was added
gene: ERCC5 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: ERCC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC5 were set to 20301571; 26884178
Phenotypes for gene: ERCC5 were set to Xeroderma pigmentosum, group G; Cockayne syndrome, MIM# 278780
Review for gene: ERCC5 was set to RED
Added comment: PMID 26884178 reports 2 siblings with the same ERCC5 variant who developed bilateral globus pallidus and posterior periventricular white matter calcification.
Sources: Expert list
Brain Calcification v1.43 ERCC3 Yetong Chen edited their review of gene: ERCC3: Changed phenotypes: Xeroderma pigmentosum, group B, MIM# 610651
Brain Calcification v1.43 ERCC3 Yetong Chen gene: ERCC3 was added
gene: ERCC3 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: ERCC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC3 were set to 16947863; 20301571
Review for gene: ERCC3 was set to RED
Added comment: PMID 20301571 reports 2 unrelated patients with ERCC3 variants who developed brain calcification.
Sources: Expert list
Brain Calcification v1.43 ECM1 Yetong Chen edited their review of gene: ECM1: Changed rating: GREEN
Brain Calcification v1.43 ECM1 Yetong Chen gene: ECM1 was added
gene: ECM1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: ECM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECM1 were set to 27398129; 26336196; 12603844
Phenotypes for gene: ECM1 were set to Urbach-Wiethe disease, MIM# 247100
Review for gene: ECM1 was set to AMBER
Added comment: Although reported cases with ECM1 status are limited, Urbach-Wiethe disease is commonly associated with brain calcification.
PMID 27398129 reports a patient with calcifications in both the hippocampi and amygdala. The patient was confirmed to have Urbach-Wiethe syndrome by skin biopsy. However, the paper does not explicitly mention whether genetic testing of the ECM1 gene or genomics testing was done for the patient.

PMID 26336196 reports 2 siblings diagnosed to have Urbach-Wiethe syndrome who developed bilateral basal ganglia calcification. The method of diagnosis and patients' ECM1 status is not mentioned.

PMID 12603844 reports unrelated 3 patients with ECM1 variants who developed temporal lobe calcification.
Sources: Expert list
Brain Calcification v1.43 DENND5A Zornitza Stark Marked gene: DENND5A as ready
Brain Calcification v1.43 DENND5A Zornitza Stark Gene: dennd5a has been classified as Red List (Low Evidence).
Brain Calcification v1.43 AP1S2 Yetong Chen edited their review of gene: AP1S2: Changed publications: 17617514
Brain Calcification v1.43 AP1S2 Yetong Chen changed review comment from: PMID 17617514 reports a linkage study of AP1S2 in 2 unrelated families with multiple generations affected by Fried syndrome. Cosegregation of the phenotype and AP1S2 variants is demonstrated. Two patients from the French family and 3 patients from the Scottish family developed brain calcification.
PMID 19161147 reports 8 individuals from 2 interrelated Omani families who developed brain calcification.; to: PMID 17617514 reports a linkage study of AP1S2 in 2 unrelated families with multiple generations affected by Fried syndrome. Cosegregation of the phenotype and AP1S2 variants is demonstrated. Two patients from the French family and 3 patients from the Scottish family developed brain calcification.
Brain Calcification v1.43 DENND5A Zornitza Stark Classified gene: DENND5A as Red List (low evidence)
Brain Calcification v1.43 DENND5A Zornitza Stark Gene: dennd5a has been classified as Red List (Low Evidence).
Brain Calcification v1.42 CYP2U1 Zornitza Stark Publications for gene: CYP2U1 were set to 23176821
Brain Calcification v1.41 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Brain Calcification v1.41 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Red List (Low Evidence).
Brain Calcification v1.41 CTC1 Zornitza Stark Publications for gene: CTC1 were set to 22267198; 22387016
Brain Calcification v1.40 COL4A2 Zornitza Stark Classified gene: COL4A2 as Red List (low evidence)
Brain Calcification v1.40 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Red List (Low Evidence).
Brain Calcification v1.39 COL4A1 Zornitza Stark Publications for gene: COL4A1 were set to
Brain Calcification v1.38 DENND5A Yetong Chen gene: DENND5A was added
gene: DENND5A was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: DENND5A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DENND5A were set to 32734340; 27866705
Phenotypes for gene: DENND5A were set to Developmental and epileptic encephalopathy 49, MIM# 617281
Review for gene: DENND5A was set to RED
Added comment: Limited evidence supports a causal role of the DENND5A gene in brain calcification.
PMID 27866705 reports that 3 individuals with DENND5A variants, who were from 2 families, developed brain calcification. Co-segregation of the DENND5A variant and pathogenic phenotype is confirmed by sequencing their parents and unaffected sibs.
Sources: Expert list
Brain Calcification v1.38 COL4A2 Yetong Chen changed review comment from: There is no sufficient evidence supporting a causal role of the COL4A2 gene in brain calcification.
PMID 33247988 reports a patient with focal lesions with increased echogenicity in the right basal ganglia, which was suspected to result from either haemorrhage or calcification. However, the patient carries full duplications and deletions of COL4A1 and COL4A2, so it is likely that the brain calcification is not caused by COL4A2.
PMID 33577044 summarises that 4 patients with COL4A2 developed brain calcification, including 1 case from PMID 21357838, 2 cases from PMID 30315939 and 1 from the present paper. This paper does not mention brain calcification found in the 2 reported cases. (Interestingly, there is a calculation mistake for the total number of patients with COL4A2 who had brain calcification. The sum should be 4 instead of 5.)
None of the patients reported by PMID 21357838 carried COL4A2 variants nor developed brain calcification.
Although PMID 30315939 reports 2 patients with COL4A2 variants, they did not show any sign of calcification.
Sources: Expert list; to: There is no sufficient evidence supporting a causal role of the COL4A2 gene in brain calcification.
PMID 33247988 reports a patient with focal lesions with increased echogenicity in the right basal ganglia, which was suspected to result from either haemorrhage or calcification. However, the patient carries full duplications and deletions of COL4A1 and COL4A2, so it is likely that the brain calcification is not caused by COL4A2.
PMID 33577044 summarises that 4 patients with COL4A2 developed brain calcification, including 1 case from PMID 21357838, 2 cases from PMID 30315939 and 1 from the present paper. This paper does not mention brain calcification found in the 2 reported cases. (There is a calculation mistake for the total number of patients with COL4A2 who had brain calcification. The sum should be 4 instead of 5.)
None of the patients reported by PMID 21357838 carried COL4A2 variants nor developed brain calcification.
Although PMID 30315939 reports 2 patients with COL4A2 variants, they did not show any sign of calcification.
Sources: Expert list
Brain Calcification v1.38 CYP2U1 Yetong Chen reviewed gene: CYP2U1: Rating: ; Mode of pathogenicity: None; Publications: 30111349, 33107650, 23176821; Phenotypes: Spastic paraplegia 56, autosomal recessive, MIM# 615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.38 CTC1 Yetong Chen changed review comment from: An additional case is found.
PMID 22532422 reports a patient with a CTC1 variant who developed right-sided thalamic calcification.

PMID 22899577 reports 4 patients with CTC1 variants who developed intracranial cysts or calcification; however, the exact number of patients who developed intracranial calcification is not specified.; to: An additional case is found.
PMID 22532422 reports a patient with a CTC1 variant who developed right-sided thalamic calcification.

PMID 22899577 reports 4 patients with CTC1 variants from 3 families who developed intracranial cysts or calcification; however, the exact number of patients who developed intracranial calcification is not specified.
Brain Calcification v1.38 CTC1 Yetong Chen reviewed gene: CTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22267198, 22532422, 22899577, 22387016, 24372060; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.38 COL4A2 Yetong Chen gene: COL4A2 was added
gene: COL4A2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A2 were set to 33577044; 33247988
Phenotypes for gene: COL4A2 were set to Brain small vessel disease 2, MIM# 614483
Review for gene: COL4A2 was set to RED
Added comment: There is no sufficient evidence supporting a causal role of the COL4A2 gene in brain calcification.
