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Microcephaly v1.295 FLVCR1 Zornitza Stark Phenotypes for gene: FLVCR1 were changed from neurodevelopmental disorder MONDO:0700092, FLVCR1-related to Neurodevelopmental disorder with microcephaly, absent speech, and hypotonia, MIM#621060
Microcephaly v1.294 FLVCR1 Zornitza Stark reviewed gene: FLVCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, absent speech, and hypotonia, MIM#621060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.294 INPP4A Chirag Patel Classified gene: INPP4A as Green List (high evidence)
Microcephaly v1.294 INPP4A Chirag Patel Gene: inpp4a has been classified as Green List (High Evidence).
Microcephaly v1.293 INPP4A Chirag Patel gene: INPP4A was added
gene: INPP4A was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP4A were set to PMID: 39315527
Phenotypes for gene: INPP4A were set to INPP4A-related neurodevelopmental disorder
Review for gene: INPP4A was set to GREEN
Added comment: PMID: 39315527
30 individuals (aged 6 months to 40 years) from 17 unrelated families with biallelic LOF variants in INPP4A gene (11 nonsense or frameshift and 3 missense, mostly exon 4).

Cardinal clinical features include: severe global developmental delay, profound speech impairment, severe-profound intellectual disability, and severe lower limb weakness/paralysis. More variable clinical features include: microcephaly, short stature, cerebellar signs, involuntary movements, axial hypotonia, spasticity, quadriparesis, joint contractures, seizures, visual impairment. Neuroimaging findings vary from normal to features of (ponto)cerebellar hypoplasia, ventriculomegaly, reduced cerebral volume and hypomyelination. A more severe presentation is seen with variants downstream of exon 4.

Preliminary fibroblast cell studies identify disruption of endocytic pathways as the likely mechanism of disease, consistent with previous findings of a role of INPP4A in endocytosis. All mouse models display a phenotype mirroring human INPP4A-related neurodevelopmental disorder entailing a severe movement disorder with inability to walk, a small brain, and poor growth/weight gain.
Sources: Literature
Microcephaly v1.292 Ain Roesley removed gene:CLASP1 from the panel
Microcephaly v1.292 CLASP1 Ain Roesley Source: Literature was removed from gene: CLASP1
Microcephaly v1.289 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Microcephaly v1.289 CLASP1 Ain Roesley gene: CLASP1 was added
gene: CLASP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CLASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLASP1 were set to 39040917
Phenotypes for gene: CLASP1 were set to neurodevelopmental disorder MONDO:0700092, CLASP1-related
Review for gene: CLASP1 was set to RED
gene: CLASP1 was marked as current diagnostic
Added comment: 3 siblings from a consanguineous family, homozygous for p.(Arg1481His)
at birth, all had low weight and microcephaly (< 3-4SD), profound dev delay, spasticity, seizures and lissencephaly

Arg1481His - 3 hets 0 Homs in v4
codon is highly conserved with a high REVEL score 0.83
Sources: Literature
Microcephaly v1.288 WDR47 Bryony Thompson Marked gene: WDR47 as ready
Microcephaly v1.288 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Microcephaly v1.288 WDR47 Bryony Thompson Classified gene: WDR47 as Green List (high evidence)
Microcephaly v1.288 WDR47 Bryony Thompson Gene: wdr47 has been classified as Green List (High Evidence).
Microcephaly v1.287 WDR47 Bryony Thompson gene: WDR47 was added
gene: WDR47 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to Complex neurodevelopmental disorder MONDO:0100038, WDR47-related
Review for gene: WDR47 was set to GREEN
Added comment: 7 cases from 5 unrelated families with biallelic variants and a complex neurodevelopmental syndrome. The most frequent phenotypes were corpus callosum dysgenesis (7/7), microcephaly (7/7), mild to severe intellectual disability (7/7), epilepsy (7/7). Additionally, mouse models recapitulate the human phenotype. Loss of function is the mechanism of disease. Heterozygous parents had no phenotype.
Sources: Literature
Microcephaly v1.286 UFC1 Zornitza Stark Tag deep intronic tag was added to gene: UFC1.
Microcephaly v1.286 UFC1 Zornitza Stark commented on gene: UFC1: Note the NM_016406.4:c.255+17G>A variant is relatively common disease-causing variant.
Microcephaly v1.286 UFC1 Zornitza Stark edited their review of gene: UFC1: Changed phenotypes: Neurodevelopmental disorder with spasticity and poor growth (MIM#618076)
Microcephaly v1.286 UFC1 Zornitza Stark reviewed gene: UFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.286 FLVCR1 Bryony Thompson Marked gene: FLVCR1 as ready
Microcephaly v1.286 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Microcephaly v1.286 FLVCR1 Zornitza Stark Marked gene: FLVCR1 as ready
Microcephaly v1.286 FLVCR1 Zornitza Stark Gene: flvcr1 has been classified as Green List (High Evidence).
Microcephaly v1.286 FLVCR1 Bryony Thompson Classified gene: FLVCR1 as Green List (high evidence)
Microcephaly v1.286 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Microcephaly v1.285 FLVCR1 Bryony Thompson gene: FLVCR1 was added
gene: FLVCR1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FLVCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLVCR1 were set to 39306721
Phenotypes for gene: FLVCR1 were set to neurodevelopmental disorder MONDO:0700092, FLVCR1-related
Review for gene: FLVCR1 was set to GREEN
gene: FLVCR1 was marked as current diagnostic
Added comment: A study with 30 patients from 23 unrelated families with biallelic ultra-rare missense and predicted loss-of-function variants in FLVCR1 with a novel FLVCR1-related phenotype characterised by severe developmental disorders with profound developmental delay, microcephaly, brain malformations, epilepsy, spasticity, and premature death. Optic disk atrophy, limb and digital malformations, and macrocytic anaemia can be present.
Sources: Literature
Microcephaly v1.284 KBTBD2 Ain Roesley Marked gene: KBTBD2 as ready
Microcephaly v1.284 KBTBD2 Ain Roesley Gene: kbtbd2 has been classified as Green List (High Evidence).
Microcephaly v1.284 KBTBD2 Ain Roesley Classified gene: KBTBD2 as Green List (high evidence)
Microcephaly v1.284 KBTBD2 Ain Roesley Gene: kbtbd2 has been classified as Green List (High Evidence).
Microcephaly v1.283 KBTBD2 Ain Roesley gene: KBTBD2 was added
gene: KBTBD2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: KBTBD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KBTBD2 were set to 39313616
Phenotypes for gene: KBTBD2 were set to neurodevelopmental disorder MONDO:0700092, KBTBD2-related
Review for gene: KBTBD2 was set to GREEN
gene: KBTBD2 was marked as current diagnostic
Added comment: 3 families - 2 compound hets and 1 hom

phenotypes include:
Microcephaly, hypotonia, failure to thrive, IUGR, delayed gross motor development, dysmorphism
Sources: Literature
Microcephaly v1.282 GABRB2 Bryony Thompson Marked gene: GABRB2 as ready
Microcephaly v1.282 GABRB2 Bryony Thompson Gene: gabrb2 has been classified as Green List (High Evidence).
Microcephaly v1.282 GABRB2 Bryony Thompson Classified gene: GABRB2 as Green List (high evidence)
Microcephaly v1.282 GABRB2 Bryony Thompson Gene: gabrb2 has been classified as Green List (High Evidence).
Microcephaly v1.281 GABRB2 Bryony Thompson gene: GABRB2 was added
gene: GABRB2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GABRB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB2 were set to 38996765
Phenotypes for gene: GABRB2 were set to epileptic encephalopathy, infantile or early childhood, 2 MONDO:0020631
Mode of pathogenicity for gene: GABRB2 was set to Other
Review for gene: GABRB2 was set to GREEN
gene: GABRB2 was marked as current diagnostic
Added comment: Microcephaly has been reported in at least 13 individuals with gain of function variants.
Sources: Literature
Microcephaly v1.280 FAM20C Bryony Thompson Marked gene: FAM20C as ready
Microcephaly v1.280 FAM20C Bryony Thompson Gene: fam20c has been classified as Green List (High Evidence).
Microcephaly v1.280 FAM20C Bryony Thompson Classified gene: FAM20C as Green List (high evidence)
Microcephaly v1.280 FAM20C Bryony Thompson Gene: fam20c has been classified as Green List (High Evidence).
Microcephaly v1.279 FAM20C Bryony Thompson gene: FAM20C was added
gene: FAM20C was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FAM20C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM20C were set to 34360805
Phenotypes for gene: FAM20C were set to lethal osteosclerotic bone dysplasia MONDO:0009821
Review for gene: FAM20C was set to GREEN
gene: FAM20C was marked as current diagnostic
Added comment: Microcephaly is present in ~36% of reported cases.
Sources: Literature
Microcephaly v1.278 ZNRF3 Bryony Thompson Marked gene: ZNRF3 as ready
Microcephaly v1.278 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.278 ZNRF3 Bryony Thompson Classified gene: ZNRF3 as Amber List (moderate evidence)
Microcephaly v1.278 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.277 ZNRF3 Bryony Thompson gene: ZNRF3 was added
gene: ZNRF3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ZNRF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNRF3 were set to 39168120
Phenotypes for gene: ZNRF3 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: ZNRF3 was set to AMBER
Added comment: 12 individuals with ZNRF3 variants and various phenotypes. 8 individuals with de novo missense and neurodevelopment disorders (NDD), including cluster of variants in the RING ligase domain with macrocephalic NDD. Plus 4 individuals from 3 families with de novo truncating or de novo/inherited large in-frame deletion variants with non-NDD phenotypes, including heart, adrenal, or nephrotic problems. Overall, 4 individuals had congenital heart defects and 2 had microcephaly. Also, supporting in vitro functional assays.
Sources: Literature
Microcephaly v1.276 PNPLA8 Zornitza Stark Marked gene: PNPLA8 as ready
Microcephaly v1.276 PNPLA8 Zornitza Stark Gene: pnpla8 has been classified as Green List (High Evidence).
Microcephaly v1.276 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
Microcephaly v1.275 PNPLA8 Chirag Patel Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases; Mitochondrial myopathy with lactic acidosis, OMIM # 251950 to PNPLA8-related neurological diseases
Microcephaly v1.274 PNPLA8 Chirag Patel Classified gene: PNPLA8 as Green List (high evidence)
Microcephaly v1.274 PNPLA8 Chirag Patel Gene: pnpla8 has been classified as Green List (High Evidence).
Microcephaly v1.273 PNPLA8 Chirag Patel gene: PNPLA8 was added
gene: PNPLA8 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to PMID: 39082157
Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases; Mitochondrial myopathy with lactic acidosis, OMIM # 251950
Review for gene: PNPLA8 was set to GREEN
gene: PNPLA8 was marked as current diagnostic
Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 17/25 individuals had congenital and/or progressive microcephaly.

Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.
Sources: Literature
Microcephaly v1.272 GTPBP1 Zornitza Stark Phenotypes for gene: GTPBP1 were changed from Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related to Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM# 620888
Microcephaly v1.271 GTPBP1 Zornitza Stark reviewed gene: GTPBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM# 620888; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.271 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Microcephaly v1.271 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Microcephaly v1.271 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Microcephaly v1.271 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Microcephaly v1.270 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID:38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Microcephaly v1.269 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Microcephaly v1.269 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Microcephaly v1.269 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Microcephaly v1.269 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Microcephaly v1.269 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Microcephaly v1.269 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Microcephaly v1.269 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Microcephaly v1.269 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Microcephaly v1.268 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CRNKL1 was set to GREEN
Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Microcephaly v1.268 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM# 617717 to Auditory neuropathy and optic atrophy, MIM# 617717; Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Microcephaly v1.267 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
Microcephaly v1.266 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Microcephaly v1.266 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Microcephaly v1.265 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly.; Changed rating: GREEN; Changed publications: 30250212, 28965846, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Auditory neuropathy and optic atrophy, MIM# 617717, Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887
Microcephaly v1.265 VPS50 Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene.

Sanger confirmed the Lys5* to be 'homozygous' in the proband.

Phenotypes include:
severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive
Microcephaly v1.265 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Microcephaly v1.265 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Microcephaly v1.264 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v1.264 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Microcephaly v1.263 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Microcephaly v1.262 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual disability, MTSS2-related (MONDO#0001071) to ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Microcephaly v1.261 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from Microcephaly; Intellectual Disability to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Microcephaly v1.260 LIG4 Santosh Varughese reviewed gene: LIG4: 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: 16357942, 32534991, 32471509, 11779494, 16088910, 15333585; Phenotypes: LIG4 syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.260 DPP6 Zornitza Stark Tag disputed tag was added to gene: DPP6.
Microcephaly v1.260 DPP6 Zornitza Stark Phenotypes for gene: DPP6 were changed from Mental retardation, autosomal dominant 33 (MIM#616311) to Intellectual disability, autosomal dominant 33 (MIM#616311)
Microcephaly v1.259 DPP6 Zornitza Stark Classified gene: DPP6 as Red List (low evidence)
Microcephaly v1.259 DPP6 Zornitza Stark Gene: dpp6 has been classified as Red List (Low Evidence).
Microcephaly v1.258 DPP6 Zornitza Stark edited their review of gene: DPP6: Added comment: DISPUTED by ClinGen.; Changed rating: RED; Changed phenotypes: Intellectual disability, autosomal dominant 33 (MIM#616311); Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.258 CYHR1 Zornitza Stark Tag new gene name tag was added to gene: CYHR1.
Microcephaly v1.258 CYHR1 Bryony Thompson reviewed gene: CYHR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38641995; Phenotypes: neurodevelopmental disorder MONDO:0700092, ZTRAF1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.258 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related to Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Microcephaly v1.257 FILIP1 Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.257 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Microcephaly v1.257 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.257 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237; 38501757; 36739862
Microcephaly v1.256 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Microcephaly v1.256 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Microcephaly v1.256 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Microcephaly v1.255 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v1.255 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Microcephaly v1.255 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.254 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Microcephaly v1.254 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.253 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Microcephaly v1.252 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Developmental and epileptic encephalopathy 113, MIM# 620772
Microcephaly v1.251 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.251 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Microcephaly v1.250 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.250 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Microcephaly v1.249 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Microcephaly v1.249 NARS Zornitza Stark edited their review of gene: NARS: Changed rating: GREEN
Microcephaly v1.249 RGS6 Seb Lunke Marked gene: RGS6 as ready
Microcephaly v1.249 RGS6 Seb Lunke Gene: rgs6 has been classified as Red List (Low Evidence).
Microcephaly v1.249 RGS6 Seb Lunke gene: RGS6 was added
gene: RGS6 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS6 were set to 38332109; 25525169
Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149
Review for gene: RGS6 was set to RED
Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice.
Sources: Literature
Microcephaly v1.248 NARS Zornitza Stark reviewed gene: NARS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, MIM# 619091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.248 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Microcephaly v1.248 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Microcephaly v1.248 GTPBP1 Zornitza Stark Classified gene: GTPBP1 as Green List (high evidence)
Microcephaly v1.248 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Microcephaly v1.247 GTPBP1 Lucy Spencer gene: GTPBP1 was added
gene: GTPBP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP1 were set to 38118446
Phenotypes for gene: GTPBP1 were set to Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related
Review for gene: GTPBP1 was set to GREEN
Added comment: PMID: 38118446- Cohort of individuals with variants in GTPBP2 (which has been previously described) and GTPBP1 (new) who have an identical neurodevelopmental syndrome. 4 homozygous individuals from 3 consanguineous families. 2 families have different NMD-predicted nonsense variants and the third has a missense, all are absent from gnomad v4.

The shared cardinal features of GTPBP1 and 2 related disease are microcephaly, profound neurodevelopmental impairment, and distinctive craniofacial features. Epilepsy was present in 10 of 20 individuals but its not clear if those individuals had GTPBP1 or 2 variants.
Sources: Literature
Microcephaly v1.247 COPB2 Zornitza Stark Publications for gene: COPB2 were set to 29036432
Microcephaly v1.246 COPB2 Rylee Peters changed review comment from: This paper reports an unrelated individual with the same homozygous variant (NM_004766.3:c.760C>T, p.Arg254Cys) identified in 2xsiblings in PMID: 29036432 (the same two siblings are also described in PMID: 34450031).

The proband is an 8.5yo Iranian female born to consanguineous parents. This individual has symptoms consistent with autosomal recessive microcephaly 19 (MIM#617800) including, global developmental delay, intellectual disability, microcephaly, seizures, spasticity, strabismus, and failure to thrive symptoms; she is unable to stand, walk, or speak.; to: PMID: 37734708 - This paper reports an unrelated individual with the same homozygous variant (NM_004766.3:c.760C>T, p.Arg254Cys) identified in 2xsiblings in PMID: 29036432 (the same two siblings are also described in PMID: 34450031).

The proband is an 8.5yo Iranian female born to consanguineous parents. This individual has symptoms consistent with autosomal recessive microcephaly 19 (MIM#617800) including, global developmental delay, intellectual disability, microcephaly, seizures, spasticity, strabismus, and failure to thrive symptoms; she is unable to stand, walk, or speak.
Microcephaly v1.246 COPB2 Rylee Peters reviewed gene: COPB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 37734708, 29036432, 34450031; Phenotypes: Microcephaly 19, primary, autosomal recessive, MIM# 617800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.246 SOX5 Zornitza Stark Marked gene: SOX5 as ready
Microcephaly v1.246 SOX5 Zornitza Stark Gene: sox5 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.246 SOX5 Zornitza Stark Classified gene: SOX5 as Amber List (moderate evidence)
Microcephaly v1.246 SOX5 Zornitza Stark Gene: sox5 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.245 SOX5 Rylee Peters gene: SOX5 was added
gene: SOX5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SOX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX5 were set to PMID: 36861937
Phenotypes for gene: SOX5 were set to Lamb-Shaffer syndrome, MIM#616803
Review for gene: SOX5 was set to AMBER
Added comment: Cohort of 16 patients with heterozygous variants in SOX5. Paper also describes 71 previously reported cases of individuals with variants in SOX5 associated with Lamb–Shaffer Syndrome.

Microcephaly is reported in 14% of individuals with variants in SOX5 (calculated from both the current and previously reported cohorts).
Sources: Literature
Microcephaly v1.245 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Microcephaly v1.244 GPT2 Zornitza Stark edited their review of gene: GPT2: Changed phenotypes: Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Microcephaly v1.244 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange-like syndrome, MONDO:0016033 to Cornelia de Lange syndrome 6, MIM# 620568
Microcephaly v1.243 BRD4 Zornitza Stark edited their review of gene: BRD4: Changed phenotypes: Cornelia de Lange syndrome 6, MIM# 620568
Microcephaly v1.243 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Microcephaly v1.242 SV2A Zornitza Stark Marked gene: SV2A as ready
Microcephaly v1.242 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Microcephaly v1.242 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Epilepsy, MONDO:0005027; microcephaly MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, SV2A-related
Microcephaly v1.241 SV2A Zornitza Stark Mode of inheritance for gene: SV2A was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.240 SV2A Zornitza Stark Classified gene: SV2A as Amber List (moderate evidence)
Microcephaly v1.240 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Microcephaly v1.239 SV2A Karina Sandoval edited their review of gene: SV2A: Added comment: Updated - Only Biallelic causes microcephaly
Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 – p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 – p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 – p.Gly660Arg, AD, de novo
Family #4 – p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) – p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers; Changed phenotypes: Epilepsy, MONDO:0005027, microcephaly MONDO:0001149, intellectual disability MONDO:0001071; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.239 SV2A Karina Sandoval changed review comment from: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 – p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 – p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 – p.Gly660Arg, AD, de novo
Family #4 – p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) – p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature; to: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 – p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 – p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 – p.Gly660Arg, AD, de novo
Family #4 – p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) – p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Microcephaly v1.239 SV2A Karina Sandoval gene: SV2A was added
gene: SV2A was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SV2A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SV2A were set to PMID: 37985816
Phenotypes for gene: SV2A were set to Epilepsy, MONDO:0005027; microcephaly MONDO:0001149
Review for gene: SV2A was set to AMBER
Added comment: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 – p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 – p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 – p.Gly660Arg, AD, de novo
Family #4 – p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) – p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Microcephaly v1.239 VARS Zornitza Stark Marked gene: VARS as ready
Microcephaly v1.239 VARS Zornitza Stark Gene: vars has been classified as Green List (High Evidence).
Microcephaly v1.239 VARS Zornitza Stark Classified gene: VARS as Green List (high evidence)
Microcephaly v1.239 VARS Zornitza Stark Gene: vars has been classified as Green List (High Evidence).
Microcephaly v1.238 VARS Zornitza Stark gene: VARS was added
gene: VARS was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: VARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VARS were set to 30755616; 30755602; 26539891; 29691655; 30275004
Phenotypes for gene: VARS were set to Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy; OMIM #617802
Review for gene: VARS was set to GREEN
Added comment: 20 individuals from 14 families. Microcephaly is part of the phenotype.
Sources: Expert Review
Microcephaly v1.237 WNK3 Zornitza Stark Phenotypes for gene: WNK3 were changed from Neurodevelopmental disorder, WNK3-related (MONDO#0700092) to Prieto syndrome, MIM# 309610
Microcephaly v1.236 WNK3 Zornitza Stark reviewed gene: WNK3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Prieto syndrome, MIM# 309610; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v1.236 HIST1H4C Zornitza Stark Tag new gene name tag was added to gene: HIST1H4C.
Microcephaly v1.236 COG3 Zornitza Stark Phenotypes for gene: COG3 were changed from Neurodevelopmental disorder (MONDO#0700092), COG3-related to Congenital disorder of glycosylation, type IIbb, MIM# 620546
Microcephaly v1.235 COG3 Zornitza Stark reviewed gene: COG3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IIbb, MIM# 620546; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.235 COG3 Elena Savva Classified gene: COG3 as Amber List (moderate evidence)
Microcephaly v1.235 COG3 Elena Savva Gene: cog3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.235 COG3 Elena Savva Classified gene: COG3 as Amber List (moderate evidence)
Microcephaly v1.235 COG3 Elena Savva Gene: cog3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.234 COG3 Elena Savva Marked gene: COG3 as ready
Microcephaly v1.234 COG3 Elena Savva Gene: cog3 has been removed from the panel.
Microcephaly v1.234 COG3 Daniel Flanagan gene: COG3 was added
gene: COG3 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: COG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG3 were set to PMID: 37711075
Phenotypes for gene: COG3 were set to Neurodevelopmental disorder (MONDO#0700092), COG3-related
Review for gene: COG3 was set to AMBER
Added comment: Two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings.
Sources: Expert list
Microcephaly v1.234 DDX3X Ain Roesley Marked gene: DDX3X as ready
Microcephaly v1.234 DDX3X Ain Roesley Gene: ddx3x has been classified as Green List (High Evidence).
Microcephaly v1.234 DDX3X Ain Roesley Classified gene: DDX3X as Green List (high evidence)
Microcephaly v1.234 DDX3X Ain Roesley Gene: ddx3x has been classified as Green List (High Evidence).
Microcephaly v1.233 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580; Alpha-thalassemia/mental retardation syndrome, MIM# 301040 to ATR-X-related syndrome MONDO:0016980
Microcephaly v1.232 ATRX Zornitza Stark edited their review of gene: ATRX: Changed phenotypes: ATR-X-related syndrome MONDO:0016980
Microcephaly v1.232 DDX3X Lauren Rogers gene: DDX3X was added
gene: DDX3X was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DDX3X 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: DDX3X were set to 26235985
Phenotypes for gene: DDX3X were set to Snijders Blok-type X-linked syndromic intellectual developmental disorder (MIM#300958)
Review for gene: DDX3X was set to GREEN
Added comment: PMID: 26235985 - microcephaly seen in 12/38 females with de novo DDX3X variants
Sources: Literature
Microcephaly v1.232 SNAPC4 Zornitza Stark Phenotypes for gene: SNAPC4 were changed from Neurodevelopmental disorder (MONDO#0700092), SNAPC4-related to Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction, MIM# 620515
Microcephaly v1.231 AGMO Zornitza Stark Phenotypes for gene: AGMO were changed from microcephaly; intellectual disability; epilepsy to Neurodevelopmental disorder, MONDO:0700092, AGMO-related
Microcephaly v1.230 GABRB3 Zornitza Stark Marked gene: GABRB3 as ready
Microcephaly v1.230 GABRB3 Zornitza Stark Gene: gabrb3 has been classified as Green List (High Evidence).
Microcephaly v1.230 GABRB3 Zornitza Stark Classified gene: GABRB3 as Green List (high evidence)
Microcephaly v1.230 GABRB3 Zornitza Stark Gene: gabrb3 has been classified as Green List (High Evidence).
Microcephaly v1.229 GABRB3 Michelle Torres gene: GABRB3 was added
gene: GABRB3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GABRB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB3 were set to 37647766
Phenotypes for gene: GABRB3 were set to Developmental and epileptic encephalopathy 43 MIM#617113
Mode of pathogenicity for gene: GABRB3 was set to Other
Review for gene: GABRB3 was set to GREEN
Added comment: Voltage-clamp electrophysiology studies have shown that gain-of-function variants clustering in the transmembrane regions part of the channel pore result in a more severe phenotype, including movement disorders (dystonia and dyskinesia) and microcephaly.

Gain-of-function variants clustered in the coupling loops responsible for receptor activation are not associated with movement disorder and microcephaly.

LoF variants have not been associated with microcephaly and movement disorders either.
Sources: Literature
Microcephaly v1.229 SOX11 Zornitza Stark changed review comment from: Over 40 additional individuals reported, e.g. PMID 35341651. The phenotype that has emerged over time is distinct from patients with mutations in ARID1B (614556) and Coffin-Siris syndrome-1 (135900). Patients with IDDMOH tend to be microcephalic and have ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism.
Sources: Expert Review; to: Over 40 individuals reported, e.g. PMID 35341651. The phenotype that has emerged over time is distinct from patients with mutations in ARID1B (614556) and Coffin-Siris syndrome-1 (135900). Patients with IDDMOH tend to be microcephalic and have ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism.
Sources: Expert Review
Microcephaly v1.229 SOX11 Zornitza Stark Marked gene: SOX11 as ready
Microcephaly v1.229 SOX11 Zornitza Stark Gene: sox11 has been classified as Green List (High Evidence).
Microcephaly v1.229 SOX11 Zornitza Stark Classified gene: SOX11 as Green List (high evidence)
Microcephaly v1.229 SOX11 Zornitza Stark Gene: sox11 has been classified as Green List (High Evidence).
Microcephaly v1.228 SOX11 Zornitza Stark gene: SOX11 was added
gene: SOX11 was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 29459093; 24886874; 33086258; 33785884; 35642566; 35341651
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866
Review for gene: SOX11 was set to GREEN
Added comment: Over 40 additional individuals reported, e.g. PMID 35341651. The phenotype that has emerged over time is distinct from patients with mutations in ARID1B (614556) and Coffin-Siris syndrome-1 (135900). Patients with IDDMOH tend to be microcephalic and have ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism.
Sources: Expert Review
Microcephaly v1.227 ATP6V0C Zornitza Stark Marked gene: ATP6V0C as ready
Microcephaly v1.227 ATP6V0C Zornitza Stark Gene: atp6v0c has been classified as Green List (High Evidence).
Microcephaly v1.227 ATP6V0C Zornitza Stark Classified gene: ATP6V0C as Green List (high evidence)
Microcephaly v1.227 ATP6V0C Zornitza Stark Gene: atp6v0c has been classified as Green List (High Evidence).
Microcephaly v1.226 ATP6V0C Zornitza Stark gene: ATP6V0C was added
gene: ATP6V0C was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: ATP6V0C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0C were set to 33190975; 33090716; 36074901
Phenotypes for gene: ATP6V0C were set to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Review for gene: ATP6V0C was set to GREEN
Added comment: PMID:36074901 - 5 out of 27 patients had severe microcephaly (having occipitofrontal circumference (OFC) beyond 3 SD below the mean for their age).
Sources: Expert Review
Microcephaly v1.225 HPDL Zornitza Stark Marked gene: HPDL as ready
Microcephaly v1.225 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Microcephaly v1.225 HPDL Zornitza Stark Classified gene: HPDL as Green List (high evidence)
Microcephaly v1.225 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Microcephaly v1.224 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Microcephaly v1.224 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Microcephaly v1.223 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Microcephaly v1.223 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Microcephaly v1.223 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Microcephaly v1.223 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Microcephaly v1.222 SLC4A10 Krithika Murali Marked gene: SLC4A10 as ready
Microcephaly v1.222 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Red List (Low Evidence).
Microcephaly v1.222 PIP5K1C Elena Savva Publications for gene: PIP5K1C were set to 37451268
Microcephaly v1.222 PIP5K1C Elena Savva Publications for gene: PIP5K1C were set to
Microcephaly v1.221 SLC4A10 Krithika Murali gene: SLC4A10 was added
gene: SLC4A10 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to PMID: 37459438
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related
Review for gene: SLC4A10 was set to GREEN
Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder.

Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies.

Isolated seizures was reported in 2/10 cases.
Sources: Literature
Microcephaly v1.220 PIP5K1C Zornitza Stark Marked gene: PIP5K1C as ready
Microcephaly v1.220 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Microcephaly v1.220 PIP5K1C Zornitza Stark Phenotypes for gene: PIP5K1C were changed from Neurodevelopmental disorder and microcephaly to Neurodevelopmental disorder and microcephaly, MONDO:0700092, PIP5K1C-related
Microcephaly v1.219 CYHR1 Zornitza Stark Marked gene: CYHR1 as ready
Microcephaly v1.219 CYHR1 Zornitza Stark Gene: cyhr1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.219 CYHR1 Zornitza Stark Phenotypes for gene: CYHR1 were changed from Neurodevelopmental disorder and microcephaly to Neurodevelopmental disorder and microcephaly, MONDO:0700092, CYHR1-related
Microcephaly v1.218 TTI1 Zornitza Stark Publications for gene: TTI1 were set to DOI:https://doi.org/10.1016/j.ajhg.2023.01.006
Microcephaly v1.217 TTI1 Zornitza Stark reviewed gene: TTI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36724785; Phenotypes: Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.217 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445 to Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445
Microcephaly v1.217 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from Neurodevelopmental disorder, MONDO:0700092, TTI1-related to to Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445
Microcephaly v1.216 DCAF15 Zornitza Stark Marked gene: DCAF15 as ready
Microcephaly v1.216 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.216 DCAF15 Zornitza Stark Phenotypes for gene: DCAF15 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033, DCAF15-related
Microcephaly v1.215 DCAF15 Zornitza Stark Classified gene: DCAF15 as Amber List (moderate evidence)
Microcephaly v1.215 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.214 PIP5K1C Chirag Patel Classified gene: PIP5K1C as Green List (high evidence)
Microcephaly v1.214 PIP5K1C Chirag Patel Gene: pip5k1c has been classified as Green List (High Evidence).
Microcephaly v1.213 PIP5K1C Chirag Patel gene: PIP5K1C was added
gene: PIP5K1C was added to Microcephaly. Sources: Other
Mode of inheritance for gene: PIP5K1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIP5K1C were set to Neurodevelopmental disorder and microcephaly
Review for gene: PIP5K1C was set to GREEN
gene: PIP5K1C was marked as current diagnostic
Added comment: ESHG 2023:
9 unrelated patients with de novo missense variants in PIP5K1C (3 x recurrent variants).
Presentation with DD/ID (mod-profound), microcephaly, seizures, visual impairment, and dysmorphism.

PIP5K1C is one of the phosphoinositolides, which control membrane composition of organelles and varying cellular processes. Patient fibroblasts showed increased PI(4,5)P2 levels, altered PI(4,5)P2 composition of early endosomes, and impaired endocytosis trafficking. Drosophila models showed microcephaly and ocular phenotype.
Sources: Other
Microcephaly v1.212 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Microcephaly v1.212 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Microcephaly v1.211 CYHR1 Chirag Patel Classified gene: CYHR1 as Amber List (moderate evidence)
Microcephaly v1.211 CYHR1 Chirag Patel Gene: cyhr1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.210 CYHR1 Chirag Patel gene: CYHR1 was added
gene: CYHR1 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: CYHR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYHR1 were set to Neurodevelopmental disorder and microcephaly
Review for gene: CYHR1 was set to AMBER
gene: CYHR1 was marked as current diagnostic
Added comment: ESHG 2023:
5 individuals from 3 families with biallelic LOF variants in CYHR1 (aka ZTRAF1). Presentation with microcephaly, hypotonia, DD, and ID. Expression studies showed mislocalisation of CYHR1. Mutant fibroblasts showed increased lysosomal markers and upregulated lysosomal proteins, leading to impaired autophagy. Zebrafish KO however did not show a phenotype.
Sources: Other
Microcephaly v1.209 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.209 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.209 DRG1 Krithika Murali Marked gene: DRG1 as ready
Microcephaly v1.209 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.209 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.209 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.208 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.208 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.208 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Microcephaly v1.208 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Microcephaly v1.207 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Microcephaly v1.207 MCM6 Zornitza Stark Classified gene: MCM6 as Amber List (moderate evidence)
Microcephaly v1.207 MCM6 Zornitza Stark Gene: mcm6 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.206 MCM6 Zornitza Stark Marked gene: MCM6 as ready
Microcephaly v1.206 MCM6 Zornitza Stark Gene: mcm6 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.206 MCM6 Zornitza Stark Classified gene: MCM6 as Amber List (moderate evidence)
Microcephaly v1.206 MCM6 Zornitza Stark Gene: mcm6 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.206 MCM6 Zornitza Stark Classified gene: MCM6 as Amber List (moderate evidence)
Microcephaly v1.206 MCM6 Zornitza Stark Gene: mcm6 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.205 MCM6 Suliman Khan changed review comment from: Sources: Literature; to: PMID: 37198333 reported 5 unrelated families with de novo variants in MCM6 gene. Two patients with the same missense variant p.(Cys158Tyr) in zinc finger domain presented with intra-uterine growth retardation, short stature, congenital microcephaly, endocrine features, developmental delay and urogenital anomalies.

In other three unrelated individuals different de novo missense variants were identified in the oligo nucleotide binding (OB)-fold domain. These patients had variable neurodevelopmental features including autism spectrum disorder, developmental delay, and epilepsy.

The clinical features and functional defects related to the zinc binding residue resembled those observed in syndromes related to other MCM components and DNA replication factors (Meier–Gorlin syndrome and Seckel syndrome), while de novo OB-fold domain missense variants were associated with more variable neurodevelopmental phenotypes (PMID: 37198333).
Sources: Literature
Microcephaly v1.205 MCM6 Suliman Khan gene: MCM6 was added
gene: MCM6 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: MCM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MCM6 were set to PMID: 37198333
Phenotypes for gene: MCM6 were set to Neurodevelopmental disorder, MONDO:0700092, MCM6-related
Review for gene: MCM6 was set to AMBER
Added comment: Sources: Literature
Microcephaly v1.205 TPR Zornitza Stark Phenotypes for gene: TPR were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related to Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Microcephaly v1.204 TPR Zornitza Stark edited their review of gene: TPR: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Microcephaly v1.204 HPDL Lucy Spencer gene: HPDL was added
gene: HPDL was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 33188300
Phenotypes for gene: HPDL were set to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (MIM#619026)
Review for gene: HPDL was set to GREEN
Added comment: PMID: 33188300 cohort of infantile neurodegenerative condition, all have biallelic HPDL variants. 7 of 14 individuals have microcephaly, however its noted that head circumference was not remarkable at birth but smaller head circumference/microcephaly was seen by 5 years old.
Sources: Literature
Microcephaly v1.204 LHX2 Zornitza Stark Marked gene: LHX2 as ready
Microcephaly v1.204 LHX2 Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence).
Microcephaly v1.204 LHX2 Zornitza Stark Classified gene: LHX2 as Green List (high evidence)
Microcephaly v1.204 LHX2 Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence).
Microcephaly v1.203 LHX2 Manny Jacobs gene: LHX2 was added
gene: LHX2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LHX2 were set to PMID: 37057675
Phenotypes for gene: LHX2 were set to Neurodevelopmental disorder (MONDO: 0700092)
Review for gene: LHX2 was set to GREEN
Added comment: PMID: 37057675

Case series of 19 individuals across 18 families.
1 whole gene deletion, 7 missense, 10 predicted LoF variants.
Proposed loss-of-function mechanism.
Variable phenotype, with variable intellectual disability and behavioural (ASD/ADHD) features common.
Microcephaly in 7 individuals.
1 variant inherited from a mildly affected parent, all other variants with parental genotype available shown to be de novo.
Sources: Literature
Microcephaly v1.203 WARS Zornitza Stark Phenotypes for gene: WARS were changed from Neurodevelopmental disorder (MONDO:0700092), WARS-related to Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities,MIM# 620317
Microcephaly v1.202 WARS Zornitza Stark reviewed gene: WARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities,MIM# 620317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.202 CAMSAP1 Zornitza Stark Phenotypes for gene: CAMSAP1 were changed from lissencephaly spectrum disorders (MONDO:0018838), CAMSAP1-related to Cortical dysplasia, complex, with other brain malformations 12, MIM# 620316
Microcephaly v1.201 CAMSAP1 Zornitza Stark reviewed gene: CAMSAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 12, MIM# 620316; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.201 CRIPT Zornitza Stark Phenotypes for gene: CRIPT were changed from Short stature with microcephaly and distinctive facies (MIM#615789) to Short stature with microcephaly and distinctive facies (MIM#615789); Rothmund-Thomson syndrome MONDO:0010002
Microcephaly v1.200 CRIPT Zornitza Stark Publications for gene: CRIPT were set to 24389050; 27250922
Microcephaly v1.199 CRIPT Zornitza Stark Classified gene: CRIPT as Green List (high evidence)
Microcephaly v1.199 CRIPT Zornitza Stark Gene: cript has been classified as Green List (High Evidence).
Microcephaly v1.198 FILIP1 Zornitza Stark Marked gene: FILIP1 as ready
Microcephaly v1.198 FILIP1 Zornitza Stark Gene: filip1 has been classified as Green List (High Evidence).
Microcephaly v1.198 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168 to Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related
Microcephaly v1.197 FILIP1 Zornitza Stark Classified gene: FILIP1 as Green List (high evidence)
Microcephaly v1.197 FILIP1 Zornitza Stark Gene: filip1 has been classified as Green List (High Evidence).
Microcephaly v1.196 CRIPT Karina Sandoval reviewed gene: CRIPT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37013901; Phenotypes: Short stature with microcephaly and distinctive facies (MIM#615789), Rothmund-Thomson syndrome MONDO:0010002; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.196 SNAPC4 Zornitza Stark Marked gene: SNAPC4 as ready
Microcephaly v1.196 SNAPC4 Zornitza Stark Gene: snapc4 has been classified as Green List (High Evidence).
Microcephaly v1.196 SNAPC4 Zornitza Stark Classified gene: SNAPC4 as Green List (high evidence)
Microcephaly v1.196 SNAPC4 Zornitza Stark Gene: snapc4 has been classified as Green List (High Evidence).
Microcephaly v1.195 SNAPC4 Ee Ming Wong changed review comment from: - Ten individuals from eight families with neurodevelopmental disorder found to be compound heterozygous for variants in SNAPC4
- Identified variants included 6x missense, 1x nonsense, 1x frameshift and 6x splice
- Depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing, similarly observed in patient fibroblasts
Sources: Literature; to: - Ten individuals from eight families with neurodevelopmental disorder found to be biallelic for variants in SNAPC4
- Identified variants included 6x missense, 1x nonsense, 1x frameshift and 6x splice
- Depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing, similarly observed in patient fibroblasts
Sources: Literature
Microcephaly v1.195 FILIP1 Paul De Fazio edited their review of gene: FILIP1: Changed phenotypes: Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related
Microcephaly v1.195 SNAPC4 Ee Ming Wong gene: SNAPC4 was added
gene: SNAPC4 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SNAPC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNAPC4 were set to 36965478
Phenotypes for gene: SNAPC4 were set to Neurodevelopmental disorder (MONDO#0700092), SNAPC4-related
Review for gene: SNAPC4 was set to GREEN
gene: SNAPC4 was marked as current diagnostic
Added comment: - Ten individuals from eight families with neurodevelopmental disorder found to be compound heterozygous for variants in SNAPC4
- Identified variants included 6x missense, 1x nonsense, 1x frameshift and 6x splice
- Depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing, similarly observed in patient fibroblasts
Sources: Literature
Microcephaly v1.195 FILIP1 Paul De Fazio gene: FILIP1 was added
gene: FILIP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FILIP1 were set to 36943452
Phenotypes for gene: FILIP1 were set to Arthrogryposis multiplex congenita MONDO:0015168
Penetrance for gene: FILIP1 were set to unknown
Review for gene: FILIP1 was set to GREEN
gene: FILIP1 was marked as current diagnostic
Added comment: 3 families, all consanguineous, reported with 3 different homozygous loss of function variants (2x NMD-predicted nonsense, 1x intragenic deletion of exons 3-6 of 6). In one family, the variant segregated in 3 affected siblings.

Phenotypes consist of congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly (-1.5 to -4 SD), and facial dysmorphism.
Sources: Literature
Microcephaly v1.195 Zornitza Stark removed gene:MTSS1 from the panel
Microcephaly v1.194 CRIPT Suliman Khan changed review comment from: PMID: 36630262 reported a patient with profound prenatal/postnatal growth restriction, developmental delay, dysmorphic facial features, and skin lesions along with the findings of bicytopenia and extensive retinal pigmentation defect. A novel truncating homozygous variant c.7_8delTG; p.(Cys3Argfs*4) was detected in CRIPT gene.; to: PMID: 36630262 reported a patient with profound prenatal/postnatal growth restriction, developmental delay, dysmorphic facial features, and skin lesions along with the findings of bicytopenia and extensive retinal pigmentation defect. A novel truncating homozygous variant was detected in CRIPT gene.
Microcephaly v1.194 CRIPT Suliman Khan reviewed gene: CRIPT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36630262; Phenotypes: short stature, microcephaly, distinctive facies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.194 ATP9A Zornitza Stark Phenotypes for gene: ATP9A were changed from Neurodevelopmental delay; Postnatal microcephaly; Failure to thrive; Gastrointestinal symptoms to Neurodevelopmental disorder with poor growth and behavioural abnormalities, MIM# 620242
Microcephaly v1.193 ATP9A Zornitza Stark edited their review of gene: ATP9A: Changed phenotypes: Neurodevelopmental disorder with poor growth and behavioural abnormalities, MIM# 620242
Microcephaly v1.193 GOLGA2 Zornitza Stark Phenotypes for gene: GOLGA2 were changed from Neuromuscular disorder to Developmental delay with hypotonia, myopathy, and brain abnormalities, MIM 620240
Microcephaly v1.192 GOLGA2 Zornitza Stark Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Microcephaly v1.191 GOLGA2 Zornitza Stark reviewed gene: GOLGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34424553; Phenotypes: Developmental delay with hypotonia, myopathy, and brain abnormalities, MIM 620240; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.191 WDR11 Zornitza Stark Phenotypes for gene: WDR11 were changed from Intellectual disability; Microcephaly; Short stature to Intellectual developmental disorder, autosomal recessive 78, MIM# 620237; Intellectual disability; Microcephaly; Short stature
Microcephaly v1.190 WDR11 Zornitza Stark edited their review of gene: WDR11: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 78, MIM# 620237, Intellectual disability, Microcephaly, Short stature
Microcephaly v1.190 CCDC84 Zornitza Stark Marked gene: CCDC84 as ready
Microcephaly v1.190 CCDC84 Zornitza Stark Gene: ccdc84 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.190 CCDC84 Zornitza Stark Classified gene: CCDC84 as Amber List (moderate evidence)
Microcephaly v1.190 CCDC84 Zornitza Stark Gene: ccdc84 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.189 TTI1 Zornitza Stark Marked gene: TTI1 as ready
Microcephaly v1.189 TTI1 Zornitza Stark Gene: tti1 has been classified as Green List (High Evidence).
Microcephaly v1.189 TTI1 Zornitza Stark Classified gene: TTI1 as Green List (high evidence)
Microcephaly v1.189 TTI1 Zornitza Stark Gene: tti1 has been classified as Green List (High Evidence).
Microcephaly v1.188 CCDC84 Lucy Spencer gene: CCDC84 was added
gene: CCDC84 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CCDC84 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC84 were set to 34009673
Phenotypes for gene: CCDC84 were set to Mosaic variegated aneuploidy syndrome 4 (MIM#620153)
Review for gene: CCDC84 was set to AMBER
Added comment: PMID: 34009673- patients with constitutional mosaic aneuploidy were found to have biallelic mutations in CENATAC(CCDC84). 2 adult siblings with mosaic aneuploidies, microcephaly, dev delay, and maculopathy. Both chet for a missense and a splice site deletion- but the paper days these both result in the creation of a novel splice site that leads to frameshifts and loss of the c-terminal 64 amino acids.

Gene is shown to be part of a spliceosome. CENATAC depletion or expression of disease mutants resulted in retention of introns in ~100 genes enriched for nucleocytoplasmic transport and cell cycle regulation, and caused chromosome segregation errors.