PMID 33247988 reports a patient with focal lesions with increased echogenicity in the right basal ganglia, which was suspected to result from either haemorrhage or calcification. However, the patient carries full duplications and deletions of COL4A1 and COL4A2, so it is likely that the brain calcification is not caused by COL4A2.
PMID 33577044 summarises that 4 patients with COL4A2 developed brain calcification, including 1 case from PMID 21357838, 2 cases from PMID 30315939 and 1 from the present paper. This paper does not mention brain calcification found in the 2 reported cases. (Interestingly, there is a calculation mistake for the total number of patients with COL4A2 who had brain calcification. The sum should be 4 instead of 5.)
None of the patients reported by PMID 21357838 carried COL4A2 variants nor developed brain calcification.
Although PMID 30315939 reports 2 patients with COL4A2 variants, they did not show any sign of calcification.
Sources: Expert list
Brain Calcification v1.38 COL4A1 Yetong Chen Deleted their comment
Brain Calcification v1.38 COL4A1 Yetong Chen edited their review of gene: COL4A1: Added comment: In total, 20 patients with COL4A1 variants who developed brain calcification were reported.
PMID 22134833 reports 5 patients with different COL4A1 variants who developed brain calcification.
PMID 24372060 mentions a patient who has been reported by PMID 22134833 (case 3).
PMID 25719457 reports 2 unrelated patients with different COL4A1 variants who developed brain calcification.
PMID 23225343 reports 7 patients with different COL4A1 variants who developed brain calcification.
PMID 22932948 reports 3 patients with COL4A1 variants who developed brain calcification, and mentions 5 patients who have been reported by PMID 22134833.; Changed publications: 24372060, 22134833, 25719457, 23225343, 22932948
Brain Calcification v1.38 COL4A1 Yetong Chen reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24372060, 22134833; Phenotypes: Brain small vessel disease with or without ocular anomalies, MIM#175780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.38 COASY Zornitza Stark Marked gene: COASY as ready
Brain Calcification v1.38 COASY Zornitza Stark Gene: coasy has been classified as Red List (Low Evidence).
Brain Calcification v1.38 COASY Zornitza Stark Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6 (COPAN); NBIA6 to Neurodegeneration with brain iron accumulation 6, MIM# 615643
Brain Calcification v1.37 COASY Zornitza Stark Classified gene: COASY as Red List (low evidence)
Brain Calcification v1.37 COASY Zornitza Stark Gene: coasy has been classified as Red List (Low Evidence).
Brain Calcification v1.36 CA2 Zornitza Stark Phenotypes for gene: CA2 were changed from Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM# 259730 to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM# 259730
Brain Calcification v1.35 CASR Zornitza Stark Marked gene: CASR as ready
Brain Calcification v1.35 CASR Zornitza Stark Gene: casr has been classified as Green List (High Evidence).
Brain Calcification v1.35 CASR Zornitza Stark Phenotypes for gene: CASR were changed from Hypocalcemia, autosomal dominant; HYPOC1; Hypercalciuric Hypocalcemia; Hypocalcemia, familial to Hypocalcemia, autosomal dominant, MIM# 601198
Brain Calcification v1.34 CASR Zornitza Stark Publications for gene: CASR were set to 32775520; 35402765
Brain Calcification v1.33 CA2 Zornitza Stark Phenotypes for gene: CA2 were changed from Osteopetrosis, autosomal recessive 3, with renal tubular acidosis; OPTB3 to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM# 259730
Brain Calcification v1.33 CASR Zornitza Stark Classified gene: CASR as Green List (high evidence)
Brain Calcification v1.33 CASR Zornitza Stark Gene: casr has been classified as Green List (High Evidence).
Brain Calcification v1.32 CA2 Zornitza Stark Marked gene: CA2 as ready
Brain Calcification v1.32 CA2 Zornitza Stark Gene: ca2 has been classified as Green List (High Evidence).
Brain Calcification v1.32 CASR Zornitza Stark reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8733126, 8813042; Phenotypes: Hypocalcemia, autosomal dominant, MIM# 601198; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.32 C1QB Zornitza Stark Phenotypes for gene: C1QB were changed from C1q deficiency; C1QD to C1q deficiency, MIM# 613652
Brain Calcification v1.32 ATN1 Zornitza Stark Marked gene: ATN1 as ready
Brain Calcification v1.32 ATN1 Zornitza Stark Gene: atn1 has been classified as Red List (Low Evidence).
Brain Calcification v1.32 CA2 Zornitza Stark Classified gene: CA2 as Green List (high evidence)
Brain Calcification v1.32 CA2 Zornitza Stark Gene: ca2 has been classified as Green List (High Evidence).
Brain Calcification v1.31 CA2 Zornitza Stark reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM# 259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.31 C1QB Zornitza Stark Classified gene: C1QB as Red List (low evidence)
Brain Calcification v1.31 C1QB Zornitza Stark Gene: c1qb has been classified as Red List (Low Evidence).
Brain Calcification v1.30 BTD Zornitza Stark Marked gene: BTD as ready
Brain Calcification v1.30 BTD Zornitza Stark Gene: btd has been classified as Red List (Low Evidence).
Brain Calcification v1.30 C1QB Zornitza Stark reviewed gene: C1QB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: None
Brain Calcification v1.30 BTD Zornitza Stark Phenotypes for gene: BTD were changed from Biotinidase Deficiency to Biotinidase deficiency, MIM# 253260
Brain Calcification v1.29 ATN1 Zornitza Stark Phenotypes for gene: ATN1 were changed from Dentatorubral-pallidoluysian atrophy; DRPLA to Dentatorubral-pallidoluysian atrophy, MIM# 125370
Brain Calcification v1.28 BTD Zornitza Stark Classified gene: BTD as Red List (low evidence)
Brain Calcification v1.28 BTD Zornitza Stark Gene: btd has been classified as Red List (Low Evidence).
Brain Calcification v1.27 BTD Zornitza Stark reviewed gene: BTD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Biotinidase deficiency, MIM# 253260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.27 ATN1 Zornitza Stark Classified gene: ATN1 as Red List (low evidence)
Brain Calcification v1.27 ATN1 Zornitza Stark Gene: atn1 has been classified as Red List (Low Evidence).
Brain Calcification v1.26 ATN1 Zornitza Stark Tag STR tag was added to gene: ATN1.
Brain Calcification v1.26 AP1S2 Zornitza Stark Publications for gene: AP1S2 were set to
Brain Calcification v1.25 ACVR1 Zornitza Stark Marked gene: ACVR1 as ready
Brain Calcification v1.25 ACVR1 Zornitza Stark Gene: acvr1 has been classified as Green List (High Evidence).
Brain Calcification v1.25 ACVR1 Zornitza Stark Phenotypes for gene: ACVR1 were changed from Fibrodysplasia ossificans progressiva; FOP to Fibrodysplasia ossificans progressiva, MIM# 135100
Brain Calcification v1.25 ADAR Zornitza Stark Publications for gene: ADAR were set to 23001123; 24262145
Brain Calcification v1.24 ACVR1 Zornitza Stark Classified gene: ACVR1 as Green List (high evidence)
Brain Calcification v1.24 ACVR1 Zornitza Stark Gene: acvr1 has been classified as Green List (High Evidence).