Functional analysis in CENATAC-depleted HeLa cells demonstrated chromosome congression defects and subsequent mitotic arrest, which could be fully rescued by wildtype but not mutant CENATAC. Expression of the MVA-associated mutants exacerbated the phenotype, suggesting that the mutant proteins dominantly repress the function of any residual wildtype protein.
Sources: Literature
Microcephaly v1.188 TTI1 Ee Ming Wong gene: TTI1 was added
gene: TTI1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TTI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTI1 were set to DOI:https://doi.org/10.1016/j.ajhg.2023.01.006
Phenotypes for gene: TTI1 were set to Neurodevelopmental disorder, MONDO:0700092, TTI1-related to
Review for gene: TTI1 was set to GREEN
gene: TTI1 was marked as current diagnostic
Added comment: - Eleven individuals from nine unrelated families with biallelic variants in TTI1 (10x missense, 2x canonical splice, 2x nonsense and 1x frameshift)
- All present with ID, and most with microcephaly, short stature, and a movement disorder
- Missense mutant constructs transfected into HEK293T cells demonstrated impairment of the TTT complex and of mTOR pathway activity which is improved by treatment with Rapamycin
Sources: Literature
Microcephaly v1.188 ZNF668 Zornitza Stark Phenotypes for gene: ZNF668 were changed from DNA damage repair defect; microcephaly; growth deficiency; severe global developmental delay; brain malformation; facial dysmorphism to Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies, MIM# 620194
Microcephaly v1.187 SMC5 Zornitza Stark Phenotypes for gene: SMC5 were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID to Atelis syndrome 2, MIM# 620185
Microcephaly v1.186 SMC5 Zornitza Stark edited their review of gene: SMC5: Changed phenotypes: Atelis syndrome 2, MIM# 620185
Microcephaly v1.186 SLF2 Zornitza Stark Phenotypes for gene: SLF2 were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID to Atelis syndrome 1, MIM# 620184
Microcephaly v1.185 TRA2B Seb Lunke Phenotypes for gene: TRA2B were changed from Neurodevelopmental disorder, TRA2B-related (MONDO#0700092) to Neurodevelopmental disorder, TRA2B-related, MONDO# 0700092
Microcephaly v1.184 TRA2B Seb Lunke Marked gene: TRA2B as ready
Microcephaly v1.184 TRA2B Seb Lunke Gene: tra2b has been classified as Green List (High Evidence).
Microcephaly v1.184 TRA2B Seb Lunke Classified gene: TRA2B as Green List (high evidence)
Microcephaly v1.184 TRA2B Seb Lunke Gene: tra2b has been classified as Green List (High Evidence).
Microcephaly v1.183 TRA2B Elena Savva gene: TRA2B was added
gene: TRA2B was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TRA2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRA2B were set to PMID: 36549593
Phenotypes for gene: TRA2B were set to Neurodevelopmental disorder, TRA2B-related (MONDO#0700092)
Review for gene: TRA2B was set to GREEN
Added comment: PMID: 36549593
- 12 individuals with ID and dev delay. Additional features include infantile spams 6/12, hypotonia 12/12, dilated brain ventricles 6/12, microcephaly 5/12
- All variants result in the loss of 1/2 transcripts (start-losses or PTCs upstream of a second translation start position). Shorter transcript expression is increased, longer transcript expression is decreased.
- Apparently het mice K/O are normal, but complete K/O cannot develop embryonically.
- DN mechanism suggested
Sources: Literature
Microcephaly v1.182 RAC1 Zornitza Stark Publications for gene: RAC1 were set to 30042656; 29276006; 30293988
Microcephaly v1.181 RAC1 Zornitza Stark Classified gene: RAC1 as Green List (high evidence)
Microcephaly v1.181 RAC1 Zornitza Stark Gene: rac1 has been classified as Green List (High Evidence).
Microcephaly v1.180 RAC1 Zornitza Stark edited their review of gene: RAC1: Added comment: Additional patients reported. Microcephaly is a feature, though variable one, and some individuals have macrocephaly.; Changed rating: GREEN; Changed publications: 30042656, 29276006, 30293988, 35139179
Microcephaly v1.180 Zornitza Stark HPO terms changed from to Microcephaly, HP:0000252
List of related panels changed from to Microcephaly; HP:0000252
Microcephaly v1.179 BUB1 Zornitza Stark Phenotypes for gene: BUB1 were changed from Neurodevelopmental disorder, BUB1-related MONDO:0700092; Intellectual disability and microcephaly to Primary microcephaly-30 (MCPH30), MIM#620183
Microcephaly v1.178 BUB1 Zornitza Stark reviewed gene: BUB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary microcephaly-30 (MCPH30), MIM#620183; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.178 BUB1B Zornitza Stark Publications for gene: BUB1B were set to 18548531
Microcephaly v1.177 CLDN5 Zornitza Stark Marked gene: CLDN5 as ready
Microcephaly v1.177 CLDN5 Zornitza Stark Added comment: Comment when marking as ready: Reported variants are missense, but zebrafish model supports loss of function mechanism.
Microcephaly v1.177 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Green List (High Evidence).
Microcephaly v1.177 CLDN5 Zornitza Stark Marked gene: CLDN5 as ready
Microcephaly v1.177 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Green List (High Evidence).
Microcephaly v1.177 CLDN5 Zornitza Stark Phenotypes for gene: CLDN5 were changed from seizures; developmental delay; microcephaly; brain calcifications to Syndromic disorder, MONDO:0002254, CLDN5-related
Microcephaly v1.176 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
Microcephaly v1.175 CLDN5 Zornitza Stark Classified gene: CLDN5 as Green List (high evidence)
Microcephaly v1.175 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Green List (High Evidence).
Microcephaly v1.174 CLDN5 Zornitza Stark reviewed gene: CLDN5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disorder, MONDO:0002254, CLDN5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.174 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Microcephaly v1.174 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Microcephaly v1.174 SETD2 Zornitza Stark Classified gene: SETD2 as Green List (high evidence)
Microcephaly v1.174 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Microcephaly v1.173 SETD2 Zornitza Stark gene: SETD2 was added
gene: SETD2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SETD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD2 were set to 32710489
Phenotypes for gene: SETD2 were set to Rabin-Pappas syndrome,MIM# 620155
Review for gene: SETD2 was set to GREEN
Added comment: PMID 32710489: 12 unrelated patients, ranging from 1 month to 12 years of age, with a multisystemic neurodevelopmental disorder associated with a specific de novo heterozygous mutation in the SETD2 gene (R1740W).

Key clinical features: severely impaired global development apparent from infancy, feeding difficulties with failure to thrive, small head circumference, and dysmorphic facial features. Affected individuals have impaired intellectual development and hypotonia; they do not achieve walking or meaningful speech. Other neurologic findings may include seizures, hearing loss, ophthalmologic defects, and brain imaging abnormalities. There is variable involvement of other organ systems, including skeletal, genitourinary, cardiac, and possibly endocrine.
Sources: Literature
Microcephaly v1.172 CLDN5 Suliman Khan gene: CLDN5 was added
gene: CLDN5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to PMID: 36477332
Phenotypes for gene: CLDN5 were set to seizures; developmental delay; microcephaly; brain calcifications
Penetrance for gene: CLDN5 were set to Complete
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 GREEN
Added comment: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature
Microcephaly v1.172 BUB1B Liyan Song reviewed gene: BUB1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 21190457, 15475955, 15098245; Phenotypes: Mosaic variegated aneuploidy syndrome 1, MIM: #257300, Premature chromatid separation trait, MIM: #176430; Mode of inheritance: Other
Microcephaly v1.172 CENPF Mark Williams Deleted their review
Microcephaly v1.172 CENPF Mark Williams reviewed gene: CENPF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35488810, 31953238, 26820108; Phenotypes: Stromme syndrome, microcephaly, intestinal atresia, intellectual disability, developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.172 ARPC4 Zornitza Stark edited their review of gene: ARPC4: Changed phenotypes: Developmental delay, language impairment, and ocular abnormalities, MIM# 620141
Microcephaly v1.172 ARPC4 Zornitza Stark Marked gene: ARPC4 as ready
Microcephaly v1.172 ARPC4 Zornitza Stark Gene: arpc4 has been classified as Green List (High Evidence).
Microcephaly v1.172 ARPC4 Zornitza Stark Phenotypes for gene: ARPC4 were changed from Microcephaly; mild motor delays; significant speech impairment to Neurodevelopmental disorder, ARPC4-related MONDO#0700092
Microcephaly v1.171 ARPC4 Zornitza Stark Publications for gene: ARPC4 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100072
Microcephaly v1.170 ARPC4 Zornitza Stark edited their review of gene: ARPC4: Changed publications: 35047857
Microcephaly v1.170 ARPC4 Zornitza Stark reviewed gene: ARPC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, ARPC4-related MONDO#0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.170 TPR Zornitza Stark Marked gene: TPR as ready
Microcephaly v1.170 TPR Zornitza Stark Gene: tpr has been classified as Red List (Low Evidence).
Microcephaly v1.170 TPR Zornitza Stark gene: TPR was added
gene: TPR was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TPR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TPR were set to 34494102
Phenotypes for gene: TPR were set to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related
Review for gene: TPR was set to RED
Added comment: Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability. Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution.
Sources: Literature
Microcephaly v1.169 MTSS1 Zornitza Stark edited their review of gene: MTSS1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.169 MTSS1 Zornitza Stark Marked gene: MTSS1 as ready
Microcephaly v1.169 MTSS1 Zornitza Stark Gene: mtss1 has been classified as Green List (High Evidence).
Microcephaly v1.169 MTSS1 Zornitza Stark Classified gene: MTSS1 as Green List (high evidence)
Microcephaly v1.169 MTSS1 Zornitza Stark Gene: mtss1 has been classified as Green List (High Evidence).
Microcephaly v1.168 MTSS1 Zornitza Stark edited their review of gene: MTSS1: Added comment: Five individuals with the same heterozygous de novo variant in MTSS2 (NM_138383.2: c.2011C>T [p.Arg671Trp]) identified by exome sequencing.

The individuals presented with global developmental delay, mild intellectual disability, ophthalmological anomalies, microcephaly or relative microcephaly, and shared mild facial dysmorphisms.

Immunoblots of fibroblasts from two affected individuals revealed that the variant does not significantly alter MTSS2 levels. We modeled the variant in Drosophila and showed that the fly ortholog missing-in-metastasis (mim) was widely expressed in most neurons and a subset of glia of the CNS. Loss of mim led to a reduction in lifespan, impaired locomotor behavior, and reduced synaptic transmission in adult flies. Expression of the human MTSS2 reference cDNA rescued the mim loss-of-function (LoF) phenotypes, whereas the c.2011C>T variant had decreased rescue ability compared to the reference, suggesting it is a partial LoF allele. However, elevated expression of the variant, but not the reference MTSS2 cDNA, led to similar defects as observed by mim LoF, suggesting that the variant is toxic and may act as a dominant-negative allele when expressed in flies.; Changed rating: GREEN
Microcephaly v1.168 MTSS1 Zornitza Stark edited their review of gene: MTSS1: Changed phenotypes: Intellectual disability, MTSS1-related (MONDO#0001071)
Microcephaly v1.168 MTSS1 Zornitza Stark reviewed gene: MTSS1: Rating: RED; Mode of pathogenicity: None; Publications: 36067766; Phenotypes: ; Mode of inheritance: None
Microcephaly v1.168 SMC5 Zornitza Stark Marked gene: SMC5 as ready
Microcephaly v1.168 SMC5 Zornitza Stark Gene: smc5 has been classified as Green List (High Evidence).
Microcephaly v1.168 SMC5 Zornitza Stark Classified gene: SMC5 as Green List (high evidence)
Microcephaly v1.168 SMC5 Zornitza Stark Gene: smc5 has been classified as Green List (High Evidence).
Microcephaly v1.167 SMC5 Zornitza Stark gene: SMC5 was added
gene: SMC5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SMC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMC5 were set to 36333305
Phenotypes for gene: SMC5 were set to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID
Review for gene: SMC5 was set to GREEN
Added comment: Four individuals from three families with a chromosome breakage disorder and bi-allelic variants in this gene. However, three of the individuals had the same homozygous missense variant. Evidence for functional impact of the variant was limited. However, zebrafish model recapitulated the phenotype and was not rescued by the introduction of this variant, arguing for functional effect. Borderline Amber/Green.
Sources: Literature
Microcephaly v1.166 SLF2 Zornitza Stark Phenotypes for gene: SLF2 were changed from Atelis syndrome; microcephaly; short stature; ID to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID
Microcephaly v1.165 SLF2 Zornitza Stark edited their review of gene: SLF2: Changed phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related, Atelis syndrome, microcephaly, short stature, ID
Microcephaly v1.165 SLF2 Zornitza Stark edited their review of gene: SLF2: Changed phenotypes: Multiple congenital anomalies/dysmorphic syndrome, SLF2-related, Atelis syndrome, microcephaly, short stature, ID
Microcephaly v1.165 SLF2 Zornitza Stark Marked gene: SLF2 as ready
Microcephaly v1.165 SLF2 Zornitza Stark Gene: slf2 has been classified as Green List (High Evidence).
Microcephaly v1.165 SLF2 Zornitza Stark Classified gene: SLF2 as Green List (high evidence)
Microcephaly v1.165 SLF2 Zornitza Stark Gene: slf2 has been classified as Green List (High Evidence).
Microcephaly v1.164 SLF2 Zornitza Stark gene: SLF2 was added
gene: SLF2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SLF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLF2 were set to 36333305
Phenotypes for gene: SLF2 were set to Atelis syndrome; microcephaly; short stature; ID
Review for gene: SLF2 was set to GREEN
Added comment: Seven individuals from 6 families with a chromosome breakage disorder and bi-allelic variants in this gene (LoF). Functional data including zebrafish model.
Sources: Literature
Microcephaly v1.163 FRA10AC1 Zornitza Stark Phenotypes for gene: FRA10AC1 were changed from Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related to Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113
Microcephaly v1.162 FRA10AC1 Zornitza Stark edited their review of gene: FRA10AC1: Changed phenotypes: Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113
Microcephaly v1.162 CAMSAP1 Zornitza Stark Marked gene: CAMSAP1 as ready
Microcephaly v1.162 CAMSAP1 Zornitza Stark Gene: camsap1 has been classified as Green List (High Evidence).
Microcephaly v1.162 CAMSAP1 Zornitza Stark Classified gene: CAMSAP1 as Green List (high evidence)
Microcephaly v1.162 CAMSAP1 Zornitza Stark Gene: camsap1 has been classified as Green List (High Evidence).
Microcephaly v1.161 CAMSAP1 Naomi Baker gene: CAMSAP1 was added
gene: CAMSAP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMSAP1 were set to 36283405
Phenotypes for gene: CAMSAP1 were set to lissencephaly spectrum disorders (MONDO:0018838), CAMSAP1-related
Review for gene: CAMSAP1 was set to GREEN
Added comment: Five unrelated families with bi-allelic loss-of-function variants. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe neurodevelopmental delay, cortical visual impairment, and seizures.
Sources: Literature
Microcephaly v1.161 BRIP1 Zornitza Stark Tag treatable tag was added to gene: BRIP1.
Microcephaly v1.161 KCNK3 Zornitza Stark Marked gene: KCNK3 as ready
Microcephaly v1.161 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Green List (High Evidence).
Microcephaly v1.161 KCNK3 Zornitza Stark Classified gene: KCNK3 as Green List (high evidence)
Microcephaly v1.161 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Green List (High Evidence).
Microcephaly v1.160 NAPB Alison Yeung Marked gene: NAPB as ready
Microcephaly v1.160 NAPB Alison Yeung Gene: napb has been classified as Green List (High Evidence).
Microcephaly v1.160 NAPB Alison Yeung Classified gene: NAPB as Green List (high evidence)
Microcephaly v1.160 NAPB Alison Yeung Gene: napb has been classified as Green List (High Evidence).
Microcephaly v1.159 MTSS1L Elena Savva Marked gene: MTSS1L as ready
Microcephaly v1.159 MTSS1L Elena Savva Gene: mtss1l has been classified as Green List (High Evidence).
Microcephaly v1.159 MTSS1L Elena Savva Classified gene: MTSS1L as Green List (high evidence)
Microcephaly v1.159 MTSS1L Elena Savva Gene: mtss1l has been classified as Green List (High Evidence).
Microcephaly v1.158 MTSS1L Elena Savva gene: MTSS1L was added
gene: MTSS1L was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: MTSS1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MTSS1L were set to PMID: 36067766
Phenotypes for gene: MTSS1L were set to Intellectual disability, MTSS2-related (MONDO#0001071)
Review for gene: MTSS1L was set to GREEN
Added comment: Alt gene name: MTSS2

Huang (2022): recurring de novo missense variant (p.R671W) causing syndromic intellectual disability in 5 unrelated individuals.
- Individuals present with microcephaly or relative microcephaly (5/5)
- Overexpression supports a DN mechanism
Sources: Literature
Microcephaly v1.157 MTSS1 Elena Savva Deleted their review
Microcephaly v1.157 MTSS1 Elena Savva Deleted their comment
Microcephaly v1.157 NAPB Paul De Fazio gene: NAPB was added
gene: NAPB was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NAPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAPB were set to 26235277; 28097321; 33189936
Phenotypes for gene: NAPB were set to Developmental and epileptic encephalopathy 107 MIM#620033
Review for gene: NAPB was set to GREEN
gene: NAPB was marked as current diagnostic
Added comment: PMID 26235277: homozygous nonsense variant identified in a 6 year old girl by trio WES with early-onset epileptic encephalopathy characterised by multifocal seizures and profound GDD. Also noted to have progressive microcephaly (9th to <0.4th centile)

PMID 28097321: exome sequencing in 152 consanguineous families with at least one member affected with ID. Homozygous nonsense variant identified in a patient with profound ID, seizures, feeding difficulties in infancy, muscularhypotonia, microcephaly, and impaired vision

PMID 33189936: homozygous canonical splice variant identified by trio exome sequencing in two siblings with seizures, intellectual disability and global developmental delay, microcephaly (<-3SD), and muscular hypotonia.
Sources: Literature
Microcephaly v1.157 MTSS1 Elena Savva gene: MTSS1 was added
gene: MTSS1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: MTSS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MTSS1 were set to PMID: 36067766
Phenotypes for gene: MTSS1 were set to Intellectual disability, MTSS1-related (MONDO#0001071)
Review for gene: MTSS1 was set to GREEN
Added comment: Alt gene name: MTSS2

Huang (2022): recurring de novo missense variant (p.R671W) causing syndromic intellectual disability in 5 unrelated individuals.
- Individuals present with microcephaly or relative microcephaly (5/5)
- Overexpression supports a DN mechanism
Sources: Literature
Microcephaly v1.156 RABGAP1 Zornitza Stark Classified gene: RABGAP1 as Green List (high evidence)
Microcephaly v1.156 RABGAP1 Zornitza Stark Gene: rabgap1 has been classified as Green List (High Evidence).
Microcephaly v1.156 RABGAP1 Zornitza Stark Marked gene: RABGAP1 as ready
Microcephaly v1.156 RABGAP1 Zornitza Stark Gene: rabgap1 has been classified as Green List (High Evidence).
Microcephaly v1.156 RABGAP1 Zornitza Stark Classified gene: RABGAP1 as Green List (high evidence)
Microcephaly v1.156 RABGAP1 Zornitza Stark Gene: rabgap1 has been classified as Green List (High Evidence).
Microcephaly v1.155 RABGAP1 Zornitza Stark gene: RABGAP1 was added
gene: RABGAP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: RABGAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RABGAP1 were set to 36083289
Phenotypes for gene: RABGAP1 were set to Neurodevelopmental disorder, RABGAP1-related,MONDO:0700092
Review for gene: RABGAP1 was set to GREEN
Added comment: 5 individuals from three families reported with ID, microcephaly, SNHL and seizures. Mouse model recapitulated the phenotype.
Sources: Literature
Microcephaly v1.154 KCNK3 Krithika Murali gene: KCNK3 was added
gene: KCNK3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: KCNK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNK3 were set to 36195757
Phenotypes for gene: KCNK3 were set to Neurodevelopmental disorder, MONDO:0700092, KCNK3-related; developmental delay with sleep apnoea (DDSA)
Review for gene: KCNK3 was set to GREEN
Added comment: PMID 36195757 Sörmann et al 2022 report 9 unrelated individuals with de novo heterozygous KCNK3 missense variants (21 weeks to 25 years old). All 8 living probands (3-25 years) had hypotonia, global developmental delay, central and/or obstructive sleep apnoea and feeding difficulties. 7/9 probands had additional anomalies including microcephaly (at least 3/9), arthrogryposis/flexion contractures/foot deformities (7/9), scoliosis, cleft palate (2/9), and ambiguous genitalia/undescended testes (5/6) and dysmorphism. IUGR reported in 3/9 probands and polyhdramnios in 2/9.

KCNK3 encodes the TASK-1 K2P channel expressed throughout the central nervous system. All identified variants clustered near the X-gate and are involved in inter- or intra-subunit interaction likely to hold the X-gate closed. Individuals with variants located in the M2 transmembrane helix had a more severe phenotype than those with variants in the M4 helix. Functional studies support a gain of function disease mechanism with increased channel activation. TASK-1 K+ channel inhibitors (some in clinical use) have been raised as a possible therapeutic strategy.

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Heterozygous LoF variants associated with a different disorder - primary pulmonary arterial hypertension
Sources: Literature
Microcephaly v1.154 DOHH Zornitza Stark Phenotypes for gene: DOHH were changed from Neurodevelopmental disorder, DOHH-related (MONDO#0700092) to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, MIM# 620066
Microcephaly v1.153 DOHH Zornitza Stark reviewed gene: DOHH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, MIM# 620066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.153 PDCD6IP Zornitza Stark Phenotypes for gene: PDCD6IP were changed from Primary microcephaly to Microcephaly 29, primary, autosomal recessive, MIM# 620047
Microcephaly v1.152 PDCD6IP Zornitza Stark edited their review of gene: PDCD6IP: Changed rating: AMBER; Changed phenotypes: Microcephaly 29, primary, autosomal recessive, MIM# 620047; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.152 TRAPPC10 Zornitza Stark Phenotypes for gene: TRAPPC10 were changed from neurodevelopmental disorder (MONDO:0700092), TRAPPC10-related to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, MIM# 620027
Microcephaly v1.151 TRAPPC10 Zornitza Stark reviewed gene: TRAPPC10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, short stature, and speech delay, MIM# 620027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.151 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023
Microcephaly v1.150 CHKA Zornitza Stark reviewed gene: CHKA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.150 PPFIBP1 Zornitza Stark Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, MIM# 620024
Microcephaly v1.149 PPFIBP1 Zornitza Stark edited their review of gene: PPFIBP1: Changed phenotypes: Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, MIM# 620024
Microcephaly v1.149 PRIM1 Zornitza Stark Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Microcephaly v1.148 PRIM1 Zornitza Stark edited their review of gene: PRIM1: Changed phenotypes: Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Microcephaly v1.148 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic disease, MONDO:0002254, THUMPD1-related to Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989
Microcephaly v1.147 THUMPD1 Zornitza Stark reviewed gene: THUMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.147 SARS Zornitza Stark Classified gene: SARS as Green List (high evidence)
Microcephaly v1.147 SARS Zornitza Stark Gene: sars has been classified as Green List (High Evidence).
Microcephaly v1.146 KIF15 Alison Yeung Marked gene: KIF15 as ready
Microcephaly v1.146 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Microcephaly v1.146 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Microcephaly v1.145 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Microcephaly v1.145 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Microcephaly v1.142 SARS Ain Roesley gene: SARS was added
gene: SARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to 35790048; 28236339; 34570399
Phenotypes for gene: SARS were set to neurodevelopmental disorder MONDO#070009, SARS1-related
Review for gene: SARS was set to GREEN
gene: SARS was marked as current diagnostic
Added comment: Total of 3 families
Sources: Literature
Microcephaly v1.142 SARS Ain Roesley Marked gene: SARS as ready
Microcephaly v1.142 SARS Ain Roesley Gene: sars has been classified as Red List (Low Evidence).
Microcephaly v1.142 SARS Ain Roesley gene: SARS was added
gene: SARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to 35790048; 28236339; 34570399
Phenotypes for gene: SARS were set to neurodevelopmental disorder MONDO#070009, SARS1-related
Review for gene: SARS was set to GREEN
gene: SARS was marked as current diagnostic
Added comment: Total of 3 families
Sources: Literature
Microcephaly v1.141 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to AMBER
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Microcephaly v1.141 WARS Seb Lunke Marked gene: WARS as ready
Microcephaly v1.141 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Microcephaly v1.141 PPFIBP1 Zornitza Stark Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Microcephaly v1.140 DOHH Zornitza Stark Marked gene: DOHH as ready
Microcephaly v1.140 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Microcephaly v1.140 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Microcephaly v1.140 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Microcephaly v1.139 WARS Seb Lunke Classified gene: WARS as Green List (high evidence)
Microcephaly v1.139 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Microcephaly v1.138 WARS Anna Ritchie gene: WARS was added
gene: WARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS were set to PMID: 35815345; 35790048
Phenotypes for gene: WARS were set to Neurodevelopmental disorder (MONDO:0700092), WARS-related
Review for gene: WARS was set to GREEN
Added comment: Seven affected individuals from four families with biallelic variants, showing varying
severities of developmental delay, intellectual disability and microcephaly. Hearing impairment and, as well as brain anomalies, skeletal system, movement/gait, and behaviour were variable features.
Sources: Literature
Microcephaly v1.138 PPFIBP1 Ee Ming Wong reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35830857; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v1.138 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Microcephaly v1.138 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Microcephaly v1.137 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Microcephaly v1.137 GINS3 Zornitza Stark Marked gene: GINS3 as ready
Microcephaly v1.137 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Microcephaly v1.137 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Microcephaly v1.137 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Microcephaly v1.136 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Microcephaly v1.135 HIST1H4E Zornitza Stark Marked gene: HIST1H4E as ready
Microcephaly v1.135 HIST1H4E Zornitza Stark Gene: hist1h4e has been classified as Green List (High Evidence).
Microcephaly v1.135 HIST1H4E Zornitza Stark Phenotypes for gene: HIST1H4E were changed from Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092 to Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950
Microcephaly v1.134 HIST1H4E Zornitza Stark Mode of inheritance for gene: HIST1H4E was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.133 HIST1H4E Zornitza Stark Classified gene: HIST1H4E as Green List (high evidence)
Microcephaly v1.133 HIST1H4E Zornitza Stark Gene: hist1h4e has been classified as Green List (High Evidence).
Microcephaly v1.132 HIST1H4E Zornitza Stark Tag new gene name tag was added to gene: HIST1H4E.
Microcephaly v1.132 HIST1H4E Zornitza Stark reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.132 AUTS2 Elena Savva Marked gene: AUTS2 as ready
Microcephaly v1.132 AUTS2 Elena Savva Gene: auts2 has been classified as Green List (High Evidence).
Microcephaly v1.132 AUTS2 Elena Savva Classified gene: AUTS2 as Green List (high evidence)
Microcephaly v1.132 AUTS2 Elena Savva Gene: auts2 has been classified as Green List (High Evidence).
Microcephaly v1.131 AUTS2 Elena Savva gene: AUTS2 was added
gene: AUTS2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: AUTS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AUTS2 were set to PMID: 35802027; 34573342
Phenotypes for gene: AUTS2 were set to Intellectual developmental disorder, autosomal dominant 26 MIM#615834
Review for gene: AUTS2 was set to GREEN
Added comment: PMID: 35802027 - human cerebral organoid model used to illustrate functionality of de novo missense variants.
Describes rat model who lacked a microcephaly presentation.
Proband has profound ID, microcephaly, epilepsy, cerebellar hypoplasia and dysmorphic features.

PMID: 34573342 - microcephaly as a feature in 3/5 patients in an internal cohort. Review of the literature found 65% freq of microcephaly (34/52 patients)
Sources: Literature
Microcephaly v1.130 WNK3 Zornitza Stark Marked gene: WNK3 as ready
Microcephaly v1.130 WNK3 Zornitza Stark Gene: wnk3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.130 WNK3 Zornitza Stark Classified gene: WNK3 as Amber List (moderate evidence)
Microcephaly v1.130 WNK3 Zornitza Stark Gene: wnk3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.129 WNK3 Lucy Spencer gene: WNK3 was added
gene: WNK3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092)
Added comment: 6 individuals with microcephaly all at -2 to -2.4SD so leaving as amber for now. Individuals also had ID and other features
Sources: Literature
Microcephaly v1.129 TAF8 Zornitza Stark changed review comment from: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature; to: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. Unclear if this is a founder variant, families of different ethnicities. One family with different compound heterozygous variants.
Sources: Literature
Microcephaly v1.129 TAF8 Zornitza Stark Tag founder was removed from gene: TAF8.
Microcephaly v1.129 TAF8 Zornitza Stark Marked gene: TAF8 as ready
Microcephaly v1.129 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Microcephaly v1.129 TAF8 Zornitza Stark Classified gene: TAF8 as Green List (high evidence)
Microcephaly v1.129 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Microcephaly v1.128 TAF8 Zornitza Stark gene: TAF8 was added
gene: TAF8 was added to Microcephaly. Sources: Literature
founder tags were added to gene: TAF8.
Mode of inheritance for gene: TAF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF8 were set to 29648665; 35759269
Phenotypes for gene: TAF8 were set to Neurodevelopmental disorder, MONDO:0700092, TAF8-related
Review for gene: TAF8 was set to GREEN
Added comment: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature
Microcephaly v1.127 BUB1 Zornitza Stark Marked gene: BUB1 as ready
Microcephaly v1.127 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.127 BUB1 Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence)
Microcephaly v1.127 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.127 BUB1 Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence)
Microcephaly v1.127 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.126 BUB1 Paul De Fazio gene: BUB1 was added
gene: BUB1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: BUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUB1 were set to 35044816; 19772675; 19117986; 23209306
Phenotypes for gene: BUB1 were set to Neurodevelopmental disorder, BUB1-related MONDO:0700092; Intellectual disability and microcephaly
Review for gene: BUB1 was set to AMBER
gene: BUB1 was marked as current diagnostic
Added comment: 2 unrelated patients with ID, microcephaly, short stature, dysmorphic features reported with biallelic variants:

P1 (3yo male): homozygous start-loss variant (2 hets and 0 hom in gnomAD). Functional testing showed a small amount of full-length protein was translated, and BUB1 recruitment to kinetochores was nearly undetectable.
P2 (16yo female): compound heterozygous for a canonical splice variant (1 het and no hom in gnomAD) and an NMD-predicted frameshift variant (absent from gnomAD). The splice variant was shown to result in an in-frame deletion of 54 amino acids in the kinase domain. P2 cells have reduced protein levels but essentially no kinase activity.

BUB1 patient cells have impaired mitotic fidelity.

Homozygous Bub1 disruption in mice is embryonic lethal (PMID:19772675). A hypomorphic mouse is viable with increased tumourigenesis with ageing and aneuploidy (PMID:19117986). A kinase-dead mouse does not show increased tumourigenesis but does have a high frequency of aneuploid cells (PMID:23209306)
Sources: Literature
Microcephaly v1.126 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from Growth delay, microcephaly and intellectual disability to Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758
Microcephaly v1.125 HIST1H4C Zornitza Stark edited their review of gene: HIST1H4C: Changed phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758
Microcephaly v1.125 SLC38A3 Zornitza Stark Phenotypes for gene: SLC38A3 were changed from Developmental epileptic encephalopathy MONDO:0100062, SLC38A3-related to Developmental and epileptic encephalopathy 102, MIM# 619881
Microcephaly v1.124 SLC38A3 Zornitza Stark reviewed gene: SLC38A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 102, MIM# 619881; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.124 ZNF526 Zornitza Stark Phenotypes for gene: ZNF526 were changed from Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia to Dentici-Novelli neurodevelopmental syndrome, MIM# 619877
Microcephaly v1.123 ZNF526 Zornitza Stark edited their review of gene: ZNF526: Changed phenotypes: Dentici-Novelli neurodevelopmental syndrome, MIM# 619877
Microcephaly v1.123 CPSF3 Zornitza Stark Phenotypes for gene: CPSF3 were changed from Neurodevelopmental disorder, CPSF3-related, MONDO:0700092 to Neurodevelopmental disorder with microcephaly, hypotonia, and seizures (NEDMHS), MIM#619876
Microcephaly v1.122 CPSF3 Zornitza Stark reviewed gene: CPSF3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, hypotonia, and seizures (NEDMHS), MIM#619876; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.122 DTYMK Zornitza Stark Marked gene: DTYMK as ready
Microcephaly v1.122 DTYMK Zornitza Stark Gene: dtymk has been classified as Green List (High Evidence).
Microcephaly v1.122 DTYMK Zornitza Stark Classified gene: DTYMK as Green List (high evidence)
Microcephaly v1.122 DTYMK Zornitza Stark Gene: dtymk has been classified as Green List (High Evidence).
Microcephaly v1.121 DTYMK Daniel Flanagan gene: DTYMK was added
gene: DTYMK was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: DTYMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DTYMK were set to 34918187; 31271740
Phenotypes for gene: DTYMK were set to Neurodegeneration, childhood-onset, with progressive microcephaly (MIM# 619847)
Review for gene: DTYMK was set to GREEN
Added comment: Three unrelated families with biallelic DTYMK variants. The probands had severe microcephaly, growth retardation and minimal neurodevelopment. Supporting zebrafish model.
Sources: Expert list
Microcephaly v1.121 DROSHA Zornitza Stark Marked gene: DROSHA as ready
Microcephaly v1.121 DROSHA Zornitza Stark Gene: drosha has been classified as Amber List (Moderate Evidence).
Microcephaly v1.121 DROSHA Zornitza Stark Classified gene: DROSHA as Amber List (moderate evidence)
Microcephaly v1.121 DROSHA Zornitza Stark Gene: drosha has been classified as Amber List (Moderate Evidence).
Microcephaly v1.120 PPFIBP1 Zornitza Stark Marked gene: PPFIBP1 as ready
Microcephaly v1.120 PPFIBP1 Zornitza Stark Gene: ppfibp1 has been classified as Green List (High Evidence).
Microcephaly v1.120 DROSHA Lucy Spencer gene: DROSHA was added
gene: DROSHA was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DROSHA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DROSHA were set to 35405010
Phenotypes for gene: DROSHA were set to Neurodevelopmental disorder (MONDO#0700092), DROSHA-related
Review for gene: DROSHA was set to AMBER
Added comment: 2 individuals with profound intellectual disability, epilepsy, white matter atrophy, microcephaly, and dysmorphic features, who carry damaging de novo heterozygous variants in DROSHA. Both variants are missense, absent from gnomad. Both individuals noted to have Rett-like features.

Functional studies in patient fibroblasts showed one of the missense altered the expression of mature miRNA. Fruit fly models with homozygous LOF variants die during larval stages. introduction of the missense seen in the patients was able to partially rescue this phenotype suggesting LOF is not the mechanism.
Sources: Literature
Microcephaly v1.120 PPFIBP1 Zornitza Stark Classified gene: PPFIBP1 as Green List (high evidence)
Microcephaly v1.120 PPFIBP1 Zornitza Stark Gene: ppfibp1 has been classified as Green List (High Evidence).
Microcephaly v1.119 PPFIBP1 Zornitza Stark gene: PPFIBP1 was added
gene: PPFIBP1 was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: PPFIBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Phenotypes for gene: PPFIBP1 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related
Review for gene: PPFIBP1 was set to GREEN
Added comment: 16 individuals from 10 unrelated families reported with moderate to profound developmental delay, often refractory early-onset epilepsy and progressive microcephaly. Drosophila model.
Sources: Expert Review
Microcephaly v1.118 TRAPPC10 Zornitza Stark Marked gene: TRAPPC10 as ready
Microcephaly v1.118 TRAPPC10 Zornitza Stark Gene: trappc10 has been classified as Green List (High Evidence).
Microcephaly v1.118 TRAPPC10 Zornitza Stark Classified gene: TRAPPC10 as Green List (high evidence)
Microcephaly v1.118 TRAPPC10 Zornitza Stark Gene: trappc10 has been classified as Green List (High Evidence).
Microcephaly v1.117 TRAPPC10 Naomi Baker gene: TRAPPC10 was added
gene: TRAPPC10 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TRAPPC10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC10 were set to PMID: 35298461; 30167849
Phenotypes for gene: TRAPPC10 were set to neurodevelopmental disorder (MONDO:0700092), TRAPPC10-related
Review for gene: TRAPPC10 was set to GREEN
Added comment: PMID: 35298461 – two Pakistani families reported with homozygous variants. Family 1 has frameshift variant in 8 affected individual and family 2 has missense variant in 2 affected individuals. Patients present with microcephaly, short stature, hypotonia, severe ID and behavioural abnormalities. Seizures also reported in 4/10 individuals. Paper also reported brain abnormalities in null mouse model and other functional in transfected cell lines.
PMID: 30167849 – initial report of family 2 above.
Sources: Literature
Microcephaly v1.117 NDUFA2 Zornitza Stark Marked gene: NDUFA2 as ready
Microcephaly v1.117 NDUFA2 Zornitza Stark Gene: ndufa2 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.117 NDUFA2 Zornitza Stark Classified gene: NDUFA2 as Amber List (moderate evidence)
Microcephaly v1.117 NDUFA2 Zornitza Stark Gene: ndufa2 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.116 NDUFA2 Krithika Murali gene: NDUFA2 was added
gene: NDUFA2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NDUFA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA2 were set to 28857146; 32154054; 18513682
Phenotypes for gene: NDUFA2 were set to Mitochondrial complex I deficiency, nuclear type 13 - MIM#618235
Review for gene: NDUFA2 was set to AMBER
Added comment: 4 unrelated patients reported in the published literature. 2 reported to have postnatal-onset microcephaly.

PMID 28857146 - report 2 unrelated patients with cystic leukoencephalopathy.

Patient 1 - born at term, unremarkable antenatal history. Presented at 8 months with encephalopathy, hepatomegaly, hyperammonemia. Exhibited developmental regression until 12 months of age and also had moderate ID, dystonia, spasticity and focal epilepsy. Initially had homozygous SLC22A5 variant associated with primary carnitine deficiency. MRI-B age 2 showed white matter + cystic changes and corpus callosum anomalies. Complex 1 deficiency suspected based on white matter anomalies. Patient-derived fibroblasts showed decrease in complex 1 enzyme activity. WES identified homozygous NDUFA2 variant with parental testing confirming carrier status.

Patient 2 - compound het NDUFA2 variants. Phenotypic features include - failure to thrive, developmental regression, upper motor neuron signs, white matter abnormalities + cystic changes on MRI-Brain, severe GDD and microcephaly.

PMID: 32154054 - report a patient with developmental regression and postnatal onset progressive microcephaly. Other features included UMN signs, spastic equinovarus deformity of the feet. At age 4 developed generalised seizures in context of VZV infection. Abnormal MRI-B including white matter changes, bilateral cavitating lesions and corpus callosum anomalies. Homozygous NDUFA2 variant identified.

PMID: 18513682 - report a patient with an isolated complex I deficiency expressed in skin fibroblasts as well as muscle tissue. Normal antenatal course reported - D5 of life diagnosed with hypertrophic cardiomyopathy was diagnosed. Other phenotypic features included developmental delay, regression, MRI anomalies (cerebral atrophy, hypoplasia corpus callosum), seizures.
Sources: Literature
Microcephaly v1.116 NAT8L Zornitza Stark Marked gene: NAT8L as ready
Microcephaly v1.116 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Microcephaly v1.116 NAT8L Zornitza Stark Phenotypes for gene: NAT8L were changed from N-acetylaspartate deficiency - MIM#614063 to N-acetylaspartate deficiency - MIM#614063
Microcephaly v1.115 NAT8L Zornitza Stark Phenotypes for gene: NAT8L were changed from ?N-acetylaspartate deficiency - MIM#614063 to N-acetylaspartate deficiency - MIM#614063
Microcephaly v1.114 NAT8L Zornitza Stark Classified gene: NAT8L as Red List (low evidence)
Microcephaly v1.114 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Microcephaly v1.113 NAT8L Zornitza Stark reviewed gene: NAT8L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: None
Microcephaly v1.113 NAT8L Krithika Murali gene: NAT8L was added
gene: NAT8L was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NAT8L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAT8L were set to 11310630; 19807691; 32275776
Phenotypes for gene: NAT8L were set to ?N-acetylaspartate deficiency - MIM#614063
Review for gene: NAT8L was set to AMBER
Added comment: Absence of brain N-acetylaspartate, has been described in only one patient, with truncal ataxia, marked developmental delay, seizures and secondary microcephaly (first described by - PMID: 11310630 Martin et al 2001). PMID: 19807691 - Wiame et al 2009 identified in this patient a homozygous 19 bp NAT8L gene deletion, resulting in a change in reading frame and the absence of production of a functional protein. The affected individual is adopted and testing of the biological parents was not possible. The authors provide supportive functional studies.
Sources: Literature
Microcephaly v1.113 NARS Zornitza Stark Marked gene: NARS as ready
Microcephaly v1.113 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Microcephaly v1.113 NARS Zornitza Stark Classified gene: NARS as Green List (high evidence)
Microcephaly v1.113 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Microcephaly v1.112 NARS Zornitza Stark Tag new gene name tag was added to gene: NARS.
Microcephaly v1.112 NALCN Zornitza Stark Marked gene: NALCN as ready
Microcephaly v1.112 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Microcephaly v1.112 NALCN Zornitza Stark Classified gene: NALCN as Green List (high evidence)
Microcephaly v1.112 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Microcephaly v1.111 NARS Krithika Murali gene: NARS was added
gene: NARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NARS were set to 32738225; 32788587
Phenotypes for gene: NARS were set to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive - MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, autosomal dominant - MIM#619092
Review for gene: NARS was set to GREEN
Added comment: HGNC approved gene symbol - NARS1

Both mono allelic and biallelic variants associated with a progressive neurological disorder with onset in infancy. Microcephaly a commonly reported feature.
Sources: Literature
Microcephaly v1.111 NALCN Krithika Murali gene: NALCN was added
gene: NALCN was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NALCN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NALCN were set to 25683120; 23749988; 24075186; 30167850
Phenotypes for gene: NALCN were set to Congenital contractures of the limbs and face, hypotonia, and developmental delay - MIM#616266; Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 - MIM#615419
Review for gene: NALCN was set to GREEN
Added comment: Monoallelic NALCN missense variants reported in individuals with congenital contractures of the limbs and face, hypotonia, and developmental delay.

Biallelic NALCN variants cause severe infantile hypotonia with psychomotor retardation and characteristic facial features. Microcephaly a reported feature. PMID: 30167850 report new cases with balletic variants and review previously published cases noting microcephaly in 14/21 individuals.
Sources: Literature
Microcephaly v1.111 CPSF3 Alison Yeung Phenotypes for gene: CPSF3 were changed from Neurodevelopmental disorder, CPSF3-related, MONDO:0700092 to Neurodevelopmental disorder, CPSF3-related, MONDO:0700092
Microcephaly v1.110 CPSF3 Alison Yeung Classified gene: CPSF3 as Green List (high evidence)
Microcephaly v1.110 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Microcephaly v1.110 CPSF3 Alison Yeung Phenotypes for gene: CPSF3 were changed from Intellectual disability syndrome to Neurodevelopmental disorder, CPSF3-related, MONDO:0700092
Microcephaly v1.110 CPSF3 Alison Yeung Classified gene: CPSF3 as Green List (high evidence)
Microcephaly v1.110 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Microcephaly v1.109 CPSF3 Alison Yeung Marked gene: CPSF3 as ready
Microcephaly v1.109 CPSF3 Alison Yeung Gene: cpsf3 has been removed from the panel.
Microcephaly v1.109 HIST1H4E Paul De Fazio gene: HIST1H4E was added
gene: HIST1H4E was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: HIST1H4E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4E were set to 35202563
Phenotypes for gene: HIST1H4E were set to Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092
Review for gene: HIST1H4E was set to GREEN
gene: HIST1H4E was marked as current diagnostic
Added comment: HGNC recognised gene name: H4C5
17 patients identified with de novo missense variants affecting Lys31, Pro32, Arg35, Leu37, Arg40 (recurrent), Arg45 (recurrent), Tyr98 (recurrent). All individuals had ID/dev delay. Additional phenotypes in some but not all individuals included epilepsy, hypotonia, facial dysmorphism. Most had reduced birth length, OFC, weight (-1 to -3SD). OFC at most recent exam (age range 11 months to 18 years) ranged from -0.15SD to < -4SD. 10/17 had OFC < -3SD.
A zebrafish model has developmental defects.
Sources: Literature
Microcephaly v1.109 HIST1H4C Paul De Fazio reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 35202563; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758, Neurodevelopmental disorder, HIST1H4C-related MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Microcephaly v1.109 CPSF3 Belinda Chong gene: CPSF3 was added
gene: CPSF3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CPSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPSF3 were set to 35121750
Phenotypes for gene: CPSF3 were set to Intellectual disability syndrome
Review for gene: CPSF3 was set to GREEN
gene: CPSF3 was marked as current diagnostic
Added comment: Study of a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes

Six homozygous carriers of missense variants in CPSF3 show severe intellectual disability, seizures, microcephaly, and abnormal muscle tone.