Brain Calcification v1.23 ACVR1 Zornitza Stark reviewed gene: ACVR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fibrodysplasia ossificans progressiva, MIM# 135100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.23 ACP5 Zornitza Stark Phenotypes for gene: ACP5 were changed from Spondyloenchondrodysplasia with immune dysregulation, MIM# 607944 to Spondyloenchondrodysplasia with immune dysregulation, MIM# 607944
Brain Calcification v1.23 ACP5 Zornitza Stark Phenotypes for gene: ACP5 were changed from Spondyloenchondrodysplasia, short stature, SLE, intracranial calcification, spasticity, chilblains, autoimmune haemolytic anaemia to Spondyloenchondrodysplasia with immune dysregulation, MIM# 607944
Brain Calcification v1.22 ACP5 Zornitza Stark edited their review of gene: ACP5: Changed phenotypes: Spondyloenchondrodysplasia with immune dysregulation, MIM# 607944
Brain Calcification v1.22 AP1S2 Yetong Chen changed review comment from: PMID 17617514 reports a linkage study of AP1S2 in 2 unrelated families with multiple generations affected by Fried syndrome. Cosegregation of the phenotype and AP1S2 variants is demonstrated. Two patients from the French family and 3 patients from the Scottish family developed brain calcification.; to: PMID 17617514 reports a linkage study of AP1S2 in 2 unrelated families with multiple generations affected by Fried syndrome. Cosegregation of the phenotype and AP1S2 variants is demonstrated. Two patients from the French family and 3 patients from the Scottish family developed brain calcification.
PMID 19161147 reports 8 individuals from 2 interrelated Omani families who developed brain calcification.
Brain Calcification v1.22 COASY Yetong Chen gene: COASY was added
gene: COASY was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 27487380; 24360804
Phenotypes for gene: COASY were set to Neurodegeneration with brain iron accumulation 6 (COPAN); NBIA6
Review for gene: COASY was set to RED
Added comment: There is limited evidence to support a causal role for the COASY gene in brain calcification.
PMID 24360804 demonstrates variants in COASY as a cause of brain iron accumulation, which includes brain calcification, by using segregation analysis. Brain calcification was found in one patient with a homozygous variant of COASY.
Sources: Expert list
Brain Calcification v1.22 CASR Yetong Chen gene: CASR was added
gene: CASR was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: CASR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASR were set to 32775520; 35402765
Phenotypes for gene: CASR were set to Hypocalcemia, autosomal dominant; HYPOC1; Hypercalciuric Hypocalcemia; Hypocalcemia, familial
Review for gene: CASR was set to RED
Added comment: PMID 32775520 reports co-segregation of a CASR variant and intracranial calcification found in 2 patients from the same family.
PMID 35402765 reports a patient with a CASR variant who developed multiple intracerebral calcifications. A pedigree including the patient and her parents can be found in the paper, but CASR genetic testing was not done on the proband's parents so it could not confirm whether the variant is de novo.
Sources: Expert list
Brain Calcification v1.22 CA2 Yetong Chen gene: CA2 was added
gene: CA2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: CA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CA2 were set to 25674028
Phenotypes for gene: CA2 were set to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis; OPTB3
Review for gene: CA2 was set to GREEN
Added comment: PMID 25674028 reports a female patient with a homozygous variant in the CA2 gene who developed extensive symmetric intracranial calcification.
PMID 22120147 reports brain calcification in 18 individuals, who carry a CA2 variant, from 10 unrelated families. Pedigrees show co-segregation of genotype (homozygous mutant allele) and phenotype.
Sources: Expert list
Brain Calcification v1.22 C1QB Yetong Chen gene: C1QB was added
gene: C1QB was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: C1QB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1QB were set to 23651859
Phenotypes for gene: C1QB were set to C1q deficiency; C1QD
Review for gene: C1QB was set to RED
Added comment: Limited evidence supports a casual role of the C1QB gene in brain calcification.
PMID 23651859 reports a patient with a novel homozygous variant in C1QB who developed bilateral frontal infarcts and basal ganglia calcification.
Sources: Expert list
Brain Calcification v1.22 BTD Yetong Chen gene: BTD was added
gene: BTD was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: BTD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTD were set to 32734340; 3399084
Phenotypes for gene: BTD were set to Biotinidase Deficiency
Review for gene: BTD was set to RED
Added comment: PMID 3399084 reports one case of Biotinidase Deficiency with basal ganglia calcification. However, no strong or moderate evidence suggests that variants in the BTN gene can cause brain calcification.
Sources: Expert list
Brain Calcification v1.22 ATN1 Yetong Chen gene: ATN1 was added
gene: ATN1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: ATN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATN1 were set to 2742549
Phenotypes for gene: ATN1 were set to Dentatorubral-pallidoluysian atrophy; DRPLA
Review for gene: ATN1 was set to RED
Added comment: PMID 2742549 reports the calcification of the globus pallidus in 4 out of the 10 assessed patients with Haw River Syndrome. Although both Haw River Syndrome and DRPLA are caused by the same expanded CAG repeat in the ATN1 gene, no genetic testing was done on the patients to confirm whether they carried ATN1 variants.
Sources: Expert list
Brain Calcification v1.22 AP1S2 Yetong Chen reviewed gene: AP1S2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19161147, 17617514; Phenotypes: Pettigrew syndrome, Fried syndrome, PG5; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Brain Calcification v1.22 ADAR Yetong Chen reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 23001123, 24262145, 30692772; Phenotypes: Aicardi-Goutieres syndrome 6, AGS6; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.22 ACVR1 Yetong Chen gene: ACVR1 was added
gene: ACVR1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: ACVR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACVR1 were set to 27565519
Phenotypes for gene: ACVR1 were set to Fibrodysplasia ossificans progressiva; FOP
Review for gene: ACVR1 was set to GREEN
Added comment: PMID 27565519 reports that 4 individuals with an ACVR1 variant developed T2-hyperintensity with calcifications, while 2 individuals developed isolated calcification in the dentate nuclei. In addition, 7 individuals with an ACVR1 variant developed striatal calcifications in the basal ganglia. (However, the relationship between the reported individuals and their clinical presentations is not clear, and the online supplementary Table S3, which contains the clinico-genetic characteristics of patients, cannot be found.)
Sources: Expert list
Brain Calcification v1.22 ACP5 Yetong Chen changed review comment from: PMID 21217755 reports 4 unrelated individuals with ACP5 variants who developed intracranial calcification.
PMID 21217752 reports 4 individuals with ACP5 variants who developed brain calcification.; to: PMID 21217755 reports 4 unrelated individuals with ACP5 variants who developed intracranial calcification.
PMID 21217752 reports 4 individuals with ACP5 variants who developed brain calcification.
Brain Calcification v1.22 ACP5 Yetong Chen reviewed gene: ACP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24372060, 21217755; Phenotypes: Spondyloenchondrodysplasia with immune dysregulation, SPENCDI; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.22 CLDN5 Zornitza Stark Phenotypes for gene: CLDN5 were changed from alternating hemiplegia, MONDO:0016210, CLDN5-related to Syndromic disorder, MONDO:0002254, CLDN5-related
Brain Calcification v1.21 CLDN5 Zornitza Stark Publications for gene: CLDN5 were set to 35714222
Brain Calcification v1.20 CLDN5 Zornitza Stark Mode of pathogenicity for gene: CLDN5 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 None
Brain Calcification v1.19 CLDN5 Zornitza Stark Classified gene: CLDN5 as Green List (high evidence)
Brain Calcification v1.19 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Green List (High Evidence).
Brain Calcification v1.18 CLDN5 Suliman Khan reviewed gene: CLDN5: 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: PMID: 36477332; Phenotypes: seizures, developmental delay, microcephaly, brain calcifications; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.18 PDGFRB Zornitza Stark Publications for gene: PDGFRB were set to 31004414; 30979360; 32613555; 34494111
Brain Calcification v1.17 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from Basal ganglia calcification, idiopathic, 4, MIM# 615007 to Basal ganglia calcification, idiopathic, 4, MIM# 615007; MONDO:0014004
Brain Calcification v1.16 PDGFRB Zornitza Stark Publications for gene: PDGFRB were set to 31004414; 30979360; 32613555
Brain Calcification v1.15 PDGFRB Achchuthan Shanmugasundram reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 34494111; Phenotypes: Basal ganglia calcification, idiopathic, 4, MIM# 615007, MONDO:0014004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v1.15 Zornitza Stark HPO terms changed from to Cerebral calcification, HP:0002514
List of related panels changed from to Cerebral calcification; HP:0002514
Brain Calcification v1.14 CLDN5 Zornitza Stark Marked gene: CLDN5 as ready
Brain Calcification v1.14 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.14 CLDN5 Zornitza Stark Classified gene: CLDN5 as Amber List (moderate evidence)
Brain Calcification v1.14 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.13 CLDN5 Zornitza Stark gene: CLDN5 was added
gene: CLDN5 was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 35714222
Phenotypes for gene: CLDN5 were set to alternating hemiplegia, MONDO:0016210, CLDN5-related
Mode of pathogenicity for gene: CLDN5 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: CLDN5 was set to AMBER
Added comment: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).

One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting. The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.

CT scans of both showed brain calcifications and aberrant blood flow patterns. Transfected cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability when compared to wildtype.
Sources: Literature
Brain Calcification v1.12 SLC20A2 Teresa Zhao reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34267336; Phenotypes: Basal ganglia calcification MIM#213600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.12 RNU7-1 Zornitza Stark Phenotypes for gene: RNU7-1 were changed from Aicardi–Goutières syndrome-like to Aicardi-Goutieres syndrome 9, MIM# 619487
Brain Calcification v1.11 RNU7-1 Zornitza Stark reviewed gene: RNU7-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 9, MIM# 619487; Mode of inheritance: None
Brain Calcification v1.11 LSM11 Zornitza Stark Phenotypes for gene: LSM11 were changed from type I interferonopathy Aicardi–Goutières syndrome to Aicardi-Goutieres syndrome 8, MIM# 619486
Brain Calcification v1.10 LSM11 Zornitza Stark reviewed gene: LSM11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 8, MIM# 619486; Mode of inheritance: None
Brain Calcification v1.10 COLGALT1 Bryony Thompson Marked gene: COLGALT1 as ready
Brain Calcification v1.10 COLGALT1 Bryony Thompson Gene: colgalt1 has been classified as Green List (High Evidence).
Brain Calcification v1.10 COLGALT1 Bryony Thompson Classified gene: COLGALT1 as Green List (high evidence)
Brain Calcification v1.10 COLGALT1 Bryony Thompson Gene: colgalt1 has been classified as Green List (High Evidence).
Brain Calcification v1.9 COLGALT1 Bryony Thompson gene: COLGALT1 was added
gene: COLGALT1 was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLGALT1 were set to 30412317; 33709034; 31759980
Phenotypes for gene: COLGALT1 were set to Brain small vessel disease 3 MIM#618360
Review for gene: COLGALT1 was set to GREEN
Added comment: 3 unrelated cases with biallelic variants, and supporting functional assays. The main features of the cases were porencephalic cysts, leukoencephalopathy, lacunar infarcts, cerebral microbleeds/haemorrhages and calcifications. A null mouse model was embryonic lethal, but had defects in the vascular networks of the embryos
Sources: Literature
Brain Calcification v1.8 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Brain Calcification v1.7 FARSA Zornitza Stark Publications for gene: FARSA were set to 31355908
Brain Calcification v1.6 FARSA Chirag Patel Classified gene: FARSA as Green List (high evidence)
Brain Calcification v1.6 FARSA Chirag Patel Gene: farsa has been classified as Green List (High Evidence).
Brain Calcification v1.5 FARSA Chirag Patel reviewed gene: FARSA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33598926; Phenotypes: Rajab interstitial lung disease with brain calcifications 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Brain Calcification v1.5 RNU7-1 Zornitza Stark Marked gene: RNU7-1 as ready
Brain Calcification v1.5 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Brain Calcification v1.5 RNU7-1 Zornitza Stark Classified gene: RNU7-1 as Green List (high evidence)
Brain Calcification v1.5 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Brain Calcification v1.4 LSM11 Zornitza Stark Marked gene: LSM11 as ready
Brain Calcification v1.4 LSM11 Zornitza Stark Gene: lsm11 has been classified as Red List (Low Evidence).
Brain Calcification v1.4 LSM11 Zornitza Stark Classified gene: LSM11 as Red List (low evidence)
Brain Calcification v1.4 LSM11 Zornitza Stark Gene: lsm11 has been classified as Red List (Low Evidence).
Brain Calcification v1.3 LSM11 Ee Ming Wong reviewed gene: LSM11: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 33230297; Phenotypes: type I interferonopathy Aicardi–Goutières syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Brain Calcification v1.3 LSM11 Ee Ming Wong Deleted their review
Brain Calcification v1.3 LSM11 Ee Ming Wong gene: LSM11 was added
gene: LSM11 was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: LSM11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM11 were set to PMID: 33230297
Phenotypes for gene: LSM11 were set to type I interferonopathy Aicardi–Goutières syndrome
gene: LSM11 was marked as current diagnostic
Added comment: - Two affected siblings from a consanguineous family carrying a homozygous variant in LSM11
- Compared to control fibroblasts, patient fibroblasts were enriched for misprocessed forms of
replication-dependent histone (RDH) mRNAs
- Knockdown of LSM11 in THP-1 cells results in an increase in misprocessed RDH mRNA and
interferon signaling

(added as Red as per discussion with Seb)
Sources: Literature
Brain Calcification v1.3 RNU7-1 Paul De Fazio gene: RNU7-1 was added
gene: RNU7-1 was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: RNU7-1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU7-1 were set to 33230297
Phenotypes for gene: RNU7-1 were set to Aicardi–Goutières syndrome-like
Review for gene: RNU7-1 was set to GREEN
gene: RNU7-1 was marked as current diagnostic
Added comment: Review originally submitted by Ming Wong
- 16 affected individuals from 11 families
- Compared to control fibroblasts, patient fibroblasts were enriched for misprocessed forms of
replication-dependent histone (RDH) mRNAs
Sources: Literature
Brain Calcification v1.2 TREM2 Zornitza Stark Marked gene: TREM2 as ready
Brain Calcification v1.2 TREM2 Zornitza Stark Gene: trem2 has been classified as Green List (High Evidence).
Brain Calcification v1.2 TREM2 Zornitza Stark Classified gene: TREM2 as Green List (high evidence)
Brain Calcification v1.2 TREM2 Zornitza Stark Gene: trem2 has been classified as Green List (High Evidence).
Brain Calcification v1.1 TREM2 Zornitza Stark gene: TREM2 was added
gene: TREM2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: TREM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TREM2 were set to 12080485; 15883308
Phenotypes for gene: TREM2 were set to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193
Review for gene: TREM2 was set to GREEN
Added comment: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-2 (PLOSL2), or Nasu-Hakola disease, is a recessively inherited presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time. The disorder culminates in a profound dementia and death by age 50 years. More than 5 unrelated families reported.
Sources: Expert list
Brain Calcification v1.0 Zornitza Stark promoted panel to version 1.0
Brain Calcification v0.90 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Brain Calcification v0.90 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Brain Calcification v0.90 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from to Brain small vessel disease with or without ocular anomalies, MIM# 175780
Brain Calcification v0.89 COL4A1 Zornitza Stark Mode of inheritance for gene: COL4A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.88 COL4A1 Zornitza Stark reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain small vessel disease with or without ocular anomalies, MIM# 175780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.88 RNASEH2B Zornitza Stark Marked gene: RNASEH2B as ready
Brain Calcification v0.88 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Brain Calcification v0.88 RNASEH2B Zornitza Stark Phenotypes for gene: RNASEH2B were changed from to Aicardi-Goutieres syndrome 2, MIM# 610181
Brain Calcification v0.88 RNASEH2B Zornitza Stark Mode of inheritance for gene: RNASEH2B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.87 RNASEH2B Zornitza Stark Publications for gene: RNASEH2B were set to
Brain Calcification v0.86 RNASEH2B Zornitza Stark reviewed gene: RNASEH2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 16845400, 33307271, 29239743; Phenotypes: Aicardi-Goutieres syndrome 2, MIM# 610181; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.86 RNASEH2A Zornitza Stark Marked gene: RNASEH2A as ready
Brain Calcification v0.86 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Brain Calcification v0.86 RNASEH2A Zornitza Stark Phenotypes for gene: RNASEH2A were changed from to Aicardi-Goutieres syndrome 4, MIM# 610333
Brain Calcification v0.85 RNASEH2A Zornitza Stark Publications for gene: RNASEH2A were set to
Brain Calcification v0.84 RNASEH2A Zornitza Stark Mode of inheritance for gene: RNASEH2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.83 RNASEH2A Zornitza Stark reviewed gene: RNASEH2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 17846997, 16845400, 23592335, 27643693; Phenotypes: Aicardi-Goutieres syndrome 4, MIM# 610333; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.83 PDGFRB Zornitza Stark Marked gene: PDGFRB as ready
Brain Calcification v0.83 PDGFRB Zornitza Stark Gene: pdgfrb has been classified as Green List (High Evidence).