- Four identified through Icelandic geneology (p.Gly468Glu), three carrier couples total of four children who had died prematurely. Tested archival samples for two of these children, and confirm a homozygous genotype.
- Two of Mexican descent (p.Ile354Thr), first-degree cousins
Sources: Literature
Microcephaly v1.109 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Microcephaly v1.109 CHKA Zornitza Stark Marked gene: CHKA as ready
Microcephaly v1.109 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Microcephaly v1.109 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Microcephaly v1.108 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Microcephaly v1.108 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Microcephaly v1.107 TSEN2 Chirag Patel Classified gene: TSEN2 as Green List (high evidence)
Microcephaly v1.107 TSEN2 Chirag Patel Gene: tsen2 has been classified as Green List (High Evidence).
Microcephaly v1.107 TSEN2 Chirag Patel Classified gene: TSEN2 as Green List (high evidence)
Microcephaly v1.107 TSEN2 Chirag Patel Gene: tsen2 has been classified as Green List (High Evidence).
Microcephaly v1.106 TSEN2 Chirag Patel reviewed gene: TSEN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Microcephaly v1.106 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Microcephaly v1.106 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange-like syndrome to Cornelia de Lange-like syndrome, MONDO:0016033
Microcephaly v1.105 EHMT1 Zornitza Stark Marked gene: EHMT1 as ready
Microcephaly v1.105 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.105 EHMT1 Zornitza Stark Classified gene: EHMT1 as Amber List (moderate evidence)
Microcephaly v1.105 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.104 EHMT1 Elena Savva gene: EHMT1 was added
gene: EHMT1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: EHMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EHMT1 were set to PMID: 29228531; 28361100; 21910222; 19264732
Phenotypes for gene: EHMT1 were set to Kleefstra syndrome 1 MIM#610253
Review for gene: EHMT1 was set to AMBER
Added comment: OMIM/PMID: 29228531/PMID: 21910222 - microcephaly describes as a feature of kleefstra syndrome

PMID: 28361100 - 18-year-old woman with intellectual disability, severely limited speech, hypotonia, microcephaly, and facial dysmorphisms, de novo single-base frameshift deletion

PMID: 19264732 - Microcephaly was noted in 6/15 patients with a deletion and 2/6 cases with a "mutation and was already present at birth" unclear what mutations these are

Common cause of disease is a microdeletion of 9q34.3, in which microcephaly is commonly reported.

Amber due to inconsistent reports in SNV cases.
Sources: Literature
Microcephaly v1.104 THUMPD1 Zornitza Stark Marked gene: THUMPD1 as ready
Microcephaly v1.104 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Microcephaly v1.104 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR to Syndromic disease, MONDO:0002254, THUMPD1-related
Microcephaly v1.103 THUMPD1 Zornitza Stark Classified gene: THUMPD1 as Green List (high evidence)
Microcephaly v1.103 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Microcephaly v1.102 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, biallelic loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Microcephaly v1.102 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Microcephaly v1.102 THUMPD1 Chern Lim gene: THUMPD1 was added
gene: THUMPD1 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: THUMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: THUMPD1 were set to Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR
Review for gene: THUMPD1 was set to GREEN
gene: THUMPD1 was marked as current diagnostic
Added comment: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Microcephaly v1.102 CENPJ Zornitza Stark Publications for gene: CENPJ were set to 15793586; 16900296; 2097801822775483; 20522431; 32677750; 32549991; 30626697
Microcephaly v1.101 CENPJ Zornitza Stark edited their review of gene: CENPJ: Added comment: PMID 34068194: two further families reported with Seckel syndrome, same homozygous missense, founder?; Changed publications: 15793586, 16900296, 2097801822775483, 20522431, 32677750, 32549991, 30626697, 34068194
Microcephaly v1.101 RBL2 Alison Yeung Marked gene: RBL2 as ready
Microcephaly v1.101 RBL2 Alison Yeung Gene: rbl2 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.101 RBL2 Alison Yeung Classified gene: RBL2 as Amber List (moderate evidence)
Microcephaly v1.101 RBL2 Alison Yeung Gene: rbl2 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.100 SLC38A3 Zornitza Stark Marked gene: SLC38A3 as ready
Microcephaly v1.100 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Microcephaly v1.100 SLC38A3 Zornitza Stark Phenotypes for gene: SLC38A3 were changed from developmental epileptic encephalopathy, SLC38A3-related MONDO:0100062 to Developmental epileptic encephalopathy MONDO:0100062, SLC38A3-related
Microcephaly v1.99 SLC38A3 Zornitza Stark Classified gene: SLC38A3 as Green List (high evidence)
Microcephaly v1.99 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Microcephaly v1.98 SLC38A3 Ain Roesley gene: SLC38A3 was added
gene: SLC38A3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SLC38A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A3 were set to 34605855
Phenotypes for gene: SLC38A3 were set to developmental epileptic encephalopathy, SLC38A3-related MONDO:0100062
Penetrance for gene: SLC38A3 were set to Complete
Review for gene: SLC38A3 was set to GREEN
gene: SLC38A3 was marked as current diagnostic
Added comment: 7 families 6 of whom are consanguineous but unique variants in all of them

Acquired microcephaly noted (8/10 with >-2 SD, 5/10 >-3 SD)
Sources: Literature
Microcephaly v1.98 RBL2 Elena Savva gene: RBL2 was added
gene: RBL2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to PMID: 33980986; 32105419; 9806916
Phenotypes for gene: RBL2 were set to Severe motor and cognitive impairment; Intellectual disability; Brunet-Wagner neurodevelopmental syndrome MIM#619690
Review for gene: RBL2 was set to AMBER
Added comment: PMID: 33980986: 2 unrelated patients (3 total) with infantile hypotonia, severe developmental delay and microcephaly. Functional studies on patient fibroblasts supports loss of protein and mRNA expression. Patients were homozygous for a PTC, and a CNV (exon 4-5 del)

PMID: 32105419: affecting siblings with severe intellectual disability, stereotypies and dysmorphic features. Chet PTC/CNV (exon 13-17 del).

3 unrelated families - 2/3 corpus callosum hypoplasia/cerebral atrophy, 2/3 epilepsy, 2/3 microcephaly

PMID: 9806916: mouse model in support
Sources: Literature
Microcephaly v1.98 FRA10AC1 Zornitza Stark Marked gene: FRA10AC1 as ready
Microcephaly v1.98 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Microcephaly v1.98 FRA10AC1 Zornitza Stark Classified gene: FRA10AC1 as Green List (high evidence)
Microcephaly v1.98 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Microcephaly v1.97 FRA10AC1 Zornitza Stark gene: FRA10AC1 was added
gene: FRA10AC1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FRA10AC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRA10AC1 were set to 34694367
Phenotypes for gene: FRA10AC1 were set to Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related
Review for gene: FRA10AC1 was set to GREEN
Added comment: PMID 34694367: 5 individuals from 3 unrelated families reported. Variable ID, possibly related to variant type with LoF variants associated with more severe ID. All individuals had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.
Sources: Literature
Microcephaly v1.96 NAA20 Zornitza Stark Marked gene: NAA20 as ready
Microcephaly v1.96 NAA20 Zornitza Stark Gene: naa20 has been classified as Green List (High Evidence).
Microcephaly v1.96 NAA20 Zornitza Stark Phenotypes for gene: NAA20 were changed from Autosomal recessive developmental delay, intellectual disability, and microcephaly to Intellectual developmental disorder, autosomal recessive 73, MIM# 619717
Microcephaly v1.95 NAA20 Zornitza Stark reviewed gene: NAA20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 73, MIM# 619717; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.95 KIF26B Zornitza Stark Marked gene: KIF26B as ready
Microcephaly v1.95 KIF26B Zornitza Stark Gene: kif26b has been classified as Red List (Low Evidence).
Microcephaly v1.95 KIF26B Zornitza Stark edited their review of gene: KIF26B: Changed rating: RED
Microcephaly v1.95 KIF26B Zornitza Stark gene: KIF26B was added
gene: KIF26B was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF26B were set to 30151950
Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity.
Sources: Expert Review
Microcephaly v1.94 TTI2 Zornitza Stark Marked gene: TTI2 as ready
Microcephaly v1.94 TTI2 Zornitza Stark Gene: tti2 has been classified as Green List (High Evidence).
Microcephaly v1.94 TTI2 Zornitza Stark Classified gene: TTI2 as Green List (high evidence)
Microcephaly v1.94 TTI2 Zornitza Stark Gene: tti2 has been classified as Green List (High Evidence).
Microcephaly v1.93 TTI2 Zornitza Stark gene: TTI2 was added
gene: TTI2 was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: TTI2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTI2 were set to 32061250; 23956177; 31737043
Phenotypes for gene: TTI2 were set to Mental retardation, autosomal recessive 39 (MIM#615541)
Review for gene: TTI2 was set to GREEN
Added comment: PMID: 32061250 reviews reports of TTI2-related ID in 6 families. Common features are microcephaly and DD, but there is phenotypic variability reported with syndromic and non-syndromic individuals. Other features include speech delay, short stature, dysmorphic features (high nasal bridge, deep-set eyes), strabismus and dyskenesia. Six missense and one NMD were reported in hom and cHet individuals. Functional evidence is limited, but suggestive of LoF (PMIDs: 23956177, 31737043).
Sources: Expert Review
Microcephaly v1.92 NSD2 Zornitza Stark Phenotypes for gene: NSD2 were changed from Microcephaly; intellectual disability to Rauch-Steindl syndrome, MIM# 619695; Microcephaly; intellectual disability
Microcephaly v1.91 NSD2 Zornitza Stark edited their review of gene: NSD2: Changed phenotypes: Rauch-Steindl syndrome, MIM# 619695, Microcephaly, intellectual disability
Microcephaly v1.91 VPS50 Zornitza Stark Phenotypes for gene: VPS50 were changed from Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685; Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum
Microcephaly v1.90 VPS50 Zornitza Stark edited their review of gene: VPS50: Changed phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685, Neonatal cholestatic liver disease, Failure to thrive, Profound global developmental delay, Postnatal microcephaly, Seizures, Abnormality of the corpus callosum
Microcephaly v1.90 CCND2 Alison Yeung Marked gene: CCND2 as ready
Microcephaly v1.90 CCND2 Alison Yeung Gene: ccnd2 has been classified as Green List (High Evidence).
Microcephaly v1.90 CCND2 Alison Yeung Classified gene: CCND2 as Green List (high evidence)
Microcephaly v1.90 CCND2 Alison Yeung Gene: ccnd2 has been classified as Green List (High Evidence).
Microcephaly v1.89 CCND2 Alison Yeung gene: CCND2 was added
gene: CCND2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CCND2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCND2 were set to 34087052
Phenotypes for gene: CCND2 were set to Neurodevelopmental disorder, CCND2-related MONDO# 0700092; Microcephaly, MONDO# 0001149
Review for gene: CCND2 was set to GREEN
Added comment: Novel phenotype of microcephaly and mild developmental delay described in three unrelated families. Variants associated with this phenotype located in the proximal region of the gene.

Variants in distal region of gene associated with a reciprocal phenotype of macrocephaly/megalencephaly with severe cortical malformation.
Sources: Literature
Microcephaly v1.88 NAA20 Chirag Patel Classified gene: NAA20 as Green List (high evidence)
Microcephaly v1.88 NAA20 Chirag Patel Gene: naa20 has been classified as Green List (High Evidence).
Microcephaly v1.87 NAA20 Chirag Patel gene: NAA20 was added
gene: NAA20 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NAA20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAA20 were set to PMID: 34230638
Phenotypes for gene: NAA20 were set to Autosomal recessive developmental delay, intellectual disability, and microcephaly
Review for gene: NAA20 was set to GREEN
Added comment: 2 consanguineous families with 5 affected individuals with developmental delay, intellectual disability, and microcephaly (-2-4SD). Exome and genome sequencing identified 2 different homozygous variants in NAA20 gene (p.Met54Val and p.Ala80Val), and segregated with affected individuals. N-terminal acetyltransferases modify proteins by adding an acetyl moiety to the first amino acid and are vital for protein and cell function. The NatB complex acetylates 20% of the human proteome and is composed of the catalytic subunit NAA20 and the auxiliary subunit NAA25. Both NAA20-M54V and NAA20-A80V were impaired in their capacity to form a NatB complex with NAA25, and in vitro acetylation assays revealed reduced catalytic activities toward different NatB substrates.
Sources: Literature
Microcephaly v1.86 HHAT Zornitza Stark Publications for gene: HHAT were set to 24784881; 30912300
Microcephaly v1.85 HHAT Zornitza Stark Classified gene: HHAT as Green List (high evidence)
Microcephaly v1.85 HHAT Zornitza Stark Gene: hhat has been classified as Green List (High Evidence).
Microcephaly v1.84 HHAT Zornitza Stark commented on gene: HHAT: Additional family reported, with severe microcephaly, skeletal dysplasia and sex reversal phenotype.
Microcephaly v1.84 HHAT Zornitza Stark edited their review of gene: HHAT: Changed rating: GREEN; Changed publications: 24784881, 30912300, 33749989
Microcephaly v1.84 ZBTB18 Zornitza Stark Marked gene: ZBTB18 as ready
Microcephaly v1.84 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Green List (High Evidence).
Microcephaly v1.84 ZBTB18 Zornitza Stark Classified gene: ZBTB18 as Green List (high evidence)
Microcephaly v1.84 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Green List (High Evidence).
Microcephaly v1.83 ZBTB18 Zornitza Stark gene: ZBTB18 was added
gene: ZBTB18 was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: ZBTB18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB18 were set to 29573576
Phenotypes for gene: ZBTB18 were set to Mental retardation, autosomal dominant 22, MIM# 612337
Review for gene: ZBTB18 was set to GREEN
Added comment: Van der Schoot et al. (2018) reported 4 unrelated patients with MRD22 and summarized clinical information on 21 previously reported patients. All 25 patients had developmental delay, including 7 of 17 with microcephaly, 9 of 15 with corpus callosum abnormalities, 10 of 13 with dysmorphic facial features, and 4 of 17 with seizures.
Sources: Expert Review
Microcephaly v1.82 WLS Zornitza Stark reviewed gene: WLS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Zaki syndrome, MIM#619648; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.82 BCAS3 Zornitza Stark Phenotypes for gene: BCAS3 were changed from Syndromic neurodevelopmental disorder to Hengel-Maroofian-Schols syndrome, MIM# 619641
Microcephaly v1.81 BCAS3 Zornitza Stark reviewed gene: BCAS3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hengel-Maroofian-Schols syndrome, MIM# 619641; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.81 AP3B2 Zornitza Stark Marked gene: AP3B2 as ready
Microcephaly v1.81 AP3B2 Zornitza Stark Gene: ap3b2 has been classified as Green List (High Evidence).
Microcephaly v1.81 AP3B2 Zornitza Stark Classified gene: AP3B2 as Green List (high evidence)
Microcephaly v1.81 AP3B2 Zornitza Stark Gene: ap3b2 has been classified as Green List (High Evidence).
Microcephaly v1.80 AP3B2 Zornitza Stark gene: AP3B2 was added
gene: AP3B2 was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: AP3B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3B2 were set to 27431290; 27866705; 32705489
Phenotypes for gene: AP3B2 were set to Developmental and epileptic encephalopathy 48, MIM# 617276
Review for gene: AP3B2 was set to GREEN
Added comment: More than 9 unrelated families reported. Disorder is characterised by ID, epilepsy, optic atrophy and microcephaly in some.
Sources: Expert Review
Microcephaly v1.79 PLK1 Zornitza Stark Marked gene: PLK1 as ready
Microcephaly v1.79 PLK1 Zornitza Stark Gene: plk1 has been classified as Green List (High Evidence).
Microcephaly v1.79 PLK1 Zornitza Stark Classified gene: PLK1 as Green List (high evidence)
Microcephaly v1.79 PLK1 Zornitza Stark Gene: plk1 has been classified as Green List (High Evidence).
Microcephaly v1.78 PLK1 Zornitza Stark gene: PLK1 was added
gene: PLK1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PLK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLK1 were set to 33875846
Phenotypes for gene: PLK1 were set to Epilepsy; microcephaly; intellectual disability
Review for gene: PLK1 was set to GREEN
Added comment: More than 5 individuals reported.
Sources: Literature
Microcephaly v1.77 ATP9A Zornitza Stark Publications for gene: ATP9A were set to http://dx.doi.org/10.1136/jmedgenet-2021-107843
Microcephaly v1.76 ATP9A Zornitza Stark Classified gene: ATP9A as Green List (high evidence)
Microcephaly v1.76 ATP9A Zornitza Stark Gene: atp9a has been classified as Green List (High Evidence).
Microcephaly v1.75 ATP9A Zornitza Stark edited their review of gene: ATP9A: Added comment: Four unrelated families and mouse model.; Changed rating: GREEN; Changed publications: 34379057, 34764295
Microcephaly v1.75 FOXR1 Zornitza Stark Marked gene: FOXR1 as ready
Microcephaly v1.75 FOXR1 Zornitza Stark Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.75 FOXR1 Zornitza Stark Classified gene: FOXR1 as Amber List (moderate evidence)
Microcephaly v1.75 FOXR1 Zornitza Stark Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.74 FOXR1 Paul De Fazio gene: FOXR1 was added
gene: FOXR1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FOXR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXR1 were set to 34723967
Phenotypes for gene: FOXR1 were set to Postnatal microcephaly, progressive brain atrophy and global developmental delay
Review for gene: FOXR1 was set to AMBER
gene: FOXR1 was marked as current diagnostic
Added comment: 1 patient described with a de novo missense variant. Phenotypes include: postnatal microcephaly, progressive brain atrophy, skeletal abnormalities, brain abnormalities, ophthalmic abnormalities, neuromuscular abnormalities, and dysmorphic features. A variant in ATP1A3 was considered to have contributed to the final phenotype.

In vitro functional evidence is supportive of pathogenicity (variant causes protein instability and abnormal nuclear aggregation).

A mouse knockout has comparable phenotypes, and a severe survival deficit.

Rated amber (1 patient, functional evidence, mouse model).
Sources: Literature
Microcephaly v1.74 ARPC4 Bryony Thompson Classified gene: ARPC4 as Green List (high evidence)
Microcephaly v1.74 ARPC4 Bryony Thompson Gene: arpc4 has been classified as Green List (High Evidence).
Microcephaly v1.73 ARPC4 Bryony Thompson gene: ARPC4 was added
gene: ARPC4 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ARPC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPC4 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100072
Phenotypes for gene: ARPC4 were set to Microcephaly; mild motor delays; significant speech impairment
Review for gene: ARPC4 was set to GREEN
Added comment: 7 affected individuals from 6 families (gonadal mosaicism was confirmed in the mother of the 2 affected siblings) with a recurrent missense variant (NM_005718.4:c.472C>T; p.R158C). 6/7 affected individuals had microcephaly. The variant was associated with a decreased amount of F-actin in cells from two affected individuals.
Sources: Literature
Microcephaly v1.72 TRIP13 Zornitza Stark Classified gene: TRIP13 as Green List (high evidence)
Microcephaly v1.72 TRIP13 Zornitza Stark Gene: trip13 has been classified as Green List (High Evidence).
Microcephaly v1.71 TRIP13 Zornitza Stark changed review comment from: Autosomal recessive disorder resulting from errors in chromosome segregation. Most affected individuals develop early-onset Wilms tumor and show either aneuploidy or premature chromatid separation in cells. Some patients may have additional developmental features, such as microcephaly, growth retardation, or developmental delay.

6 unrelated families reported, but 5 shared the same homozygous stop variant, p.Arg354X, suggestive of founder effect. Microcephaly present in 3/6.; to: Autosomal recessive disorder resulting from errors in chromosome segregation. Most affected individuals develop early-onset Wilms tumor and show either aneuploidy or premature chromatid separation in cells. Some patients may have additional developmental features, such as microcephaly, growth retardation, or developmental delay.

6 unrelated families reported, but 5 shared the same homozygous stop variant, p.Arg354X, suggestive of founder effect. Microcephaly present in 3/6.

Supportive functional data.
Microcephaly v1.71 TRIP13 Zornitza Stark edited their review of gene: TRIP13: Changed rating: GREEN
Microcephaly v1.71 SPATA5L1 Zornitza Stark Phenotypes for gene: SPATA5L1 were changed from Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss to Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616
Microcephaly v1.70 SPATA5L1 Zornitza Stark reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.70 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations to Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602
Microcephaly v1.69 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Changed rating: GREEN
Microcephaly v1.69 ATP1A2 Zornitza Stark reviewed gene: ATP1A2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602; Mode of inheritance: None
Microcephaly v1.69 CHAMP1 Zornitza Stark Marked gene: CHAMP1 as ready
Microcephaly v1.69 CHAMP1 Zornitza Stark Added comment: Comment when marking as ready: Sufficient number with microcephaly for Green rating.
Microcephaly v1.69 CHAMP1 Zornitza Stark Gene: champ1 has been classified as Green List (High Evidence).
Microcephaly v1.69 GON7 Zornitza Stark Phenotypes for gene: GON7 were changed from Galloway-Mowat syndrome to Galloway-Mowat syndrome 9, MIM# 619603
Microcephaly v1.68 GON7 Zornitza Stark edited their review of gene: GON7: Changed phenotypes: Galloway-Mowat syndrome 9, MIM# 619603
Microcephaly v1.68 MYH10 Zornitza Stark Marked gene: MYH10 as ready
Microcephaly v1.68 MYH10 Zornitza Stark Gene: myh10 has been classified as Green List (High Evidence).
Microcephaly v1.68 MYH10 Zornitza Stark Classified gene: MYH10 as Green List (high evidence)
Microcephaly v1.68 MYH10 Zornitza Stark Gene: myh10 has been classified as Green List (High Evidence).
Microcephaly v1.67 MYH10 Krithika Murali gene: MYH10 was added
gene: MYH10 was added to Microcephaly. Sources: Expert list,Literature
Mode of inheritance for gene: MYH10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH10 were set to 24825879; 24901346; 25356899; 22495309; 25003005
Phenotypes for gene: MYH10 were set to Microcephaly; Intellectual Disability
Review for gene: MYH10 was set to GREEN
Added comment: De novo variants were identified in 5 unrelated individuals with moderate-severe ID and developmental delay.

Other reported phenotypic features include microcephaly (4/5), IUGR/failure to thrive (4/5), cerebral atrophy (3/5), hydrocephalus (2/5), congenital bilateral hip dysplasia (2/5), cerebellar atrophy (1/5), congenital diaphragmatic hernia (1/5), cranial nerve palsy (1/5), nystagmus (1/5), dysplastic kidney (1/5).

Defects in heart development, body wall closure and other birth defects noted in mouse models.
Sources: Expert list, Literature
Microcephaly v1.67 NUP85 Zornitza Stark Marked gene: NUP85 as ready
Microcephaly v1.67 NUP85 Zornitza Stark Gene: nup85 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.67 NUP85 Zornitza Stark Classified gene: NUP85 as Amber List (moderate evidence)
Microcephaly v1.67 NUP85 Zornitza Stark Gene: nup85 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.66 NUP85 Zornitza Stark gene: NUP85 was added
gene: NUP85 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NUP85 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP85 were set to 34170319
Phenotypes for gene: NUP85 were set to Primary microcephaly
Review for gene: NUP85 was set to AMBER
Added comment: Bi-allelic variants in this gene are associated with nephrotic syndrome in 3 families.

Phenotypic expansion:
PMID: 34170319 - Ravindran et al 2021 report two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS. In the first family, a 9 yo female, with consanguineous parents, is reported to have a missense variant in NUP85 (c.932G > A; p.R311Q). Intrauterine growth restriction was noticed. At birth microcephaly was observed (OFC < 3rd centile, < −3.6 SD) as well as hypotrophy [weight −2.8 SD), length 45 cm (−2.7 SD), both <3rd centile], facial dysmorphism, syndactyly, long and thin fingers, and bilateral pes adductus. She has severe developmental delay with strongly delayed motor milestones and absent speech. Drug-resistant, genetic epilepsy with focal-onset seizures started in the first year of life. She had no clinical, laboratory or radiological findings indicative of kidney dysfunction. In the second family, compound heterozygous missense variants in NUP85 were detected (c.1109A > G, c.1589 T > C;p.N370S, p.M530T ) in a fetus. MRI of the fetal brain at 24 + 2 GW indicated complete agenesis of the corpus callosum, abnormal sulcation in the left frontal lobe, nodularity of the frontal horn and trigone with focal puckering of the left lateral ventricle.
Sources: Literature
Microcephaly v1.65 SPATA5L1 Zornitza Stark Marked gene: SPATA5L1 as ready
Microcephaly v1.65 SPATA5L1 Zornitza Stark Gene: spata5l1 has been classified as Green List (High Evidence).
Microcephaly v1.65 SPATA5L1 Zornitza Stark Classified gene: SPATA5L1 as Green List (high evidence)
Microcephaly v1.65 SPATA5L1 Zornitza Stark Gene: spata5l1 has been classified as Green List (High Evidence).
Microcephaly v1.64 SPATA5L1 Paul De Fazio gene: SPATA5L1 was added
gene: SPATA5L1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss
Review for gene: SPATA5L1 was set to GREEN
gene: SPATA5L1 was marked as current diagnostic
Added comment: 47 individuals from 26 unrelated families from various ethnicities with biallelic variants reported. Phenotypes include ID, hearing impairment, movement disorder, abnormal MRI, hypotonia, visual impairment, epilepsy, and microcephaly.