Brain Calcification v0.83 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from to Basal ganglia calcification, idiopathic, 4, MIM# 615007
Brain Calcification v0.82 PDGFRB Zornitza Stark Publications for gene: PDGFRB were set to
Brain Calcification v0.81 PDGFRB Zornitza Stark Mode of inheritance for gene: PDGFRB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.80 PDGFRB Zornitza Stark reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31004414, 30979360, 32613555; Phenotypes: Basal ganglia calcification, idiopathic, 4, MIM# 615007; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.80 PDGFB Zornitza Stark changed review comment from: Well established gene-disease association.; to: Idiopathic basal ganglia calcification-5 (IBGC5) is an autosomal dominant disorder characterized by progressive neurologic symptoms that are associated with brain calcifications mainly affecting the basal ganglia. Calcifications may also occur in the thalamus, cerebellum, or white matter. Affected individuals have motor symptoms, such as dyskinesias or parkinsonism, headache, cognitive impairment, and psychiatric manifestations, including apathy and depression. Some individuals are asymptomatic. The age at symptom onset ranges from late childhood to adulthood; the disorder is progressive. Multiple families reported.
Brain Calcification v0.80 PDGFB Zornitza Stark Marked gene: PDGFB as ready
Brain Calcification v0.80 PDGFB Zornitza Stark Gene: pdgfb has been classified as Green List (High Evidence).
Brain Calcification v0.80 PDGFB Zornitza Stark Phenotypes for gene: PDGFB were changed from to Basal ganglia calcification, idiopathic, 5 , MIM#615483
Brain Calcification v0.79 PDGFB Zornitza Stark Publications for gene: PDGFB were set to
Brain Calcification v0.78 PDGFB Zornitza Stark Mode of inheritance for gene: PDGFB was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.77 PDGFB Zornitza Stark Mode of inheritance for gene: PDGFB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.76 PDGFB Zornitza Stark reviewed gene: PDGFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23913003, 30952898, 30609140; Phenotypes: Basal ganglia calcification, idiopathic, 5 , MIM#615483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.76 RNASEH2C Zornitza Stark Marked gene: RNASEH2C as ready
Brain Calcification v0.76 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Brain Calcification v0.76 RNASEH2C Zornitza Stark Phenotypes for gene: RNASEH2C were changed from to Aicardi-Goutieres syndrome 3, MIM# 610329
Brain Calcification v0.75 RNASEH2C Zornitza Stark Publications for gene: RNASEH2C were set to
Brain Calcification v0.74 RNASEH2C Zornitza Stark Mode of inheritance for gene: RNASEH2C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.73 RNASEH2C Zornitza Stark reviewed gene: RNASEH2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 16845400, 29239743, 29150899, 27643693; Phenotypes: Aicardi-Goutieres syndrome 3, MIM# 610329; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.73 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Brain Calcification v0.73 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Brain Calcification v0.73 SAMHD1 Zornitza Stark Phenotypes for gene: SAMHD1 were changed from to Aicardi-Goutieres syndrome 5, MIM# 612952
Brain Calcification v0.72 SAMHD1 Zornitza Stark Publications for gene: SAMHD1 were set to
Brain Calcification v0.71 SAMHD1 Zornitza Stark Mode of inheritance for gene: SAMHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.70 SAMHD1 Zornitza Stark reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19525956, 21102625, 33307271; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.70 TREX1 Zornitza Stark Marked gene: TREX1 as ready
Brain Calcification v0.70 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Brain Calcification v0.70 TREX1 Zornitza Stark Phenotypes for gene: TREX1 were changed from to Aicardi-Goutieres syndrome 1, dominant and recessive, MIM# 225750
Brain Calcification v0.69 TREX1 Zornitza Stark Publications for gene: TREX1 were set to
Brain Calcification v0.68 TREX1 Zornitza Stark Mode of inheritance for gene: TREX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v0.67 TREX1 Zornitza Stark reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17846997; Phenotypes: Aicardi-Goutieres syndrome 1, dominant and recessive, MIM# 225750; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v0.67 ERCC8 Zornitza Stark Marked gene: ERCC8 as ready
Brain Calcification v0.67 ERCC8 Zornitza Stark Gene: ercc8 has been classified as Green List (High Evidence).
Brain Calcification v0.67 ERCC8 Zornitza Stark Phenotypes for gene: ERCC8 were changed from to Cockayne syndrome, type A, MIM# 216400
Brain Calcification v0.66 ERCC8 Zornitza Stark Publications for gene: ERCC8 were set to
Brain Calcification v0.65 ERCC8 Zornitza Stark Mode of inheritance for gene: ERCC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.64 ERCC8 Zornitza Stark reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 26204423; Phenotypes: Cockayne syndrome, type A, MIM# 216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.64 ADAR Zornitza Stark Mode of inheritance for gene: ADAR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v0.63 ADAR Zornitza Stark edited their review of gene: ADAR: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v0.63 CTC1 Zornitza Stark Marked gene: CTC1 as ready
Brain Calcification v0.63 CTC1 Zornitza Stark Gene: ctc1 has been classified as Green List (High Evidence).
Brain Calcification v0.63 CTC1 Zornitza Stark Phenotypes for gene: CTC1 were changed from to Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199
Brain Calcification v0.62 CTC1 Zornitza Stark Publications for gene: CTC1 were set to
Brain Calcification v0.61 CTC1 Zornitza Stark Mode of inheritance for gene: CTC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.60 CTC1 Zornitza Stark reviewed gene: CTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22267198, 22387016; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.60 OCLN Zornitza Stark Marked gene: OCLN as ready
Brain Calcification v0.60 OCLN Zornitza Stark Gene: ocln has been classified as Green List (High Evidence).
Brain Calcification v0.60 OCLN Zornitza Stark Phenotypes for gene: OCLN were changed from to Pseudo-TORCH syndrome 1, MIM#251290
Brain Calcification v0.59 OCLN Zornitza Stark Publications for gene: OCLN were set to
Brain Calcification v0.58 OCLN Zornitza Stark Mode of inheritance for gene: OCLN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.57 OCLN Zornitza Stark reviewed gene: OCLN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20727516, 32240828, 29192239, 28386946; Phenotypes: Pseudo-TORCH syndrome 1, MIM#251290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.57 ERCC6 Zornitza Stark Marked gene: ERCC6 as ready
Brain Calcification v0.57 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Green List (High Evidence).
Brain Calcification v0.57 ERCC6 Zornitza Stark Phenotypes for gene: ERCC6 were changed from to Cockayne syndrome, type B, MIM#133540
Brain Calcification v0.56 ERCC6 Zornitza Stark Mode of inheritance for gene: ERCC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.55 ERCC6 Zornitza Stark reviewed gene: ERCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cockayne syndrome, type B, MIM#133540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.55 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Brain Calcification v0.55 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Brain Calcification v0.55 JAM3 Zornitza Stark Phenotypes for gene: JAM3 were changed from to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Brain Calcification v0.54 JAM3 Zornitza Stark Publications for gene: JAM3 were set to
Brain Calcification v0.53 JAM3 Zornitza Stark Mode of inheritance for gene: JAM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.52 JAM3 Zornitza Stark reviewed gene: JAM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255084, 21109224; Phenotypes: Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.52 IFIH1 Zornitza Stark Marked gene: IFIH1 as ready
Brain Calcification v0.52 IFIH1 Zornitza Stark Gene: ifih1 has been classified as Green List (High Evidence).