~53% of affected individuals had microcephaly.
Sources: Literature
Microcephaly v1.64 ZNHIT3 Zornitza Stark Marked gene: ZNHIT3 as ready
Microcephaly v1.64 ZNHIT3 Zornitza Stark Gene: znhit3 has been classified as Green List (High Evidence).
Microcephaly v1.64 ZNHIT3 Zornitza Stark Classified gene: ZNHIT3 as Green List (high evidence)
Microcephaly v1.64 ZNHIT3 Zornitza Stark Gene: znhit3 has been classified as Green List (High Evidence).
Microcephaly v1.63 ZNHIT3 Zornitza Stark gene: ZNHIT3 was added
gene: ZNHIT3 was added to Microcephaly. Sources: Expert Review
founder tags were added to gene: ZNHIT3.
Mode of inheritance for gene: ZNHIT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNHIT3 were set to 28335020; 28335020; 31048081
Phenotypes for gene: ZNHIT3 were set to PEHO syndrome, MIM# 260565
Review for gene: ZNHIT3 was set to GREEN
Added comment: PEHO is a severe autosomal recessive neurodevelopmental disorder characterized by extreme cerebellar atrophy due to almost total loss of granule neurons. Affected individuals present in early infancy with hypotonia, profoundly delayed psychomotor development, optic atrophy, progressive atrophy of the cerebellum and brainstem, and dysmyelination. Most patients also develop infantile seizures that are often associated with hypsarrhythmia on EEG, and many have peripheral oedema. More than 20 affected individuals reported of Finnish origin, p.Ser31Leu is a founder variant. One compound het reported and supportive animal model.
Sources: Expert Review
Microcephaly v1.62 NSRP1 Zornitza Stark Marked gene: NSRP1 as ready
Microcephaly v1.62 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Microcephaly v1.62 NSRP1 Zornitza Stark Classified gene: NSRP1 as Green List (high evidence)
Microcephaly v1.62 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Microcephaly v1.61 NSRP1 Zornitza Stark reviewed gene: NSRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.61 NSRP1 Krithika Murali gene: NSRP1 was added
gene: NSRP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSRP1 were set to 34385670
Phenotypes for gene: NSRP1 were set to Epilepsy; Cerebral palsy; microcephaly; Intellectual disability
Review for gene: NSRP1 was set to AMBER
Added comment: Novel gene regulating splicing. Biallelic LoF pathogenic variants reported in 6 individuals from 3 unrelated families associated with a phenotype characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.
Sources: Literature
Microcephaly v1.61 TNPO2 Zornitza Stark Phenotypes for gene: TNPO2 were changed from Intellectual disability, neurologic deficits and dysmorphic features to Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556
Microcephaly v1.60 TNPO2 Zornitza Stark edited their review of gene: TNPO2: Changed phenotypes: Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556
Microcephaly v1.60 WLS Zornitza Stark Marked gene: WLS as ready
Microcephaly v1.60 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Microcephaly v1.60 WLS Zornitza Stark Classified gene: WLS as Green List (high evidence)
Microcephaly v1.60 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Microcephaly v1.59 WLS Zornitza Stark Classified gene: WLS as Green List (high evidence)
Microcephaly v1.59 WLS Zornitza Stark Gene: wls has been classified as Green List (High Evidence).
Microcephaly v1.58 WLS Teresa Zhao gene: WLS was added
gene: WLS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WLS were set to PMID: 34587386
Phenotypes for gene: WLS were set to Syndromic structural birth defects
Review for gene: WLS was set to GREEN
Added comment: - Homozygous mutations in 10 affected persons from 5 unrelated families.
- Patients had multiorgan defects, including microcephal, facial dysmorphism, foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects.
- The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis.
Sources: Literature
Microcephaly v1.58 RNF113A Zornitza Stark edited their review of gene: RNF113A: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v1.58 RNF113A Zornitza Stark Publications for gene: RNF113A were set to 25612912; 31793730
Microcephaly v1.57 RNF113A Zornitza Stark Classified gene: RNF113A as Green List (high evidence)
Microcephaly v1.57 RNF113A Zornitza Stark Gene: rnf113a has been classified as Green List (High Evidence).
Microcephaly v1.56 RNF113A Zornitza Stark edited their review of gene: RNF113A: Added comment: Two more individuals reported with different variants, at least one had microcephaly, upgrade to Green.; Changed rating: GREEN; Changed publications: 25612912, 31793730, 31880405
Microcephaly v1.56 EIF3F Zornitza Stark Phenotypes for gene: EIF3F were changed from EIF3F-related neurodevelopmental disorder to EIF3F-related neurodevelopmental disorder; Mental retardation, autosomal recessive 67, MIM# 618295
Microcephaly v1.55 EIF3F Zornitza Stark reviewed gene: EIF3F: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal recessive 67, MIM# 618295; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.55 EIF3F Zornitza Stark Marked gene: EIF3F as ready
Microcephaly v1.55 EIF3F Zornitza Stark Gene: eif3f has been classified as Green List (High Evidence).
Microcephaly v1.55 EIF3F Chirag Patel Classified gene: EIF3F as Green List (high evidence)
Microcephaly v1.55 EIF3F Chirag Patel Gene: eif3f has been classified as Green List (High Evidence).
Microcephaly v1.54 EIF3F Chirag Patel gene: EIF3F was added
gene: EIF3F was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF3F were set to PMID: 33736665
Phenotypes for gene: EIF3F were set to EIF3F-related neurodevelopmental disorder
Review for gene: EIF3F was set to GREEN
Added comment: Hüffmeier et al (2021) reported 21 patients who were homozygous/compound heterozygous for Phe232Val variant in EIF3F. All affected individuals had developmental delay and speech delay. About half had behavioural problems, altered muscular tone, hearing loss, and short stature. The study suggests that microcephaly, reduced sensitivity to pain, cleft lip/palate, gastrointestinal symptoms and ophthalmological symptoms are part of the phenotypic spectrum.
Sources: Literature
Microcephaly v1.53 MINPP1 Zornitza Stark Phenotypes for gene: MINPP1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia, type 16, MIM# 619527
Microcephaly v1.52 MINPP1 Zornitza Stark edited their review of gene: MINPP1: Changed phenotypes: Pontocerebellar hypoplasia, type 16, MIM# 619527
Microcephaly v1.52 TAF2 Zornitza Stark Publications for gene: TAF2 were set to 21937992; 22633631; 26350204
Microcephaly v1.51 HMGB1 Zornitza Stark Marked gene: HMGB1 as ready
Microcephaly v1.51 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Green List (High Evidence).
Microcephaly v1.51 HMGB1 Chirag Patel Phenotypes for gene: HMGB1 were changed from Developmental delay and microcephaly, no OMIM # to Developmental delay and microcephaly, no OMIM #
Microcephaly v1.51 HMGB1 Chirag Patel Phenotypes for gene: HMGB1 were changed from 0 ALDH5A1 1 ALDH7A1 0 ALG1 0 ALG11 1 ALG12 1 ALG13 1 ALG14 1 ALG3 1 ALG6 1 ALG8 1 ALG9 1 ALKBH8 1 ALMS1 0 AMER1 0 AMPD2 0 AMT 0 ANK2 2 ANKRD11 0 ANKRD17 2 AP1B1 1 AP1G1 1 AP1S1 0 AP1S2 0 AP2M1 1 AP3B1 0 AP3B2 1 AP4B1 1 AP4E1 1 AP4M1 1 AP4S1 1 APC2 1 APOPT1 1 ARCN1 1 ARF1 1 ARFGEF2 0 ARG1 0 ARHGEF9 1 ARID1A 1 ARID1B 1 ARID2 2 ARL13B 1 ARL6 1 ARMC9 1 ARSA 0 ARSB 1 ARSE 1 ARV1 0 ARX 0 ASAH1 0 ASH1L 1 ASL 1 ASNS 1 ASPA 0 ASPM 1 ASS1 0 ASTN1 1 ASXL1 0 ASXL2 0 ASXL3 1 ATAD1 1 ATAD3A 1 ATG7 1 ATIC 1 ATM 0 ATN1 1 ATP13A2 0 ATP1A1 1 ATP1A2 1 ATP1A3 2 ATP6AP1 1 ATP6AP2 0 ATP6V0A2 0 ATP6V1A 1 ATP6V1B2 0 ATP7A 0 ATP8A2 1 ATR 0 ATRX 0 AUH 0 AUTS2 1 B3GALNT2 1 B3GLCT 0 B4GALNT1 0 B4GALT1 1 B4GALT7 1 B9D2 1 BAZ2B 1 BBS1 0 BBS10 0 BBS12 0 BBS2 0 BBS4 1 BBS5 1 BBS7 1 BBS9 1 BCAP31 0 BCAS3 1 BCKDHA 0 BCKDHB 0 BCKDK 0 BCL11A 0 BCL11B 1 BCOR 1 BCORL1 1 BCS1L 0 BICRA 3 BLM 0 BMP4 0 BOLA3 0 BPTF 1 BRAF 0 BRAT1 1 BRD4 2 BRF1 1 BRIP1 1 BRPF1 1 BRSK2 1 BRWD3 0 BSCL2 0 BSND 1 BTD 0 BUB1B 0 C12orf4 0 C12orf57 0 C12orf65 0 C2CD3 1 C2orf69 1 C5orf42 1 CA2 1 CA8 1 CACNA1A 0 CACNA1B 1 CACNA1C 0 CACNA1D 1 CACNA1E 1 CACNA1G 2 CACNA1I 1 CACNA2D2 1 CAD 1 CAMK2A 0 CAMK2B 1 CAMK4 1 CAMTA1 2 CAPN15 1 CARS 1 CARS2 1 CASK 0 CBL 0 CBS 0 CBY1 1 CC2D1A 1 CC2D2A 0 CCBE1 1 CCDC22 0 CCDC47 1 CCDC88A 1 CCDC88C 2 CCND2 0 CDC42 0 CDC42BPB 1 CDH11 2 CDH15 0 CDH2 1 CDK10 0 CDK13 1 CDK19 1 CDK5RAP2 1 CDK8 1 CDKL5 0 CDON 0 CELF2 1 CENPF 0 CENPJ 0 CEP104 1 CEP120 1 CEP135 1 CEP152 1 CEP164 1 CEP290 0 CEP41 0 CEP55 1 CEP57 1 CEP83 1 CEP85L 1 CHAMP1 0 CHD1 1 CHD2 0 CHD3 1 CHD4 1 CHD5 1 CHD7 0 CHD8 0 CHKB 0 CHMP1A 1 CIC 0 CIT 0 CKAP2L 0 CLCN3 1 CLCN4 1 CLCN6 1 CLCNKB 1 CLN3 0 CLN5 1 CLN6 0 CLN8 0 CLP1 1 CLPB 1 CLTC 1 CNKSR2 0 CNNM2 0 CNOT1 3 CNOT2 1 CNOT3 2 CNPY3 1 CNTNAP1 1 CNTNAP2 0 COASY 1 COG1 0 COG4 1 COG5 1 COG6 1 COG7 0 COG8 1 COL4A1 0 COL4A2 0 COL4A3BP 0 COLEC11 0 COPB2 2 COQ4 0 COQ8A 0 COX10 1 COX15 0 CPS1 0 CRADD 1 CRB2 0 CREBBP 1 CSDE1 1 CSNK1G1 2 CSNK2A1 0 CSNK2B 0 CSPP1 1 CSTB 0 CTBP1 1 CTCF 1 CTDP1 0 CTNNA2 1 CTNNB1 0 CTSA 0 CTSD 0 CTU2 1 CUL3 2 CUL4B 0 CUX1 1 CUX2 1 CWC27 0 CWF19L1 1 CXorf56 1 CYB5R3 0 CYC1 0 CYFIP2 1 D2HGDH 0 DAG1 0 DARS 1 DARS2 0 DBT 0 DCAF17 0 DCHS1 0 DCPS 1 DCX 0 DDB1 2 DDC 0 DDHD2 0 DDX11 1 DDX23 2 DDX3X 0 DDX59 1 DDX6 1 DEAF1 1 DEGS1 1 DENND5A 1 DEPDC5 0 DHCR24 0 DHCR7 0 DHDDS 1 DHFR 1 DHPS 1 DHTKD1 0 DHX30 1 DHX37 2 DIAPH1 0 DIS3L2 0 DKC1 0 DLD 0 DLG3 1 DLG4 2 DLL1 1 DMD 0 DMXL2 1 DNAJC12 1 DNAJC19 0 DNM1 1 DNM1L 1 DNMT3A 1 DNMT3B 0 DOCK3 1 DOCK6 1 DOCK7 1 DOCK8 0 DOLK 1 DPAGT1 1 DPF2 0 DPH1 1 DPM1 0 DPM2 1 DPYD 1 DPYS 1 DPYSL5 1 DYM 1 DYNC1H1 0 DYNC1I2 1 DYRK1A 1 EARS2 1 EBF3 1 EBP 1 EDEM3 2 EED 1 EEF1A2 1 EEF2 1 EFTUD2 1 EHMT1 1 EIF2AK2 2 EIF2AK3 0 EIF2S3 1 EIF3F 1 EIF4A3 1 EIF5A 1 ELAC2 0 ELOVL4 0 ELP2 0 EMC1 1 EMC10 2 EML1 1 EP300 0 EPG5 1 ERCC1 1 ERCC2 0 ERCC3 0 ERCC5 1 ERCC6 0 ERCC6L2 0 ERCC8 0 ERLIN2 1 ESCO2 0 ETFA 1 ETFB 1 ETFDH 1 ETHE1 0 EXOC7 1 EXOSC3 0 EXOSC8 1 EXT2 1 EXTL3 1 EZH2 1 FAM111A 0 FAM126A 0 FAM20C 0 FAM50A 1 FAR1 1 FARS2 1 FARSA 1 FARSB 1 FAT4 0 FBRSL1 1 FBXL3 2 FBXL4 0 FBXO11 1 FBXO28 1 FBXO31 2 FBXW11 2 FBXW7 1 FDFT1 1 FGD1 1 FGF12 0 FGF13 1 FGF14 1 FGFR1 1 FGFR3 1 FH 0 FIG4 0 FITM2 1 FKRP 0 FKTN 0 FLNA 0 FLVCR2 0 FMN2 0 FMR1 0 FOLR1 1 FOXG1 0 FOXP1 2 FOXP2 1 FOXRED1 0 FRAS1 1 FRMPD4 1 FRRS1L 1 FTCD 1 FTSJ1 0 FUCA1 0 FUT8 1 GABBR2 1 GABRA1 1 GABRA2 1 GABRA5 1 GABRB2 0 GABRB3 1 GABRG2 1 GAD1 1 GALC 0 GALE 0 GALNT2 1 GALT 1 GAMT 0 GATA6 1 GATAD2B 1 GATM 1 GCDH 0 GCH1 0 GDI1 0 GEMIN5 1 GFAP 0 GFER 1 GFM1 0 GJC2 0 GK 0 GLB1 0 GLDC 0 GLI2 0 GLI3 0 GLIS3 1 GLS 1 GLUL 0 GLYCTK 0 GM2A 0 GMPPA 0 GMPPB 0 GNAI1 2 GNAO1 1 GNAS 1 GNB1 1 GNB2 3 GNB5 1 GNE 1 GNPAT 0 GNPTAB 0 GNPTG 1 GNS 0 GOLGA2 2 GOT2 1 GPAA1 1 GPC3 0 GPC4 1 GPT2 1 GRIA1 1 GRIA2 2 GRIA3 1 GRIA4 0 GRID2 0 GRIK2 1 GRIN1 1 GRIN2A 1 GRIN2B 1 GRIN2D 1 GRM1 0 GRM7 1 GSS 1 GTF2H5 0 GTF3C3 1 GTPBP2 1 GTPBP3 0 GUSB 1 H3F3A 1 H3F3B 1 HACE1 1 HADHA 0 HADHB 1 HCCS 0 HCFC1 0 HCN1 0 HDAC4 2 HDAC8 1 HECW2 2 HEPACAM 0 HERC1 0 HERC2 2 HESX1 0 HEXA 0 HEXB 0 HGSNAT 1 HIBCH 0 HID1 1 HIRA 1 HIST1H1E 1 HIST1H4C 2 HIVEP2 1 HK1 2 HLCS 0 HMGB1 1 HMGCL 0 HNMT 1 HNRNPH1 1 HNRNPH2 0 HNRNPK 0 HNRNPR 1 HNRNPU 1 HOXA1 0 HPD 0 HPDL 2 HPRT1 0 HRAS 1 HS2ST1 3 HSD17B10 0 HSD17B4 1 HSPD1 0 HSPG2 1 HTRA2 0 HUWE1 1 IARS 1 IBA57 1 IDH2 0 IDS 0 IDUA 0 IER3IP1 1 IFIH1 0 IFT172 0 IFT27 1 IFT74 1 IGF1 1 IGF1R 1 IKBKG 0 IL1RAPL1 0 IMPDH2 2 INPP5E 1 INPP5K 0 INTS1 1 IQSEC1 1 IQSEC2 1 IREB2 1 IRF2BPL 1 ISCA1 1 ISCA2 1 ISPD 0 ITPA 0 ITPR1 0 IVD 0 JAM3 1 JARID2 1 JMJD1C 2 KANSL1 1 KARS 1 KAT5 2 KAT6A 0 KAT6B 0 KAT8 1 KATNB1 1 KCNA2 1 KCNB1 1 KCNC1 0 KCNH1 1 KCNJ10 0 KCNJ11 0 KCNJ6 1 KCNK4 1 KCNK9 1 KCNMA1 1 KCNN2 1 KCNN3 1 KCNQ2 0 KCNQ3 1 KCNQ5 1 KCNT1 0 KCNT2 1 KCTD3 0 KCTD7 0 KDM1A 1 KDM3B 2 KDM4B 2 KDM5B 1 KDM5C 1 KDM6A 0 KDM6B 1 KIAA0586 0 KIAA1109 0 KIDINS220 1 KIF11 2 KIF14 1 KIF1A 2 KIF1BP 1 KIF21B 1 KIF2A 1 KIF5A 0 KIF5C 1 KIF7 0 KLF7 1 KLHL7 0 KMT2A 1 KMT2B 1 KMT2C 1 KMT2D 2 KMT2E 1 KMT5B 1 KNL1 1 KPTN 1 KRAS 0 L1CAM 0 L2HGDH 0 LAMA1 0 LAMA2 1 LAMB1 1 LAMB2 1 LAMC3 0 LAMP2 0 LARGE1 0 LARP7 1 LARS 2 LARS2 0 LIAS 1 LIG4 0 LINGO4 1 LINS1 0 LIPT1 1 LMBRD1 1 LMBRD2 2 LMNB1 2 LMNB2 2 LONP1 0 LRP2 0 LRPPRC 0 LSS 1 LTBP1 1 LYRM7 1 LZTFL1 1 LZTR1 1 MAB21L1 2 MAB21L2 1 MACF1 1 MADD 3 MAF 0 MAGEL2 1 MAN1B1 1 MAN2B1 1 MANBA 1 MAOA 1 MAP1B 1 MAP2K1 0 MAP2K2 0 MAPK1 2 MAPK8IP3 2 MAPKAPK5 1 MAPRE2 1 MASP1 1 MAST1 1 MAST3 1 MAT1A 0 MBD5 1 MBOAT7 0 MBTPS2 0 MCCC1 0 MCCC2 0 MCM3AP 1 MCOLN1 1 MCPH1 1 MDH2 0 MECP2 1 MED12 0 MED12L 1 MED13 1 MED13L 0 MED17 1 MED23 0 MED25 1 MED27 2 MEF2C 1 MEGF8 2 MEIS2 0 METTL23 2 METTL5 1 MFF 0 MFSD2A 1 MFSD8 1 MGAT2 1 MICU1 1 MID1 0 MIR17HG 2 MKKS 0 MKS1 0 MLC1 0 MLYCD 1 MMAA 0 MMAB 0 MMACHC 0 MMADHC 0 MN1 2 MOCS1 1 MOCS2 0 MOGS 1 MORC2 2 MPDU1 1 MPDZ 1 MPLKIP 1 MPP5 1 MPV17 1 MRPS22 0 MRPS34 1 MSL3 1 MSMO1 1 MTFMT 0 MTHFR 0 MTHFS 1 MTO1 1 MTOR 0 MTR 1 MTRR 1 MUT 0 MVK 0 MYCN 0 MYO5A 0 MYT1L 2 NAA10 0 NAA15 1 NACC1 0 NAGA 0 NAGLU 0 NALCN 0 NANS 0 NARS 2 NBEA 1 NCAPD2 2 NCAPG2 1 NCDN 2 NCKAP1 1 NDE1 1 NDP 0 NDST1 0 NDUFA1 0 NDUFA2 1 NDUFAF1 1 NDUFS1 1 NDUFS4 1 NDUFS7 0 NDUFS8 0 NDUFV1 0 NEDD4L 1 NEMF 2 NEU1 0 NEUROD2 1 NEXMIF 1 NF1 0 NFASC 1 NFIA 0 NFIB 1 NFIX 0 NFU1 1 NGLY1 0 NHS 0 NIPBL 1 NKAP 1 NKX2-1 0 NLGN3 0 NONO 0 NOVA2 1 NPC1 0 NPC2 0 NPHP1 0 NPHP3 1 NR2F1 1 NR4A2 2 NRAS 0 NRROS 1 NRXN1 0 NSD1 0 NSD2 1 NSDHL 1 NSUN2 0 NT5C2 1 NTNG2 1 NTRK1 0 NTRK2 1 NUBPL 0 NUDT2 1 NUP188 1 NUP214 2 NUS1 1 OCLN 0 OCRL 0 ODC1 1 OFD1 0 OGT 1 OPA3 0 OPHN1 0 OSGEP 1 OTC 0 OTUD5 2 OTUD6B 0 OTX2 0 OXR1 1 P4HTM 1 PACS1 1 PACS2 1 PAFAH1B1 1 PAH 0 PAK1 1 PAK3 1 PAM16 1 PARN 0 PARP6 1 PAX6 0 PAX8 0 PBX1 0 PC 0 PCCA 0 PCCB 0 PCDH12 1 PCDH19 0 PCDHGC4 1 PCGF2 1 PCNT 0 PCYT2 1 PDE10A 1 PDE4D 0 PDE6D 1 PDGFRB 0 PDHA1 0 PDHB 1 PDHX 0 PDP1 1 PDSS1 1 PDSS2 0 PEPD 0 PET100 1 PEX1 0 PEX10 0 PEX11B 0 PEX12 0 PEX13 0 PEX14 0 PEX16 0 PEX19 0 PEX2 0 PEX26 0 PEX3 0 PEX5 0 PEX6 0 PEX7 0 PGAP1 0 PGAP2 1 PGAP3 1 PGK1 1 PGM2L1 1 PGM3 1 PHACTR1 1 PHF21A 2 PHF6 0 PHF8 1 PHGDH 0 PHIP 1 PI4KA 1 PIBF1 2 PIDD1 1 PIGA 1 PIGB 2 PIGC 1 PIGG 1 PIGH 1 PIGK 1 PIGL 1 PIGN 1 PIGO 1 PIGP 2 PIGQ 1 PIGS 1 PIGT 1 PIGU 1 PIGV 1 PIGW 0 PIK3C2A 1 PIK3CA 0 PIK3R2 1 PISD 1 PITRM1 1 PLA2G6 0 PLAA 0 PLCB1 1 PLK4 1 PLP1 0 PLPBP 1 PMM2 0 PMPCA 1 PMPCB 1 PNKP 1 PNPLA6 0 PNPT1 1 POGZ 1 POLA1 1 POLG 0 POLR1C 1 POLR2A 1 POLR3A 0 POLR3B 0 POLRMT 1 POMGNT1 0 POMGNT2 0 POMK 1 POMT1 0 POMT2 0 PORCN 0 POU3F3 1 PPIL1 1 PPM1D 1 PPP1CB 1 PPP1R12A 1 PPP1R15B 0 PPP1R21 1 PPP2CA 1 PPP2R1A 1 PPP2R5D 1 PPP3CA 0 PPT1 0 PQBP1 1 PRICKLE2 1 PRKAR1A 1 PRKAR1B 1 PRMT7 0 PRODH 0 PRPS1 0 PRR12 1 PRSS12 0 PRUNE1 1 PSAP 1 PSMD12 0 PSPH 0 PTCH1 0 PTCHD1 0 PTDSS1 0 PTEN 0 PTF1A 0 PTPN11 0 PTPN23 1 PTPN4 1 PTRHD1 1 PTS 0 PUF60 1 PUM1 1 PURA 1 PUS1 0 PUS3 1 PUS7 1 PYCR1 0 PYCR2 0 QARS 1 QDPR 0 QRICH1 1 RAB11B 1 RAB18 0 RAB23 0 RAB39B 0 RAB3GAP1 1 RAB3GAP2 0 RAC1 1 RAC3 1 RAD21 1 RAF1 0 RAI1 1 RALA 1 RALGAPA1 1 RAP1B 2 RARB 1 RARS 1 RARS2 0 RBBP8 0 RBM10 1 RELN 0 RERE 1 RFT1 1 RFX3 1 RFX4 1 RFX7 1 RHEB 1 RHOBTB2 1 RIT1 0 RLIM 1 RMND1 0 RNASEH2A 0 RNASEH2B 0 RNASEH2C 0 RNASET2 0 RNF125 0 RNF13 1 RNF220 1 RNU4ATAC 1 RNU7-1 2 ROGDI 1 ROR2 0 RORA 1 RPGRIP1L 0 RPIA 1 RPL10 1 RPS6KA3 0 RRM2B 0 RSRC1 1 RTEL1 0 RTN4IP1 1 RTTN 1 SAMD9 0 SAMHD1 0 SARS2 1 SATB1 2 SATB2 1 SBF1 1 SC5D 0 SCAF4 1 SCAMP5 2 SCAPER 1 SCN1A 1 SCN1B 1 SCN2A 0 SCN3A 1 SCN8A 0 SCO2 0 SDCCAG8 1 SDHA 0 SDHAF1 1 SEPSECS 1 SERAC1 0 SET 0 SETBP1 0 SETD1A 1 SETD1B 1 SETD2 1 SETD5 1 SFXN4 1 SGPL1 0 SGSH 1 SHANK2 0 SHANK3 1 SHH 0 SHMT2 2 SHOC2 1 SIAH1 1 SIK1 0 SIL1 1 SIN3A 0 SIN3B 1 SIX3 0 SKI 0 SLC12A2 3 SLC12A5 0 SLC12A6 0 SLC13A5 1 SLC16A2 1 SLC17A5 0 SLC18A2 1 SLC19A3 0 SLC1A1 1 SLC1A2 1 SLC1A4 1 SLC25A1 0 SLC25A12 0 SLC25A15 0 SLC25A22 0 SLC2A1 0 SLC33A1 0 SLC35A1 0 SLC35A2 0 SLC35C1 0 SLC39A14 0 SLC39A8 1 SLC46A1 1 SLC4A4 0 SLC5A6 1 SLC6A1 1 SLC6A17 0 SLC6A19 0 SLC6A3 0 SLC6A8 0 SLC6A9 1 SLC9A6 1 SLX4 0 SMAD4 0 SMARCA2 1 SMARCA4 0 SMARCA5 1 SMARCB1 0 SMARCC2 1 SMARCD1 1 SMARCE1 0 SMC1A 0 SMC3 0 SMG8 2 SMG9 1 SMOC1 1 SMPD1 1 SMPD4 1 SMS 0 SNAP25 1 SNAP29 0 SNRPB 1 SNX14 0 SNX27 1 SON 1 SOS1 1 SOS2 1 SOX10 0 SOX11 0 SOX2 1 SOX4 1 SOX5 1 SOX6 2 SOX9 0 SPART 1 SPATA5 1 SPECC1L 0 SPEN 2 SPG11 1 SPOP 1 SPR 0 SPRED1 1 SPTAN1 1 SPTBN1 1 SPTBN2 0 SPTBN4 2 SRCAP 2 SRD5A3 0 SSR4 0 ST3GAL3 0 ST3GAL5 2 STAG1 0 STAG2 1 STAMBP 1 STIL 1 STRA6 0 STRADA 1 STT3A 2 STX1B 0 STXBP1 0 SUCLA2 1 SUCLG1 0 SUFU 1 SUMF1 1 SUOX 0 SUPT16H 1 SURF1 0 SUZ12 2 SVBP 2 SYN1 0 SYNCRIP 2 SYNGAP1 1 SYNJ1 0 SYP 0 SYT1 2 SZT2 0 TAF1 1 TAF2 2 TAF6 1 TANC2 2 TANGO2 0 TAOK1 1 TASP1 1 TAT 0 TAZ 0 TBC1D20 1 TBC1D23 0 TBC1D24 0 TBCD 1 TBCE 0 TBCK 0 TBL1XR1 0 TBR1 1 TBX1 1 TCF20 1 TCF4 0 TCF7L2 2 TCN2 1 TCTN2 0 TCTN3 1 TDP2 1 TECPR2 1 TELO2 1 TENM3 1 TERT 2 TET3 1 TFE3 2 TGIF1 1 TH 0 THOC2 1 THOC6 0 THRA 0 TIMM50 1 TINF2 1 TLK2 1 TMCO1 0 TMEM106B 1 TMEM165 1 TMEM216 0 TMEM222 2 TMEM237 1 TMEM240 0 TMEM5 0 TMEM67 1 TMEM70 0 TMEM94 1 TMTC3 1 TMX2 1 TNPO2 1 TNR 1 TNRC6B 2 TOE1 1 TOGARAM1 1 TP73 1 TPP1 1 TPP2 1 TRAF7 1 TRAIP 1 TRAK1 1 TRAPPC11 1 TRAPPC12 1 TRAPPC4 1 TRAPPC6B 1 TRAPPC9 2 TREX1 0 TRIM8 1 TRIO 1 TRIP12 1 TRIT1 1 TRMT1 1 TRMT10A 1 TRNT1 1 TRPM3 1 TRRAP 1 TSC1 0 TSC2 0 TSEN15 1 TSEN2 0 TSEN54 0 TSFM 0 TSHB 0 TSPAN7 0 TSPOAP1 1 TTC19 0 TTC37 0 TTC5 2 TTC8 1 TTI2 1 TUBA1A 0 TUBB 1 TUBB2A 1 TUBB2B 0 TUBB3 0 TUBB4A 0 TUBG1 0 TUBGCP2 1 TUBGCP6 1 TUSC3 1 TWIST1 0 UBA5 0 UBE2A 1 UBE3A 0 UBE3B 1 UBE4A 1 UBR1 1 UBR7 1 UBTF 1 UFC1 1 UFM1 1 UFSP2 2 UGDH 1 UGP2 1 UMPS 1 UNC80 1 UPB1 2 UPF3B 2 USP18 1 USP7 2 USP9X 1 VAMP2 2 VARS 1 VARS2 1 VIPAS39 1 VLDLR 0 VPS11 1 VPS13B 0 VPS33B 1 VPS41 1 VPS4A 3 VPS53 0 VRK1 0 WAC 1 WARS2 1 WASF1 2 WASHC4 3 WDFY3 1 WDPCP 1 WDR11 2 WDR26 1 WDR37 1 WDR4 2 WDR45 0 WDR45B 1 WDR62 1 WDR73 0 WDR81 1 WNT1 1 WNT5A 2 WWOX 0 XPA 2 XRCC4 0 XYLT1 2 YARS 1 YIF1B 2 YWHAG 1 YY1 0 ZBTB18 0 ZBTB20 0 ZBTB24 1 ZC4H2 0 ZDHHC9 0 ZEB2 1 ZFHX4 1 ZFYVE26 0 ZIC1 1 ZIC2 0 ZMIZ1 2 ZMYM2 2 ZMYND11 1 ZNF142 1 ZNF148 1 ZNF292 2 ZNF335 1 ZNF462 2 ZNF526 1 ZNF699 1 ZNF711 1 ZSWIM6 1 AASS 1 ACADSB 1 ACAT1 1 ADAM22 1 AKAP6 1 ALDOA 1 ALX1 1 ALX3 1 ALX4 1 AP2S1 1 ARF3 2 ARHGAP31 1 ARHGAP35 1 ARNT2 1 ATP6V0A1 1 ATP9A 1 ATXN2L 1 B3GALT6 1 B9D1 1 BBIP1 1 C16orf62 1 C8orf37 1 CACNB4 1 CAPZA2 1 CCDC174 1 CCDC78 1 CD96 1 CDK16 1 CDK6 1 CDKN1C 1 CEP63 1 CEP89 1 CHRM1 1 CHST14 1 CLCN2 1 CNKSR1 1 COPB1 1 COQ2 1 COQ9 1 COX14 1 COX20 1 COX7B 1 CPE 1 CRBN 1 CTC1 1 CTNND1 1 CTNND2 1 DDOST 1 DHX32 1 DLAT 1 DPH2 1 DPP6 2 DSCAM 1 EEF1B2 1 EEF1D 1 EIF2A 1 EMG1 1 EMX2 1 EPHA7 1 ERGIC3 2 EXOC2 2 EXOSC2 1 FANCB 1 FANCD2 1 FANCG 1 FASTKD2 1 FEM1B 1 FGFR2 1 FIBP 1 FOXP4 1 FRMD4A 1 FRY 1 FTO 1 FUK 1 GBA 1 GEMIN4 1 GIGYF1 1 GMNN 1 GNAI2 1 GNAQ 1 GORAB 1 GPHN 1 GSX2 1 GTF2E2 2 HARS 2 HAX1 1 HEATR5B 1 HIST1H4J 1 HNRNPD 1 HSPA9 1 HTT 1 HYLS1 1 ICE1 1 IMPA1 1 INPP4A 1 IQSEC3 2 ITCH 1 ITFG2 2 ITGA7 1 JAKMIP1 1 KCNJ1 1 KLHL15 1 LAS1L 1 LINGO1 1 LIPT2 1 LMAN2L 1 LNPK 1 LRRC32 1 LYST 1 MAGT1 1 MMGT1 1 MRPL3 2 MSL2 1 NBN 1 NDUFA10 1 NDUFA11 1 NDUFA9 1 NDUFAF2 1 NDUFAF3 1 NDUFAF4 1 NDUFAF5 1 NDUFAF6 1 NDUFB3 1 NDUFB9 1 NDUFS2 1 NDUFS3 1 NDUFS6 1 NDUFV2 1 NECAP1 1 NHP2 1 NMNAT1 1 NR2F2 1 NSF 1 PAX1 1 PDCD6IP 1 PDE2A 1 PHC1 1 PIEZO2 1 PIGY 1 PJA1 1 PLCH1 1 PLEKHG2 1 PLOD3 1 PLXNA2 1 PPP2R5C 1 PRKACB 2 PRKD1 2 PRRT2 1 PSAT1 1 PSMB1 1 PSMC3 1 PSMC5 1 PTRH2 1 RAB11A 1 RAB14 1 RAP1GDS1 1 RIC1 1 RMRP 1 RNF113A 1 RNF2 1 RPS23 1 RSPRY1 1 RUSC2 1 SACS 1 SEC31A 1 SEMA3E 1 SEMA5A 1 SHROOM4 1 SLC2A2 1 SLC35A3 2 SLC45A1 1 SLC5A5 1 SLC9A7 1 SMARCD2 1 SNORD118 1 SNRPN 1 SOX3 2 SRRM2 1 STN1 1 TACO1 1 TAF13 1 TAF1C 1 TARS 1 TBC1D2B 2 TBC1D7 1 TGFB1 1 THRB 1 TKFC 1 TKT 2 TMEM231 1 TMLHE 1 TNIK 1 TOP2B 1 TRAPPC2L 1 TRIP13 1 TTI1 2 TUBGCP4 1 TUFM 1 U2AF2 1 UPF1 1 UQCC2 1 USP27X 1 VPS37A 1 VPS50 1 VPS51 1 WFS1 2 YAP1 1 ZBTB11 1 ZBTB16 1 ZC3H14 4 ZFHX3 2 ZNF407 2 ZNF668 1 ABCC6 2 ABCG5 1 ACOX2 1 ACTA1 1 ADA2 1 ADAMTSL2 1 ADCY5 1 ADGRB3 1 ADGRG6 2 ADRA2B 1 AFG3L2 1 AGGF1 1 AGK 1 AGL 1 AGO3 1 AGPS 1 AGT 1 AGTR2 1 AKR1C2 1 ALDOB 1 ALG2 1 ALS2 1 ANK3 1 ANKH 1 APTX 1 AR 1 ARHGEF6 1 ASMT 1 ATL1 1 ATP10A 1 ATP2A2 1 ATP2B3 1 ATP2C2 1 ATXN10 1 AVP 1 AVPR1A 1 AVPR2 1 B3GAT3 1 BDNF 1 BICD2 1 BIN1 1 BMPER 1 C19orf12 1 C3orf58 1 CA5A 1 CACNG2 1 CANT1 1 CCDC8 1 CDC6 1 CDK5R1 1 CDT1 1 CFH 1 CFHR1 1 CFHR3 1 CHRNA4 1 CISD2 1 CLCNKA 1 CLIC2 1 CLIP2 1 CLPP 1 CMAS 1 CNTN3 1 CNTN4 1 CNTN6 1 CNTNAP5 1 COA3 1 COL18A1 1 COL1A2 1 COLEC10 1 COQ5 1 CORO1A 1 COX4I2 1 COX6B1 1 CP 1 CPA6 1 CRKL 1 CRLF1 1 CRTAP 1 CTSF 1 CUBN 1 CYFIP1 1 CYP27A1 1 CYP2U1 1 DDR2 1 DISP1 1 DLGAP2 1 DLK1 2 DNAJA1 1 DNAJC3 1 DNAJC6 1 DOCK4 1 DOK7 1 DPM3 1 DPP10 1 DSCR3 1 DSE 1 DTYMK 1 DUOXA2 1 DYNC2H1 1 EDC3 1 EDNRB 1 EFNB1 1 EFNB2 1 EIF2AK1 1 EIF2B1 1 EIF2B2 1 EIF2B3 1 EIF2B4 1 EIF2B5 1 ELMOD1 1 EOGT 1 EOMES 1 EPB41L1 1 EPM2A 1 ERCC4 1 ERF 1 ERMARD 1 ETS1 1 EVC 1 EVC2 1 FA2H 1 FAAH2 1 FAM160B1 1 FBLN5 1 FBN1 1 FDXR 1 FGF3 1 FLNB 1 FLVCR1 1 FTL 1 FZD3 1 G6PC3 1 GABRG1 1 GAN 1 GATA1 1 GBA2 1 GBE1 1 GCK 1 GCSH 1 GHR 1 GJA1 1 GJB1 1 GLRA1 1 GLUD1 1 GNA14 1 GOSR2 1 GPSM2 1 GRPR 1 GSPT2 1 GTF2I 1 GTF2IRD1 1 GYS2 1 H19 1 HADH 1 HAL 1 HARS2 1 HOXD10 1 IFT140 1 IGBP1 1 IGF2 1 IMMP2L 1 INS 1 INSR 1 INTS8 1 IRX5 1 IYD 1 JAG1 1 JPH3 1 KANK1 1 KATNAL2 1 KCNC3 1 KCND3 1 KCTD13 1 KIF16B 1 KIF1B 1 KIF21A 1 KIF4A 1 KIRREL3 1 KLF8 1 KLLN 1 KYNU 1 LBR 1 LGI4 1 LHX3 1 LMNA 1 LRP5 1 LSM1 1 LSM11 2 MACROD2 1 MAP4K4 2 MARS2 2 MCM4 1 MEPCE 1 MET 1 METAP1 1 MFN2 1 MGME1 1 MGP 1 MID2 1 MLH1 1 MNX1 1 MPI 1 MPZ 1 MRAP 1 MRPS16 1 MSH6 1 MTM1 1 MTMR2 1 MTPAP 1 MYH3 1 MYMK 1 MYO7A 1 MYT1 1 NAGS 1 NDN 1 NEGR1 1 NGF 1 NHEJ1 1 NHLRC1 1 NIN 1 NLGN1 1 NLGN4X 1 NOP10 1 NOTCH3 1 NRXN2 1 NTNG1 1 NUP62 1 ORC1 1 ORC4 1 ORC6 1 OTUD7A 2 PANK2 1 PAX2 1 PAX3 1 PAX7 1 PCBD1 1 PCDH10 1 PCDH15 1 PCDH9 1 PCLO 1 PDE11A 1 PDGFB 1 PHKA2 1 PHKG2 1 PIGF 2 PIK3R1 1 PINK1 1 PIP5K1B 1 PNP 1 POC1A 1 POLD1 1 POLD2 1 PON3 1 POP1 1 POU1F1 1 PPM1K 1 PPOX 1 PRDM8 1 PREPL 1 PRF1 1 PRICKLE1 1 PRKDC 1 PRKN 1 PRKRA 1 PRRX1 1 PRX 1 PYGL 1 RAB27A 1 RAB40AL 1 RALGAPB 1 RANBP2 1 RAPSN 1 RASA1 2 RAX 1 RBFOX1 1 RBL2 1 RBM28 1 RBM8A 1 RBPJ 1 RECQL4 1 RET 1 RFX6 1 RIMS1 1 RIN2 1 RING1 1 RNF135 2 RPL11 1 RPS19 1 RPS28 1 RUBCN 1 SALL1 1 SAMD9L 1 SBDS 1 SCN11A 1 SCN9A 1 SCO1 1 SECISBP2 1 SELENOI 1 SELENON 1 SF3B4 1 SGCA 1 SH3TC2 1 SHANK1 1 SLC12A1 1 SLC19A2 1 SLC1A3 1 SLC20A2 1 SLC22A5 1 SLC25A13 1 SLC25A19 1 SLC25A20 1 SLC25A24 1 SLC25A4 2 SLC29A3 1 SLC2A10 1 SLC39A4 1 SLC44A1 2 SLC5A2 1 SLC6A4 1 SLC7A7 1 SLC9A9 1 SMCHD1 1 SMG6 1 SNIP1 1 SNRPA 1 SNRPE 2 SOBP 1 SOST 1 SP7 1 SPAST 1 SPEG 1 SPG7 2 SPINK5 1 SPRTN 1 SPTLC1 1 SRPX2 1 ST7 1 STAC3 1 STAT5B 1 STK3 1 STT3B 1 STX11 1 SYT14 1 TAF8 1 TDGF1 2 TECR 1 TFAP2A 1 TFAP2B 1 TFG 1 TG 1 TGFBR1 1 TGFBR2 1 THAP1 1 TIMM8A 1 TMEM260 1 TP63 1 TPH2 1 TPK1 1 TRAPPC6A 1 TREM2 1 TRHR 1 TRIM32 1 TRIM37 1 TSEN34 1 TSHR 1 TTC21B 1 TTR 1 TUBA8 1 TWNK 1 TXNL4A 1 UBE2U 1 UBR4 2 UCHL1 1 UGT1A1 1 UNC13A 1 UNC13D 1 UQCRB 1 UQCRC2 1 UQCRQ 1 UROC1 1 VAMP1 1 VANGL1 1 VPS45 1 WASHC5 1 WDR13 1 WDR19 1 WDR34 1 WIPI2 1 WRAP53 1 XIST 1 XPNPEP3 1 ZCCHC12 1 ZDHHC15 1 ZFP57 1 ZMYM3 1 ZNF41 1 ZNF423 1 ZNF507 1 ZNF674 1 ZNF804A 1 ZNF81 2 ZNHIT6 1 DIP2B 2 DMPK 2 Add a gene STRs in panel DM1 1 FRAXE 1 FRA12A 1 Add a STR Regions in panel Add a Region Intellectual disability syndromic and non-syndromic Gene: HMGB1 Green List (high evidence) You reviewed HMGB1 (high mobility group box 1) EnsemblGeneIds (GRCh38): ENSG00000189403 EnsemblGeneIds (GRCh37): ENSG00000189403 OMIM: 163905, Gene2Phenotype HMGB1 is in 3 panels Reviews (1) Details History Review feedback Review gene Rating: Rating Mode of Inheritance: Mode of Inheritance Mode of pathogenicity: Mode of pathogenicity Publications (PMID: 1234; 4321): Publications (PMID: 1234; 4321) Phenotypes (separate using a semi-colon -; ): Phenotypes (separate using a semi-colon -; ) Current diagnostic: Current diagnostic Comments: Comments 1 review Your review Chirag Patel (Genetic Health Queensland) Green List (high evidence) 13q12.3 microdeletion syndrome is a rare cause of syndromic ID. Previous studies identified four genes within the ~300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1. Uguen et al. (2021) report 6 patients with LOF variants involving HMGB1 with features similar to 13q12.3 microdeletion syndrome (i.e. developmental delay, language delay, microcephaly, obesity and dysmorphic features). In silico analyses suggest that HMGB1 is likely to be intolerant to LOF, and previous in vitro data are in line with the role of HMGB1 in neurodevelopment. They suggest that haploinsufficiency of the HMGB1 gene may play a critical role in the pathogenesis of the 13q12.3 microdeletion syndrome. Sources: Literature Created: 17 Sep 2021, 4:56 a.m. Mode of inheritance MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes Developmental delay and microcephaly, no OMIM # to Developmental delay and microcephaly, no OMIM #
Microcephaly v1.50 HMGB1 Chirag Patel edited their review of gene: HMGB1: Changed phenotypes: Developmental delay and microcephaly, no OMIM #
Microcephaly v1.50 HMGB1 Chirag Patel Classified gene: HMGB1 as Green List (high evidence)
Microcephaly v1.50 HMGB1 Chirag Patel Gene: hmgb1 has been classified as Green List (High Evidence).
Microcephaly v1.49 HMGB1 Chirag Patel gene: HMGB1 was added
gene: HMGB1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: HMGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HMGB1 were set to PMID: 34164801
Phenotypes for gene: HMGB1 were set to 0 ALDH5A1 1 ALDH7A1 0 ALG1 0 ALG11 1 ALG12 1 ALG13 1 ALG14 1 ALG3 1 ALG6 1 ALG8 1 ALG9 1 ALKBH8 1 ALMS1 0 AMER1 0 AMPD2 0 AMT 0 ANK2 2 ANKRD11 0 ANKRD17 2 AP1B1 1 AP1G1 1 AP1S1 0 AP1S2 0 AP2M1 1 AP3B1 0 AP3B2 1 AP4B1 1 AP4E1 1 AP4M1 1 AP4S1 1 APC2 1 APOPT1 1 ARCN1 1 ARF1 1 ARFGEF2 0 ARG1 0 ARHGEF9 1 ARID1A 1 ARID1B 1 ARID2 2 ARL13B 1 ARL6 1 ARMC9 1 ARSA 0 ARSB 1 ARSE 1 ARV1 0 ARX 0 ASAH1 0 ASH1L 1 ASL 1 ASNS 1 ASPA 0 ASPM 1 ASS1 0 ASTN1 1 ASXL1 0 ASXL2 0 ASXL3 1 ATAD1 1 ATAD3A 1 ATG7 1 ATIC 1 ATM 0 ATN1 1 ATP13A2 0 ATP1A1 1 ATP1A2 1 ATP1A3 2 ATP6AP1 1 ATP6AP2 0 ATP6V0A2 0 ATP6V1A 1 ATP6V1B2 0 ATP7A 0 ATP8A2 1 ATR 0 ATRX 0 AUH 0 AUTS2 1 B3GALNT2 1 B3GLCT 0 B4GALNT1 0 B4GALT1 1 B4GALT7 1 B9D2 1 BAZ2B 1 BBS1 0 BBS10 0 BBS12 0 BBS2 0 BBS4 1 BBS5 1 BBS7 1 BBS9 1 BCAP31 0 BCAS3 1 BCKDHA 0 BCKDHB 0 BCKDK 0 BCL11A 0 BCL11B 1 BCOR 1 BCORL1 1 BCS1L 0 BICRA 3 BLM 0 BMP4 0 BOLA3 0 BPTF 1 BRAF 0 BRAT1 1 BRD4 2 BRF1 1 BRIP1 1 BRPF1 1 BRSK2 1 BRWD3 0 BSCL2 0 BSND 1 BTD 0 BUB1B 0 C12orf4 0 C12orf57 0 C12orf65 0 C2CD3 1 C2orf69 1 C5orf42 1 CA2 1 CA8 1 CACNA1A 0 CACNA1B 1 CACNA1C 0 CACNA1D 1 CACNA1E 1 CACNA1G 2 CACNA1I 1 CACNA2D2 1 CAD 1 CAMK2A 0 CAMK2B 1 CAMK4 1 CAMTA1 2 CAPN15 1 CARS 1 CARS2 1 CASK 0 CBL 0 CBS 0 CBY1 1 CC2D1A 1 CC2D2A 0 CCBE1 1 CCDC22 0 CCDC47 1 CCDC88A 1 CCDC88C 2 CCND2 0 CDC42 0 CDC42BPB 1 CDH11 2 CDH15 0 CDH2 1 CDK10 0 CDK13 1 CDK19 1 CDK5RAP2 1 CDK8 1 CDKL5 0 CDON 0 CELF2 1 CENPF 0 CENPJ 0 CEP104 1 CEP120 1 CEP135 1 CEP152 1 CEP164 1 CEP290 0 CEP41 0 CEP55 1 CEP57 1 CEP83 1 CEP85L 1 CHAMP1 0 CHD1 1 CHD2 0 CHD3 1 CHD4 1 CHD5 1 CHD7 0 CHD8 0 CHKB 0 CHMP1A 1 CIC 0 CIT 0 CKAP2L 0 CLCN3 1 CLCN4 1 CLCN6 1 CLCNKB 1 CLN3 0 CLN5 1 CLN6 0 CLN8 0 CLP1 1 CLPB 1 CLTC 1 CNKSR2 0 CNNM2 0 CNOT1 3 CNOT2 1 CNOT3 2 CNPY3 1 CNTNAP1 1 CNTNAP2 0 COASY 1 COG1 0 COG4 1 COG5 1 COG6 1 COG7 0 COG8 1 COL4A1 0 COL4A2 0 COL4A3BP 0 COLEC11 0 COPB2 2 COQ4 0 COQ8A 0 COX10 1 COX15 0 CPS1 0 CRADD 1 CRB2 0 CREBBP 1 CSDE1 1 CSNK1G1 2 CSNK2A1 0 CSNK2B 0 CSPP1 1 CSTB 0 CTBP1 1 CTCF 1 CTDP1 0 CTNNA2 1 CTNNB1 0 CTSA 0 CTSD 0 CTU2 1 CUL3 2 CUL4B 0 CUX1 1 CUX2 1 CWC27 0 CWF19L1 1 CXorf56 1 CYB5R3 0 CYC1 0 CYFIP2 1 D2HGDH 0 DAG1 0 DARS 1 DARS2 0 DBT 0 DCAF17 0 DCHS1 0 DCPS 1 DCX 0 DDB1 2 DDC 0 DDHD2 0 DDX11 1 DDX23 2 DDX3X 0 DDX59 1 DDX6 1 DEAF1 1 DEGS1 1 DENND5A 1 DEPDC5 0 DHCR24 0 DHCR7 0 DHDDS 1 DHFR 1 DHPS 1 DHTKD1 0 DHX30 1 DHX37 2 DIAPH1 0 DIS3L2 0 DKC1 0 DLD 0 DLG3 1 DLG4 2 DLL1 1 DMD 0 DMXL2 1 DNAJC12 1 DNAJC19 0 DNM1 1 DNM1L 1 DNMT3A 1 DNMT3B 0 DOCK3 1 DOCK6 1 DOCK7 1 DOCK8 0 DOLK 1 DPAGT1 1 DPF2 0 DPH1 1 DPM1 0 DPM2 1 DPYD 1 DPYS 1 DPYSL5 1 DYM 1 DYNC1H1 0 DYNC1I2 1 DYRK1A 1 EARS2 1 EBF3 1 EBP 1 EDEM3 2 EED 1 EEF1A2 1 EEF2 1 EFTUD2 1 EHMT1 1 EIF2AK2 2 EIF2AK3 0 EIF2S3 1 EIF3F 1 EIF4A3 1 EIF5A 1 ELAC2 0 ELOVL4 0 ELP2 0 EMC1 1 EMC10 2 EML1 1 EP300 0 EPG5 1 ERCC1 1 ERCC2 0 ERCC3 0 ERCC5 1 ERCC6 0 ERCC6L2 0 ERCC8 0 ERLIN2 1 ESCO2 0 ETFA 1 ETFB 1 ETFDH 1 ETHE1 0 EXOC7 1 EXOSC3 0 EXOSC8 1 EXT2 1 EXTL3 1 EZH2 1 FAM111A 0 FAM126A 0 FAM20C 0 FAM50A 1 FAR1 1 FARS2 1 FARSA 1 FARSB 1 FAT4 0 FBRSL1 1 FBXL3 2 FBXL4 0 FBXO11 1 FBXO28 1 FBXO31 2 FBXW11 2 FBXW7 1 FDFT1 1 FGD1 1 FGF12 0 FGF13 1 FGF14 1 FGFR1 1 FGFR3 1 FH 0 FIG4 0 FITM2 1 FKRP 0 FKTN 0 FLNA 0 FLVCR2 0 FMN2 0 FMR1 0 FOLR1 1 FOXG1 0 FOXP1 2 FOXP2 1 FOXRED1 0 FRAS1 1 FRMPD4 1 FRRS1L 1 FTCD 1 FTSJ1 0 FUCA1 0 FUT8 1 GABBR2 1 GABRA1 1 GABRA2 1 GABRA5 1 GABRB2 0 GABRB3 1 GABRG2 1 GAD1 1 GALC 0 GALE 0 GALNT2 1 GALT 1 GAMT 0 GATA6 1 GATAD2B 1 GATM 1 GCDH 0 GCH1 0 GDI1 0 GEMIN5 1 GFAP 0 GFER 1 GFM1 0 GJC2 0 GK 0 GLB1 0 GLDC 0 GLI2 0 GLI3 0 GLIS3 1 GLS 1 GLUL 0 GLYCTK 0 GM2A 0 GMPPA 0 GMPPB 0 GNAI1 2 GNAO1 1 GNAS 1 GNB1 1 GNB2 3 GNB5 1 GNE 1 GNPAT 0 GNPTAB 0 GNPTG 1 GNS 0 GOLGA2 2 GOT2 1 GPAA1 1 GPC3 0 GPC4 1 GPT2 1 GRIA1 1 GRIA2 2 GRIA3 1 GRIA4 0 GRID2 0 GRIK2 1 GRIN1 1 GRIN2A 1 GRIN2B 1 GRIN2D 1 GRM1 0 GRM7 1 GSS 1 GTF2H5 0 GTF3C3 1 GTPBP2 1 GTPBP3 0 GUSB 1 H3F3A 1 H3F3B 1 HACE1 1 HADHA 0 HADHB 1 HCCS 0 HCFC1 0 HCN1 0 HDAC4 2 HDAC8 1 HECW2 2 HEPACAM 0 HERC1 0 HERC2 2 HESX1 0 HEXA 0 HEXB 0 HGSNAT 1 HIBCH 0 HID1 1 HIRA 1 HIST1H1E 1 HIST1H4C 2 HIVEP2 1 HK1 2 HLCS 0 HMGB1 1 HMGCL 0 HNMT 1 HNRNPH1 1 HNRNPH2 0 HNRNPK 0 HNRNPR 1 HNRNPU 1 HOXA1 0 HPD 0 HPDL 2 HPRT1 0 HRAS 1 HS2ST1 3 HSD17B10 0 HSD17B4 1 HSPD1 0 HSPG2 1 HTRA2 0 HUWE1 1 IARS 1 IBA57 1 IDH2 0 IDS 0 IDUA 0 IER3IP1 1 IFIH1 0 IFT172 0 IFT27 1 IFT74 1 IGF1 1 IGF1R 1 IKBKG 0 IL1RAPL1 0 IMPDH2 2 INPP5E 1 INPP5K 0 INTS1 1 IQSEC1 1 IQSEC2 1 IREB2 1 IRF2BPL 1 ISCA1 1 ISCA2 1 ISPD 0 ITPA 0 ITPR1 0 IVD 0 JAM3 1 JARID2 1 JMJD1C 2 KANSL1 1 KARS 1 KAT5 2 KAT6A 0 KAT6B 0 KAT8 1 KATNB1 1 KCNA2 1 KCNB1 1 KCNC1 0 KCNH1 1 KCNJ10 0 KCNJ11 0 KCNJ6 1 KCNK4 1 KCNK9 1 KCNMA1 1 KCNN2 1 KCNN3 1 KCNQ2 0 KCNQ3 1 KCNQ5 1 KCNT1 0 KCNT2 1 KCTD3 0 KCTD7 0 KDM1A 1 KDM3B 2 KDM4B 2 KDM5B 1 KDM5C 1 KDM6A 0 KDM6B 1 KIAA0586 0 KIAA1109 0 KIDINS220 1 KIF11 2 KIF14 1 KIF1A 2 KIF1BP 1 KIF21B 1 KIF2A 1 KIF5A 0 KIF5C 1 KIF7 0 KLF7 1 KLHL7 0 KMT2A 1 KMT2B 1 KMT2C 1 KMT2D 2 KMT2E 1 KMT5B 1 KNL1 1 KPTN 1 KRAS 0 L1CAM 0 L2HGDH 0 LAMA1 0 LAMA2 1 LAMB1 1 LAMB2 1 LAMC3 0 LAMP2 0 LARGE1 0 LARP7 1 LARS 2 LARS2 0 LIAS 1 LIG4 0 LINGO4 1 LINS1 0 LIPT1 1 LMBRD1 1 LMBRD2 2 LMNB1 2 LMNB2 2 LONP1 0 LRP2 0 LRPPRC 0 LSS 1 LTBP1 1 LYRM7 1 LZTFL1 1 LZTR1 1 MAB21L1 2 MAB21L2 1 MACF1 1 MADD 3 MAF 0 MAGEL2 1 MAN1B1 1 MAN2B1 1 MANBA 1 MAOA 1 MAP1B 1 MAP2K1 0 MAP2K2 0 MAPK1 2 MAPK8IP3 2 MAPKAPK5 1 MAPRE2 1 MASP1 1 MAST1 1 MAST3 1 MAT1A 0 MBD5 1 MBOAT7 0 MBTPS2 0 MCCC1 0 MCCC2 0 MCM3AP 1 MCOLN1 1 MCPH1 1 MDH2 0 MECP2 1 MED12 0 MED12L 1 MED13 1 MED13L 0 MED17 1 MED23 0 MED25 1 MED27 2 MEF2C 1 MEGF8 2 MEIS2 0 METTL23 2 METTL5 1 MFF 0 MFSD2A 1 MFSD8 1 MGAT2 1 MICU1 1 MID1 0 MIR17HG 2 MKKS 0 MKS1 0 MLC1 0 MLYCD 1 MMAA 0 MMAB 0 MMACHC 0 MMADHC 0 MN1 2 MOCS1 1 MOCS2 0 MOGS 1 MORC2 2 MPDU1 1 MPDZ 1 MPLKIP 1 MPP5 1 MPV17 1 MRPS22 0 MRPS34 1 MSL3 1 MSMO1 1 MTFMT 0 MTHFR 0 MTHFS 1 MTO1 1 MTOR 0 MTR 1 MTRR 1 MUT 0 MVK 0 MYCN 0 MYO5A 0 MYT1L 2 NAA10 0 NAA15 1 NACC1 0 NAGA 0 NAGLU 0 NALCN 0 NANS 0 NARS 2 NBEA 1 NCAPD2 2 NCAPG2 1 NCDN 2 NCKAP1 1 NDE1 1 NDP 0 NDST1 0 NDUFA1 0 NDUFA2 1 NDUFAF1 1 NDUFS1 1 NDUFS4 1 NDUFS7 0 NDUFS8 0 NDUFV1 0 NEDD4L 1 NEMF 2 NEU1 0 NEUROD2 1 NEXMIF 1 NF1 0 NFASC 1 NFIA 0 NFIB 1 NFIX 0 NFU1 1 NGLY1 0 NHS 0 NIPBL 1 NKAP 1 NKX2-1 0 NLGN3 0 NONO 0 NOVA2 1 NPC1 0 NPC2 0 NPHP1 0 NPHP3 1 NR2F1 1 NR4A2 2 NRAS 0 NRROS 1 NRXN1 0 NSD1 0 NSD2 1 NSDHL 1 NSUN2 0 NT5C2 1 NTNG2 1 NTRK1 0 NTRK2 1 NUBPL 0 NUDT2 1 NUP188 1 NUP214 2 NUS1 1 OCLN 0 OCRL 0 ODC1 1 OFD1 0 OGT 1 OPA3 0 OPHN1 0 OSGEP 1 OTC 0 OTUD5 2 OTUD6B 0 OTX2 0 OXR1 1 P4HTM 1 PACS1 1 PACS2 1 PAFAH1B1 1 PAH 0 PAK1 1 PAK3 1 PAM16 1 PARN 0 PARP6 1 PAX6 0 PAX8 0 PBX1 0 PC 0 PCCA 0 PCCB 0 PCDH12 1 PCDH19 0 PCDHGC4 1 PCGF2 1 PCNT 0 PCYT2 1 PDE10A 1 PDE4D 0 PDE6D 1 PDGFRB 0 PDHA1 0 PDHB 1 PDHX 0 PDP1 1 PDSS1 1 PDSS2 0 PEPD 0 PET100 1 PEX1 0 PEX10 0 PEX11B 0 PEX12 0 PEX13 0 PEX14 0 PEX16 0 PEX19 0 PEX2 0 PEX26 0 PEX3 0 PEX5 0 PEX6 0 PEX7 0 PGAP1 0 PGAP2 1 PGAP3 1 PGK1 1 PGM2L1 1 PGM3 1 PHACTR1 1 PHF21A 2 PHF6 0 PHF8 1 PHGDH 0 PHIP 1 PI4KA 1 PIBF1 2 PIDD1 1 PIGA 1 PIGB 2 PIGC 1 PIGG 1 PIGH 1 PIGK 1 PIGL 1 PIGN 1 PIGO 1 PIGP 2 PIGQ 1 PIGS 1 PIGT 1 PIGU 1 PIGV 1 PIGW 0 PIK3C2A 1 PIK3CA 0 PIK3R2 1 PISD 1 PITRM1 1 PLA2G6 0 PLAA 0 PLCB1 1 PLK4 1 PLP1 0 PLPBP 1 PMM2 0 PMPCA 1 PMPCB 1 PNKP 1 PNPLA6 0 PNPT1 1 POGZ 1 POLA1 1 POLG 0 POLR1C 1 POLR2A 1 POLR3A 0 POLR3B 0 POLRMT 1 POMGNT1 0 POMGNT2 0 POMK 1 POMT1 0 POMT2 0 PORCN 0 POU3F3 1 PPIL1 1 PPM1D 1 PPP1CB 1 PPP1R12A 1 PPP1R15B 0 PPP1R21 1 PPP2CA 1 PPP2R1A 1 PPP2R5D 1 PPP3CA 0 PPT1 0 PQBP1 1 PRICKLE2 1 PRKAR1A 1 PRKAR1B 1 PRMT7 0 PRODH 0 PRPS1 0 PRR12 1 PRSS12 0 PRUNE1 1 PSAP 1 PSMD12 0 PSPH 0 PTCH1 0 PTCHD1 0 PTDSS1 0 PTEN 0 PTF1A 0 PTPN11 0 PTPN23 1 PTPN4 1 PTRHD1 1 PTS 0 PUF60 1 PUM1 1 PURA 1 PUS1 0 PUS3 1 PUS7 1 PYCR1 0 PYCR2 0 QARS 1 QDPR 0 QRICH1 1 RAB11B 1 RAB18 0 RAB23 0 RAB39B 0 RAB3GAP1 1 RAB3GAP2 0 RAC1 1 RAC3 1 RAD21 1 RAF1 0 RAI1 1 RALA 1 RALGAPA1 1 RAP1B 2 RARB 1 RARS 1 RARS2 0 RBBP8 0 RBM10 1 RELN 0 RERE 1 RFT1 1 RFX3 1 RFX4 1 RFX7 1 RHEB 1 RHOBTB2 1 RIT1 0 RLIM 1 RMND1 0 RNASEH2A 0 RNASEH2B 0 RNASEH2C 0 RNASET2 0 RNF125 0 RNF13 1 RNF220 1 RNU4ATAC 1 RNU7-1 2 ROGDI 1 ROR2 0 RORA 1 RPGRIP1L 0 RPIA 1 RPL10 1 RPS6KA3 0 RRM2B 0 RSRC1 1 RTEL1 0 RTN4IP1 1 RTTN 1 SAMD9 0 SAMHD1 0 SARS2 1 SATB1 2 SATB2 1 SBF1 1 SC5D 0 SCAF4 1 SCAMP5 2 SCAPER 1 SCN1A 1 SCN1B 1 SCN2A 0 SCN3A 1 SCN8A 0 SCO2 0 SDCCAG8 1 SDHA 0 SDHAF1 1 SEPSECS 1 SERAC1 0 SET 0 SETBP1 0 SETD1A 1 SETD1B 1 SETD2 1 SETD5 1 SFXN4 1 SGPL1 0 SGSH 1 SHANK2 0 SHANK3 1 SHH 0 SHMT2 2 SHOC2 1 SIAH1 1 SIK1 0 SIL1 1 SIN3A 0 SIN3B 1 SIX3 0 SKI 0 SLC12A2 3 SLC12A5 0 SLC12A6 0 SLC13A5 1 SLC16A2 1 SLC17A5 0 SLC18A2 1 SLC19A3 0 SLC1A1 1 SLC1A2 1 SLC1A4 1 SLC25A1 0 SLC25A12 0 SLC25A15 0 SLC25A22 0 SLC2A1 0 SLC33A1 0 SLC35A1 0 SLC35A2 0 SLC35C1 0 SLC39A14 0 SLC39A8 1 SLC46A1 1 SLC4A4 0 SLC5A6 1 SLC6A1 1 SLC6A17 0 SLC6A19 0 SLC6A3 0 SLC6A8 0 SLC6A9 1 SLC9A6 1 SLX4 0 SMAD4 0 SMARCA2 1 SMARCA4 0 SMARCA5 1 SMARCB1 0 SMARCC2 1 SMARCD1 1 SMARCE1 0 SMC1A 0 SMC3 0 SMG8 2 SMG9 1 SMOC1 1 SMPD1 1 SMPD4 1 SMS 0 SNAP25 1 SNAP29 0 SNRPB 1 SNX14 0 SNX27 1 SON 1 SOS1 1 SOS2 1 SOX10 0 SOX11 0 SOX2 1 SOX4 1 SOX5 1 SOX6 2 SOX9 0 SPART 1 SPATA5 1 SPECC1L 0 SPEN 2 SPG11 1 SPOP 1 SPR 0 SPRED1 1 SPTAN1 1 SPTBN1 1 SPTBN2 0 SPTBN4 2 SRCAP 2 SRD5A3 0 SSR4 0 ST3GAL3 0 ST3GAL5 2 STAG1 0 STAG2 1 STAMBP 1 STIL 1 STRA6 0 STRADA 1 STT3A 2 STX1B 0 STXBP1 0 SUCLA2 1 SUCLG1 0 SUFU 1 SUMF1 1 SUOX 0 SUPT16H 1 SURF1 0 SUZ12 2 SVBP 2 SYN1 0 SYNCRIP 2 SYNGAP1 1 SYNJ1 0 SYP 0 SYT1 2 SZT2 0 TAF1 1 TAF2 2 TAF6 1 TANC2 2 TANGO2 0 TAOK1 1 TASP1 1 TAT 0 TAZ 0 TBC1D20 1 TBC1D23 0 TBC1D24 0 TBCD 1 TBCE 0 TBCK 0 TBL1XR1 0 TBR1 1 TBX1 1 TCF20 1 TCF4 0 TCF7L2 2 TCN2 1 TCTN2 0 TCTN3 1 TDP2 1 TECPR2 1 TELO2 1 TENM3 1 TERT 2 TET3 1 TFE3 2 TGIF1 1 TH 0 THOC2 1 THOC6 0 THRA 0 TIMM50 1 TINF2 1 TLK2 1 TMCO1 0 TMEM106B 1 TMEM165 1 TMEM216 0 TMEM222 2 TMEM237 1 TMEM240 0 TMEM5 0 TMEM67 1 TMEM70 0 TMEM94 1 TMTC3 1 TMX2 1 TNPO2 1 TNR 1 TNRC6B 2 TOE1 1 TOGARAM1 1 TP73 1 TPP1 1 TPP2 1 TRAF7 1 TRAIP 1 TRAK1 1 TRAPPC11 1 TRAPPC12 1 TRAPPC4 1 TRAPPC6B 1 TRAPPC9 2 TREX1 0 TRIM8 1 TRIO 1 TRIP12 1 TRIT1 1 TRMT1 1 TRMT10A 1 TRNT1 1 TRPM3 1 TRRAP 1 TSC1 0 TSC2 0 TSEN15 1 TSEN2 0 TSEN54 0 TSFM 0 TSHB 0 TSPAN7 0 TSPOAP1 1 TTC19 0 TTC37 0 TTC5 2 TTC8 1 TTI2 1 TUBA1A 0 TUBB 1 TUBB2A 1 TUBB2B 0 TUBB3 0 TUBB4A 0 TUBG1 0 TUBGCP2 1 TUBGCP6 1 TUSC3 1 TWIST1 0 UBA5 0 UBE2A 1 UBE3A 0 UBE3B 1 UBE4A 1 UBR1 1 UBR7 1 UBTF 1 UFC1 1 UFM1 1 UFSP2 2 UGDH 1 UGP2 1 UMPS 1 UNC80 1 UPB1 2 UPF3B 2 USP18 1 USP7 2 USP9X 1 VAMP2 2 VARS 1 VARS2 1 VIPAS39 1 VLDLR 0 VPS11 1 VPS13B 0 VPS33B 1 VPS41 1 VPS4A 3 VPS53 0 VRK1 0 WAC 1 WARS2 1 WASF1 2 WASHC4 3 WDFY3 1 WDPCP 1 WDR11 2 WDR26 1 WDR37 1 WDR4 2 WDR45 0 WDR45B 1 WDR62 1 WDR73 0 WDR81 1 WNT1 1 WNT5A 2 WWOX 0 XPA 2 XRCC4 0 XYLT1 2 YARS 1 YIF1B 2 YWHAG 1 YY1 0 ZBTB18 0 ZBTB20 0 ZBTB24 1 ZC4H2 0 ZDHHC9 0 ZEB2 1 ZFHX4 1 ZFYVE26 0 ZIC1 1 ZIC2 0 ZMIZ1 2 ZMYM2 2 ZMYND11 1 ZNF142 1 ZNF148 1 ZNF292 2 ZNF335 1 ZNF462 2 ZNF526 1 ZNF699 1 ZNF711 1 ZSWIM6 1 AASS 1 ACADSB 1 ACAT1 1 ADAM22 1 AKAP6 1 ALDOA 1 ALX1 1 ALX3 1 ALX4 1 AP2S1 1 ARF3 2 ARHGAP31 1 ARHGAP35 1 ARNT2 1 ATP6V0A1 1 ATP9A 1 ATXN2L 1 B3GALT6 1 B9D1 1 BBIP1 1 C16orf62 1 C8orf37 1 CACNB4 1 CAPZA2 1 CCDC174 1 CCDC78 1 CD96 1 CDK16 1 CDK6 1 CDKN1C 1 CEP63 1 CEP89 1 CHRM1 1 CHST14 1 CLCN2 1 CNKSR1 1 COPB1 1 COQ2 1 COQ9 1 COX14 1 COX20 1 COX7B 1 CPE 1 CRBN 1 CTC1 1 CTNND1 1 CTNND2 1 DDOST 1 DHX32 1 DLAT 1 DPH2 1 DPP6 2 DSCAM 1 EEF1B2 1 EEF1D 1 EIF2A 1 EMG1 1 EMX2 1 EPHA7 1 ERGIC3 2 EXOC2 2 EXOSC2 1 FANCB 1 FANCD2 1 FANCG 1 FASTKD2 1 FEM1B 1 FGFR2 1 FIBP 1 FOXP4 1 FRMD4A 1 FRY 1 FTO 1 FUK 1 GBA 1 GEMIN4 1 GIGYF1 1 GMNN 1 GNAI2 1 GNAQ 1 GORAB 1 GPHN 1 GSX2 1 GTF2E2 2 HARS 2 HAX1 1 HEATR5B 1 HIST1H4J 1 HNRNPD 1 HSPA9 1 HTT 1 HYLS1 1 ICE1 1 IMPA1 1 INPP4A 1 IQSEC3 2 ITCH 1 ITFG2 2 ITGA7 1 JAKMIP1 1 KCNJ1 1 KLHL15 1 LAS1L 1 LINGO1 1 LIPT2 1 LMAN2L 1 LNPK 1 LRRC32 1 LYST 1 MAGT1 1 MMGT1 1 MRPL3 2 MSL2 1 NBN 1 NDUFA10 1 NDUFA11 1 NDUFA9 1 NDUFAF2 1 NDUFAF3 1 NDUFAF4 1 NDUFAF5 1 NDUFAF6 1 NDUFB3 1 NDUFB9 1 NDUFS2 1 NDUFS3 1 NDUFS6 1 NDUFV2 1 NECAP1 1 NHP2 1 NMNAT1 1 NR2F2 1 NSF 1 PAX1 1 PDCD6IP 1 PDE2A 1 PHC1 1 PIEZO2 1 PIGY 1 PJA1 1 PLCH1 1 PLEKHG2 1 PLOD3 1 PLXNA2 1 PPP2R5C 1 PRKACB 2 PRKD1 2 PRRT2 1 PSAT1 1 PSMB1 1 PSMC3 1 PSMC5 1 PTRH2 1 RAB11A 1 RAB14 1 RAP1GDS1 1 RIC1 1 RMRP 1 RNF113A 1 RNF2 1 RPS23 1 RSPRY1 1 RUSC2 1 SACS 1 SEC31A 1 SEMA3E 1 SEMA5A 1 SHROOM4 1 SLC2A2 1 SLC35A3 2 SLC45A1 1 SLC5A5 1 SLC9A7 1 SMARCD2 1 SNORD118 1 SNRPN 1 SOX3 2 SRRM2 1 STN1 1 TACO1 1 TAF13 1 TAF1C 1 TARS 1 TBC1D2B 2 TBC1D7 1 TGFB1 1 THRB 1 TKFC 1 TKT 2 TMEM231 1 TMLHE 1 TNIK 1 TOP2B 1 TRAPPC2L 1 TRIP13 1 TTI1 2 TUBGCP4 1 TUFM 1 U2AF2 1 UPF1 1 UQCC2 1 USP27X 1 VPS37A 1 VPS50 1 VPS51 1 WFS1 2 YAP1 1 ZBTB11 1 ZBTB16 1 ZC3H14 4 ZFHX3 2 ZNF407 2 ZNF668 1 ABCC6 2 ABCG5 1 ACOX2 1 ACTA1 1 ADA2 1 ADAMTSL2 1 ADCY5 1 ADGRB3 1 ADGRG6 2 ADRA2B 1 AFG3L2 1 AGGF1 1 AGK 1 AGL 1 AGO3 1 AGPS 1 AGT 1 AGTR2 1 AKR1C2 1 ALDOB 1 ALG2 1 ALS2 1 ANK3 1 ANKH 1 APTX 1 AR 1 ARHGEF6 1 ASMT 1 ATL1 1 ATP10A 1 ATP2A2 1 ATP2B3 1 ATP2C2 1 ATXN10 1 AVP 1 AVPR1A 1 AVPR2 1 B3GAT3 1 BDNF 1 BICD2 1 BIN1 1 BMPER 1 C19orf12 1 C3orf58 1 CA5A 1 CACNG2 1 CANT1 1 CCDC8 1 CDC6 1 CDK5R1 1 CDT1 1 CFH 1 CFHR1 1 CFHR3 1 CHRNA4 1 CISD2 1 CLCNKA 1 CLIC2 1 CLIP2 1 CLPP 1 CMAS 1 CNTN3 1 CNTN4 1 CNTN6 1 CNTNAP5 1 COA3 1 COL18A1 1 COL1A2 1 COLEC10 1 COQ5 1 CORO1A 1 COX4I2 1 COX6B1 1 CP 1 CPA6 1 CRKL 1 CRLF1 1 CRTAP 1 CTSF 1 CUBN 1 CYFIP1 1 CYP27A1 1 CYP2U1 1 DDR2 1 DISP1 1 DLGAP2 1 DLK1 2 DNAJA1 1 DNAJC3 1 DNAJC6 1 DOCK4 1 DOK7 1 DPM3 1 DPP10 1 DSCR3 1 DSE 1 DTYMK 1 DUOXA2 1 DYNC2H1 1 EDC3 1 EDNRB 1 EFNB1 1 EFNB2 1 EIF2AK1 1 EIF2B1 1 EIF2B2 1 EIF2B3 1 EIF2B4 1 EIF2B5 1 ELMOD1 1 EOGT 1 EOMES 1 EPB41L1 1 EPM2A 1 ERCC4 1 ERF 1 ERMARD 1 ETS1 1 EVC 1 EVC2 1 FA2H 1 FAAH2 1 FAM160B1 1 FBLN5 1 FBN1 1 FDXR 1 FGF3 1 FLNB 1 FLVCR1 1 FTL 1 FZD3 1 G6PC3 1 GABRG1 1 GAN 1 GATA1 1 GBA2 1 GBE1 1 GCK 1 GCSH 1 GHR 1 GJA1 1 GJB1 1 GLRA1 1 GLUD1 1 GNA14 1 GOSR2 1 GPSM2 1 GRPR 1 GSPT2 1 GTF2I 1 GTF2IRD1 1 GYS2 1 H19 1 HADH 1 HAL 1 HARS2 1 HOXD10 1 IFT140 1 IGBP1 1 IGF2 1 IMMP2L 1 INS 1 INSR 1 INTS8 1 IRX5 1 IYD 1 JAG1 1 JPH3 1 KANK1 1 KATNAL2 1 KCNC3 1 KCND3 1 KCTD13 1 KIF16B 1 KIF1B 1 KIF21A 1 KIF4A 1 KIRREL3 1 KLF8 1 KLLN 1 KYNU 1 LBR 1 LGI4 1 LHX3 1 LMNA 1 LRP5 1 LSM1 1 LSM11 2 MACROD2 1 MAP4K4 2 MARS2 2 MCM4 1 MEPCE 1 MET 1 METAP1 1 MFN2 1 MGME1 1 MGP 1 MID2 1 MLH1 1 MNX1 1 MPI 1 MPZ 1 MRAP 1 MRPS16 1 MSH6 1 MTM1 1 MTMR2 1 MTPAP 1 MYH3 1 MYMK 1 MYO7A 1 MYT1 1 NAGS 1 NDN 1 NEGR1 1 NGF 1 NHEJ1 1 NHLRC1 1 NIN 1 NLGN1 1 NLGN4X 1 NOP10 1 NOTCH3 1 NRXN2 1 NTNG1 1 NUP62 1 ORC1 1 ORC4 1 ORC6 1 OTUD7A 2 PANK2 1 PAX2 1 PAX3 1 PAX7 1 PCBD1 1 PCDH10 1 PCDH15 1 PCDH9 1 PCLO 1 PDE11A 1 PDGFB 1 PHKA2 1 PHKG2 1 PIGF 2 PIK3R1 1 PINK1 1 PIP5K1B 1 PNP 1 POC1A 1 POLD1 1 POLD2 1 PON3 1 POP1 1 POU1F1 1 PPM1K 1 PPOX 1 PRDM8 1 PREPL 1 PRF1 1 PRICKLE1 1 PRKDC 1 PRKN 1 PRKRA 1 PRRX1 1 PRX 1 PYGL 1 RAB27A 1 RAB40AL 1 RALGAPB 1 RANBP2 1 RAPSN 1 RASA1 2 RAX 1 RBFOX1 1 RBL2 1 RBM28 1 RBM8A 1 RBPJ 1 RECQL4 1 RET 1 RFX6 1 RIMS1 1 RIN2 1 RING1 1 RNF135 2 RPL11 1 RPS19 1 RPS28 1 RUBCN 1 SALL1 1 SAMD9L 1 SBDS 1 SCN11A 1 SCN9A 1 SCO1 1 SECISBP2 1 SELENOI 1 SELENON 1 SF3B4 1 SGCA 1 SH3TC2 1 SHANK1 1 SLC12A1 1 SLC19A2 1 SLC1A3 1 SLC20A2 1 SLC22A5 1 SLC25A13 1 SLC25A19 1 SLC25A20 1 SLC25A24 1 SLC25A4 2 SLC29A3 1 SLC2A10 1 SLC39A4 1 SLC44A1 2 SLC5A2 1 SLC6A4 1 SLC7A7 1 SLC9A9 1 SMCHD1 1 SMG6 1 SNIP1 1 SNRPA 1 SNRPE 2 SOBP 1 SOST 1 SP7 1 SPAST 1 SPEG 1 SPG7 2 SPINK5 1 SPRTN 1 SPTLC1 1 SRPX2 1 ST7 1 STAC3 1 STAT5B 1 STK3 1 STT3B 1 STX11 1 SYT14 1 TAF8 1 TDGF1 2 TECR 1 TFAP2A 1 TFAP2B 1 TFG 1 TG 1 TGFBR1 1 TGFBR2 1 THAP1 1 TIMM8A 1 TMEM260 1 TP63 1 TPH2 1 TPK1 1 TRAPPC6A 1 TREM2 1 TRHR 1 TRIM32 1 TRIM37 1 TSEN34 1 TSHR 1 TTC21B 1 TTR 1 TUBA8 1 TWNK 1 TXNL4A 1 UBE2U 1 UBR4 2 UCHL1 1 UGT1A1 1 UNC13A 1 UNC13D 1 UQCRB 1 UQCRC2 1 UQCRQ 1 UROC1 1 VAMP1 1 VANGL1 1 VPS45 1 WASHC5 1 WDR13 1 WDR19 1 WDR34 1 WIPI2 1 WRAP53 1 XIST 1 XPNPEP3 1 ZCCHC12 1 ZDHHC15 1 ZFP57 1 ZMYM3 1 ZNF41 1 ZNF423 1 ZNF507 1 ZNF674 1 ZNF804A 1 ZNF81 2 ZNHIT6 1 DIP2B 2 DMPK 2 Add a gene STRs in panel DM1 1 FRAXE 1 FRA12A 1 Add a STR Regions in panel Add a Region Intellectual disability syndromic and non-syndromic Gene: HMGB1 Green List (high evidence) You reviewed HMGB1 (high mobility group box 1) EnsemblGeneIds (GRCh38): ENSG00000189403 EnsemblGeneIds (GRCh37): ENSG00000189403 OMIM: 163905, Gene2Phenotype HMGB1 is in 3 panels Reviews (1) Details History Review feedback Review gene Rating: Rating Mode of Inheritance: Mode of Inheritance Mode of pathogenicity: Mode of pathogenicity Publications (PMID: 1234; 4321): Publications (PMID: 1234; 4321) Phenotypes (separate using a semi-colon -; ): Phenotypes (separate using a semi-colon -; ) Current diagnostic: Current diagnostic Comments: Comments 1 review Your review Chirag Patel (Genetic Health Queensland) Green List (high evidence) 13q12.3 microdeletion syndrome is a rare cause of syndromic ID. Previous studies identified four genes within the ~300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1. Uguen et al. (2021) report 6 patients with LOF variants involving HMGB1 with features similar to 13q12.3 microdeletion syndrome (i.e. developmental delay, language delay, microcephaly, obesity and dysmorphic features). In silico analyses suggest that HMGB1 is likely to be intolerant to LOF, and previous in vitro data are in line with the role of HMGB1 in neurodevelopment. They suggest that haploinsufficiency of the HMGB1 gene may play a critical role in the pathogenesis of the 13q12.3 microdeletion syndrome. Sources: Literature Created: 17 Sep 2021, 4:56 a.m. Mode of inheritance MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes Developmental delay and microcephaly, no OMIM #
Review for gene: HMGB1 was set to GREEN
Added comment: 13q12.3 microdeletion syndrome is a rare cause of syndromic ID. Previous studies identified four genes within the ~300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1. Uguen et al. (2021) report 6 patients with LOF variants involving HMGB1 with features similar to 13q12.3 microdeletion syndrome (i.e. developmental delay, language delay, microcephaly, obesity and dysmorphic features). In silico analyses suggest that HMGB1 is likely to be intolerant to LOF, and previous in vitro data are in line with the role of HMGB1 in neurodevelopment. They suggest that haploinsufficiency of the HMGB1 gene may play a critical role in the pathogenesis of the 13q12.3 microdeletion syndrome.
Sources: Literature
Microcephaly v1.48 TAF2 Chirag Patel Classified gene: TAF2 as Green List (high evidence)
Microcephaly v1.48 TAF2 Chirag Patel Gene: taf2 has been classified as Green List (High Evidence).
Microcephaly v1.47 TAF2 Chirag Patel Classified gene: TAF2 as Green List (high evidence)
Microcephaly v1.47 TAF2 Chirag Patel Gene: taf2 has been classified as Green List (High Evidence).
Microcephaly v1.46 TAF2 Chirag Patel reviewed gene: TAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34474177; Phenotypes: Mental retardation, autosomal recessive 40, OMIM # 615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.46 COPB2 Zornitza Stark Classified gene: COPB2 as Amber List (moderate evidence)
Microcephaly v1.46 COPB2 Zornitza Stark Gene: copb2 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.45 COPB2 Zornitza Stark edited their review of gene: COPB2: Added comment: Loss-of-function variants in COPB2, a component of the COPI coatomer complex, in six individuals from five unrelated families. 4 are heterozygous and one family with two sibs with homozygous variant, previously reported.
All presenting with a clinical spectrum of osteoporosis or osteopaenia, many with recurrent fractures, and developmental delay of variable severity. Functional data.

Note one of the individuals with heterozygous variant had significant microcephaly in addition to the two sibs with bi-allelic variants.; Changed rating: AMBER; Changed publications: 29036432, 34450031; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Microcephaly v1.45 ZNF668 Zornitza Stark Marked gene: ZNF668 as ready
Microcephaly v1.45 ZNF668 Zornitza Stark Gene: znf668 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.45 ZNF668 Zornitza Stark Classified gene: ZNF668 as Amber List (moderate evidence)
Microcephaly v1.45 ZNF668 Zornitza Stark Gene: znf668 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.44 ZNF668 Paul De Fazio edited their review of gene: ZNF668: Changed rating: AMBER
Microcephaly v1.44 ZNF668 Paul De Fazio changed review comment from: 5 individuals from 3 consanguineous families reported with different biallelic truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism.

Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts.
Sources: Literature; to: 2 consanguineous families reported with different biallelic truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism.

Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts.
Sources: Literature
Microcephaly v1.44 ZNF668 Paul De Fazio gene: ZNF668 was added
gene: ZNF668 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ZNF668 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF668 were set to 34313816; 26633546
Phenotypes for gene: ZNF668 were set to DNA damage repair defect; microcephaly; growth deficiency; severe global developmental delay; brain malformation; facial dysmorphism
Review for gene: ZNF668 was set to GREEN
gene: ZNF668 was marked as current diagnostic
Added comment: 5 individuals from 3 consanguineous families reported with different biallelic truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism.

Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts.
Sources: Literature
Microcephaly v1.44 WDR11 Zornitza Stark Marked gene: WDR11 as ready
Microcephaly v1.44 WDR11 Zornitza Stark Gene: wdr11 has been classified as Green List (High Evidence).
Microcephaly v1.44 WDR11 Zornitza Stark Classified gene: WDR11 as Green List (high evidence)
Microcephaly v1.44 WDR11 Zornitza Stark Gene: wdr11 has been classified as Green List (High Evidence).
Microcephaly v1.43 WDR11 Zornitza Stark gene: WDR11 was added
gene: WDR11 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WDR11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR11 were set to 34413497
Phenotypes for gene: WDR11 were set to Intellectual disability; Microcephaly; Short stature
Review for gene: WDR11 was set to GREEN
Added comment: Haag et al (2021 - PMID: 34413497) report on 6 individuals from 3 unrelated families, harboring biallelic LoF WDR11 variants.

Common features included microcephaly (6/6 - range: -2.43 SD to -4.93SD) and intellectual disability (6/6, in 5 cases mild, in 1 severe) with some individuals presenting also with mild short stature.

Homozygosity or compound heterozygosity for LoF variants in affected individuals was identified following exome sequencing (fam1: NM_018117.12:c.1255C>T/p.Q419* hmz, fam2:c.3033_3036del/D1011Efs*21 in trans with c.1439del/p.N480Tfs*32, fam3:c.2931+1G>A hmz).

Segregation studies supported carrier state of parents and unaffected sibs (or homozygosity for wt allele in the latter).

Variable previous investigations incl. standard karyotype and CMA were normal in several subjects (notably index cases from each family).
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As the authors comment WDR11 encodes for the WD repeat domain 11 protein and has broad expression in the developing mouse CNS. Mutations in other genes encoding for WD repeat proteins have been associated with neurological, endocrine or other disorders incl. ciliopathies.

Heterozygous missense WDR11 variants are associated with hypogonadotropic hypogonadism (HH) 14 with or without anosmia (MIM #614858). [Gene2Phenotype : monoallelic, all missense/in-frame].

The authors performed extensive hormonal studies and argue that the phenotype associated with biallelic variants differs significantly from the dominantly inherited variants (HH) suggesting that biallelic variants result in a clinically distinct entity. In addition, carrier parents of the individuals reported by Haag et al had no obvious signs of congenital HH. However, there was no endocrinological examination performed.
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Variant effect:
Immunofluorescence studies demonstrated strong juxtanuclear WDR11 staining in control fibroblasts , but only cell-ubiquitous background labeling in patient fibroblasts (for Q419*). There was also evidence for colocalization of wt WDR11 to the trans-Golgi network (TGN) with loss of this pattern in patient fibroblasts (Q419*).

Western blot in whole cell lysates of cultured patient fibroblasts (same variant) proved loss of WDR11 irrespectively of the antibody used (against N- or C-terminal epitopes of WDR11). There was no indication of a truncated protein.
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Animal models:
The authors discuss previous evidence from mice/zebrafish models suggesting abnormal Hedgehog signaling in the primary cilium and impaired ciliogenesis due to loss of WDR11.

Wdr11-null mice display features of holoprosencephaly incl. microcephaly, hypotelorism, micro/anophthalmia, abnormal pituitary gland, growth retardation, heart defects, hypoplasia of reproductive organs and infertility. There was evidence of reduced length of the ciliary axoneme and reduced frequency of ciliated cells.

Knockdown of wdr11 in zebrafish led to microcephaly, aberrant head cartilage formation, microphthalmia, curved body axis, motility defects.

Overall the authors consider that the phenotype of microcephaly, variable growth delay and/or some visual/skeletal anomalies are recapitulated to some degree in animal models, although a more severe phenotype is observed in mice.

In the cohort presented by Haag et al there was no evidence of congenital heart defects, brain malformations, abnormal sexual hormone profiles or pituitary (MRI) abnormalities based on the investigations performed.
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The authors discuss briefly on the previously proposed role for WDR11 in endosome to trans Golgi network vesicular trafficking which might also be supported by their colocalization experiments in patient fibroblasts.
Sources: Literature
Microcephaly v1.42 BRD4 Zornitza Stark Publications for gene: BRD4 were set to 29379197; 30302754
Microcephaly v1.41 BRD4 Zornitza Stark Classified gene: BRD4 as Green List (high evidence)
Microcephaly v1.41 BRD4 Zornitza Stark Gene: brd4 has been classified as Green List (High Evidence).
Microcephaly v1.40 BRD4 Zornitza Stark reviewed gene: BRD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 29379197, 30302754, 11997514, 34035299; Phenotypes: Cornelia de Lange syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.40 VPS50 Zornitza Stark Marked gene: VPS50 as ready
Microcephaly v1.40 VPS50 Zornitza Stark Gene: vps50 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.40 VPS50 Zornitza Stark Classified gene: VPS50 as Amber List (moderate evidence)
Microcephaly v1.40 VPS50 Zornitza Stark Gene: vps50 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.39 VPS50 Zornitza Stark gene: VPS50 was added
gene: VPS50 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS50 were set to 34037727
Phenotypes for gene: VPS50 were set to Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum
Review for gene: VPS50 was set to AMBER
Added comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants.

Common features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging.

Both individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)).

VPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor.

As discussed by Schneeberger et al (refs provided in text):
- VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development.
- Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality.

Studies performed by Schneeberger et al included:
- Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del).
- Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels.
- Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts.
- Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function.

As the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term "GARP and/or EARP deficiency disorders".

There is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes.
Sources: Literature
Microcephaly v1.38 TMEM222 Zornitza Stark Phenotypes for gene: TMEM222 were changed from Intellectual disability; Epilepsy; Microcephaly to Neurodevelopmental disorder with motor and speech delay and behavioural abnormalities, MIM# 619470; Intellectual disability; Epilepsy; Microcephaly
Microcephaly v1.37 TMEM222 Zornitza Stark edited their review of gene: TMEM222: Changed phenotypes: Neurodevelopmental disorder with motor and speech delay and behavioural abnormalities, MIM# 619470, Intellectual disability, Epilepsy, Microcephaly
Microcephaly v1.37 TNPO2 Zornitza Stark Marked gene: TNPO2 as ready
Microcephaly v1.37 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Microcephaly v1.37 TNPO2 Zornitza Stark Classified gene: TNPO2 as Green List (high evidence)
Microcephaly v1.37 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Microcephaly v1.36 TNPO2 Zornitza Stark gene: TNPO2 was added
gene: TNPO2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TNPO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNPO2 were set to 34314705
Phenotypes for gene: TNPO2 were set to Intellectual disability, neurologic deficits and dysmorphic features
Mode of pathogenicity for gene: TNPO2 was set to Other
Review for gene: TNPO2 was set to GREEN
Added comment: PMID: 34314705 - all de novo missense variants with intellectual disability (9/9), speech impairment (15/15), motor impairment (15/15), ophthalmologic abnormalities (10/15), muscle tone abnormalities (11/15, primarily hypotonia), seizures (6/15, febrile to non-febrile), microcephaly (5/15) and MRI anomalies (7/13, 3/13 had cerebellar hypoplasia/dysplasia). Null fly model was homozygous lethal, no obvious phenotypes in heterozygotes. Upregulated gene expression also resulted in lethality. Overexpression of some human variants in fly models resulted in "toxicity" and phenotypic defects, authors speculate two variants are GOF, 1 variant is LOF. gnomAD: minimal PTCs present
Sources: Literature
Microcephaly v1.35 RRP7A Zornitza Stark Phenotypes for gene: RRP7A were changed from Microcephaly to Microcephaly 28, primary, autosomal recessive MIM#619453
Microcephaly v1.34 RRP7A Zornitza Stark edited their review of gene: RRP7A: Changed phenotypes: Microcephaly 28, primary, autosomal recessive MIM#619453
Microcephaly v1.34 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Microcephaly v1.34 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Microcephaly v1.34 SPATA5 Zornitza Stark Classified gene: SPATA5 as Green List (high evidence)
Microcephaly v1.34 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Microcephaly v1.33 SPATA5 Elena Savva gene: SPATA5 was added
gene: SPATA5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5 were set to PMID: 26299366
Phenotypes for gene: SPATA5 were set to Epilepsy, hearing loss, and mental retardation syndrome MIM#616577
Review for gene: SPATA5 was set to GREEN
Added comment: PMID: 26299366 - 12/14 patients presented with microcephaly, incl 4x with congenital microcephaly and another 4 with acquired microcephaly
Sources: Literature
Microcephaly v1.33 NUF2 Zornitza Stark Marked gene: NUF2 as ready
Microcephaly v1.33 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Microcephaly v1.33 NUF2 Zornitza Stark gene: NUF2 was added
gene: NUF2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NUF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NUF2 were set to 33721060
Phenotypes for gene: NUF2 were set to microcephaly; short stature; bilateral vocal cord paralysis; micrognathia; atrial septal defect
Review for gene: NUF2 was set to RED
Added comment: PMID: 33721060 - de novo missense variant identified in one male patient with microcephaly and short stature, with additional features, such as bilateral vocal cord paralysis, micrognathia and atrial septal defect.
Sources: Literature
Microcephaly v1.32 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Microcephaly v1.31 ATP9A Zornitza Stark Marked gene: ATP9A as ready
Microcephaly v1.31 ATP9A Zornitza Stark Gene: atp9a has been classified as Amber List (Moderate Evidence).
Microcephaly v1.31 ATP9A Zornitza Stark Classified gene: ATP9A as Amber List (moderate evidence)
Microcephaly v1.31 ATP9A Zornitza Stark Gene: atp9a has been classified as Amber List (Moderate Evidence).
Microcephaly v1.30 ATP9A Zornitza Stark gene: ATP9A was added
gene: ATP9A was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ATP9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP9A were set to http://dx.doi.org/10.1136/jmedgenet-2021-107843
Phenotypes for gene: ATP9A were set to Neurodevelopmental delay; Postnatal microcephaly; Failure to thrive; Gastrointestinal symptoms
Review for gene: ATP9A was set to AMBER
Added comment: Vogt et al. 2021 report on 3 individuals from 2 unrelated consanguineous families with different homozygous truncating variants in ATP9A, presenting with DD/ID of variable degree (2 mild, 1 severe), postnatal microcephaly (OFC range: −2.33 SD to −3.58 SD), failure to thrive, and gastrointestinal symptoms. Patient-derived fibroblasts showed reduced expression of ATP9A, and consistent with previous findings also overexpression of interacting partners, ARPC3 and SNX3.
Sources: Literature
Microcephaly v1.29 KMT2E Zornitza Stark Marked gene: KMT2E as ready
Microcephaly v1.29 KMT2E Zornitza Stark Gene: kmt2e has been classified as Green List (High Evidence).
Microcephaly v1.29 KMT2E Zornitza Stark Classified gene: KMT2E as Green List (high evidence)
Microcephaly v1.29 KMT2E Zornitza Stark Gene: kmt2e has been classified as Green List (High Evidence).
Microcephaly v1.28 KMT2E Elena Savva gene: KMT2E was added
gene: KMT2E was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: KMT2E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2E were set to PMID: 31079897; 33111303
Phenotypes for gene: KMT2E were set to O'Donnell-Luria-Rodan syndrome MIM#618512
Mode of pathogenicity for gene: KMT2E was set to Other
Review for gene: KMT2E was set to GREEN
Added comment: PMID: 31079897: microcephaly was reported in 2/3 patients with de novo missense variants

PMID: 33111303: also reports patients with missense variants and microcephaly

Potentially alternative mechanism due to the more severe presentation
Sources: Literature
Microcephaly v1.28 PPP2R1A Zornitza Stark Marked gene: PPP2R1A as ready
Microcephaly v1.28 PPP2R1A Zornitza Stark Gene: ppp2r1a has been classified as Green List (High Evidence).
Microcephaly v1.28 PPP2R1A Zornitza Stark Phenotypes for gene: PPP2R1A were changed from Mental retardation, autosomal dominant 36 MIM#616362 to Mental retardation, autosomal dominant 36, MIM#616362; Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605
Microcephaly v1.27 PPP2R1A Zornitza Stark Classified gene: PPP2R1A as Green List (high evidence)
Microcephaly v1.27 PPP2R1A Zornitza Stark Gene: ppp2r1a has been classified as Green List (High Evidence).
Microcephaly v1.26 PPP2R1A Elena Savva gene: PPP2R1A was added
gene: PPP2R1A was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PPP2R1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP2R1A were set to PMID: 33106617; 26168268
Phenotypes for gene: PPP2R1A were set to Mental retardation, autosomal dominant 36 MIM#616362
Mode of pathogenicity for gene: PPP2R1A was set to Other
Review for gene: PPP2R1A was set to GREEN
gene: PPP2R1A was marked as current diagnostic
Added comment: Likely dominant negative. For some variants, binding assays using HEK293T cells transfected with either WT or mutant constructs demonstrated decreased binding to B subunit families or C subunit with corresponding decrease in PP2A activity by affecting the trimeric holoenzyme (hypothesized by authors) ((PMIDs: 26168268, 33106617).

11/29 patients were macrocephalic, conversely 7/29 patients were microcephalic. All variants were in the same region and all were missense.
Sources: Literature
Microcephaly v1.26 PARP6 Zornitza Stark Publications for gene: PARP6 were set to Cells 2021, 10(6), 1289; https://doi.org/10.3390/cells10061289
Microcephaly v1.25 PARP6 Zornitza Stark edited their review of gene: PARP6: Changed publications: 34067418
Microcephaly v1.25 EIF5A Zornitza Stark Phenotypes for gene: EIF5A were changed from Intellectual disability; microcephaly; dysmorphism to Faundes-Banka syndrome, MIM# 619376; Intellectual disability; microcephaly; dysmorphism
Microcephaly v1.24 EIF5A Zornitza Stark edited their review of gene: EIF5A: Changed phenotypes: Faundes-Banka syndrome, MIM# 619376, Intellectual disability, microcephaly, dysmorphism
Microcephaly v1.24 BCAS3 Sue White Marked gene: BCAS3 as ready
Microcephaly v1.24 BCAS3 Sue White Gene: bcas3 has been classified as Green List (High Evidence).
Microcephaly v1.24 BCAS3 Sue White Classified gene: BCAS3 as Green List (high evidence)
Microcephaly v1.24 BCAS3 Sue White Gene: bcas3 has been classified as Green List (High Evidence).
Microcephaly v1.23 BCAS3 Paul De Fazio gene: BCAS3 was added
gene: BCAS3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: BCAS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCAS3 were set to 34022130
Phenotypes for gene: BCAS3 were set to Syndromic neurodevelopmental disorder
Review for gene: BCAS3 was set to GREEN
gene: BCAS3 was marked as current diagnostic
Added comment: 15 individuals from eight unrelated families with germline bi-allelic loss-of-function variants in BCAS3. All probands share a global developmental delay accompanied by pyramidal tract involvement, microcephaly, short stature, strabismus, dysmorphic facial features, and seizures. Patient fibroblasts confirmed absence of BCAS3 protein.

7 patients had microcephaly (head circumference <= -3 SD)
Sources: Literature
Microcephaly v1.23 ZEB2 Zornitza Stark Phenotypes for gene: ZEB2 were changed from Mowat-Wilson syndrome (MIM#235730) to Mowat-Wilson syndrome, MIM# 235730; MONDO:0009341
Microcephaly v1.22 ZEB2 Zornitza Stark Tag SV/CNV tag was added to gene: ZEB2.
Microcephaly v1.22 UBE3B Zornitza Stark Marked gene: UBE3B as ready
Microcephaly v1.22 UBE3B Zornitza Stark Gene: ube3b has been classified as Green List (High Evidence).
Microcephaly v1.22 UBE3B Zornitza Stark Classified gene: UBE3B as Green List (high evidence)
Microcephaly v1.22 UBE3B Zornitza Stark Gene: ube3b has been classified as Green List (High Evidence).
Microcephaly v1.21 UBE3B Zornitza Stark gene: UBE3B was added
gene: UBE3B was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: UBE3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE3B were set to 23200864; 23200864; 34012380; 32949109
Phenotypes for gene: UBE3B were set to Kaufman oculocerebrofacial syndrome, MIM# 244450; MONDO:0009485
Review for gene: UBE3B was set to GREEN
Added comment: Intellectual disability, microcephaly, dysmorphic features, including blepharophimosis and ptosis. Over 20 families reported.
Sources: Expert Review
Microcephaly v1.20 MCM7 Zornitza Stark Marked gene: MCM7 as ready
Microcephaly v1.20 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.20 MCM7 Zornitza Stark Classified gene: MCM7 as Amber List (moderate evidence)
Microcephaly v1.20 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.19 MCM7 Zornitza Stark gene: MCM7 was added
gene: MCM7 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: MCM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM7 were set to 33654309; 34059554
Phenotypes for gene: MCM7 were set to Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Review for gene: MCM7 was set to AMBER
Added comment: MCM7 is a component of the MCM complex, a DNA helicase which is essential for DNA replication. Other components have been linked to disease with phenotypes including microcephaly and ID. MCM7 is not associated with any phenotype in OMIM or G2P at present. ------ Currently there are 3 unrelated pedigrees in literature with different biallelic MCM7 variants associated with disease (see below). Although there is some functional data in support of variant-level deleteriousness or gene-level pathogenicity, the clinical gestalt is very different between the 3 families.

- PMID: 33654309 (2021) - Two unrelated individuals with different compound het variants in MCM7 but disparate clinical features. One patient had typical Meier-Gorlin syndrome (including growth retardation, microcephaly, congenital lung emphysema, absent breast development, microtia, facial dysmorphism) whereas the second case had a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. While small at birth, the second patient did not demonstrate reduced stature or microcephaly at age 14.5 years. Both individuals had normal neurodevelopment. Functional studies using patient-derived fibroblasts demonstrate that the identified MCM7 variants were deleterious at either transcript or protein levels and through interfering with MCM complex formation, impact efficiency of S phase progression.

- PMID: 34059554 (2021) - Homozygous missense variant identified in three affected individuals from a consanguineous family with severe primary microcephaly, severe ID and behavioural abnormalities. Knockdown of Mcm7 in mouse neuroblastoma cells lead to reduced cell viability and proliferation with increased apoptosis, which were rescued by overexpression of wild-type but not mutant MCM7.
Sources: Literature
Microcephaly v1.18 PARP6 Zornitza Stark Marked gene: PARP6 as ready
Microcephaly v1.18 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Microcephaly v1.18 PARP6 Zornitza Stark Classified gene: PARP6 as Green List (high evidence)
Microcephaly v1.18 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Microcephaly v1.17 PARP6 Zornitza Stark Classified gene: PARP6 as Green List (high evidence)
Microcephaly v1.17 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Microcephaly v1.16 PARP6 Zornitza Stark gene: PARP6 was added
gene: PARP6 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PARP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PARP6 were set to Cells 2021, 10(6), 1289; https://doi.org/10.3390/cells10061289
Phenotypes for gene: PARP6 were set to Intellectual disability; Epilepsy; Microcephaly
Review for gene: PARP6 was set to GREEN
Added comment: Four unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype. Supportive functional data. One pair of siblings with a homozygous missense: limited evidence for bi-allelic variants causing disease.
Sources: Literature
Microcephaly v1.15 SMARCA5 Zornitza Stark Marked gene: SMARCA5 as ready
Microcephaly v1.15 SMARCA5 Zornitza Stark Gene: smarca5 has been classified as Green List (High Evidence).
Microcephaly v1.15 SMARCA5 Zornitza Stark Classified gene: SMARCA5 as Green List (high evidence)
Microcephaly v1.15 SMARCA5 Zornitza Stark Gene: smarca5 has been classified as Green List (High Evidence).
Microcephaly v1.14 SMARCA5 Zornitza Stark gene: SMARCA5 was added
gene: SMARCA5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SMARCA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA5 were set to 33980485
Phenotypes for gene: SMARCA5 were set to Neurodevelopmental disorder; microcephaly; dysmorphic features
Review for gene: SMARCA5 was set to GREEN
Added comment: 12 individuals reported with either de novo or appropriately segregating variants in this gene and mild developmental delay, frequent postnatal short stature and microcephaly, and recurrent dysmorphic features. Functional data supports gene-disease association.
Sources: Literature
Microcephaly v1.13 AFF3 Zornitza Stark Marked gene: AFF3 as ready
Microcephaly v1.13 AFF3 Zornitza Stark Gene: aff3 has been classified as Green List (High Evidence).
Microcephaly v1.13 AFF3 Zornitza Stark Classified gene: AFF3 as Green List (high evidence)
Microcephaly v1.13 AFF3 Zornitza Stark Gene: aff3 has been classified as Green List (High Evidence).
Microcephaly v1.12 AFF3 Zornitza Stark gene: AFF3 was added
gene: AFF3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: AFF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AFF3 were set to 31388108; 33961779
Phenotypes for gene: AFF3 were set to KINSSHIP syndrome, MIM# 619297
Review for gene: AFF3 was set to GREEN
Added comment: 16 affected individuals reported with de novo missense variants. All variants occurred within the degron motif of the ALF domain. The highly conserved 9-amino acid motif mediates the interaction with SIAH E3 ubiquitin ligases and regulates their degradation. Thirteen of the probands carried variants affecting the same codon in exon 6, ala258.