Brain Calcification v0.52 IFIH1 Zornitza Stark Phenotypes for gene: IFIH1 were changed from to Aicardi-Goutieres syndrome 7, MIM#615846
Brain Calcification v0.51 IFIH1 Zornitza Stark Publications for gene: IFIH1 were set to
Brain Calcification v0.50 IFIH1 Zornitza Stark Mode of inheritance for gene: IFIH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.49 IFIH1 Zornitza Stark reviewed gene: IFIH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24686847; Phenotypes: Aicardi-Goutieres syndrome 7, MIM#615846; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.49 ADAR Zornitza Stark Marked gene: ADAR as ready
Brain Calcification v0.49 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Brain Calcification v0.49 ADAR Zornitza Stark Phenotypes for gene: ADAR were changed from to Aicardi-Goutieres syndrome 6, MIM#615010
Brain Calcification v0.48 ADAR Zornitza Stark Publications for gene: ADAR were set to
Brain Calcification v0.47 ADAR Zornitza Stark Mode of inheritance for gene: ADAR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.46 ADAR Zornitza Stark reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 23001123, 24262145; Phenotypes: Aicardi-Goutieres syndrome 6, MIM#615010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.46 STN1 Zornitza Stark Publications for gene: STN1 were set to 27432940
Brain Calcification v0.45 STN1 Zornitza Stark Classified gene: STN1 as Green List (high evidence)
Brain Calcification v0.45 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Brain Calcification v0.44 STN1 Zornitza Stark edited their review of gene: STN1: Added comment: Third unrelated family reported, promoted to Green.; Changed rating: GREEN; Changed publications: 27432940, 32627942; Changed phenotypes: Cerebroretinal microangiopathy with calcifications and cysts 2, MIM# 617341
Brain Calcification v0.44 XPR1 Zornitza Stark Marked gene: XPR1 as ready
Brain Calcification v0.44 XPR1 Zornitza Stark Gene: xpr1 has been classified as Green List (High Evidence).
Brain Calcification v0.44 XPR1 Zornitza Stark Phenotypes for gene: XPR1 were changed from to Basal ganglia calcification, idiopathic, 6, MIM# 616413
Brain Calcification v0.43 XPR1 Zornitza Stark Publications for gene: XPR1 were set to
Brain Calcification v0.42 XPR1 Zornitza Stark Mode of inheritance for gene: XPR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.41 XPR1 Zornitza Stark reviewed gene: XPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25938945; Phenotypes: Basal ganglia calcification, idiopathic, 6, MIM# 616413; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.41 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317 to Basal ganglia calcification, idiopathic, 7, MIM#618317
Brain Calcification v0.40 KIAA1161 Zornitza Stark Publications for gene: KIAA1161 were set to PubMed: 30656188, 30649222, 30460687, 29910000
Brain Calcification v0.39 KIAA1161 Zornitza Stark Mode of inheritance for gene: KIAA1161 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v0.38 KIAA1161 Zornitza Stark Tag new gene name tag was added to gene: KIAA1161.
Brain Calcification v0.38 KIAA1161 Zornitza Stark changed review comment from: In a cohort study comprising 435 individuals with primary brain calcification, 38 individuals identified with mono-allelic variants in this gene, in addition to 14 with bi-allelic variants. Clinical and imaging penetrance of individuals with bi-allelic variants were 100%, whereas among individuals with heterozygous variants, penetrance of imaging phenotype was reduced to 73.7% (28 of 38) and clinical penetrance was much lower. Most (34 of 38) remained asymptomatic whereas 4 had symptoms of uncertain clinical significance (nonspecific depression, epilepsy and late-onset parkinsonism). Compared with individuals with biallelic MYORG variants, individuals with heterozygous variants had brain calcifications with much lower calcification scores (P < 2e-16).; to: In a cohort study comprising 435 individuals with primary brain calcification, 38 individuals identified with mono-allelic variants in this gene, in addition to 14 with bi-allelic variants. Clinical and imaging penetrance of individuals with bi-allelic variants were 100%, whereas among individuals with heterozygous variants, penetrance of imaging phenotype was reduced to 73.7% (28 of 38) and clinical penetrance was much lower. Most (34 of 38) remained asymptomatic whereas 4 had symptoms of uncertain clinical significance (nonspecific depression, epilepsy and late-onset parkinsonism). Compared with individuals with biallelic MYORG variants, individuals with heterozygous variants had brain calcifications with much lower calcification scores (P < 2e-16).

HGNC approved name is MYORG.
Brain Calcification v0.38 KIAA1161 Zornitza Stark reviewed gene: KIAA1161: Rating: GREEN; Mode of pathogenicity: None; Publications: 31951047; Phenotypes: Basal ganglia calcification, idiopathic, 7, MIM#618317; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v0.38 FARSA Zornitza Stark Marked gene: FARSA as ready
Brain Calcification v0.38 FARSA Zornitza Stark Gene: farsa has been classified as Red List (Low Evidence).
Brain Calcification v0.38 FARSA Zornitza Stark gene: FARSA was added
gene: FARSA was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: FARSA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FARSA were set to 31355908
Phenotypes for gene: FARSA were set to Rajab interstitial lung disease with brain calcifications 2, MIM# 619013
Review for gene: FARSA was set to RED
Added comment: Autosomal recessive disorder characterized by growth delay, interstitial lung disease, liver disease, and abnormal brain MRI findings, including brain calcifications and periventricular cysts. Single affected individual reported, but FARSA interacts with FARSB, which causes a similar disorder.
Sources: Expert list
Brain Calcification v0.37 SLC20A2 Zornitza Stark Marked gene: SLC20A2 as ready
Brain Calcification v0.37 SLC20A2 Zornitza Stark Gene: slc20a2 has been classified as Green List (High Evidence).
Brain Calcification v0.37 SLC20A2 Zornitza Stark Phenotypes for gene: SLC20A2 were changed from to Basal ganglia calcification, idiopathic, 1, MIM# 213600
Brain Calcification v0.36 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to
Brain Calcification v0.35 SLC20A2 Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.34 SLC20A2 Zornitza Stark reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22327515, 23334463; Phenotypes: Basal ganglia calcification, idiopathic, 1, MIM# 213600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.34 TINF2 Zornitza Stark Marked gene: TINF2 as ready
Brain Calcification v0.34 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Brain Calcification v0.34 TINF2 Zornitza Stark Classified gene: TINF2 as Green List (high evidence)
Brain Calcification v0.34 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Brain Calcification v0.33 TINF2 Zornitza Stark gene: TINF2 was added
gene: TINF2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: TINF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TINF2 were set to 21477109; 18252230
Phenotypes for gene: TINF2 were set to Revesz syndrome, MIM# 268130
Review for gene: TINF2 was set to GREEN
Added comment: Brain calcifications are part of the phenotype.
Sources: Expert list
Brain Calcification v0.32 TYROBP Zornitza Stark Marked gene: TYROBP as ready
Brain Calcification v0.32 TYROBP Zornitza Stark Gene: tyrobp has been classified as Green List (High Evidence).
Brain Calcification v0.32 TYROBP Zornitza Stark Classified gene: TYROBP as Green List (high evidence)
Brain Calcification v0.32 TYROBP Zornitza Stark Gene: tyrobp has been classified as Green List (High Evidence).
Brain Calcification v0.31 TYROBP Zornitza Stark gene: TYROBP was added
gene: TYROBP was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: TYROBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYROBP were set to 30242731
Phenotypes for gene: TYROBP were set to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, MIM# 221770
Review for gene: TYROBP was set to GREEN
Added comment: Brain calcifications are part of the phenotype.
Sources: Expert list
Brain Calcification v0.30 RNASET2 Zornitza Stark Marked gene: RNASET2 as ready
Brain Calcification v0.30 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Green List (High Evidence).
Brain Calcification v0.30 RNASET2 Zornitza Stark Classified gene: RNASET2 as Green List (high evidence)
Brain Calcification v0.30 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Green List (High Evidence).