All probands presented with severe developmental epileptic encephalopathy along with mesomelic dysplasia (12/18) and failure to thrive (14/18). The skeletal features included short forearms, radial head dislocation/subluxation, triangular and/or short tibia, fibular hypoplasia, hip dislocation, and tarsal and/or metatarsal synostosis resembling Nievergelt/Savarirayan mesomelic skeletal dysplasia. Other features included microcephaly (9/18), global brain atrophy and/or ventriculomegaly (13/15), fibular hypoplasia (12/16), horseshoe or hypoplastic kidney (13/17), abnormalities of muscle tone (12/16), gastroesophageal reflux disease (6/16), and other gastrointestinal symptoms (14/17). The patients also shared common dysmorphic facial features such as a bulbous nasal tip (10/15), a wide mouth (10/16) often with a square upper lip, abnormalities of the teeth and gums (12/15), and hypertrichosis (12/15). The constellation of features recalled some features of CHOPS syndrome, which is caused by mutations in a related gene, AFF4.
Sources: Literature
Microcephaly v1.11 TMEM222 Zornitza Stark Marked gene: TMEM222 as ready
Microcephaly v1.11 TMEM222 Zornitza Stark Gene: tmem222 has been classified as Green List (High Evidence).
Microcephaly v1.11 TMEM222 Zornitza Stark Classified gene: TMEM222 as Green List (high evidence)
Microcephaly v1.11 TMEM222 Zornitza Stark Gene: tmem222 has been classified as Green List (High Evidence).
Microcephaly v1.10 TMEM222 Zornitza Stark gene: TMEM222 was added
gene: TMEM222 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TMEM222 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM222 were set to 33824500
Phenotypes for gene: TMEM222 were set to Intellectual disability; Epilepsy; Microcephaly
Review for gene: TMEM222 was set to GREEN
Added comment: Polla et al (2021 - PMID: 33824500) report 17 individuals from 9 unrelated families, with biallelic TMEM222 pathogenic variants. The phenotype included motor, speech delay and moderate to severe ID (as universal features). Other manifestations included hypotonia (10/15), broad gait (5/12), seizures (7/17 - belonging to 6/9 families), MRI abnormalities (5/8). Variable behavioral abnormalities were observed (aggressive behavior, shy character, stereotypic movements etc). Abnormal OFC was a feature in several with microcephaly in 7 subjects from 4 families (measurements not available for all 17). Nonspecific facial features were reported in 10/17.
Sources: Literature
Microcephaly v1.9 PPIL1 Zornitza Stark Phenotypes for gene: PPIL1 were changed from Pontocerebellar hypoplasia; microcephaly; seizures to Pontocerebellar hypoplasia, type 14, MIM# 619301; microcephaly; seizures
Microcephaly v1.8 PPIL1 Zornitza Stark edited their review of gene: PPIL1: Changed phenotypes: Pontocerebellar hypoplasia, type 14, MIM# 619301, microcephaly, seizures
Microcephaly v1.8 KCNJ6 Zornitza Stark Publications for gene: KCNJ6 were set to 25620207
Microcephaly v1.7 KCNJ6 Zornitza Stark changed review comment from: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth.

Three unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model.
Sources: Expert Review; to: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth.

Four unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model. One of the individuals did not have lipodystrophy but had a prominent hyperkinetic movement disorder.
Sources: Expert Review
Microcephaly v1.7 KCNJ6 Zornitza Stark edited their review of gene: KCNJ6: Changed publications: 25620207, 29852244
Microcephaly v1.7 KCNJ6 Zornitza Stark Marked gene: KCNJ6 as ready
Microcephaly v1.7 KCNJ6 Zornitza Stark Gene: kcnj6 has been classified as Green List (High Evidence).
Microcephaly v1.7 KCNJ6 Zornitza Stark Classified gene: KCNJ6 as Green List (high evidence)
Microcephaly v1.7 KCNJ6 Zornitza Stark Gene: kcnj6 has been classified as Green List (High Evidence).
Microcephaly v1.6 KCNJ6 Zornitza Stark gene: KCNJ6 was added
gene: KCNJ6 was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: KCNJ6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ6 were set to 25620207
Phenotypes for gene: KCNJ6 were set to Keppen-Lubinsky syndrome, MIM# 614098; MONDO:0013572
Review for gene: KCNJ6 was set to GREEN
Added comment: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth.

Three unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model.
Sources: Expert Review
Microcephaly v1.5 VPS4A Zornitza Stark Phenotypes for gene: VPS4A were changed from Neurodevelopmental disorder to CIMDAG syndrome MIM# 619273
Microcephaly v1.4 VPS4A Zornitza Stark reviewed gene: VPS4A: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: CIMDAG syndrome MIM# 619273; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.4 YIPF5 Zornitza Stark Phenotypes for gene: YIPF5 were changed from Neonatal diabetes; microcephaly; seizures to Microcephaly, epilepsy, and diabetes syndrome 2 , MIM#619278
Microcephaly v1.3 YIPF5 Zornitza Stark edited their review of gene: YIPF5: Changed phenotypes: Microcephaly, epilepsy, and diabetes syndrome 2 , MIM#619278
Microcephaly v1.3 DDX11 Zornitza Stark Phenotypes for gene: DDX11 were changed from Warsaw breakage syndrome, MIM#613398 to Warsaw breakage syndrome, MIM# 613398; MONDO:0013252
Microcephaly v1.2 DDX11 Zornitza Stark Publications for gene: DDX11 were set to 31824187; 20137776; 23033317; 30216658
Microcephaly v1.2 DDX11 Zornitza Stark Publications for gene: DDX11 were set to PMID: 31824187; 20137776; 23033317.
Microcephaly v1.1 DDX11 Zornitza Stark reviewed gene: DDX11: Rating: GREEN; Mode of pathogenicity: None; Publications: 20137776, 23033317, 30216658; Phenotypes: Warsaw breakage syndrome, MIM# 613398, MONDO:0013252; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.1 COPB1 Zornitza Stark Phenotypes for gene: COPB1 were changed from Severe intellectual disability; variable microcephaly; cataracts to Baralle-Macken syndrome, MIM# 619255; Severe intellectual disability; variable microcephaly; cataracts
Microcephaly v1.0 COPB1 Zornitza Stark edited their review of gene: COPB1: Changed phenotypes: Baralle-Macken syndrome, MIM# 619255, Severe intellectual disability, variable microcephaly, cataracts
Microcephaly v1.0 Zornitza Stark promoted panel to version 1.0
Microcephaly v0.639 PRIM1 Zornitza Stark changed review comment from: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature; to: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Microcephaly v0.639 PRIM1 Zornitza Stark Marked gene: PRIM1 as ready
Microcephaly v0.639 PRIM1 Zornitza Stark Gene: prim1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.639 PRIM1 Zornitza Stark Tag deep intronic tag was added to gene: PRIM1.
Tag founder tag was added to gene: PRIM1.
Microcephaly v0.639 PRIM1 Zornitza Stark Classified gene: PRIM1 as Amber List (moderate evidence)
Microcephaly v0.639 PRIM1 Zornitza Stark Gene: prim1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.638 PRIM1 Zornitza Stark gene: PRIM1 was added
gene: PRIM1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIM1 were set to 33060134
Phenotypes for gene: PRIM1 were set to Microcephalic primordial dwarfism, MONDO:0017950
Review for gene: PRIM1 was set to AMBER
Added comment: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Microcephaly v0.637 TTC5 Zornitza Stark Phenotypes for gene: TTC5 were changed from Intellectual disability; microcephaly to Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism , MIM#619244; Intellectual disability; microcephaly
Microcephaly v0.636 TTC5 Zornitza Stark reviewed gene: TTC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism , MIM#619244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.636 NUP37 Zornitza Stark Marked gene: NUP37 as ready
Microcephaly v0.636 NUP37 Zornitza Stark Gene: nup37 has been classified as Red List (Low Evidence).
Microcephaly v0.636 NUP37 Zornitza Stark gene: NUP37 was added
gene: NUP37 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: NUP37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP37 were set to 30179222
Phenotypes for gene: NUP37 were set to Microcephaly 24, primary, autosomal recessive, MIM# 618179
Review for gene: NUP37 was set to RED
Added comment: Single family reported with nephrotic syndrome and microcephaly.
Sources: Expert list
Microcephaly v0.635 C7orf43 Zornitza Stark Marked gene: C7orf43 as ready
Microcephaly v0.635 C7orf43 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name TRAPPC14
Microcephaly v0.635 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.635 C7orf43 Zornitza Stark Deleted their comment
Microcephaly v0.635 C7orf43 Zornitza Stark Tag new gene name tag was added to gene: C7orf43.
Microcephaly v0.635 WDFY3 Zornitza Stark Marked gene: WDFY3 as ready
Microcephaly v0.635 WDFY3 Zornitza Stark Gene: wdfy3 has been classified as Green List (High Evidence).
Microcephaly v0.635 WDFY3 Zornitza Stark Classified gene: WDFY3 as Green List (high evidence)
Microcephaly v0.635 WDFY3 Zornitza Stark Gene: wdfy3 has been classified as Green List (High Evidence).
Microcephaly v0.634 WDFY3 Zornitza Stark gene: WDFY3 was added
gene: WDFY3 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: WDFY3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDFY3 were set to 31327001; 27008544
Phenotypes for gene: WDFY3 were set to Microcephaly 18, primary, autosomal dominant, MIM#617520
Review for gene: WDFY3 was set to GREEN
Added comment: >10 individuals with heterozygous variants in this gene and mild/moderate intellectual disability now described in the literature. Some evidence for opposing effects on brain size depending on variant location.
Sources: Expert list
Microcephaly v0.633 COPB2 Zornitza Stark Marked gene: COPB2 as ready
Microcephaly v0.633 COPB2 Zornitza Stark Gene: copb2 has been classified as Red List (Low Evidence).
Microcephaly v0.633 COPB2 Zornitza Stark edited their review of gene: COPB2: Changed rating: RED; Changed phenotypes: Microcephaly 19, primary, autosomal recessive, MIM# 617800
Microcephaly v0.633 COPB2 Zornitza Stark gene: COPB2 was added
gene: COPB2 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: COPB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPB2 were set to 29036432
Phenotypes for gene: COPB2 were set to Microcephaly 19, primary, autosomal recessive, MIM# 617800
Review for gene: COPB2 was set to GREEN
Added comment: Two sibs with homozygous missense variant in this gene, mice homozygous for this variant had normal brain size however. Mice compound het for null allele and missense variant had some brain features, suggesting the missense variant is hypomorphic.
Sources: Expert list
Microcephaly v0.632 STIL Zornitza Stark Marked gene: STIL as ready
Microcephaly v0.632 STIL Zornitza Stark Gene: stil has been classified as Green List (High Evidence).
Microcephaly v0.632 WDR62 Zornitza Stark Marked gene: WDR62 as ready
Microcephaly v0.632 WDR62 Zornitza Stark Gene: wdr62 has been classified as Green List (High Evidence).
Microcephaly v0.632 WDR62 Zornitza Stark Phenotypes for gene: WDR62 were changed from to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MIM# 604317; MONDO:0011435
Microcephaly v0.631 WDR62 Zornitza Stark Publications for gene: WDR62 were set to
Microcephaly v0.630 WDR62 Zornitza Stark Mode of inheritance for gene: WDR62 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.629 WDR62 Zornitza Stark edited their review of gene: WDR62: Changed phenotypes: Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MIM# 604317, MONDO:0011435
Microcephaly v0.629 WDR62 Zornitza Stark reviewed gene: WDR62: Rating: GREEN; Mode of pathogenicity: None; Publications: 20890279, 20729831, 20890278, 21496009, 21834044, 22775483, 32677750, 31788460; Phenotypes: Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MIM# 604317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.629 TRMT10A Zornitza Stark Marked gene: TRMT10A as ready
Microcephaly v0.629 TRMT10A Zornitza Stark Gene: trmt10a has been classified as Green List (High Evidence).
Microcephaly v0.629 TRMT10A Zornitza Stark Phenotypes for gene: TRMT10A were changed from to Microcephaly, short stature, and impaired glucose metabolism 1, MIM# 616033; MONDO:0000208
Microcephaly v0.628 TRMT10A Zornitza Stark Publications for gene: TRMT10A were set to
Microcephaly v0.627 TRMT10A Zornitza Stark Mode of inheritance for gene: TRMT10A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.626 TRMT10A Zornitza Stark edited their review of gene: TRMT10A: Changed phenotypes: Microcephaly, short stature, and impaired glucose metabolism 1, MIM# 616033, MONDO:0000208
Microcephaly v0.626 TRMT10A Zornitza Stark reviewed gene: TRMT10A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24204302, 25053765, 33448213, 33067246, 26535115, 26526202, 26297882; Phenotypes: Microcephaly, short stature, and impaired glucose metabolism 1, MIM# 616033; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.626 TRAIP Zornitza Stark Marked gene: TRAIP as ready
Microcephaly v0.626 TRAIP Zornitza Stark Gene: traip has been classified as Green List (High Evidence).
Microcephaly v0.626 TRAIP Zornitza Stark Phenotypes for gene: TRAIP were changed from to Seckel syndrome 9, MIM# 616777
Microcephaly v0.625 TRAIP Zornitza Stark Publications for gene: TRAIP were set to
Microcephaly v0.624 TRAIP Zornitza Stark Mode of inheritance for gene: TRAIP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.623 TRAIP Zornitza Stark reviewed gene: TRAIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 26595769; Phenotypes: Seckel syndrome 9, MIM# 616777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.623 TOP3A Zornitza Stark Marked gene: TOP3A as ready
Microcephaly v0.623 TOP3A Zornitza Stark Gene: top3a has been classified as Green List (High Evidence).
Microcephaly v0.623 TOP3A Zornitza Stark Phenotypes for gene: TOP3A were changed from to Microcephaly, growth restriction, and increased sister chromatid exchange 2, MIM# 618097
Microcephaly v0.622 TOP3A Zornitza Stark Publications for gene: TOP3A were set to
Microcephaly v0.621 TOP3A Zornitza Stark Mode of inheritance for gene: TOP3A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.620 TOP3A Zornitza Stark reviewed gene: TOP3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30057030, 33631320; Phenotypes: Microcephaly, growth restriction, and increased sister chromatid exchange 2, MIM# 618097; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.620 STIL Zornitza Stark Phenotypes for gene: STIL were changed from to Microcephaly 7, primary, autosomal recessive, MIM# 612703; MONDO:0012989
Microcephaly v0.619 STIL Zornitza Stark Publications for gene: STIL were set to
Microcephaly v0.618 STIL Zornitza Stark Mode of inheritance for gene: STIL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.617 STIL Zornitza Stark reviewed gene: STIL: Rating: GREEN; Mode of pathogenicity: None; Publications: 19215732, 22989186, 25218063, 33132204, 32677750, 29230157; Phenotypes: Microcephaly 7, primary, autosomal recessive, MIM# 612703, MONDO_0012989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.617 HHAT Zornitza Stark Marked gene: HHAT as ready
Microcephaly v0.617 HHAT Zornitza Stark Gene: hhat has been classified as Amber List (Moderate Evidence).
Microcephaly v0.617 TRAPPC6B Zornitza Stark Marked gene: TRAPPC6B as ready
Microcephaly v0.617 TRAPPC6B Zornitza Stark Gene: trappc6b has been classified as Green List (High Evidence).
Microcephaly v0.617 STAMBP Zornitza Stark Marked gene: STAMBP as ready
Microcephaly v0.617 STAMBP Zornitza Stark Gene: stambp has been classified as Green List (High Evidence).
Microcephaly v0.617 STAMBP Zornitza Stark Phenotypes for gene: STAMBP were changed from to Microcephaly-capillary malformation syndrome, MIM# 614261; MONDO:0013659
Microcephaly v0.616 STAMBP Zornitza Stark Publications for gene: STAMBP were set to
Microcephaly v0.615 STAMBP Zornitza Stark Mode of inheritance for gene: STAMBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.614 STAMBP Zornitza Stark reviewed gene: STAMBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23542699, 31638258, 29907875, 27531570, 25692795, 25266620; Phenotypes: Microcephaly-capillary malformation syndrome, MIM# 614261, MONDO:0013659; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.614 SLC9A6 Zornitza Stark Marked gene: SLC9A6 as ready
Microcephaly v0.614 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Microcephaly v0.614 SLC9A6 Zornitza Stark Phenotypes for gene: SLC9A6 were changed from to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243
Microcephaly v0.613 SLC9A6 Zornitza Stark Mode of inheritance for gene: SLC9A6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v0.612 SLC9A6 Zornitza Stark reviewed gene: SLC9A6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v0.612 SLC25A19 Zornitza Stark Marked gene: SLC25A19 as ready
Microcephaly v0.612 SLC25A19 Zornitza Stark Gene: slc25a19 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.612 SLC25A19 Zornitza Stark Phenotypes for gene: SLC25A19 were changed from to Microcephaly, Amish type, MIM# 607196
Microcephaly v0.611 SLC25A19 Zornitza Stark Publications for gene: SLC25A19 were set to
Microcephaly v0.610 SLC25A19 Zornitza Stark Mode of inheritance for gene: SLC25A19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.609 SLC25A19 Zornitza Stark Classified gene: SLC25A19 as Amber List (moderate evidence)
Microcephaly v0.609 SLC25A19 Zornitza Stark Gene: slc25a19 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.608 SLC25A19 Zornitza Stark Tag founder tag was added to gene: SLC25A19.
Microcephaly v0.608 SLC25A19 Zornitza Stark reviewed gene: SLC25A19: Rating: AMBER; Mode of pathogenicity: None; Publications: 12185364; Phenotypes: Microcephaly, Amish type, MIM# 607196; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.608 RTTN Zornitza Stark Marked gene: RTTN as ready
Microcephaly v0.608 RTTN Zornitza Stark Gene: rttn has been classified as Green List (High Evidence).
Microcephaly v0.608 RTTN Zornitza Stark Phenotypes for gene: RTTN were changed from to Microcephaly, short stature, and polymicrogyria with seizures, MIM# 614833; Microcephalic primordial dwarfism due to RTTN deficiency MONDO:0018764
Microcephaly v0.607 RTTN Zornitza Stark Publications for gene: RTTN were set to
Microcephaly v0.606 RTTN Zornitza Stark Mode of inheritance for gene: RTTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.605 RTTN Zornitza Stark edited their review of gene: RTTN: Changed phenotypes: Microcephaly, short stature, and polymicrogyria with seizures, MIM# 614833, Microcephalic primordial dwarfism due to RTTN deficiency MONDO:0018764
Microcephaly v0.605 RTTN Zornitza Stark reviewed gene: RTTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 22939636, 26608784, 26940245, 30121372, 29967526, 30927481, 30121372; Phenotypes: Microcephaly, short stature, and polymicrogyria with seizures, MIM# 614833; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.605 RBBP8 Zornitza Stark Marked gene: RBBP8 as ready
Microcephaly v0.605 RBBP8 Zornitza Stark Gene: rbbp8 has been classified as Green List (High Evidence).
Microcephaly v0.605 RBBP8 Zornitza Stark Phenotypes for gene: RBBP8 were changed from to Jawad syndrome, MIM# 251255; Seckel syndrome 2, MIM# 606744
Microcephaly v0.604 RBBP8 Zornitza Stark Publications for gene: RBBP8 were set to
Microcephaly v0.603 RBBP8 Zornitza Stark Mode of inheritance for gene: RBBP8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.602 RBBP8 Zornitza Stark changed review comment from: Well established gene-disease association, microcephaly is a feature of both conditions.; to: Microcephaly is a feature of both conditions, which overlap phenotypically.
Microcephaly v0.602 RBBP8 Zornitza Stark edited their review of gene: RBBP8: Changed publications: 26333564, 24440292, 21998596, 24389050
Microcephaly v0.602 RBBP8 Zornitza Stark reviewed gene: RBBP8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Jawad syndrome, MIM# 251255, Seckel syndrome 2, MIM# 606744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.602 PQBP1 Zornitza Stark Marked gene: PQBP1 as ready
Microcephaly v0.602 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Green List (High Evidence).
Microcephaly v0.602 PQBP1 Zornitza Stark Phenotypes for gene: PQBP1 were changed from to Renpenning syndrome, MIM# 309500
Microcephaly v0.601 PQBP1 Zornitza Stark Mode of inheritance for gene: PQBP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v0.600 PQBP1 Zornitza Stark reviewed gene: PQBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Renpenning syndrome, MIM# 309500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v0.600 PNKP Zornitza Stark Phenotypes for gene: PNKP were changed from Microcephaly, seizures, and developmental delay, MIM# 613402 to Microcephaly, seizures, and developmental delay, MIM# 613402; MONDO:0013254
Microcephaly v0.599 PNKP Zornitza Stark Marked gene: PNKP as ready
Microcephaly v0.599 PNKP Zornitza Stark Gene: pnkp has been classified as Green List (High Evidence).
Microcephaly v0.599 PNKP Zornitza Stark Phenotypes for gene: PNKP were changed from to Microcephaly, seizures, and developmental delay, MIM# 613402
Microcephaly v0.598 PNKP Zornitza Stark Publications for gene: PNKP were set to
Microcephaly v0.597 PNKP Zornitza Stark Mode of inheritance for gene: PNKP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.596 PNKP Zornitza Stark reviewed gene: PNKP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20118933, 23224214, 32980744, 31707899; Phenotypes: Microcephaly, seizures, and developmental delay, MIM# 613402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.596 PCNT Zornitza Stark Marked gene: PCNT as ready
Microcephaly v0.596 PCNT Zornitza Stark Gene: pcnt has been classified as Green List (High Evidence).
Microcephaly v0.596 PCNT Zornitza Stark Phenotypes for gene: PCNT were changed from to Microcephalic osteodysplastic primordial dwarfism, type II, MIM# 210720; MONDO:0008872
Microcephaly v0.595 PCNT Zornitza Stark Publications for gene: PCNT were set to
Microcephaly v0.594 PCNT Zornitza Stark Mode of inheritance for gene: PCNT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.593 PCNT Zornitza Stark reviewed gene: PCNT: Rating: GREEN; Mode of pathogenicity: None; Publications: 18174396, 12210304, 30922925, 33460028, 32557621, 32267100; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type II, MIM# 210720, MONDO:0008872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.593 ORC6 Zornitza Stark Marked gene: ORC6 as ready
Microcephaly v0.593 ORC6 Zornitza Stark Gene: orc6 has been classified as Green List (High Evidence).
Microcephaly v0.593 ORC6 Zornitza Stark Phenotypes for gene: ORC6 were changed from to Meier-Gorlin syndrome 3, MIM# 613803
Microcephaly v0.592 ORC6 Zornitza Stark Mode of inheritance for gene: ORC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.591 ORC6 Zornitza Stark reviewed gene: ORC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Meier-Gorlin syndrome 3, MIM# 613803; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.591 ORC4 Zornitza Stark Marked gene: ORC4 as ready
Microcephaly v0.591 ORC4 Zornitza Stark Gene: orc4 has been classified as Green List (High Evidence).
Microcephaly v0.591 ORC4 Zornitza Stark Phenotypes for gene: ORC4 were changed from to Meier-Gorlin syndrome 2, MIM# 613800; MONDO:0013428
Microcephaly v0.590 ORC4 Zornitza Stark Mode of inheritance for gene: ORC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.589 ORC4 Zornitza Stark reviewed gene: ORC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Meier-Gorlin syndrome 2, MIM# 613800, MONDO:0013428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.589 ORC1 Zornitza Stark Marked gene: ORC1 as ready
Microcephaly v0.589 ORC1 Zornitza Stark Gene: orc1 has been classified as Green List (High Evidence).
Microcephaly v0.589 ORC1 Zornitza Stark Phenotypes for gene: ORC1 were changed from to Meier-Gorlin syndrome 1, MIM# 224690; MONDO:0009143
Microcephaly v0.588 ORC1 Zornitza Stark Mode of inheritance for gene: ORC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.587 ORC1 Zornitza Stark reviewed gene: ORC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Meier-Gorlin syndrome 1, MIM# 224690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.587 NHEJ1 Zornitza Stark Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291 to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Cernunnos-XLF deficiency MONDO:0012650
Microcephaly v0.586 NHEJ1 Zornitza Stark edited their review of gene: NHEJ1: Changed phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291, Cernunnos-XLF deficiency MONDO:0012650
Microcephaly v0.586 NHEJ1 Zornitza Stark Marked gene: NHEJ1 as ready
Microcephaly v0.586 NHEJ1 Zornitza Stark Gene: nhej1 has been classified as Green List (High Evidence).
Microcephaly v0.586 NHEJ1 Zornitza Stark Phenotypes for gene: NHEJ1 were changed from to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291
Microcephaly v0.585 NHEJ1 Zornitza Stark Publications for gene: NHEJ1 were set to
Microcephaly v0.584 NHEJ1 Zornitza Stark Mode of inheritance for gene: NHEJ1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.583 NHEJ1 Zornitza Stark reviewed gene: NHEJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30898087, 30666249, 28741180, 25288157, 24511403, 21721379, 21535335; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.583 NDE1 Zornitza Stark Phenotypes for gene: NDE1 were changed from Lissencephaly 4 (with microcephaly), MIM# 614019; Microhydranencephaly, MIM# 605013 to Lissencephaly 4 (with microcephaly), MIM# 614019; MONDO:0013527; Microhydranencephaly, MIM# 605013; MONDO:0011504
Microcephaly v0.582 NDE1 Zornitza Stark Marked gene: NDE1 as ready
Microcephaly v0.582 NDE1 Zornitza Stark Gene: nde1 has been classified as Green List (High Evidence).
Microcephaly v0.582 NDE1 Zornitza Stark Phenotypes for gene: NDE1 were changed from to Lissencephaly 4 (with microcephaly), MIM# 614019; Microhydranencephaly, MIM# 605013
Microcephaly v0.581 NDE1 Zornitza Stark Publications for gene: NDE1 were set to
Microcephaly v0.580 NDE1 Zornitza Stark Mode of inheritance for gene: NDE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.579 NDE1 Zornitza Stark reviewed gene: NDE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21529752, 21529751, 30637988, 15473967; Phenotypes: Lissencephaly 4 (with microcephaly), MIM# 614019, Microhydranencephaly, MIM# 605013; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.579 NBN Zornitza Stark Marked gene: NBN as ready
Microcephaly v0.579 NBN Zornitza Stark Gene: nbn has been classified as Green List (High Evidence).
Microcephaly v0.579 NBN Zornitza Stark Publications for gene: NBN were set to
Microcephaly v0.578 NBN Zornitza Stark Phenotypes for gene: NBN were changed from to Nijmegen breakage syndrome, MIM# 251260; MONDO:0009623
Microcephaly v0.577 NBN Zornitza Stark Mode of inheritance for gene: NBN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.576 NBN Zornitza Stark Deleted their comment
Microcephaly v0.576 NBN Zornitza Stark edited their review of gene: NBN: Added comment: The Nijmegen breakage syndrome and the phenotypically indistinguishable Berlin breakage syndrome are autosomal recessive chromosomal instability syndromes characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer.

>100 patients reported.; Changed publications: 33488600, 33082212
Microcephaly v0.576 NBN Zornitza Stark reviewed gene: NBN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nijmegen breakage syndrome, MIM# 251260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.576 MSMO1 Zornitza Stark Marked gene: MSMO1 as ready
Microcephaly v0.576 MSMO1 Zornitza Stark Gene: msmo1 has been classified as Green List (High Evidence).
Microcephaly v0.576 MSMO1 Zornitza Stark Publications for gene: MSMO1 were set to
Microcephaly v0.575 MSMO1 Zornitza Stark Mode of inheritance for gene: MSMO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.574 MSMO1 Zornitza Stark Phenotypes for gene: MSMO1 were changed from to Microcephaly, congenital cataract, and psoriasiform dermatitis, MIM# 616834; MONDO:0014793
Microcephaly v0.573 MSMO1 Zornitza Stark reviewed gene: MSMO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21285510, 24144731, 28673550, 33161406; Phenotypes: Microcephaly, congenital cataract, and psoriasiform dermatitis, MIM# 616834; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.573 MCPH1 Zornitza Stark Phenotypes for gene: MCPH1 were changed from Microcephaly 1, primary, autosomal recessive, MIM# 251200 to Microcephaly 1, primary, autosomal recessive, MIM# 251200; MONDO:0009617
Microcephaly v0.572 MCPH1 Zornitza Stark Marked gene: MCPH1 as ready
Microcephaly v0.572 MCPH1 Zornitza Stark Gene: mcph1 has been classified as Green List (High Evidence).
Microcephaly v0.572 MCPH1 Zornitza Stark Phenotypes for gene: MCPH1 were changed from to Microcephaly 1, primary, autosomal recessive, MIM# 251200
Microcephaly v0.571 MCPH1 Zornitza Stark Publications for gene: MCPH1 were set to
Microcephaly v0.570 MCPH1 Zornitza Stark Mode of inheritance for gene: MCPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.569 MCPH1 Zornitza Stark reviewed gene: MCPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12046007, 15199523, 16311745, 20978018, 32294449, 30351297, 29026105; Phenotypes: Microcephaly 1, primary, autosomal recessive, MIM# 251200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.569 LIG4 Zornitza Stark Phenotypes for gene: LIG4 were changed from LIG4 syndrome, MIM# 606593 to LIG4 syndrome, MIM# 606593; DNA ligase IV deficiency, MONDO:0011686
Microcephaly v0.568 LIG4 Zornitza Stark Marked gene: LIG4 as ready
Microcephaly v0.568 LIG4 Zornitza Stark Gene: lig4 has been classified as Green List (High Evidence).
Microcephaly v0.568 LIG4 Zornitza Stark Phenotypes for gene: LIG4 were changed from to LIG4 syndrome, MIM# 606593
Microcephaly v0.567 LIG4 Zornitza Stark Publications for gene: LIG4 were set to
Microcephaly v0.566 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.565 LIG4 Zornitza Stark reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11779494, 16088910, 15333585, 16357942, 32534991, 32471509; Phenotypes: LIG4 syndrome, MIM# 606593; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.565 LARP7 Zornitza Stark Marked gene: LARP7 as ready
Microcephaly v0.565 LARP7 Zornitza Stark Gene: larp7 has been classified as Green List (High Evidence).
Microcephaly v0.565 LARP7 Zornitza Stark Phenotypes for gene: LARP7 were changed from to Alazami syndrome, MIM# 615071; Microcephalic primordial dwarfism, Alazami type MONDO:0014031
Microcephaly v0.564 LARP7 Zornitza Stark Publications for gene: LARP7 were set to
Microcephaly v0.563 LARP7 Zornitza Stark Mode of inheritance for gene: LARP7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.563 LARP7 Zornitza Stark Mode of inheritance for gene: LARP7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.562 LARP7 Zornitza Stark reviewed gene: LARP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 22865833, 21937992, 30006060, 33569879; Phenotypes: Alazami syndrome, MIM# 615071, Microcephalic primordial dwarfism, Alazami type MONDO:0014031; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.562 KNL1 Zornitza Stark Marked gene: KNL1 as ready
Microcephaly v0.562 KNL1 Zornitza Stark Gene: knl1 has been classified as Green List (High Evidence).
Microcephaly v0.562 KNL1 Zornitza Stark Phenotypes for gene: KNL1 were changed from to Microcephaly 4, primary, autosomal recessive, MIM# 604321; MONDO:0011437
Microcephaly v0.561 KNL1 Zornitza Stark Publications for gene: KNL1 were set to
Microcephaly v0.560 KNL1 Zornitza Stark Mode of inheritance for gene: KNL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.559 KNL1 Zornitza Stark edited their review of gene: KNL1: Changed phenotypes: Microcephaly 4, primary, autosomal recessive, MIM# 604321, MONDO:0011437
Microcephaly v0.559 KNL1 Zornitza Stark reviewed gene: KNL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22983954, 26626498, 27149178, 30304678, 27784895; Phenotypes: Microcephaly 4, primary, autosomal recessive, MIM# 604321; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.559 KIF11 Zornitza Stark Marked gene: KIF11 as ready
Microcephaly v0.559 KIF11 Zornitza Stark Gene: kif11 has been classified as Green List (High Evidence).
Microcephaly v0.559 KIF11 Zornitza Stark Phenotypes for gene: KIF11 were changed from to Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation, MIM# 152950; MONDO:0007918
Microcephaly v0.558 KIF11 Zornitza Stark Publications for gene: KIF11 were set to
Microcephaly v0.557 KIF11 Zornitza Stark Mode of inheritance for gene: KIF11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.556 KIF11 Zornitza Stark reviewed gene: KIF11: Rating: GREEN; Mode of pathogenicity: None; Publications: 22284827, 25115524, 25124931, 27212378, 32730767, 31993640, 25996076; Phenotypes: Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation, MIM# 152950, MONDO:0007918; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.556 IER3IP1 Zornitza Stark Marked gene: IER3IP1 as ready
Microcephaly v0.556 IER3IP1 Zornitza Stark Gene: ier3ip1 has been classified as Green List (High Evidence).
Microcephaly v0.556 IER3IP1 Zornitza Stark Phenotypes for gene: IER3IP1 were changed from to Microcephaly, epilepsy, and diabetes syndrome, MIM# 614231; Primary microcephaly-epilepsy-permanent neonatal diabetes syndrome, MONDO:0013647
Microcephaly v0.555 IER3IP1 Zornitza Stark Publications for gene: IER3IP1 were set to
Microcephaly v0.554 IER3IP1 Zornitza Stark Mode of inheritance for gene: IER3IP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.553 IER3IP1 Zornitza Stark edited their review of gene: IER3IP1: Changed phenotypes: Microcephaly, epilepsy, and diabetes syndrome, MIM# 614231, Primary microcephaly-epilepsy-permanent neonatal diabetes syndrome, MONDO:0013647
Microcephaly v0.553 IER3IP1 Zornitza Stark reviewed gene: IER3IP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21835305, 22991235, 24138066, 28711742; Phenotypes: Microcephaly, epilepsy, and diabetes syndrome, MIM# 614231; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.553 EFTUD2 Zornitza Stark Marked gene: EFTUD2 as ready
Microcephaly v0.553 EFTUD2 Zornitza Stark Gene: eftud2 has been classified as Green List (High Evidence).
Microcephaly v0.553 EFTUD2 Zornitza Stark Phenotypes for gene: EFTUD2 were changed from Mandibulofacial dysostosis, Guion-Almeida type, MIM# 610536; Mandibulofacial dysostosis-microcephaly syndrome MONDO:0012516 to Mandibulofacial dysostosis, Guion-Almeida type, MIM# 610536; Mandibulofacial dysostosis-microcephaly syndrome MONDO:0012516
Microcephaly v0.552 EFTUD2 Zornitza Stark Phenotypes for gene: EFTUD2 were changed from to Mandibulofacial dysostosis, Guion-Almeida type, MIM# 610536; Mandibulofacial dysostosis-microcephaly syndrome MONDO:0012516
Microcephaly v0.551 EFTUD2 Zornitza Stark Publications for gene: EFTUD2 were set to
Microcephaly v0.550 EFTUD2 Zornitza Stark Mode of inheritance for gene: EFTUD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.549 EFTUD2 Zornitza Stark reviewed gene: EFTUD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22305528, 23188108, 33601405, 33262786, 26507355; Phenotypes: Mandibulofacial dysostosis, Guion-Almeida type, MIM# 610536, Mandibulofacial dysostosis-microcephaly syndrome MONDO:0012516; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.549 CEP152 Zornitza Stark changed review comment from: Bi-allelic variants in this gene have been reported in both primary microcephaly (-5-7 SD) and in Seckel syndrome. Gene encodes centriole protein.; to: Bi-allelic variants in this gene have been reported in both primary microcephaly (-5-7 SD) and in Seckel syndrome, at least 3 of each. Gene encodes centriole protein.
Microcephaly v0.549 CEP152 Zornitza Stark Marked gene: CEP152 as ready
Microcephaly v0.549 CEP152 Zornitza Stark Gene: cep152 has been classified as Green List (High Evidence).
Microcephaly v0.549 CEP152 Zornitza Stark Phenotypes for gene: CEP152 were changed from to Microcephaly 9, primary, autosomal recessive, MIM# 614852; MONDO:0013923; Seckel syndrome 5, MIM# 613823; MONDO:0013443
Microcephaly v0.548 CEP152 Zornitza Stark Publications for gene: CEP152 were set to
Microcephaly v0.547 CEP152 Zornitza Stark Mode of inheritance for gene: CEP152 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.546 CEP152 Zornitza Stark reviewed gene: CEP152: Rating: GREEN; Mode of pathogenicity: None; Publications: 20598275, 22775483, 21131973, 23199753; Phenotypes: Microcephaly 9, primary, autosomal recessive, MIM# 614852, MONDO:0013923, Seckel syndrome 5, MIM# 613823, MONDO:0013443; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.546 CDK5RAP2 Zornitza Stark Marked gene: CDK5RAP2 as ready
Microcephaly v0.546 CDK5RAP2 Zornitza Stark Gene: cdk5rap2 has been classified as Green List (High Evidence).
Microcephaly v0.546 COPB1 Zornitza Stark Marked gene: COPB1 as ready
Microcephaly v0.546 COPB1 Zornitza Stark Gene: copb1 has been classified as Red List (Low Evidence).
Microcephaly v0.546 COPB1 Zornitza Stark gene: COPB1 was added
gene: COPB1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: COPB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPB1 were set to 33632302
Phenotypes for gene: COPB1 were set to Severe intellectual disability; variable microcephaly; cataracts
Review for gene: COPB1 was set to RED
Added comment: Two unrelated families, some supportive functional data. Microcephaly is not a consistent feature in the families reported to date.
Sources: Literature
Microcephaly v0.545 SLC1A4 Zornitza Stark Phenotypes for gene: SLC1A4 were changed from Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657 to Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657; MONDO:0014725
Microcephaly v0.544 CENPJ Zornitza Stark Marked gene: CENPJ as ready
Microcephaly v0.544 CENPJ Zornitza Stark Gene: cenpj has been classified as Green List (High Evidence).
Microcephaly v0.544 CENPJ Zornitza Stark Phenotypes for gene: CENPJ were changed from to Microcephaly 6, primary, autosomal recessive, MIM# 608393, MONDO:0012029; Seckel syndrome 4, MIM# 613676, MONDO:0013358
Microcephaly v0.543 CENPJ Zornitza Stark Publications for gene: CENPJ were set to
Microcephaly v0.542 CENPJ Zornitza Stark Mode of inheritance for gene: CENPJ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.541 CENPJ Zornitza Stark reviewed gene: CENPJ: Rating: GREEN; Mode of pathogenicity: None; Publications: 15793586, 16900296, 2097801822775483, 20522431, 32677750, 32549991, 30626697; Phenotypes: Microcephaly 6, primary, autosomal recessive, MIM# 608393, MONDO:0012029, Seckel syndrome 4, MIM# 613676, MONDO:0013358; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.541 CDT1 Zornitza Stark changed review comment from: Established gene-disease association, microcephaly is part of the phenotype.; to: Established gene-disease association, more than 5 unrelated families reported. Microcephaly is part of the phenotype.
Microcephaly v0.541 CDT1 Zornitza Stark Marked gene: CDT1 as ready
Microcephaly v0.541 CDT1 Zornitza Stark Gene: cdt1 has been classified as Green List (High Evidence).
Microcephaly v0.541 CDT1 Zornitza Stark Publications for gene: CDT1 were set to
Microcephaly v0.540 CDT1 Zornitza Stark Phenotypes for gene: CDT1 were changed from to Meier-Gorlin syndrome 4, MIM# 613804; MONDO:0013431
Microcephaly v0.539 CDT1 Zornitza Stark Mode of inheritance for gene: CDT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.538 CDT1 Zornitza Stark reviewed gene: CDT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21358632, 21358631, 33338304, 22333897; Phenotypes: Meier-Gorlin syndrome 4, MIM# 613804; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.538 DYRK1A Zornitza Stark Publications for gene: DYRK1A were set to 21294719; 23160955; 23099646; 33159716
Microcephaly v0.537 DYRK1A Zornitza Stark edited their review of gene: DYRK1A: Changed publications: 21294719, 23160955, 23099646, 33159716, 25707398
Microcephaly v0.537 DYRK1A Zornitza Stark Marked gene: DYRK1A as ready
Microcephaly v0.537 DYRK1A Zornitza Stark Gene: dyrk1a has been classified as Green List (High Evidence).
Microcephaly v0.537 DYRK1A Zornitza Stark Phenotypes for gene: DYRK1A were changed from to Mental retardation, autosomal dominant 7, MIM# 614104; MONDO:0013578
Microcephaly v0.536 DYRK1A Zornitza Stark Publications for gene: DYRK1A were set to
Microcephaly v0.535 DYRK1A Zornitza Stark Tag SV/CNV tag was added to gene: DYRK1A.
Microcephaly v0.535 DYRK1A Zornitza Stark Mode of inheritance for gene: DYRK1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.534 DYRK1A Zornitza Stark reviewed gene: DYRK1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 21294719, 23160955, 23099646, 33159716; Phenotypes: Mental retardation, autosomal dominant 7, MIM# 614104, MONDO:0013578; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.534 CDK5RAP2 Zornitza Stark Phenotypes for gene: CDK5RAP2 were changed from to Microcephaly 3, primary, autosomal recessive, MIM# 604804; MONDO:0011488
Microcephaly v0.533 CDK5RAP2 Zornitza Stark Publications for gene: CDK5RAP2 were set to
Microcephaly v0.532 CDK5RAP2 Zornitza Stark Mode of inheritance for gene: CDK5RAP2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.532 CDK5RAP2 Zornitza Stark Mode of inheritance for gene: CDK5RAP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.531 CDK5RAP2 Zornitza Stark edited their review of gene: CDK5RAP2: Changed phenotypes: Microcephaly 3, primary, autosomal recessive, MIM# 604804, MONDO:0011488
Microcephaly v0.531 CDK5RAP2 Zornitza Stark reviewed gene: CDK5RAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15793586, 22887808, 23995685, 23726037, 27761245, 20460369, 32677750, 32015000; Phenotypes: Microcephaly 3, primary, autosomal recessive, MIM# 604804; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.531 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230 to Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230; MONDO:0009619
Microcephaly v0.530 DONSON Zornitza Stark Marked gene: DONSON as ready
Microcephaly v0.530 DONSON Zornitza Stark Gene: donson has been classified as Green List (High Evidence).
Microcephaly v0.530 DONSON Zornitza Stark Phenotypes for gene: DONSON were changed from to Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230
Microcephaly v0.529 DONSON Zornitza Stark Publications for gene: DONSON were set to
Microcephaly v0.528 DONSON Zornitza Stark Mode of inheritance for gene: DONSON was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.527 DONSON Zornitza Stark reviewed gene: DONSON: Rating: GREEN; Mode of pathogenicity: None; Publications: 28191891, 28630177, 28191891]; Phenotypes: Microcephaly, short stature, and limb abnormalities, MIM# 617604, Microcephaly-micromelia syndrome, MIM# 251230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.527 ATRX Zornitza Stark Marked gene: ATRX as ready
Microcephaly v0.527 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Microcephaly v0.527 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from to Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580; Alpha-thalassemia/mental retardation syndrome, MIM# 301040
Microcephaly v0.526 ATRX Zornitza Stark Mode of inheritance for gene: ATRX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Microcephaly v0.525 ATRX Zornitza Stark reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580, Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Microcephaly v0.525 EIF5A Zornitza Stark Marked gene: EIF5A as ready
Microcephaly v0.525 EIF5A Zornitza Stark Gene: eif5a has been classified as Green List (High Evidence).
Microcephaly v0.525 EIF5A Zornitza Stark Classified gene: EIF5A as Green List (high evidence)
Microcephaly v0.525 EIF5A Zornitza Stark Gene: eif5a has been classified as Green List (High Evidence).
Microcephaly v0.524 EIF5A Zornitza Stark gene: EIF5A was added
gene: EIF5A was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: EIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF5A were set to 33547280
Phenotypes for gene: EIF5A were set to Intellectual disability; microcephaly; dysmorphism
Review for gene: EIF5A was set to GREEN
Added comment: 7 unrelated individuals reported with de novo variants in this gene and variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism.
Sources: Literature
Microcephaly v0.523 LMNB2 Zornitza Stark Phenotypes for gene: LMNB2 were changed from Congenital microcephaly; Global developmental delay; Intellectual disability to Microcephaly 27, primary, autosomal dominant, MIM# 619180; Congenital microcephaly; Global developmental delay; Intellectual disability
Microcephaly v0.522 LMNB2 Zornitza Stark reviewed gene: LMNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly 27, primary, autosomal dominant, MIM# 619180; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.522 LMNB1 Zornitza Stark Phenotypes for gene: LMNB1 were changed from Global developmental delay; Intellectual disability; Microcephaly; Short stature; Seizures; Abnormality of the corpus callosum; Cortical gyral simplification; Feeding difficulties; Scoliosis to Microcephaly 26, primary, autosomal dominant, MIM# 619179; Global developmental delay; Intellectual disability; Microcephaly; Short stature; Seizures; Abnormality of the corpus callosum; Cortical gyral simplification; Feeding difficulties; Scoliosis
Microcephaly v0.521 LMNB1 Zornitza Stark edited their review of gene: LMNB1: Changed phenotypes: Microcephaly 26, primary, autosomal dominant, MIM# 619179, Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis
Microcephaly v0.521 PRUNE1 Zornitza Stark Publications for gene: PRUNE1 were set to 26539891; 28334956
Microcephaly v0.520 PRUNE1 Zornitza Stark edited their review of gene: PRUNE1: Added comment: Further clinical analysis of previously reported patients and functional analysis of some of the variants in PMID:33105479 - Nistala et al 2020 - detailed phenotypic analysis of a previously reported family (SZ51, Karaca et al 2015) plus detailed literature and clinical review of all 35 NMIHBA patients reported to date. They also characterized 4 variants (p.D30N, p.D106N, p.R128Q and p.G174*) within the conserved N-terminal domain. Wild type or mutant proteins were transfected into HEK293 cells. Cells showed either no protein expression (p.G174*) or loss of PRUNE1 function due to impaired protein stability or loss of enzymatic function (3 missense variants). Prune1−/− mice show midgestational lethality, associated with changes in embryonic growth and vascular development.; Changed publications: 26539891, 28334956, 33105479; Changed phenotypes: Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies , MIM#617481
Microcephaly v0.520 ZNF526 Zornitza Stark Marked gene: ZNF526 as ready
Microcephaly v0.520 ZNF526 Zornitza Stark Gene: znf526 has been classified as Green List (High Evidence).
Microcephaly v0.520 ZNF526 Zornitza Stark Classified gene: ZNF526 as Green List (high evidence)
Microcephaly v0.520 ZNF526 Zornitza Stark Gene: znf526 has been classified as Green List (High Evidence).
Microcephaly v0.519 ZNF526 Zornitza Stark gene: ZNF526 was added
gene: ZNF526 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ZNF526 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF526 were set to 21937992; 25558065; 33397746
Phenotypes for gene: ZNF526 were set to Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia
Review for gene: ZNF526 was set to GREEN
Added comment: - PMID: 21937992 (2011) - Two unrelated families (with 4 affected individuals in each) with non-syndromic ID (mild or moderate, respectively) identified harbouring different biallelic missense variants in the ZNF526 gene.

- PMID: 25558065 (2015) - One family with ID, Noonan-like facies, pulmonary stenosis and a homozygous missense variant in this gene. No further details provided.

- PMID: 33397746 (2021) - Five individuals from four unrelated families with homozygous ZNF526 variants. Four harboured truncating variants, and were all affected by profound DD and severe ID, microcephaly (ranging from -4 SD to -8 SD), bilateral progressive cataracts, hypertonic-dystonic movements, epilepsy and brain MRI anomalies. The fifth patient had a homozygous missense variant and a slightly less severe disorder, with postnatal microcephaly (-2 SD), progressive bilateral cataracts, severe ID, and normal brain MRI. Zebrafish model demonstrated brain and eye malformations resembling findings seen in the human holoprosencephaly spectrum
Sources: Literature
Microcephaly v0.518 FBRSL1 Zornitza Stark Marked gene: FBRSL1 as ready
Microcephaly v0.518 FBRSL1 Zornitza Stark Gene: fbrsl1 has been classified as Green List (High Evidence).
Microcephaly v0.518 CAMK2B Zornitza Stark Marked gene: CAMK2B as ready
Microcephaly v0.518 CAMK2B Zornitza Stark Gene: camk2b has been classified as Green List (High Evidence).
Microcephaly v0.518 CAMK2B Zornitza Stark Phenotypes for gene: CAMK2B were changed from microcephaly; intellectual disability; behavioural problems to Mental retardation, autosomal dominant 54, MIM# 617799; microcephaly; intellectual disability; behavioural problems
Microcephaly v0.517 FBRSL1 Sue White Classified gene: FBRSL1 as Green List (high evidence)
Microcephaly v0.517 FBRSL1 Sue White Gene: fbrsl1 has been classified as Green List (High Evidence).
Microcephaly v0.516 FBRSL1 Elena Savva gene: FBRSL1 was added
gene: FBRSL1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FBRSL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FBRSL1 were set to PMID: 32424618
Phenotypes for gene: FBRSL1 were set to Malformation and intellectual disability syndrome
Review for gene: FBRSL1 was set to GREEN
Added comment: Three children with de novo PTCs that escape NMD, and an overlapping syndromic phenotype with respiratory insufficiency, postnatal growth restriction, microcephaly, global developmental delay and other malformations. 2/3 had heart defects, cleft palate and hearing impairment.
Supported by Xenopus oocyte functional studies
Sources: Literature
Microcephaly v0.516 CAMK2B Sue White Classified gene: CAMK2B as Green List (high evidence)
Microcephaly v0.516 CAMK2B Sue White Gene: camk2b has been classified as Green List (High Evidence).
Microcephaly v0.515 CAMK2B Sue White gene: CAMK2B was added
gene: CAMK2B was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CAMK2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2B were set to 32875707
Phenotypes for gene: CAMK2B were set to microcephaly; intellectual disability; behavioural problems
Review for gene: CAMK2B was set to GREEN
Added comment: 5 individuals in review of literature with same de novo monoallelic variant reported with microcephaly
Sources: Literature
Microcephaly v0.514 YIF1B Zornitza Stark Phenotypes for gene: YIF1B were changed from Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement to Kaya-Barakat-Masson syndrome, MIM# 619125; Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Microcephaly v0.513 YIF1B Zornitza Stark edited their review of gene: YIF1B: Changed phenotypes: Kaya-Barakat-Masson syndrome, MIM# 619125, Central hypotonia, Failure to thrive, Microcephaly, Global developmental delay, Intellectual disability, Seizures, Spasticity, Abnormality of movement
Microcephaly v0.513 SHMT2 Zornitza Stark Phenotypes for gene: SHMT2 were changed from Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly to Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB), MIM#619121; Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Microcephaly v0.512 SHMT2 Zornitza Stark edited their review of gene: SHMT2: Changed phenotypes: Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB), MIM#619121, Congenital microcephaly, Infantile axial hypotonia, Spastic paraparesis, Global developmental delay, Intellectual disability, Abnormality of the corpus callosum, Abnormal cortical gyration, Hypertrophic cardiomyopathy, Abnormality of the face, Proximal placement of thumb, 2-3 toe syndactyly
Microcephaly v0.512 PPIL1 Zornitza Stark Marked gene: PPIL1 as ready
Microcephaly v0.512 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Microcephaly v0.512 PPIL1 Zornitza Stark Classified gene: PPIL1 as Green List (high evidence)
Microcephaly v0.512 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Microcephaly v0.511 PPIL1 Zornitza Stark gene: PPIL1 was added
gene: PPIL1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PPIL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIL1 were set to 33220177
Phenotypes for gene: PPIL1 were set to Pontocerebellar hypoplasia; microcephaly; seizures
Review for gene: PPIL1 was set to GREEN
Added comment: 17 individuals from 9 unrelated families reported with bi-allelic variants in the gene and PCH, microcephaly, hypotonia, seizures, severe DD/ID. Mouse models support gene-disease association.
Sources: Literature
Microcephaly v0.510 MORC2 Zornitza Stark Marked gene: MORC2 as ready
Microcephaly v0.510 MORC2 Zornitza Stark Gene: morc2 has been classified as Green List (High Evidence).
Microcephaly v0.510 MORC2 Zornitza Stark Classified gene: MORC2 as Green List (high evidence)
Microcephaly v0.510 MORC2 Zornitza Stark Gene: morc2 has been classified as Green List (High Evidence).
Microcephaly v0.509 MORC2 Zornitza Stark gene: MORC2 was added
gene: MORC2 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: MORC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MORC2 were set to 32693025
Phenotypes for gene: MORC2 were set to Developmental delay; Intellectual disability; Growth retardation; Microcephaly; Craniofacial dysmorphism; Charcot-Marie-Tooth disease, axonal, type 2Z, OMIM:616688
Review for gene: MORC2 was set to GREEN
Added comment: MORC2 variants have commonly been associated with CMT, presenting axonal neuropathy with progressive weakness, muscle cramps and sensory impairment. However, Sacoto et al (2020) (PMID: 32693025) present a cohort of 20 individuals (19 kindreds) with a neurodevelopmental disorder characterised by DD, ID (18/20 - mild to severe), short stature (18/20), microcephaly (15/20) and variable craniofacial dysmorphisms. Hearing loss was observed in 11/19 subjects, primarily SNHL.
Sources: Expert list
Microcephaly v0.508 VPS4A Elena Savva changed review comment from: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Microcephaly v0.508 VPS4A Elena Savva Added comment: Comment on mode of pathogenicity: Dominant negative
Microcephaly v0.508 VPS4A Elena Savva Mode of pathogenicity for gene: VPS4A was changed from None to Other
Microcephaly v0.508 VPS4A Elena Savva Marked gene: VPS4A as ready
Microcephaly v0.508 VPS4A Elena Savva Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Microcephaly v0.508 VPS4A Elena Savva Gene: vps4a has been classified as Green List (High Evidence).
Microcephaly v0.508 VPS4A Elena Savva Classified gene: VPS4A as Green List (high evidence)
Microcephaly v0.508 VPS4A Elena Savva Gene: vps4a has been classified as Green List (High Evidence).
Microcephaly v0.507 VPS4A Kristin Rigbye gene: VPS4A was added
gene: VPS4A was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to 33186543; 33186545
Phenotypes for gene: VPS4A were set to Neurodevelopmental disorder
Review for gene: VPS4A was set to GREEN
Added comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).
Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).
Demonstrated that the variants had a dominant-negative effect on VPS4A function.

"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Sources: Literature
Microcephaly v0.507 RRP7A Zornitza Stark Marked gene: RRP7A as ready
Microcephaly v0.507 RRP7A Zornitza Stark Gene: rrp7a has been classified as Amber List (Moderate Evidence).
Microcephaly v0.507 RRP7A Zornitza Stark Classified gene: RRP7A as Amber List (moderate evidence)
Microcephaly v0.507 RRP7A Zornitza Stark Gene: rrp7a has been classified as Amber List (Moderate Evidence).
Microcephaly v0.506 RRP7A Zornitza Stark gene: RRP7A was added
gene: RRP7A was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: RRP7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRP7A were set to 33199730
Phenotypes for gene: RRP7A were set to Microcephaly
Review for gene: RRP7A was set to AMBER
Added comment: 10 affected individuals from a single large consanguineous family where bi-allelic variant segregated with severe microcephaly (-6-8SD), variable ID. Supportive functional data from mouse and zebrafish.
Sources: Literature
Microcephaly v0.505 MINPP1 Zornitza Stark Marked gene: MINPP1 as ready
Microcephaly v0.505 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Microcephaly v0.505 MINPP1 Zornitza Stark Classified gene: MINPP1 as Green List (high evidence)
Microcephaly v0.505 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Microcephaly v0.504 MINPP1 Zornitza Stark gene: MINPP1 was added
gene: MINPP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MINPP1 were set to 33257696
Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia
Review for gene: MINPP1 was set to GREEN
Added comment: 8 individuals from 6 unrelated families reported with bi-allelic LOF variants. All presented with almost complete absence of motor and cognitive development, progressive or congenital microcephaly, spastic tetraplegia or dystonia, and vision impairments. For most, the first symptoms included neonatal severe axial hypotonia and epilepsy that started during the first months or years of life. Prenatal symptoms of microcephaly associated with increased thalami echogenicity were detected in one, while the seven other individuals presented with progressive microcephaly. Some exhibited rapidly progressive phenotype and the affected children died in their infancy or middle-childhood. Strikingly, all the affected children had a unique brain MRI showing a mild to severe PCH, fluid-filled posterior fossa, with dilated lateral ventricles. In addition, severe atrophy at the level of the basal ganglia or thalami often associated with typical T2 hypersignal were identified in all the patients MRI.

Supportive functional data showing accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions.
Sources: Literature
Microcephaly v0.503 HHAT Zornitza Stark Classified gene: HHAT as Amber List (moderate evidence)
Microcephaly v0.503 HHAT Zornitza Stark Gene: hhat has been classified as Amber List (Moderate Evidence).
Microcephaly v0.502 HHAT Zornitza Stark gene: HHAT was added
gene: HHAT was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HHAT were set to 24784881; 30912300
Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome 600092
Review for gene: HHAT was set to AMBER
Added comment: Two unrelated families reported. Clinical features include progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Variable features include infantile-onset seizures, dwarfism, generalized chondrodysplasia, and micromelia.
Sources: Expert list
Microcephaly v0.501 YIPF5 Zornitza Stark Marked gene: YIPF5 as ready
Microcephaly v0.501 YIPF5 Zornitza Stark Gene: yipf5 has been classified as Green List (High Evidence).
Microcephaly v0.501 YIPF5 Zornitza Stark Classified gene: YIPF5 as Green List (high evidence)
Microcephaly v0.501 YIPF5 Zornitza Stark Gene: yipf5 has been classified as Green List (High Evidence).
Microcephaly v0.500 YIPF5 Zornitza Stark gene: YIPF5 was added
gene: YIPF5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: YIPF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIPF5 were set to 33164986
Phenotypes for gene: YIPF5 were set to Neonatal diabetes; microcephaly; seizures
Review for gene: YIPF5 was set to GREEN
Added comment: Six individuals from 5 unrelated consanguineous families reported with bi-allelic variants in this gene and neonatal/early-onset diabetes, severe microcephaly, and epilepsy. Functional data supports gene-disease association.
Sources: Literature
Microcephaly v0.499 PIGH Zornitza Stark Classified gene: PIGH as Green List (high evidence)
Microcephaly v0.499 PIGH Zornitza Stark Gene: pigh has been classified as Green List (High Evidence).
Microcephaly v0.498 PIGH Zornitza Stark edited their review of gene: PIGH: Added comment: Three further families reported, including two sibs with microcephaly.; Changed rating: GREEN; Changed publications: 29573052, 33156547, 29603516
Microcephaly v0.498 POLE Zornitza Stark edited their review of gene: POLE: Changed rating: GREEN
Microcephaly v0.498 POLE Zornitza Stark Marked gene: POLE as ready
Microcephaly v0.498 POLE Zornitza Stark Added comment: Comment when marking as ready: The association with microcephaly relates to IMAGE-I syndrome.
Microcephaly v0.498 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Microcephaly v0.498 POLE Zornitza Stark Phenotypes for gene: POLE were changed from FILS syndrome 615139; IMAGE-I syndrome 618336 to IMAGE-I syndrome, MIM# 618336
Microcephaly v0.497 POLE Zornitza Stark Classified gene: POLE as Green List (high evidence)
Microcephaly v0.497 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Microcephaly v0.496 POLE Elena Savva gene: POLE was added
gene: POLE was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: POLE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLE were set to PMID: 30503519
Phenotypes for gene: POLE were set to FILS syndrome 615139; IMAGE-I syndrome 618336
Review for gene: POLE was set to GREEN
Added comment: PMID: 30503519 - microcephaly reported in multiple patients with biallelic LOF variants
Sources: Literature
Microcephaly v0.496 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 MIM#616801 to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Microcephaly v0.495 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.495 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Microcephaly v0.494 UBE3A Zornitza Stark Tag SV/CNV tag was added to gene: UBE3A.
Microcephaly v0.494 UBE3A Zornitza Stark edited their review of gene: UBE3A: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Microcephaly v0.494 ZEB2 Zornitza Stark Marked gene: ZEB2 as ready
Microcephaly v0.494 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Green List (High Evidence).
Microcephaly v0.494 ZEB2 Zornitza Stark Phenotypes for gene: ZEB2 were changed from to Mowat-Wilson syndrome (MIM#235730)
Microcephaly v0.493 ZEB2 Zornitza Stark Publications for gene: ZEB2 were set to
Microcephaly v0.492 ZEB2 Zornitza Stark Mode of inheritance for gene: ZEB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.491 ZEB2 Zornitza Stark reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29300384; Phenotypes: Mowat-Wilson syndrome (MIM#235730); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.491 LMNB2 Zornitza Stark Marked gene: LMNB2 as ready
Microcephaly v0.491 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Microcephaly v0.491 LMNB2 Zornitza Stark Classified gene: LMNB2 as Green List (high evidence)
Microcephaly v0.491 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Microcephaly v0.490 LMNB1 Zornitza Stark Publications for gene: LMNB1 were set to 32910914
Microcephaly v0.489 LMNB2 Konstantinos Varvagiannis gene: LMNB2 was added
gene: LMNB2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: LMNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LMNB2 were set to 33033404
Phenotypes for gene: LMNB2 were set to Congenital microcephaly; Global developmental delay; Intellectual disability
Penetrance for gene: LMNB2 were set to Complete
Mode of pathogenicity for gene: LMNB2 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: LMNB2 was set to GREEN
Added comment: Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6).

LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event.

LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His.

LMNB1/2 common phenotypes :
All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) apart from one individual, without history of IUGR or postnatally abnormal height (the latter in most).

Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2.

LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13).

LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occurred at the age of 6y in 1/6).

Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some).

Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some).

Animal model:
Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different.

Variant effect :
variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments.

Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency.

[Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]
Sources: Literature
Microcephaly v0.489 LMNB1 Konstantinos Varvagiannis reviewed gene: LMNB1: 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: 33033404; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Microcephaly v0.489 TRAPPC9 Zornitza Stark Publications for gene: TRAPPC9 were set to 22549410; 20004765; 20004763; 30853973
Microcephaly v0.488 TRAPPC9 Zornitza Stark Tag SV/CNV tag was added to gene: TRAPPC9.
Microcephaly v0.488 TRAPPC9 Zornitza Stark edited their review of gene: TRAPPC9: Added comment: Note multiple intragenic CNVs reported for this gene.; Changed publications: 22549410, 20004765, 20004763, 30853973, 29187737
Microcephaly v0.488 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Microcephaly v0.488 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Microcephaly v0.488 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Microcephaly v0.488 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Microcephaly v0.487 SHMT2 Zornitza Stark gene: SHMT2 was added
gene: SHMT2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).
Sources: Literature
Microcephaly v0.484 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract; structural brain abnormalities; hypoventilation to Sandestig-Stefanova syndrome, 618804; microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Microcephaly v0.483 NUP188 Zornitza Stark edited their review of gene: NUP188: Changed phenotypes: Sandestig-Stefanova syndrome, 618804, microcephaly, ID, cataract, structural brain abnormalities, hypoventilation
Microcephaly v0.483 LMNB1 Zornitza Stark Marked gene: LMNB1 as ready
Microcephaly v0.483 LMNB1 Zornitza Stark Gene: lmnb1 has been classified as Green List (High Evidence).
Microcephaly v0.483 LMNB1 Zornitza Stark Classified gene: LMNB1 as Green List (high evidence)
Microcephaly v0.483 LMNB1 Zornitza Stark Gene: lmnb1 has been classified as Green List (High Evidence).
Microcephaly v0.482 LMNB1 Zornitza Stark gene: LMNB1 was added
gene: LMNB1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: LMNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMNB1 were set to 32910914
Phenotypes for gene: LMNB1 were set to Global developmental delay; Intellectual disability; Microcephaly; Short stature; Seizures; Abnormality of the corpus callosum; Cortical gyral simplification; Feeding difficulties; Scoliosis
Mode of pathogenicity for gene: LMNB1 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: LMNB1 was set to GREEN
Added comment: Cristofoli et al (2020 - PMID: 32910914) report 7 individuals (from 5 families) harboring mostly de novo LMNB1 variants. The common phenotype consisted of primary microcephaly (7/7 ranging from -4.4 to -10 SD), DD/ID (7/7), relative short stature in most (+0.7 to -4 SD). Additional features included brain MRI abnormalities (abnormal CC in 3, simplified gyral pattern in 3, small structurally normal brain, etc), seizures (4 individuals from 2 families), limb spasticity (1/7), cortical visual impairment (in 3), feeding difficulties (5/7), scoliosis (4/7). Non-overlapping dysmorphic features were reported in some. Variants were identified by WES or custom-designed gene panel and included 3 missense variants, 1 in-frame deletion and a splice variant. The in-frame deletion was inherited from a similarly affected parent in whom the variant occurred as a dn event. The splice SNV(NM_005573.3:c.939+1G>A) occurred in 3 sibs and was present as mosaic variant (15%) in the parent. This variant was predicted to result to extension of exon 5 by 6 amino-acids (samples were unavailable for mRNA studies). LMNB1 encodes a B-type lamin (the other being encoded by LMNB2). A- and B- type lamins are major components of the nuclear lamina. As the authors comment, LMNB1 is expressed in almost all cell types beginning at the earliest stages of development. Lamin-deficient mouse models support an essential role of B-type lamins in organogenesis, neuronal migration, patterning during brain development. Functional studies performed, demonstrated impaired formation of LMNB1 nuclear lamina in LMNB1-null HeLa cells transfected with cDNAs for 3 missense variants. Two variants (Lys33Glu/Arg42Trp) were shown to result in decreased nuclear localization with increased abundance in the cytosolic fraction. In patient derived LCLs these variants led to abnormal nuclear morphology. A missense variant in another domain (Ala152Gly - 1st coil domain) resulted also in lower abundance of lamin B1, irregular lamin A/C nuclear lamina, as well as more condensed nuclei (HeLa cells). LMNB1 duplications or missense mutations increasing LMNB1 expression are associated with a different presentation of AD leuodystrophy. A variant previously associated with leukodystrophy (Arg29Trp) was shown to behave differently (present in the nuclear extract but not in the cytosol, lamin B1 to A/C ratio in nuclear extract was not significantly altered compared to wt as was the case for Arg42Trp, Lys33Glu). Given the pLI score of 0.55 as well as the phenotype of individuals with deletions (not presenting microcephaly) the authors predict that a dominant-negative effect applies (rather than haploinsufficiency).
Sources: Literature
Microcephaly v0.481 SVBP Zornitza Stark Tag founder tag was added to gene: SVBP.
Microcephaly v0.481 SVBP Zornitza Stark changed review comment from: 5 unrelated families with homozygous mutations in SVBP. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls.
Sources: Literature; to: 5 unrelated families with homozygous mutations in SVBP. Some shared the same founder variant, p.Q28*. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls.
Sources: Literature
Microcephaly v0.481 GTPBP2 Zornitza Stark Marked gene: GTPBP2 as ready
Microcephaly v0.481 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Green List (High Evidence).
Microcephaly v0.481 GTPBP2 Zornitza Stark Classified gene: GTPBP2 as Green List (high evidence)
Microcephaly v0.481 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Green List (High Evidence).
Microcephaly v0.480 GTPBP2 Zornitza Stark gene: GTPBP2 was added
gene: GTPBP2 was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: GTPBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP2 were set to 26675814; 29449720; 30790272
Phenotypes for gene: GTPBP2 were set to Jaberi-Elahi syndrome, MIM#617988
Review for gene: GTPBP2 was set to GREEN
Added comment: Nine individuals from six unrelated families with bi-allelic variants in this gene causing a neuro-ectodermal syndrome. Key features include prenatal onset microcephaly, tone abnormalities, and movement disorders, epilepsy, dysmorphic features, retinal dysfunction, ectodermal dysplasia, and brain iron accumulation.
Sources: Expert Review
Microcephaly v0.479 CASK Zornitza Stark Marked gene: CASK as ready
Microcephaly v0.479 CASK Zornitza Stark Gene: cask has been classified as Green List (High Evidence).
Microcephaly v0.479 CASK Zornitza Stark Phenotypes for gene: CASK were changed from to Mental retardation and microcephaly with pontine and cerebellar hypoplasia, MIM# 300749
Microcephaly v0.478 CASK Zornitza Stark Publications for gene: CASK were set to
Microcephaly v0.477 CASK Zornitza Stark Mode of inheritance for gene: CASK was changed from Unknown to Other
Microcephaly v0.476 CASK Zornitza Stark reviewed gene: CASK: Rating: GREEN; Mode of pathogenicity: None; Publications: 21954287, 19165920, 21735175; Phenotypes: Mental retardation and microcephaly with pontine and cerebellar hypoplasia, MIM# 300749; Mode of inheritance: Other
Microcephaly v0.476 ATR Zornitza Stark Marked gene: ATR as ready
Microcephaly v0.476 ATR Zornitza Stark Gene: atr has been classified as Green List (High Evidence).
Microcephaly v0.476 ATR Zornitza Stark Phenotypes for gene: ATR were changed from to Seckel syndrome 1, MIM# 210600
Microcephaly v0.475 ATR Zornitza Stark Publications for gene: ATR were set to
Microcephaly v0.474 ATR Zornitza Stark Mode of inheritance for gene: ATR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.473 ATR Zornitza Stark reviewed gene: ATR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12640452, 19620979, 30199583, 23111928; Phenotypes: Seckel syndrome 1, MIM# 210600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.473 UGP2 Zornitza Stark edited their review of gene: UGP2: Changed rating: GREEN
Microcephaly v0.473 UBE3A Zornitza Stark reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angelman syndrome MIM#105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Microcephaly v0.473 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Microcephaly v0.472 DPM1 Zornitza Stark reviewed gene: DPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ie 608799; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.472 DNMT3A Zornitza Stark edited their review of gene: DNMT3A: Changed rating: GREEN
Microcephaly v0.472 FOXG1 Zornitza Stark Marked gene: FOXG1 as ready
Microcephaly v0.472 FOXG1 Zornitza Stark Gene: foxg1 has been classified as Green List (High Evidence).
Microcephaly v0.472 FOXG1 Zornitza Stark Phenotypes for gene: FOXG1 were changed from to Rett syndrome, congenital variant, MIM# 613454
Microcephaly v0.471 FOXG1 Zornitza Stark Publications for gene: FOXG1 were set to
Microcephaly v0.470 FOXG1 Zornitza Stark Mode of inheritance for gene: FOXG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.469 FOXG1 Zornitza Stark edited their review of gene: FOXG1: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.469 FOXG1 Zornitza Stark reviewed gene: FOXG1: Rating: ; Mode of pathogenicity: None; Publications: 21441262, 19564653, 19578037; Phenotypes: Rett syndrome, congenital variant, MIM# 613454; Mode of inheritance: None
Microcephaly v0.469 FDXR Zornitza Stark Marked gene: FDXR as ready
Microcephaly v0.469 FDXR Zornitza Stark Gene: fdxr has been classified as Red List (Low Evidence).
Microcephaly v0.469 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from to Auditory neuropathy and optic atrophy, MIM# 617717
Microcephaly v0.468 FDXR Zornitza Stark Publications for gene: FDXR were set to
Microcephaly v0.467 FDXR Zornitza Stark Mode of inheritance for gene: FDXR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.466 FDXR Zornitza Stark Classified gene: FDXR as Red List (low evidence)
Microcephaly v0.466 FDXR Zornitza Stark Gene: fdxr has been classified as Red List (Low Evidence).
Microcephaly v0.465 FDXR Zornitza Stark reviewed gene: FDXR: Rating: RED; Mode of pathogenicity: None; Publications: 30250212; Phenotypes: Auditory neuropathy and optic atrophy, MIM# 617717; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.465 EIF2S3 Zornitza Stark Marked gene: EIF2S3 as ready
Microcephaly v0.465 EIF2S3 Zornitza Stark Gene: eif2s3 has been classified as Green List (High Evidence).
Microcephaly v0.465 EIF2S3 Zornitza Stark Phenotypes for gene: EIF2S3 were changed from to MEHMO syndrome, MIM# 300148
Microcephaly v0.464 EIF2S3 Zornitza Stark Publications for gene: EIF2S3 were set to
Microcephaly v0.463 EIF2S3 Zornitza Stark Mode of inheritance for gene: EIF2S3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v0.462 EIF2S3 Zornitza Stark reviewed gene: EIF2S3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23063529, 27333055, 28055140, 32799315; Phenotypes: MEHMO syndrome, MIM# 300148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v0.462 TRIP13 Zornitza Stark Marked gene: TRIP13 as ready
Microcephaly v0.462 TRIP13 Zornitza Stark Gene: trip13 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.462 TRIP13 Zornitza Stark Phenotypes for gene: TRIP13 were changed from to Mosaic variegated aneuploidy syndrome 3, MIM# 617598
Microcephaly v0.461 TRIP13 Zornitza Stark Publications for gene: TRIP13 were set to
Microcephaly v0.460 TRIP13 Zornitza Stark Tag founder tag was added to gene: TRIP13.
Microcephaly v0.460 TRIP13 Zornitza Stark Mode of inheritance for gene: TRIP13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.459 TRIP13 Zornitza Stark Classified gene: TRIP13 as Amber List (moderate evidence)
Microcephaly v0.459 TRIP13 Zornitza Stark Gene: trip13 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.458 TRIP13 Zornitza Stark reviewed gene: TRIP13: Rating: AMBER; Mode of pathogenicity: None; Publications: 28553959; Phenotypes: Mosaic variegated aneuploidy syndrome 3, MIM# 617598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.458 TRAPPC6B Zornitza Stark Phenotypes for gene: TRAPPC6B were changed from to Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, MIM# 617862
Microcephaly v0.457 TRAPPC6B Zornitza Stark Publications for gene: TRAPPC6B were set to
Microcephaly v0.456 TRAPPC6B Zornitza Stark Mode of inheritance for gene: TRAPPC6B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.455 TRAPPC6B Zornitza Stark reviewed gene: TRAPPC6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28626029, 28397838, 31687267; Phenotypes: Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, MIM# 617862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.455 TRAPPC12 Zornitza Stark Marked gene: TRAPPC12 as ready
Microcephaly v0.455 TRAPPC12 Zornitza Stark Gene: trappc12 has been classified as Green List (High Evidence).
Microcephaly v0.455 TRAPPC12 Zornitza Stark Phenotypes for gene: TRAPPC12 were changed from to Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM# 617669
Microcephaly v0.454 TRAPPC12 Zornitza Stark Publications for gene: TRAPPC12 were set to
Microcephaly v0.453 TRAPPC12 Zornitza Stark Mode of inheritance for gene: TRAPPC12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.452 TRAPPC12 Zornitza Stark reviewed gene: TRAPPC12: Rating: GREEN; Mode of pathogenicity: None; Publications: 32369837, 28777934; Phenotypes: Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM# 617669; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.452 TPRKB Zornitza Stark Marked gene: TPRKB as ready
Microcephaly v0.452 TPRKB Zornitza Stark Gene: tprkb has been classified as Green List (High Evidence).
Microcephaly v0.452 TPRKB Zornitza Stark Phenotypes for gene: TPRKB were changed from to Galloway-Mowat syndrome 5, MIM# 617731
Microcephaly v0.451 TPRKB Zornitza Stark Publications for gene: TPRKB were set to
Microcephaly v0.450 TPRKB Zornitza Stark Mode of inheritance for gene: TPRKB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.449 TPRKB Zornitza Stark reviewed gene: TPRKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 30053862; Phenotypes: Galloway-Mowat syndrome 5, MIM# 617731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.449 TP53RK Zornitza Stark Marked gene: TP53RK as ready
Microcephaly v0.449 TP53RK Zornitza Stark Gene: tp53rk has been classified as Green List (High Evidence).
Microcephaly v0.449 TP53RK Zornitza Stark Phenotypes for gene: TP53RK were changed from to Galloway-Mowat syndrome 4, MIM# 617730
Microcephaly v0.448 TP53RK Zornitza Stark Publications for gene: TP53RK were set to
Microcephaly v0.447 TP53RK Zornitza Stark Mode of inheritance for gene: TP53RK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.446 TP53RK Zornitza Stark reviewed gene: TP53RK: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 30053862; Phenotypes: Galloway-Mowat syndrome 4, MIM# 617730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.446 TCF4 Zornitza Stark Marked gene: TCF4 as ready
Microcephaly v0.446 TCF4 Zornitza Stark Gene: tcf4 has been classified as Green List (High Evidence).
Microcephaly v0.446 TCF4 Zornitza Stark Phenotypes for gene: TCF4 were changed from to Pitt-Hopkins syndrome, MIM# 610954
Microcephaly v0.445 TCF4 Zornitza Stark Publications for gene: TCF4 were set to
Microcephaly v0.444 TCF4 Zornitza Stark Mode of inheritance for gene: TCF4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.443 TCF4 Zornitza Stark reviewed gene: TCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 18728071, 22934316; Phenotypes: Pitt-Hopkins syndrome, MIM# 610954; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.443 TBC1D20 Zornitza Stark Marked gene: TBC1D20 as ready
Microcephaly v0.443 TBC1D20 Zornitza Stark Gene: tbc1d20 has been classified as Green List (High Evidence).
Microcephaly v0.443 TBC1D20 Zornitza Stark Phenotypes for gene: TBC1D20 were changed from to Warburg micro syndrome 4, MIM# 615663
Microcephaly v0.442 TBC1D20 Zornitza Stark Publications for gene: TBC1D20 were set to
Microcephaly v0.441 TBC1D20 Zornitza Stark Mode of inheritance for gene: TBC1D20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.440 TBC1D20 Zornitza Stark reviewed gene: TBC1D20: Rating: GREEN; Mode of pathogenicity: None; Publications: 24239381; Phenotypes: Warburg micro syndrome 4, MIM# 615663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.440 CLTC Zornitza Stark Marked gene: CLTC as ready
Microcephaly v0.440 CLTC Zornitza Stark Gene: cltc has been classified as Amber List (Moderate Evidence).
Microcephaly v0.440 CLTC Zornitza Stark Phenotypes for gene: CLTC were changed from to Mental retardation, autosomal dominant 56 (MIM#617854)
Microcephaly v0.439 CLTC Zornitza Stark Publications for gene: CLTC were set to
Microcephaly v0.438 CLTC Zornitza Stark Mode of inheritance for gene: CLTC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.437 CLTC Zornitza Stark Classified gene: CLTC as Amber List (moderate evidence)
Microcephaly v0.437 CLTC Zornitza Stark Gene: cltc has been classified as Amber List (Moderate Evidence).
Microcephaly v0.436 RAB3GAP2 Zornitza Stark Marked gene: RAB3GAP2 as ready
Microcephaly v0.436 RAB3GAP2 Zornitza Stark Gene: rab3gap2 has been classified as Green List (High Evidence).
Microcephaly v0.436 STAG1 Zornitza Stark Marked gene: STAG1 as ready
Microcephaly v0.436 STAG1 Zornitza Stark Gene: stag1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.436 STAG1 Zornitza Stark Phenotypes for gene: STAG1 were changed from to Mental retardation, autosomal dominant 47, MIM# 617635
Microcephaly v0.435 STAG1 Zornitza Stark Publications for gene: STAG1 were set to
Microcephaly v0.434 STAG1 Zornitza Stark Mode of inheritance for gene: STAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.433 STAG1 Zornitza Stark Classified gene: STAG1 as Amber List (moderate evidence)
Microcephaly v0.433 STAG1 Zornitza Stark Gene: stag1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.432 STAG1 Zornitza Stark reviewed gene: STAG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28119487; Phenotypes: Mental retardation, autosomal dominant 47, MIM# 617635; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.432 SMC3 Zornitza Stark Marked gene: SMC3 as ready
Microcephaly v0.432 SMC3 Zornitza Stark Gene: smc3 has been classified as Green List (High Evidence).
Microcephaly v0.432 SMC3 Zornitza Stark Classified gene: SMC3 as Green List (high evidence)
Microcephaly v0.432 SMC3 Zornitza Stark Gene: smc3 has been classified as Green List (High Evidence).
Microcephaly v0.431 SMC3 Zornitza Stark gene: SMC3 was added
gene: SMC3 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: SMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMC3 were set to Cornelia de Lange syndrome 3, MIM# 610759
Review for gene: SMC3 was set to GREEN
Added comment: Well established gene-disease association, microcephaly is part of the phenotype.
Sources: Expert list
Microcephaly v0.430 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Microcephaly v0.430 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Microcephaly v0.430 SMC1A Zornitza Stark Classified gene: SMC1A as Green List (high evidence)
Microcephaly v0.430 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Microcephaly v0.429 SMC1A Zornitza Stark gene: SMC1A was added
gene: SMC1A was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: SMC1A was set to Other
Phenotypes for gene: SMC1A were set to Cornelia de Lange syndrome 2, MIM# 300590
Review for gene: SMC1A was set to GREEN
Added comment: XLD. Well established gene-disease association. Microcephaly is part of the phenotype.
Sources: Expert list
Microcephaly v0.428 SLX4 Zornitza Stark Marked gene: SLX4 as ready
Microcephaly v0.428 SLX4 Zornitza Stark Gene: slx4 has been classified as Green List (High Evidence).
Microcephaly v0.428 SLX4 Zornitza Stark Classified gene: SLX4 as Green List (high evidence)
Microcephaly v0.428 SLX4 Zornitza Stark Gene: slx4 has been classified as Green List (High Evidence).
Microcephaly v0.427 SLX4 Zornitza Stark gene: SLX4 was added
gene: SLX4 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: SLX4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLX4 were set to Fanconi anemia, complementation group P, MIM#613951
Review for gene: SLX4 was set to GREEN
Added comment: Established gene-disease association, microcephaly is part of the phenotype.
Sources: Expert list
Microcephaly v0.426 SLC2A1 Zornitza Stark Marked gene: SLC2A1 as ready
Microcephaly v0.426 SLC2A1 Zornitza Stark Gene: slc2a1 has been classified as Green List (High Evidence).
Microcephaly v0.426 SLC2A1 Zornitza Stark Phenotypes for gene: SLC2A1 were changed from to GLUT1 deficiency syndrome 1, infantile onset, severe, MIM# 606777
Microcephaly v0.425 SLC2A1 Zornitza Stark Mode of inheritance for gene: SLC2A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Microcephaly v0.424 SLC2A1 Zornitza Stark reviewed gene: SLC2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GLUT1 deficiency syndrome 1, infantile onset, severe, MIM# 606777; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Microcephaly v0.424 SLC1A4 Zornitza Stark Marked gene: SLC1A4 as ready
Microcephaly v0.424 SLC1A4 Zornitza Stark Gene: slc1a4 has been classified as Green List (High Evidence).
Microcephaly v0.424 SLC1A4 Zornitza Stark Phenotypes for gene: SLC1A4 were changed from to Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657
Microcephaly v0.423 SLC1A4 Zornitza Stark Publications for gene: SLC1A4 were set to
Microcephaly v0.422 SLC1A4 Zornitza Stark Tag founder tag was added to gene: SLC1A4.
Microcephaly v0.422 SLC1A4 Zornitza Stark Mode of inheritance for gene: SLC1A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.421 SLC1A4 Zornitza Stark reviewed gene: SLC1A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25930971, 26138499, 26041762, 27193218, 29989513; Phenotypes: Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.421 RUSC2 Zornitza Stark reviewed gene: RUSC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27612186; Phenotypes: Mental retardation, autosomal recessive 61, MIM# 617773; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.421 RPL10 Zornitza Stark Marked gene: RPL10 as ready
Microcephaly v0.421 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Microcephaly v0.421 RPL10 Zornitza Stark Classified gene: RPL10 as Green List (high evidence)
Microcephaly v0.421 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Microcephaly v0.420 RPL10 Zornitza Stark gene: RPL10 was added
gene: RPL10 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: RPL10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RPL10 were set to 25316788; 25846674; 26290468
Phenotypes for gene: RPL10 were set to Mental retardation, X-linked, syndromic, 35, MIM# 300998
Review for gene: RPL10 was set to GREEN
Added comment: At least three families reported. Progressive microcephaly, up to -9.6 SD described.
Sources: Expert list
Microcephaly v0.419 RNU4ATAC Zornitza Stark Marked gene: RNU4ATAC as ready
Microcephaly v0.419 RNU4ATAC Zornitza Stark Gene: rnu4atac has been classified as Green List (High Evidence).
Microcephaly v0.419 RNU4ATAC Zornitza Stark Classified gene: RNU4ATAC as Green List (high evidence)
Microcephaly v0.419 RNU4ATAC Zornitza Stark Gene: rnu4atac has been classified as Green List (High Evidence).
Microcephaly v0.418 RNU4ATAC Zornitza Stark gene: RNU4ATAC was added
gene: RNU4ATAC was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: RNU4ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU4ATAC were set to 21474760; 20301772
Phenotypes for gene: RNU4ATAC were set to Microcephalic osteodysplastic primordial dwarfism, type I, MIM# 210710
Review for gene: RNU4ATAC was set to GREEN
Added comment: Established gene-disease association
Sources: Expert list
Microcephaly v0.417 RARS2 Zornitza Stark Marked gene: RARS2 as ready
Microcephaly v0.417 RARS2 Zornitza Stark Gene: rars2 has been classified as Green List (High Evidence).
Microcephaly v0.417 RARS2 Zornitza Stark Phenotypes for gene: RARS2 were changed from to Pontocerebellar hypoplasia, type 6, MIM# 611523
Microcephaly v0.416 RARS2 Zornitza Stark Publications for gene: RARS2 were set to
Microcephaly v0.415 RARS2 Zornitza Stark Mode of inheritance for gene: RARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.414 RARS2 Zornitza Stark reviewed gene: RARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17847012, 20635367, 25809939; Phenotypes: Pontocerebellar hypoplasia, type 6, MIM# 611523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.414 RAD21 Zornitza Stark Marked gene: RAD21 as ready
Microcephaly v0.414 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Microcephaly v0.414 RAD21 Zornitza Stark Classified gene: RAD21 as Green List (high evidence)
Microcephaly v0.414 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Microcephaly v0.413 RAD21 Zornitza Stark gene: RAD21 was added
gene: RAD21 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: RAD21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAD21 were set to 22633399; 32193685
Phenotypes for gene: RAD21 were set to Cornelia de Lange syndrome 4, MIM# 614701
Review for gene: RAD21 was set to GREEN
Added comment: Microcephaly reported in around 50% of affected individuals in a recent large series.
Sources: Expert list
Microcephaly v0.412 RAB3GAP2 Zornitza Stark Phenotypes for gene: RAB3GAP2 were changed from to Warburg micro syndrome 2, MIM# 614225
Microcephaly v0.411 RAB3GAP2 Zornitza Stark Publications for gene: RAB3GAP2 were set to
Microcephaly v0.410 RAB3GAP2 Zornitza Stark Mode of inheritance for gene: RAB3GAP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.409 RAB3GAP2 Zornitza Stark reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23420520, 20967465; Phenotypes: Warburg micro syndrome 2, MIM# 614225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.409 RAB3GAP1 Zornitza Stark Marked gene: RAB3GAP1 as ready
Microcephaly v0.409 RAB3GAP1 Zornitza Stark Gene: rab3gap1 has been classified as Green List (High Evidence).
Microcephaly v0.409 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from to Warburg micro syndrome 1, MIM# 600118
Microcephaly v0.408 RAB3GAP1 Zornitza Stark Publications for gene: RAB3GAP1 were set to
Microcephaly v0.407 RAB3GAP1 Zornitza Stark Mode of inheritance for gene: RAB3GAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.406 RAB3GAP1 Zornitza Stark reviewed gene: RAB3GAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15696165, 20512159, 23420520; Phenotypes: Warburg micro syndrome 1, MIM# 600118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.406 RAB18 Zornitza Stark Marked gene: RAB18 as ready
Microcephaly v0.406 RAB18 Zornitza Stark Gene: rab18 has been classified as Green List (High Evidence).
Microcephaly v0.406 RAB18 Zornitza Stark Phenotypes for gene: RAB18 were changed from to Warburg micro syndrome 3, MIM# 614222
Microcephaly v0.405 RAB18 Zornitza Stark Tag founder tag was added to gene: RAB18.
Microcephaly v0.405 RAB18 Zornitza Stark Publications for gene: RAB18 were set to
Microcephaly v0.404 RAB18 Zornitza Stark Mode of inheritance for gene: RAB18 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.403 RAB18 Zornitza Stark reviewed gene: RAB18: Rating: GREEN; Mode of pathogenicity: None; Publications: 11237903, 23420520; Phenotypes: Warburg micro syndrome 3, MIM# 614222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.403 PUS7 Zornitza Stark edited their review of gene: PUS7: Changed rating: GREEN
Microcephaly v0.403 PUF60 Zornitza Stark Marked gene: PUF60 as ready
Microcephaly v0.403 PUF60 Zornitza Stark Gene: puf60 has been classified as Green List (High Evidence).
Microcephaly v0.403 PUF60 Zornitza Stark Phenotypes for gene: PUF60 were changed from to Verheij syndrome, MIM# 615583
Microcephaly v0.402 PUF60 Zornitza Stark Publications for gene: PUF60 were set to
Microcephaly v0.401 PUF60 Zornitza Stark Mode of inheritance for gene: PUF60 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.400 PUF60 Zornitza Stark reviewed gene: PUF60: Rating: GREEN; Mode of pathogenicity: None; Publications: 28327570; Phenotypes: Verheij syndrome, MIM# 615583; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.400 PTPN23 Zornitza Stark Marked gene: PTPN23 as ready
Microcephaly v0.400 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Green List (High Evidence).
Microcephaly v0.400 PTPN23 Zornitza Stark Phenotypes for gene: PTPN23 were changed from to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890
Microcephaly v0.399 PTPN23 Zornitza Stark Publications for gene: PTPN23 were set to
Microcephaly v0.398 PTPN23 Zornitza Stark Mode of inheritance for gene: PTPN23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.397 PTPN23 Zornitza Stark reviewed gene: PTPN23: Rating: GREEN; Mode of pathogenicity: None; Publications: 31395947, 29899372, 29090338, 27848944, 25558065; Phenotypes: Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.397 PRUNE1 Zornitza Stark Marked gene: PRUNE1 as ready
Microcephaly v0.397 PRUNE1 Zornitza Stark Gene: prune1 has been classified as Green List (High Evidence).
Microcephaly v0.397 PRUNE1 Zornitza Stark Classified gene: PRUNE1 as Green List (high evidence)
Microcephaly v0.397 PRUNE1 Zornitza Stark Gene: prune1 has been classified as Green List (High Evidence).
Microcephaly v0.396 PRUNE1 Zornitza Stark gene: PRUNE1 was added
gene: PRUNE1 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: PRUNE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRUNE1 were set to 26539891; 28334956
Phenotypes for gene: PRUNE1 were set to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies , MIM#617481
Review for gene: PRUNE1 was set to GREEN
Added comment: 8 unrelated families reported with an autosomal recessive neurodevelopmental, and neurodegenerative disorder characterised by global developmental delay apparent from infancy and profound intellectual disability. Affected individuals have microcephaly with accompanying dysmorphic features, truncal hypotonia, peripheral spasticity, and lack of independent ambulation or speech acquisition. Brain imaging shows variable abnormalities, including cortical atrophy, thin corpus callosum, cerebellar hypoplasia, and delayed myelination
Sources: Expert list
Microcephaly v0.395 PPP1R15B Zornitza Stark Marked gene: PPP1R15B as ready
Microcephaly v0.395 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Microcephaly v0.395 PPP1R15B Zornitza Stark Phenotypes for gene: PPP1R15B were changed from to Microcephaly, short stature, and impaired glucose metabolism 2, MIM# 616817
Microcephaly v0.394 PPP1R15B Zornitza Stark Publications for gene: PPP1R15B were set to
Microcephaly v0.393 PPP1R15B Zornitza Stark Mode of inheritance for gene: PPP1R15B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.392 PPP1R15B Zornitza Stark Classified gene: PPP1R15B as Amber List (moderate evidence)
Microcephaly v0.392 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Microcephaly v0.391 PPP1R15B Zornitza Stark reviewed gene: PPP1R15B: Rating: AMBER; Mode of pathogenicity: None; Publications: 26159176, 26307080, 27640355; Phenotypes: Microcephaly, short stature, and impaired glucose metabolism 2, MIM# 616817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.391 POMT1 Zornitza Stark Marked gene: POMT1 as ready
Microcephaly v0.391 POMT1 Zornitza Stark Gene: pomt1 has been classified as Green List (High Evidence).
Microcephaly v0.391 POMT1 Zornitza Stark Phenotypes for gene: POMT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, MIM# 236670
Microcephaly v0.390 POMT1 Zornitza Stark Mode of inheritance for gene: POMT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.389 POMT1 Zornitza Stark reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, MIM# 236670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.389 POGZ Zornitza Stark Marked gene: POGZ as ready
Microcephaly v0.389 POGZ Zornitza Stark Gene: pogz has been classified as Green List (High Evidence).
Microcephaly v0.389 POGZ Zornitza Stark Phenotypes for gene: POGZ were changed from to White-Sutton syndrome, MIM# 616364
Microcephaly v0.388 POGZ Zornitza Stark Publications for gene: POGZ were set to
Microcephaly v0.387 POGZ Zornitza Stark Mode of inheritance for gene: POGZ was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.386 POGZ Zornitza Stark reviewed gene: POGZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 26942287; Phenotypes: White-Sutton syndrome, MIM# 616364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.386 POC1A Zornitza Stark Marked gene: POC1A as ready
Microcephaly v0.386 POC1A Zornitza Stark Gene: poc1a has been classified as Green List (High Evidence).
Microcephaly v0.386 POC1A Zornitza Stark Phenotypes for gene: POC1A were changed from to Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM# 614813
Microcephaly v0.385 POC1A Zornitza Stark Classified gene: POC1A as Green List (high evidence)
Microcephaly v0.385 POC1A Zornitza Stark Gene: poc1a has been classified as Green List (High Evidence).
Microcephaly v0.384 POC1A Zornitza Stark edited their review of gene: POC1A: Changed rating: GREEN
Microcephaly v0.384 POC1A Zornitza Stark edited their review of gene: POC1A: Changed phenotypes: Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM# 614813
Microcephaly v0.384 POC1A Zornitza Stark gene: POC1A was added
gene: POC1A was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: POC1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POC1A were set to 22840364; 22840363; 26374189; 26162852; 26791357
Added comment: SOFT syndrome is characterized by severely short long bones, peculiar facies associated with paucity of hair, and nail anomalies. Growth retardation is evident on prenatal ultrasound as early as the second trimester of pregnancy, and affected individuals reach a final stature consistent with a height age of 6 years to 8 years. Relative macrocephaly is present during early childhood but head circumference is markedly low by adulthood. Over 5 unrelated families reported.
Sources: Expert list
Microcephaly v0.383 PLK4 Zornitza Stark Marked gene: PLK4 as ready
Microcephaly v0.383 PLK4 Zornitza Stark Gene: plk4 has been classified as Green List (High Evidence).
Microcephaly v0.383 PLK4 Zornitza Stark Classified gene: PLK4 as Green List (high evidence)
Microcephaly v0.383 PLK4 Zornitza Stark Gene: plk4 has been classified as Green List (High Evidence).
Microcephaly v0.382 PLK4 Zornitza Stark gene: PLK4 was added
gene: PLK4 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: PLK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLK4 were set to 25344692; 25320347; 27650967
Phenotypes for gene: PLK4 were set to Microcephaly and chorioretinopathy, autosomal recessive, 2, MIM# 616171
Review for gene: PLK4 was set to GREEN
Added comment: At least 3 unrelated families reported with autosomal recessive developmental disorder characterised by delayed psychomotor development, visual impairment, and microcephaly.
Sources: Expert list
Microcephaly v0.381 PIGH Zornitza Stark Marked gene: PIGH as ready
Microcephaly v0.381 PIGH Zornitza Stark Gene: pigh has been classified as Amber List (Moderate Evidence).
Microcephaly v0.381 PIGH Zornitza Stark Phenotypes for gene: PIGH were changed from to Glycosylphosphatidylinositol biosynthesis defect 17, MIM# 618010
Microcephaly v0.380 PIGH Zornitza Stark Publications for gene: PIGH were set to
Microcephaly v0.379 PIGH Zornitza Stark Mode of inheritance for gene: PIGH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.378 PIGH Zornitza Stark Classified gene: PIGH as Amber List (moderate evidence)
Microcephaly v0.378 PIGH Zornitza Stark Gene: pigh has been classified as Amber List (Moderate Evidence).
Microcephaly v0.377 PIGH Zornitza Stark reviewed gene: PIGH: Rating: AMBER; Mode of pathogenicity: None; Publications: 29573052; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 17, MIM# 618010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.377 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
Microcephaly v0.377 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Microcephaly v0.377 PDHA1 Zornitza Stark Classified gene: PDHA1 as Green List (high evidence)
Microcephaly v0.377 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Microcephaly v0.376 PDHA1 Zornitza Stark gene: PDHA1 was added
gene: PDHA1 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: PDHA1 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: PDHA1 were set to 8032855
Phenotypes for gene: PDHA1 were set to Pyruvate dehydrogenase E1-alpha deficiency, MIM# 312170
Review for gene: PDHA1 was set to GREEN
Added comment: Well established gene-disease association. Variable phenotype, but microcephaly is a feature.
Sources: Expert list
Microcephaly v0.375 PCYT2 Zornitza Stark Marked gene: PCYT2 as ready
Microcephaly v0.375 PCYT2 Zornitza Stark Gene: pcyt2 has been classified as Red List (Low Evidence).
Microcephaly v0.375 PCYT2 Zornitza Stark Phenotypes for gene: PCYT2 were changed from to Spastic paraplegia 82, autosomal recessive 618770
Microcephaly v0.374 PCYT2 Zornitza Stark Publications for gene: PCYT2 were set to
Microcephaly v0.373 PCYT2 Zornitza Stark Mode of inheritance for gene: PCYT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.372 PCYT2 Zornitza Stark Classified gene: PCYT2 as Red List (low evidence)
Microcephaly v0.372 PCYT2 Zornitza Stark Gene: pcyt2 has been classified as Red List (Low Evidence).
Microcephaly v0.371 PCYT2 Zornitza Stark reviewed gene: PCYT2: Rating: RED; Mode of pathogenicity: None; Publications: 31637422; Phenotypes: Spastic paraplegia 82, autosomal recessive 618770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.371 TOGARAM1 Zornitza Stark Marked gene: TOGARAM1 as ready
Microcephaly v0.371 TOGARAM1 Zornitza Stark Gene: togaram1 has been classified as Red List (Low Evidence).
Microcephaly v0.371 TOGARAM1 Zornitza Stark gene: TOGARAM1 was added
gene: TOGARAM1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TOGARAM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOGARAM1 were set to 32747439
Phenotypes for gene: TOGARAM1 were set to Cleft of the lip and palate; Microphthalmia; Cerebral dysgenesis; Hydrocephalus
Review for gene: TOGARAM1 was set to RED
Added comment: PMID: 32747439 (2020) - Novel gene-disease association. In two sibling fetuses with a malformation disorder characterised by microcephaly, severe cleft lip and palate, microphthalmia, and brain anomalies, WES revealed compound heterozygous variants ([c.1102C>T, p.Arg368Trp] and [c.3619C>T, p.Arg1207*]) in the TOGARAM1 gene. Functional analysis of the missense variant in a C. elegans model showed impaired lipophilic dye uptake, with shorter and altered cilia in sensory neurons. In vitro analysis revealed faster microtubule polymerisation compared to wild-type, suggesting aberrant tubulin binding.
Sources: Literature
Microcephaly v0.370 DPP6 Zornitza Stark changed review comment from: Comment when marking as ready: Single LP variant in ClinVar but reported phenotype is schizophrenia. Original study dates to 2013.; to: Comment when marking as ready: Single LP variant in ClinVar but reported phenotype is schizophrenia. Original study dates to 2013. Association studies with dementia, and suggested role in tardive dyskinesia.
Microcephaly v0.370 DPP6 Zornitza Stark Marked gene: DPP6 as ready
Microcephaly v0.370 DPP6 Zornitza Stark Added comment: Comment when marking as ready: Single LP variant in ClinVar but reported phenotype is schizophrenia. Original study dates to 2013.
Microcephaly v0.370 DPP6 Zornitza Stark Gene: dpp6 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.370 DPP6 Zornitza Stark Marked gene: DPP6 as ready
Microcephaly v0.370 DPP6 Zornitza Stark Gene: dpp6 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.370 DPP6 Zornitza Stark Classified gene: DPP6 as Amber List (moderate evidence)
Microcephaly v0.370 DPP6 Zornitza Stark Gene: dpp6 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.369 DPP6 Zornitza Stark Tag SV/CNV tag was added to gene: DPP6.
Microcephaly v0.369 DPP6 Ain Roesley gene: DPP6 was added
gene: DPP6 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DPP6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DPP6 were set to 23832105
Phenotypes for gene: DPP6 were set to Mental retardation, autosomal dominant 33 (MIM#616311)
Penetrance for gene: DPP6 were set to unknown
Review for gene: DPP6 was set to AMBER
Added comment: PMID: 23832105
- 1x proband (OFC < -3 SD) with a missense which segregated in 3 other family members
- 2x probands with 336kb deletion. Both OFCs < -3 SD
- mouse KO model with significantly smaller brain weight