Brain Calcification v0.29 RNASET2 Zornitza Stark gene: RNASET2 was added
gene: RNASET2 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: RNASET2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASET2 were set to 19525954
Phenotypes for gene: RNASET2 were set to Leukoencephalopathy, cystic, without megalencephaly, MIM# 612951
Review for gene: RNASET2 was set to GREEN
Added comment: Intracranial calcification is a feature of this condition.
Sources: Expert list
Brain Calcification v0.28 GALC Zornitza Stark Marked gene: GALC as ready
Brain Calcification v0.28 GALC Zornitza Stark Gene: galc has been classified as Green List (High Evidence).
Brain Calcification v0.28 GALC Zornitza Stark Classified gene: GALC as Green List (high evidence)
Brain Calcification v0.28 GALC Zornitza Stark Gene: galc has been classified as Green List (High Evidence).
Brain Calcification v0.27 GALC Zornitza Stark gene: GALC was added
gene: GALC was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALC were set to Krabbe disease, MIM# 245200
Review for gene: GALC was set to GREEN
Added comment: Thalamus calcification is a feature of Krabbe disease.
Sources: Expert list
Brain Calcification v0.26 TSC2 Zornitza Stark Marked gene: TSC2 as ready
Brain Calcification v0.26 TSC2 Zornitza Stark Gene: tsc2 has been classified as Green List (High Evidence).
Brain Calcification v0.26 TSC2 Zornitza Stark Phenotypes for gene: TSC2 were changed from to Tuberous sclerosis 2, MIM# 613254
Brain Calcification v0.25 TSC2 Zornitza Stark Mode of inheritance for gene: TSC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.24 TSC2 Zornitza Stark reviewed gene: TSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tuberous sclerosis 2, MIM# 613254; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.24 TSC1 Zornitza Stark Marked gene: TSC1 as ready
Brain Calcification v0.24 TSC1 Zornitza Stark Gene: tsc1 has been classified as Green List (High Evidence).
Brain Calcification v0.24 TSC1 Zornitza Stark Phenotypes for gene: TSC1 were changed from to Tuberous sclerosis 1, MIM# 191100
Brain Calcification v0.23 TSC1 Zornitza Stark Mode of inheritance for gene: TSC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.22 TSC1 Zornitza Stark reviewed gene: TSC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tuberous sclerosis 1, MIM# 191100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.22 CYP2U1 Zornitza Stark Marked gene: CYP2U1 as ready
Brain Calcification v0.22 CYP2U1 Zornitza Stark Gene: cyp2u1 has been classified as Green List (High Evidence).
Brain Calcification v0.22 CYP2U1 Zornitza Stark Classified gene: CYP2U1 as Green List (high evidence)
Brain Calcification v0.22 CYP2U1 Zornitza Stark Gene: cyp2u1 has been classified as Green List (High Evidence).
Brain Calcification v0.21 CYP2U1 Zornitza Stark gene: CYP2U1 was added
gene: CYP2U1 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: CYP2U1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP2U1 were set to 23176821
Phenotypes for gene: CYP2U1 were set to Spastic paraplegia 56, autosomal recessive, MIM# 615030
Review for gene: CYP2U1 was set to GREEN
Added comment: Established gene-disease association, basal ganglia calcification is a feature.
Sources: Expert list
Brain Calcification v0.20 ACP5 Zornitza Stark Marked gene: ACP5 as ready
Brain Calcification v0.20 ACP5 Zornitza Stark Gene: acp5 has been classified as Green List (High Evidence).
Brain Calcification v0.20 ACP5 Zornitza Stark Classified gene: ACP5 as Green List (high evidence)
Brain Calcification v0.20 ACP5 Zornitza Stark Gene: acp5 has been classified as Green List (High Evidence).
Brain Calcification v0.19 ACP5 Zornitza Stark gene: ACP5 was added
gene: ACP5 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: ACP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACP5 were set to 21217755; 21217752
Phenotypes for gene: ACP5 were set to Spondyloenchondrodysplasia, short stature, SLE, intracranial calcification, spasticity, chilblains, autoimmune haemolytic anaemia
Review for gene: ACP5 was set to GREEN
Added comment: Established gene-disease association, intracranial calcification is part of the phenotype.
Sources: Expert list
Brain Calcification v0.18 USP18 Zornitza Stark Marked gene: USP18 as ready
Brain Calcification v0.18 USP18 Zornitza Stark Gene: usp18 has been classified as Green List (High Evidence).
Brain Calcification v0.18 USP18 Zornitza Stark Classified gene: USP18 as Green List (high evidence)
Brain Calcification v0.18 USP18 Zornitza Stark Gene: usp18 has been classified as Green List (High Evidence).
Brain Calcification v0.17 USP18 Zornitza Stark gene: USP18 was added
gene: USP18 was added to Brain Calcification. Sources: Expert list
Mode of inheritance for gene: USP18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP18 were set to 31940699; 27325888
Phenotypes for gene: USP18 were set to Pseudo-TORCH syndrome 2, MIM# 617397
Review for gene: USP18 was set to GREEN
Added comment: Three unrelated families reported. Note cryptic 3' deletion identified in one.
Sources: Expert list
Brain Calcification v0.16 NRROS Zornitza Stark Marked gene: NRROS as ready
Brain Calcification v0.16 NRROS Zornitza Stark Gene: nrros has been classified as Green List (High Evidence).
Brain Calcification v0.16 NRROS Zornitza Stark Classified gene: NRROS as Green List (high evidence)
Brain Calcification v0.16 NRROS Zornitza Stark Gene: nrros has been classified as Green List (High Evidence).
Brain Calcification v0.15 NRROS Zornitza Stark gene: NRROS was added
gene: NRROS was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: NRROS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRROS were set to 32100099; 32197075
Phenotypes for gene: NRROS were set to neurodegeneration; intracranial calcification; epilepsy
Review for gene: NRROS was set to GREEN
Added comment: Normal development or mild developmental delay until onset of regression around age of 1 concurrent with epilepsy
Biallelic LOF mutations with functional evidence of pathogenicity reported in 6 unrelated families.
Sources: Literature
Brain Calcification v0.14 JAM2 Zornitza Stark edited their review of gene: JAM2: Changed rating: GREEN
Brain Calcification v0.14 Zornitza Stark Panel name changed from Brain calcification to Brain Calcification
Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Brain Calcification v0.13 Zornitza Stark Panel name changed from Brain calcification_VCGS to Brain calcification
Panel types changed to Victorian Clinical Genetics Services
Brain Calcification v0.12 STN1 Zornitza Stark Marked gene: STN1 as ready
Brain Calcification v0.12 STN1 Zornitza Stark Gene: stn1 has been classified as Amber List (Moderate Evidence).
Brain Calcification v0.12 STN1 Zornitza Stark Classified gene: STN1 as Amber List (moderate evidence)
Brain Calcification v0.12 STN1 Zornitza Stark Gene: stn1 has been classified as Amber List (Moderate Evidence).
Brain Calcification v0.11 STN1 Zornitza Stark gene: STN1 was added
gene: STN1 was added to Brain calcification_VCGS. Sources: Expert list
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 27432940
Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcifications and cysts 2, MIM# 617341
Review for gene: STN1 was set to AMBER
Added comment: Two individuals from unrelated families described with a multisystem disorder characterized by premature aging, pancytopaenia, hypocellular bone marrow, osteopenia, liver fibrosis, and vascular telangiectasia resulting in gastrointestinal bleeding, as well as intracranial calcifications and leukodystrophy, resulting in spasticity, ataxia, or dystonia.
Sources: Expert list
Brain Calcification v0.10 SNORD118 Zornitza Stark Marked gene: SNORD118 as ready
Brain Calcification v0.10 SNORD118 Zornitza Stark Gene: snord118 has been classified as Green List (High Evidence).
Brain Calcification v0.10 SNORD118 Zornitza Stark Classified gene: SNORD118 as Green List (high evidence)
Brain Calcification v0.10 SNORD118 Zornitza Stark Gene: snord118 has been classified as Green List (High Evidence).
Brain Calcification v0.9 SNORD118 Zornitza Stark gene: SNORD118 was added
gene: SNORD118 was added to Brain calcification_VCGS. Sources: Expert list
Mode of inheritance for gene: SNORD118 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNORD118 were set to 27571260
Phenotypes for gene: SNORD118 were set to Leukoencephalopathy, brain calcifications, and cysts, MIM#614561
Review for gene: SNORD118 was set to GREEN
Added comment: Over 30 families reported.
Sources: Expert list
Brain Calcification v0.8 FARSB Zornitza Stark Marked gene: FARSB as ready
Brain Calcification v0.8 FARSB Zornitza Stark Gene: farsb has been classified as Green List (High Evidence).
Brain Calcification v0.8 FARSB Zornitza Stark Classified gene: FARSB as Green List (high evidence)
Brain Calcification v0.8 FARSB Zornitza Stark Gene: farsb has been classified as Green List (High Evidence).
Brain Calcification v0.7 FARSB Zornitza Stark gene: FARSB was added
gene: FARSB was added to Brain calcification_VCGS. Sources: Expert list
Mode of inheritance for gene: FARSB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FARSB were set to 29573043; 19161147; 29979980; 30014610
Phenotypes for gene: FARSB were set to Rajab syndrome, MIM#613658; interstitial lung disease; brain calcifications; microcephaly; intellectual disability
Review for gene: FARSB was set to GREEN
Added comment: 7 unrelated families reported.
Sources: Expert list
Brain Calcification v0.6 AP1S2 Zornitza Stark Marked gene: AP1S2 as ready
Brain Calcification v0.6 AP1S2 Zornitza Stark Gene: ap1s2 has been classified as Green List (High Evidence).
Brain Calcification v0.6 AP1S2 Zornitza Stark Classified gene: AP1S2 as Green List (high evidence)
Brain Calcification v0.6 AP1S2 Zornitza Stark Gene: ap1s2 has been classified as Green List (High Evidence).
Brain Calcification v0.5 AP1S2 Zornitza Stark gene: AP1S2 was added
gene: AP1S2 was added to Brain calcification_VCGS. Sources: Expert list
Mode of inheritance for gene: AP1S2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: AP1S2 were set to Mental retardation, X-linked syndromic 5, MIM#304340
Review for gene: AP1S2 was set to GREEN
Added comment: Iron and calcium deposition in the brain is a feature of this condition.
Sources: Expert list
Brain Calcification v0.4 JAM2 Zornitza Stark Marked gene: JAM2 as ready
Brain Calcification v0.4 JAM2 Zornitza Stark Gene: jam2 has been classified as Green List (High Evidence).
Brain Calcification v0.4 JAM2 Zornitza Stark Classified gene: JAM2 as Green List (high evidence)
Brain Calcification v0.4 JAM2 Zornitza Stark Gene: jam2 has been classified as Green List (High Evidence).
Brain Calcification v0.3 JAM2 Zornitza Stark gene: JAM2 was added
gene: JAM2 was added to Brain calcification_VCGS. Sources: Literature
Mode of inheritance for gene: JAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAM2 were set to 31851307
Phenotypes for gene: JAM2 were set to Primary brain calcification
Added comment: Three unrelated families with bi-allelic variants reported. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and probable asymptomatic (1/4), with diverse onset ages.
Sources: Literature
Brain Calcification v0.2 KIAA1161 Zornitza Stark Marked gene: KIAA1161 as ready
Brain Calcification v0.2 KIAA1161 Zornitza Stark Gene: kiaa1161 has been classified as Green List (High Evidence).
Brain Calcification v0.2 KIAA1161 Chirag Patel Classified gene: KIAA1161 as Green List (high evidence)
Brain Calcification v0.2 KIAA1161 Chirag Patel Gene: kiaa1161 has been classified as Green List (High Evidence).
Brain Calcification v0.1 KIAA1161 Chirag Patel gene: KIAA1161 was added
gene: KIAA1161 was added to Brain calcification_VCGS. Sources: Literature
Mode of inheritance for gene: KIAA1161 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1161 were set to PubMed: 30656188, 30649222, 30460687, 29910000
Phenotypes for gene: KIAA1161 were set to Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317
Review for gene: KIAA1161 was set to GREEN
Added comment: Total 9 families, but no functional evidence:

12 patients from 6 unrelated Chinese families reported by Yao et al. (2018) and homozygous or compound heterozygous mutations in the MYORG gene. Functional studies of the variants and studies of patient cells were not performed, but the presence of nonsense mutations suggested a loss of function.

1 Chinese woman identified with homozygous nonsense mutation in the MYORG gene, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed.

2 unrelated Middle Eastern families with homozygous mutations in the MYORG gene, which segregated with the disorder in the families. Functional studies of the variants were not performed.

4 sibs from one Turkish family with homozygous missense mutation in the MYORG gene, which segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed.
Sources: Literature
Brain Calcification v0.0 XPR1 Zornitza Stark gene: XPR1 was added
gene: XPR1 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: XPR1 was set to Unknown
Brain Calcification v0.0 TSC2 Zornitza Stark gene: TSC2 was added
gene: TSC2 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TSC2 was set to Unknown
Brain Calcification v0.0 TSC1 Zornitza Stark gene: TSC1 was added
gene: TSC1 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TSC1 was set to Unknown
Brain Calcification v0.0 TREX1 Zornitza Stark gene: TREX1 was added
gene: TREX1 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TREX1 was set to Unknown
Brain Calcification v0.0 SLC20A2 Zornitza Stark gene: SLC20A2 was added
gene: SLC20A2 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC20A2 was set to Unknown
Brain Calcification v0.0 SAMHD1 Zornitza Stark gene: SAMHD1 was added
gene: SAMHD1 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SAMHD1 was set to Unknown
Brain Calcification v0.0 RNASEH2C Zornitza Stark gene: RNASEH2C was added
gene: RNASEH2C was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RNASEH2C was set to Unknown
Brain Calcification v0.0 RNASEH2B Zornitza Stark gene: RNASEH2B was added
gene: RNASEH2B was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RNASEH2B was set to Unknown
Brain Calcification v0.0 RNASEH2A Zornitza Stark gene: RNASEH2A was added
gene: RNASEH2A was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RNASEH2A was set to Unknown
Brain Calcification v0.0 PDGFRB Zornitza Stark gene: PDGFRB was added
gene: PDGFRB was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PDGFRB was set to Unknown
Brain Calcification v0.0 PDGFB Zornitza Stark gene: PDGFB was added
gene: PDGFB was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PDGFB was set to Unknown
Brain Calcification v0.0 OCLN Zornitza Stark gene: OCLN was added
gene: OCLN was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: OCLN was set to Unknown
Brain Calcification v0.0 JAM3 Zornitza Stark gene: JAM3 was added
gene: JAM3 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: JAM3 was set to Unknown
Brain Calcification v0.0 IFIH1 Zornitza Stark gene: IFIH1 was added
gene: IFIH1 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: IFIH1 was set to Unknown
Brain Calcification v0.0 ERCC8 Zornitza Stark gene: ERCC8 was added
gene: ERCC8 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERCC8 was set to Unknown
Brain Calcification v0.0 ERCC6 Zornitza Stark gene: ERCC6 was added
gene: ERCC6 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERCC6 was set to Unknown
Brain Calcification v0.0 CTC1 Zornitza Stark gene: CTC1 was added
gene: CTC1 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CTC1 was set to Unknown
Brain Calcification v0.0 COL4A1 Zornitza Stark gene: COL4A1 was added
gene: COL4A1 was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: COL4A1 was set to Unknown
Brain Calcification v0.0 ADAR Zornitza Stark gene: ADAR was added
gene: ADAR was added to Brain calcification_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ADAR was set to Unknown
Brain Calcification v0.0 Zornitza Stark Added panel Brain calcification_VCGS