*unable to find new reports since
Sources: Literature
Microcephaly v0.369 CTU2 Zornitza Stark Marked gene: CTU2 as ready
Microcephaly v0.369 CTU2 Zornitza Stark Gene: ctu2 has been classified as Green List (High Evidence).
Microcephaly v0.369 CTU2 Zornitza Stark Phenotypes for gene: CTU2 were changed from to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome (MIM#618142)
Microcephaly v0.368 CTU2 Zornitza Stark Publications for gene: CTU2 were set to
Microcephaly v0.367 CTU2 Zornitza Stark Mode of inheritance for gene: CTU2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.366 CTU2 Ain Roesley reviewed gene: CTU2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26633546; Phenotypes: Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome (MIM#618142); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.366 PCGF2 Zornitza Stark Marked gene: PCGF2 as ready
Microcephaly v0.366 PCGF2 Zornitza Stark Gene: pcgf2 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.366 PCGF2 Zornitza Stark Phenotypes for gene: PCGF2 were changed from to Turnpenny-Fry syndrome, MIM# 618371
Microcephaly v0.365 PCGF2 Zornitza Stark Publications for gene: PCGF2 were set to
Microcephaly v0.364 PCGF2 Zornitza Stark Mode of inheritance for gene: PCGF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.363 PCGF2 Zornitza Stark Classified gene: PCGF2 as Amber List (moderate evidence)
Microcephaly v0.363 PCGF2 Zornitza Stark Gene: pcgf2 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.362 PCGF2 Zornitza Stark changed review comment from: developmental delay, impaired intellectual development, impaired growth, and recognizable facial features that include frontal bossing, sparse hair, malar hypoplasia, small palpebral fissures and oral stoma, and dysplastic 'satyr' ears. Other common findings include feeding problems, constipation, and a range of brain, cardiac, vascular, and skeletal malformations. Head size is variable, with some patients showing relative macrocephaly and others showing microcephaly. Over 10 affected individuals reported to date, all variants affect residue p.Pro65; to: Key features include developmental delay, impaired intellectual development, impaired growth, and recognizable facial features (frontal bossing, sparse hair, malar hypoplasia, small palpebral fissures and oral stoma, and dysplastic 'satyr' ears). Other common findings include feeding problems, constipation, and a range of brain, cardiac, vascular, and skeletal malformations. Head size is variable, with some patients showing relative macrocephaly and others showing microcephaly. Over 10 affected individuals reported to date, all variants affect residue p.Pro65
Microcephaly v0.362 PCGF2 Zornitza Stark edited their review of gene: PCGF2: Changed rating: AMBER
Microcephaly v0.362 PCGF2 Zornitza Stark reviewed gene: PCGF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30343942; Phenotypes: Turnpenny-Fry syndrome, MIM# 618371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.362 CTNNB1 Zornitza Stark Marked gene: CTNNB1 as ready
Microcephaly v0.362 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Microcephaly v0.362 CTNNB1 Zornitza Stark Classified gene: CTNNB1 as Green List (high evidence)
Microcephaly v0.362 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Microcephaly v0.361 CTNNB1 Ain Roesley gene: CTNNB1 was added
gene: CTNNB1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CTNNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTNNB1 were set to 25326669; 32039639
Phenotypes for gene: CTNNB1 were set to Neurodevelopmental disorder with spastic diplegia and visual defects (MIM#615075); Exudative vitreoretinopathy 7 (MIM#617572)
Penetrance for gene: CTNNB1 were set to unknown
Review for gene: CTNNB1 was set to GREEN
Added comment: PMID: 32039639;
-1x proband with familial exudative vitreoretinopathy (FEVR) and microcephaly. Head circumference <1st centile

PMID: 25326669
- 15 families with 16 affecteds. de novo PTVs
- included 5 patients from published literature
- 10 out of 20 presented with microcephaly, head circumference < -3 SD
Sources: Literature
Microcephaly v0.361 PCDH12 Zornitza Stark Phenotypes for gene: PCDH12 were changed from DIENCEPHALIC-MESENCEPHALIC JUNCTION DYSPLASIA SYNDROME 1 to Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280
Microcephaly v0.360 PCDH12 Zornitza Stark Publications for gene: PCDH12 were set to 27164683; 22822038
Microcephaly v0.359 PCDH12 Zornitza Stark reviewed gene: PCDH12: Rating: GREEN; Mode of pathogenicity: None; Publications: 27164683, 30178464; Phenotypes: Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.359 TRIT1 Zornitza Stark Marked gene: TRIT1 as ready
Microcephaly v0.359 TRIT1 Zornitza Stark Gene: trit1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.359 TRIT1 Zornitza Stark Phenotypes for gene: TRIT1 were changed from to Combined oxidative phosphorylation deficiency 35 MIM#617873
Microcephaly v0.358 TRIT1 Zornitza Stark Publications for gene: TRIT1 were set to
Microcephaly v0.357 TRIT1 Zornitza Stark Mode of inheritance for gene: TRIT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.356 TRIT1 Zornitza Stark Classified gene: TRIT1 as Amber List (moderate evidence)
Microcephaly v0.356 TRIT1 Zornitza Stark Gene: trit1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.355 TRIT1 Paul De Fazio reviewed gene: TRIT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32088416, 24901367, 28185376, 30977854; Phenotypes: Combined oxidative phosphorylation deficiency 35 MIM#617873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v0.355 CTCF Zornitza Stark Marked gene: CTCF as ready
Microcephaly v0.355 CTCF Zornitza Stark Gene: ctcf has been classified as Green List (High Evidence).
Microcephaly v0.355 CTCF Zornitza Stark Phenotypes for gene: CTCF were changed from to Mental retardation, autosomal dominant 21 (MIM#615502)
Microcephaly v0.354 CTCF Zornitza Stark Publications for gene: CTCF were set to
Microcephaly v0.353 CTCF Zornitza Stark Mode of inheritance for gene: CTCF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.352 TBCD Zornitza Stark Marked gene: TBCD as ready
Microcephaly v0.352 TBCD Zornitza Stark Gene: tbcd has been classified as Green List (High Evidence).
Microcephaly v0.352 TBCD Zornitza Stark Phenotypes for gene: TBCD were changed from to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, MIM#617193
Microcephaly v0.351 TBCD Zornitza Stark Publications for gene: TBCD were set to
Microcephaly v0.350 TBCD Zornitza Stark Mode of inheritance for gene: TBCD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.349 TBCD Zornitza Stark changed review comment from: 15 children from 9 unrelated families with bi-allelic variants in this gene and a progressive neurodegenerative encephalopathy.
Sources: Expert Review; to: 15 children from 9 unrelated families with bi-allelic variants in this gene and a progressive neurodegenerative encephalopathy including progressive microcephaly.
Sources: Expert Review
Microcephaly v0.349 TSEN15 Zornitza Stark Marked gene: TSEN15 as ready
Microcephaly v0.349 TSEN15 Zornitza Stark Gene: tsen15 has been classified as Green List (High Evidence).
Microcephaly v0.349 TSEN15 Zornitza Stark Classified gene: TSEN15 as Green List (high evidence)
Microcephaly v0.349 TSEN15 Zornitza Stark Gene: tsen15 has been classified as Green List (High Evidence).
Microcephaly v0.348 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Microcephaly v0.347 TSEN2 Zornitza Stark Marked gene: TSEN2 as ready
Microcephaly v0.347 TSEN2 Zornitza Stark Gene: tsen2 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.347 TSEN2 Zornitza Stark Phenotypes for gene: TSEN2 were changed from to Pontocerebellar hypoplasia type 2B (MIM#612389)
Microcephaly v0.346 TSEN2 Zornitza Stark Publications for gene: TSEN2 were set to
Microcephaly v0.345 TSEN2 Zornitza Stark Mode of inheritance for gene: TSEN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.344 TSEN15 Paul De Fazio gene: TSEN15 was added
gene: TSEN15 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TSEN15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN15 were set to 27392077
Phenotypes for gene: TSEN15 were set to Pontocerebellar hypoplasia, type 2F MIM#617026
Review for gene: TSEN15 was set to GREEN
gene: TSEN15 was marked as current diagnostic
Added comment: PMID 27392077 Reports four individuals from three families with PCH type 2 and different homozygous missense variants, all had progressive microcephaly (between -3SD and -9.7SD). Functional studies indicated that all variants resulted in almost complete lack of in vitro tRNA cleavage activity.
Sources: Literature
Microcephaly v0.344 TSEN2 Zornitza Stark Classified gene: TSEN2 as Amber List (moderate evidence)
Microcephaly v0.344 TSEN2 Zornitza Stark Gene: tsen2 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.343 TSEN54 Zornitza Stark Marked gene: TSEN54 as ready
Microcephaly v0.343 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Green List (High Evidence).
Microcephaly v0.343 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from to Pontocerebellar hypoplasia type 2A (MIM#277470) and type 4 (MIM#225753)
Microcephaly v0.342 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to
Microcephaly v0.341 TSEN54 Zornitza Stark Mode of inheritance for gene: TSEN54 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.340 TUBB2B Zornitza Stark Marked gene: TUBB2B as ready
Microcephaly v0.340 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Green List (High Evidence).
Microcephaly v0.340 TUBB2B Zornitza Stark Phenotypes for gene: TUBB2B were changed from to Cortical dysplasia, complex, with other brain malformations 7 MIM#610031
Microcephaly v0.339 TUBB2B Zornitza Stark Publications for gene: TUBB2B were set to
Microcephaly v0.338 TUBB2B Zornitza Stark Mode of inheritance for gene: TUBB2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.337 COASY Zornitza Stark Marked gene: COASY as ready
Microcephaly v0.337 COASY Zornitza Stark Gene: coasy has been classified as Green List (High Evidence).
Microcephaly v0.337 COASY Zornitza Stark Classified gene: COASY as Green List (high evidence)
Microcephaly v0.337 COASY Zornitza Stark Gene: coasy has been classified as Green List (High Evidence).
Microcephaly v0.336 VPS51 Zornitza Stark Marked gene: VPS51 as ready
Microcephaly v0.336 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.336 VPS51 Zornitza Stark Classified gene: VPS51 as Amber List (moderate evidence)
Microcephaly v0.336 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.335 TSEN2 Paul De Fazio reviewed gene: TSEN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23562994, 20952379, 27392077; Phenotypes: Pontocerebellar hypoplasia type 2B (MIM#612389); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v0.335 CRIPT Zornitza Stark Marked gene: CRIPT as ready
Microcephaly v0.335 CRIPT Zornitza Stark Gene: cript has been classified as Amber List (Moderate Evidence).
Microcephaly v0.335 CRIPT Zornitza Stark Classified gene: CRIPT as Amber List (moderate evidence)
Microcephaly v0.335 CRIPT Zornitza Stark Gene: cript has been classified as Amber List (Moderate Evidence).
Microcephaly v0.334 CREBBP Zornitza Stark Marked gene: CREBBP as ready
Microcephaly v0.334 CREBBP Zornitza Stark Gene: crebbp has been classified as Green List (High Evidence).
Microcephaly v0.334 CREBBP Zornitza Stark Classified gene: CREBBP as Green List (high evidence)
Microcephaly v0.334 CREBBP Zornitza Stark Gene: crebbp has been classified as Green List (High Evidence).
Microcephaly v0.333 ERCC5 Zornitza Stark Publications for gene: ERCC5 were set to 32052936
Microcephaly v0.332 ERCC5 Zornitza Stark Publications for gene: ERCC5 were set to 32052936; 32052936
Microcephaly v0.331 ERCC5 Zornitza Stark Marked gene: ERCC5 as ready
Microcephaly v0.331 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.331 ERCC5 Zornitza Stark Classified gene: ERCC5 as Amber List (moderate evidence)
Microcephaly v0.331 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.330 TTC5 Zornitza Stark Marked gene: TTC5 as ready
Microcephaly v0.330 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Microcephaly v0.330 TTC5 Zornitza Stark Classified gene: TTC5 as Green List (high evidence)
Microcephaly v0.330 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Microcephaly v0.329 CKAP2L Zornitza Stark Marked gene: CKAP2L as ready
Microcephaly v0.329 CKAP2L Zornitza Stark Gene: ckap2l has been classified as Green List (High Evidence).
Microcephaly v0.329 CKAP2L Zornitza Stark Classified gene: CKAP2L as Green List (high evidence)
Microcephaly v0.329 CKAP2L Zornitza Stark Gene: ckap2l has been classified as Green List (High Evidence).
Microcephaly v0.328 TSEN54 Paul De Fazio reviewed gene: TSEN54: Rating: GREEN; Mode of pathogenicity: None; Publications: 20952379, 20301773; Phenotypes: Pontocerebellar hypoplasia type 2A (MIM#277470) and type 4 (MIM#225753); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v0.328 TTC5 Paul De Fazio gene: TTC5 was added
gene: TTC5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC5 were set to 29302074; 32439809
Phenotypes for gene: TTC5 were set to Intellectual disability; microcephaly
Review for gene: TTC5 was set to GREEN
gene: TTC5 was marked as current diagnostic
Added comment: PMID 29302074: 3 affected individuals from 2 consaguinous families described. All had head circumference < -3SD

PMID 32439809: Report another 8 affected individuals from 5 families but only 3 individuals from 2 families were microcephalic (OFCs 31cm (unsure age), 32cm (12yo), 31cm (5yo)).
Sources: Literature
Microcephaly v0.328 CTCF Ain Roesley reviewed gene: CTCF: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746550, 30893510, 28619046; Phenotypes: Mental retardation, autosomal dominant 21 (MIM#615502); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Microcephaly v0.328 CRIPT Ain Roesley gene: CRIPT was added
gene: CRIPT was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CRIPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRIPT were set to 24389050; 27250922
Phenotypes for gene: CRIPT were set to Short stature with microcephaly and distinctive facies (MIM#615789)
Penetrance for gene: CRIPT were set to unknown
Review for gene: CRIPT was set to AMBER
Added comment: PMID: 24389050
- 2 unrelated probands homozygous for PTVs. However 1 was deceased and DNA was unavailable therefore parents were sequenced
- OFCs -2.5 and -2.7SD

PMID: 27250922
- 1x proband with a head circumference of Z= -2.7.
- het for a missense which was maternally inherited. Because the father was negative for SNVs, they did CMA and found a small heterozygous deletion 1.6kb in size encompassing exon 1 of CRIPT. This deletion was paternally inherited

*did not find new reports since
Sources: Literature
Microcephaly v0.328 CREBBP Ain Roesley gene: CREBBP was added
gene: CREBBP was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CREBBP were set to 27311832; 29460469; 24989455
Phenotypes for gene: CREBBP were set to Menke-Hennekam syndrome 1(MIM#618332); Rubinstein-Taybi syndrome 1(MIM#180849)
Penetrance for gene: CREBBP were set to unknown
Review for gene: CREBBP was set to GREEN
Added comment: Microcephaly is a feature of both syndromes (OMIM, GeneReviews)

Variants causing Menke-Hennekam syndrome occur in 3' end of exon 30 and 5' end of exon 31 and are de novo missense versus Rubinstein-Taybi which are LoF variants.


PMID: 27311832
7 out of 11 Menke-Hennekam probands with microcephaly (<3rd centile)

PMID: 29460469
13 new Menke-Hennekam probands with 3 having OFCs of <-3 SD

PMID: 24989455 provides growth charts of 92 molecularly diagnosed Rubinstein-Taybi patients. Mean of -1.89 SD for males and -2.71 SD for females
Sources: Literature
Microcephaly v0.328 COASY Seb Lunke gene: COASY was added
gene: COASY was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 30089828; 28489334
Phenotypes for gene: COASY were set to Pontocerebellar hypoplasia, type 12, MIM#618266
Review for gene: COASY was set to GREEN
Added comment: 6 patients from 3 families published with microcephaly. One paper (2018, 30089828) describes two families, one consanguineous with hom splice region variant c.1486-3 C>G, the other family with a compound heterozygous c.[1549_1550delAG]; [1486-3 C>G] genotype. An earlier paper (2017, 28489334) describes an additional family with two affected siblings compound het c.1495C > T; p.(R499C) and c.C641T; p(A214V) variants.
Sources: Literature
Microcephaly v0.327 CLTC Ain Roesley reviewed gene: CLTC: Rating: AMBER; Mode of pathogenicity: None; Publications: 31776469; Phenotypes: Mental retardation, autosomal dominant 56 (MIM#617854); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Microcephaly v0.327 ERCC5 Paul De Fazio gene: ERCC5 was added
gene: ERCC5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ERCC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC5 were set to 32052936; 32052936
Phenotypes for gene: ERCC5 were set to Cerebrooculofacioskeletal syndrome 3 MIM#616570
Review for gene: ERCC5 was set to AMBER
gene: ERCC5 was marked as current diagnostic
Added comment: PMID 9096355 identified a homozygous LoF variant in a boy with microcephaly but this publication was later retracted over data in Figure 6.

PMID 24700531 describes 4 fetuses from a large consanguineous Pakistani kindred with a homozygous LoF variant. All were said to be microcephalic with no measurements given.

PMID 32052936 describes another 3 microcephalic fetuses from 2 families with homozygous LoF variants, again no measurements given.

3 families described in total but head circumference measurements of affected fetuses not provided so rated Amber.
Sources: Literature
Microcephaly v0.327 ERCC8 Seb Lunke Marked gene: ERCC8 as ready
Microcephaly v0.327 ERCC8 Seb Lunke Gene: ercc8 has been classified as Green List (High Evidence).
Microcephaly v0.327 ERCC8 Seb Lunke Classified gene: ERCC8 as Green List (high evidence)
Microcephaly v0.327 ERCC8 Seb Lunke Gene: ercc8 has been classified as Green List (High Evidence).
Microcephaly v0.326 DIAPH1 Seb Lunke Marked gene: DIAPH1 as ready
Microcephaly v0.326 DIAPH1 Seb Lunke Gene: diaph1 has been classified as Green List (High Evidence).
Microcephaly v0.326 DIAPH1 Seb Lunke Classified gene: DIAPH1 as Green List (high evidence)
Microcephaly v0.326 DIAPH1 Seb Lunke Gene: diaph1 has been classified as Green List (High Evidence).
Microcephaly v0.325 ERCC8 Belinda Chong gene: ERCC8 was added
gene: ERCC8 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ERCC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC8 were set to 14661080; 21108394
Phenotypes for gene: ERCC8 were set to Cockayne syndrome, type A, MIM# 216400
Review for gene: ERCC8 was set to GREEN
gene: ERCC8 was marked as current diagnostic
Added comment: Well established gene-disease association, with microcephaly a reported feature.
(https://www.ncbi.nlm.nih.gov/books/NBK1342/)
Sources: Literature
Microcephaly v0.325 DIAPH1 Dean Phelan gene: DIAPH1 was added
gene: DIAPH1 was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: DIAPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DIAPH1 were set to PMID: 24781755; 26463574
Phenotypes for gene: DIAPH1 were set to Seizures, cortical blindness, microcephaly syndrome 616632
Review for gene: DIAPH1 was set to GREEN
Added comment: PMID: 24781755 (2015) - five individuals from a consanguineous family with severe microcephaly >2SD below the mean for age with homozygous nonsense variant in DIAPH1

PMID: 26463574 (2016) - two different homozygous LOF variants identified in two unrelated consanguineous families. The affected individuals were diagnosed with postnatal microcephaly (>2SD), early-onset epilepsy, severe vision impairment, and pulmonary symptoms including bronchiectasis and recurrent respiratory infections.
Sources: Expert Review
Microcephaly v0.325 ERCC6 Seb Lunke Marked gene: ERCC6 as ready
Microcephaly v0.325 ERCC6 Seb Lunke Gene: ercc6 has been classified as Green List (High Evidence).
Microcephaly v0.325 ERCC6 Seb Lunke Classified gene: ERCC6 as Green List (high evidence)
Microcephaly v0.325 ERCC6 Seb Lunke Gene: ercc6 has been classified as Green List (High Evidence).
Microcephaly v0.324 ERCC4 Seb Lunke Marked gene: ERCC4 as ready
Microcephaly v0.324 ERCC4 Seb Lunke Gene: ercc4 has been classified as Green List (High Evidence).
Microcephaly v0.324 ERCC6 Naomi Baker gene: ERCC6 was added
gene: ERCC6 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ERCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC6 were set to PMID: 20301516
Phenotypes for gene: ERCC6 were set to Cockayne syndrome, type B, MIM#133540; Cerebrooculofacioskeletal syndrome 1, MIM#214150; De Sanctis-Cacchione syndrome, MIM#278800
Penetrance for gene: ERCC6 were set to Complete
Review for gene: ERCC6 was set to GREEN
Added comment: Well established gene-disease association, with microcephaly a reported feature.
Sources: Literature
Microcephaly v0.324 CKAP2L Zornitza Stark Classified gene: CKAP2L as Green List (high evidence)
Microcephaly v0.324 CKAP2L Zornitza Stark Gene: ckap2l has been classified as Green List (High Evidence).
Microcephaly v0.324 FANCF Zornitza Stark Marked gene: FANCF as ready
Microcephaly v0.324 FANCF Zornitza Stark Gene: fancf has been classified as Green List (High Evidence).
Microcephaly v0.324 ERCC4 Seb Lunke Classified gene: ERCC4 as Green List (high evidence)
Microcephaly v0.324 ERCC4 Seb Lunke Gene: ercc4 has been classified as Green List (High Evidence).
Microcephaly v0.323 BRIP1 Zornitza Stark Marked gene: BRIP1 as ready
Microcephaly v0.323 BRIP1 Zornitza Stark Gene: brip1 has been classified as Green List (High Evidence).
Microcephaly v0.323 FANCD2 Seb Lunke Marked gene: FANCD2 as ready
Microcephaly v0.323 FANCD2 Seb Lunke Gene: fancd2 has been classified as Green List (High Evidence).
Microcephaly v0.323 FANCD2 Seb Lunke Classified gene: FANCD2 as Green List (high evidence)
Microcephaly v0.323 FANCD2 Seb Lunke Gene: fancd2 has been classified as Green List (High Evidence).
Microcephaly v0.323 BRIP1 Zornitza Stark Publications for gene: BRIP1 were set to
Microcephaly v0.322 BRIP1 Zornitza Stark Classified gene: BRIP1 as Green List (high evidence)
Microcephaly v0.322 BRIP1 Zornitza Stark Gene: brip1 has been classified as Green List (High Evidence).
Microcephaly v0.321 FANCD2 Dean Phelan gene: FANCD2 was added
gene: FANCD2 was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: FANCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCD2 were set to PMID:20301575
Phenotypes for gene: FANCD2 were set to Fanconi anemia 227646
Review for gene: FANCD2 was set to GREEN
Added comment: Well established gene-disease association, microcephaly is a key feature.
Sources: Expert Review
Microcephaly v0.321 FANCG Seb Lunke Marked gene: FANCG as ready
Microcephaly v0.321 FANCG Seb Lunke Gene: fancg has been classified as Green List (High Evidence).
Microcephaly v0.321 FANCG Seb Lunke Classified gene: FANCG as Green List (high evidence)
Microcephaly v0.321 FANCG Seb Lunke Gene: fancg has been classified as Green List (High Evidence).
Microcephaly v0.320 FANCF Zornitza Stark Classified gene: FANCF as Green List (high evidence)
Microcephaly v0.320 FANCF Zornitza Stark Gene: fancf has been classified as Green List (High Evidence).
Microcephaly v0.319 ERCC4 Ain Roesley gene: ERCC4 was added
gene: ERCC4 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ERCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC4 were set to Fanconi anemia, complementation group Q (MIM#615272); Cockayne syndrome (MIM#278760)
Penetrance for gene: ERCC4 were set to unknown
Review for gene: ERCC4 was set to GREEN
Added comment: Microcephaly is a well established feature in Cockayne syndrome
Sources: Literature
Microcephaly v0.319 FANCE Seb Lunke Marked gene: FANCE as ready
Microcephaly v0.319 FANCE Seb Lunke Gene: fance has been classified as Green List (High Evidence).
Microcephaly v0.319 FANCE Seb Lunke Classified gene: FANCE as Green List (high evidence)
Microcephaly v0.319 FANCE Seb Lunke Gene: fance has been classified as Green List (High Evidence).
Microcephaly v0.318 FANCI Zornitza Stark Marked gene: FANCI as ready
Microcephaly v0.318 FANCI Zornitza Stark Gene: fanci has been classified as Green List (High Evidence).
Microcephaly v0.318 FANCI Zornitza Stark Classified gene: FANCI as Green List (high evidence)
Microcephaly v0.318 FANCI Zornitza Stark Gene: fanci has been classified as Green List (High Evidence).
Microcephaly v0.317 FANCF Belinda Chong gene: FANCF was added
gene: FANCF was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FANCF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCF were set to 20301575
Phenotypes for gene: FANCF were set to Fanconi anemia, complementation group F, MIM# 603467
Review for gene: FANCF was set to GREEN
Added comment: Well established gene disease association
Sources: https://www.ncbi.nlm.nih.gov/books/NBK1401/
Sources: Literature
Microcephaly v0.317 FANCG Paul De Fazio gene: FANCG was added
gene: FANCG was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FANCG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCG were set to 20301575
Phenotypes for gene: FANCG were set to Fanconi anemia, complementation group G MIM#614082
Review for gene: FANCG was set to GREEN
gene: FANCG was marked as current diagnostic
Added comment: Well-established gene-disease association, microcephaly is a feature.
Sources: Literature
Microcephaly v0.317 FANCL Zornitza Stark Marked gene: FANCL as ready
Microcephaly v0.317 FANCL Zornitza Stark Gene: fancl has been classified as Green List (High Evidence).
Microcephaly v0.317 FANCL Zornitza Stark Classified gene: FANCL as Green List (high evidence)
Microcephaly v0.317 FANCL Zornitza Stark Gene: fancl has been classified as Green List (High Evidence).
Microcephaly v0.316 FANCL Zornitza Stark gene: FANCL was added
gene: FANCL was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: FANCL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCL were set to 20301575
Phenotypes for gene: FANCL were set to Fanconi anemia, complementation group L, MIM# 614083
Review for gene: FANCL was set to GREEN
Added comment: Well established gene-disease association, microcephaly is a key feature.
Sources: Expert list
Microcephaly v0.316 FANCC Seb Lunke Marked gene: FANCC as ready
Microcephaly v0.316 FANCC Seb Lunke Gene: fancc has been classified as Green List (High Evidence).
Microcephaly v0.316 FANCC Seb Lunke Classified gene: FANCC as Green List (high evidence)
Microcephaly v0.316 FANCC Seb Lunke Gene: fancc has been classified as Green List (High Evidence).
Microcephaly v0.315 FANCI Ain Roesley gene: FANCI was added
gene: FANCI was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FANCI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCI were set to 20301575
Phenotypes for gene: FANCI were set to Fanconi anemia, complementation group I (MIM#609053)
Penetrance for gene: FANCI were set to unknown
Review for gene: FANCI was set to GREEN
Added comment: 75% of Fanconi Anemia (FA) patients have microcephaly and approx 1% cases is caused by FANCI
Sources: Literature
Microcephaly v0.315 FANCA Seb Lunke Marked gene: FANCA as ready
Microcephaly v0.315 FANCA Seb Lunke Gene: fanca has been classified as Green List (High Evidence).
Microcephaly v0.315 FANCA Seb Lunke Classified gene: FANCA as Green List (high evidence)
Microcephaly v0.315 FANCA Seb Lunke Gene: fanca has been classified as Green List (High Evidence).
Microcephaly v0.314 FANCE Naomi Baker gene: FANCE was added
gene: FANCE was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FANCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCE were set to PMID: 20301575
Phenotypes for gene: FANCE were set to Fanconi anemia, complementation group E, MIM#600901
Penetrance for gene: FANCE were set to Complete
Review for gene: FANCE was set to GREEN
Added comment: Well established gene-disease association, with microcephaly a reported feature.
Sources: Literature
Microcephaly v0.314 FANCA Seb Lunke gene: FANCA was added
gene: FANCA was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: FANCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCA were set to 20301575
Phenotypes for gene: FANCA were set to Fanconi anemia, complementation group A (MIM#227650)
Review for gene: FANCA was set to GREEN
gene: FANCA was marked as current diagnostic
Added comment: Well established gene disease association
Sources: Expert Review
Microcephaly v0.314 FANCB Zornitza Stark Marked gene: FANCB as ready
Microcephaly v0.314 FANCB Zornitza Stark Gene: fancb has been classified as Green List (High Evidence).
Microcephaly v0.314 FANCB Zornitza Stark Classified gene: FANCB as Green List (high evidence)
Microcephaly v0.314 FANCB Zornitza Stark Gene: fancb has been classified as Green List (High Evidence).
Microcephaly v0.313 FANCB Zornitza Stark gene: FANCB was added
gene: FANCB was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: FANCB was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FANCB were set to 20301575
Phenotypes for gene: FANCB were set to Fanconi anemia, complementation group B, MIM# 300514
Review for gene: FANCB was set to GREEN
Added comment: Well established gene-disease association, microcephaly is a key feature.
Sources: Expert list
Microcephaly v0.312 FANCC Ain Roesley gene: FANCC was added
gene: FANCC was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FANCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCC were set to 20301575
Phenotypes for gene: FANCC were set to Fanconi anemia, complementation group C (MIM#227645)
Penetrance for gene: FANCC were set to unknown
Review for gene: FANCC was set to GREEN
Added comment: 75% of Fanconi Anemia (FA) patients have microcephaly and approx 14% cases is caused by FANCC
Sources: Literature
Microcephaly v0.312 UFC1 Seb Lunke Marked gene: UFC1 as ready
Microcephaly v0.312 UFC1 Seb Lunke Gene: ufc1 has been classified as Green List (High Evidence).
Microcephaly v0.312 UFC1 Seb Lunke Publications for gene: UFC1 were set to 29868776
Microcephaly v0.311 UFC1 Seb Lunke Classified gene: UFC1 as Green List (high evidence)
Microcephaly v0.311 UFC1 Seb Lunke Gene: ufc1 has been classified as Green List (High Evidence).
Microcephaly v0.310 CHD4 Seb Lunke Marked gene: CHD4 as ready
Microcephaly v0.310 CHD4 Seb Lunke Gene: chd4 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.310 CHD4 Seb Lunke Phenotypes for gene: CHD4 were changed from to Sifrim-Hitz-Weiss syndrome (MIM#617159)
Microcephaly v0.309 UFC1 Paul De Fazio edited their review of gene: UFC1: Changed rating: GREEN
Microcephaly v0.309 TUBGCP4 Zornitza Stark Marked gene: TUBGCP4 as ready
Microcephaly v0.309 TUBGCP4 Zornitza Stark Gene: tubgcp4 has been classified as Green List (High Evidence).
Microcephaly v0.309 UFC1 Paul De Fazio changed review comment from: PMID 29868776: 8 affected individuals from 4 families reported. 7 were described to be postnatally microcephalic (at or below 3rd percentile). One was -5.1SD and one was -3.6SD. SD values for the others weren't provided.

The following head circumference measurements were provided for 6 of the affecteds:

51cm at 16yo; 50cm at 19yo; 42.5cm at 12mo, 45cm at 28mo, 45.2cm at 7yo; 45cm at 4yo.

3 of the families were consanguineous Saudi families with the same homozygous missense variant.
Sources: Literature; to: PMID 29868776: 8 affected individuals from 4 families reported. 7 were described to be postnatally microcephalic (at or below 3rd percentile). One was -5.1SD and one was -3.6SD. SD values for the others weren't provided.

The following head circumference measurements were provided for 6 of the affecteds:

51cm at 16yo; 50cm at 19yo; 42.5cm at 12mo, 45cm at 28mo, 45.2cm at 7yo; 45cm at 4yo.

3 of the families were consanguineous Saudi families with the same homozygous missense variant.

In vitro functional expression studies showed that both mutations caused impaired thioester binding with UFM1. Patient cells also showed decreased UFC1 intermediate formation with UFM1. The decrease in function was consistent with a hypomorphic allele, and the authors suggested that complete loss of function would be embryonic lethal.

PMID 30552426: 1 more individual with epileptic encephalopathy reported with a different homozygous missense variant in UFC1. The patient had microcephaly <3rd percentile.

Sources: Literature
Microcephaly v0.309 TUBGCP4 Zornitza Stark Classified gene: TUBGCP4 as Green List (high evidence)
Microcephaly v0.309 TUBGCP4 Zornitza Stark Gene: tubgcp4 has been classified as Green List (High Evidence).
Microcephaly v0.309 CHD4 Seb Lunke Publications for gene: CHD4 were set to
Microcephaly v0.308 CHD4 Seb Lunke Mode of inheritance for gene: CHD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Microcephaly v0.308 UBA5 Zornitza Stark Marked gene: UBA5 as ready
Microcephaly v0.308 UBA5 Zornitza Stark Gene: uba5 has been classified as Green List (High Evidence).
Microcephaly v0.308 UBA5 Zornitza Stark Classified gene: UBA5 as Green List (high evidence)
Microcephaly v0.308 UBA5 Zornitza Stark Gene: uba5 has been classified as Green List (High Evidence).
Microcephaly v0.307 CHD4 Seb Lunke Classified gene: CHD4 as Amber List (moderate evidence)
Microcephaly v0.307 CHD4 Seb Lunke Added comment: Comment on list classification: Unclear what would differentiate Macro- from micro-cephaly in this gene, or if micro-cephaly is actually a feature of the condition
Microcephaly v0.307 CHD4 Seb Lunke Gene: chd4 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.306 DNM1L Zornitza Stark Marked gene: DNM1L as ready
Microcephaly v0.306 DNM1L Zornitza Stark Added comment: Comment when marking as ready: Borderline Amber/Green, but overall a small proportion of individuals have microcephaly.
Microcephaly v0.306 DNM1L Zornitza Stark Gene: dnm1l has been classified as Amber List (Moderate Evidence).
Microcephaly v0.306 DNM1L Zornitza Stark Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MIM#614388
Microcephaly v0.305 UFC1 Paul De Fazio edited their review of gene: UFC1: Changed publications: 29868776, 30552426
Microcephaly v0.305 DNM1L Zornitza Stark Classified gene: DNM1L as Amber List (moderate evidence)
Microcephaly v0.305 DNM1L Zornitza Stark Gene: dnm1l has been classified as Amber List (Moderate Evidence).
Microcephaly v0.305 DNM1L Zornitza Stark Publications for gene: DNM1L were set to
Microcephaly v0.304 DNM1L Zornitza Stark Mode of inheritance for gene: DNM1L was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Microcephaly v0.303 CENPF Zornitza Stark Marked gene: CENPF as ready
Microcephaly v0.303 CENPF Zornitza Stark Gene: cenpf has been classified as Green List (High Evidence).
Microcephaly v0.303 CIT Zornitza Stark Marked gene: CIT as ready
Microcephaly v0.303 CIT Zornitza Stark Gene: cit has been classified as Green List (High Evidence).
Microcephaly v0.303 CIT Zornitza Stark Classified gene: CIT as Green List (high evidence)
Microcephaly v0.303 CIT Zornitza Stark Gene: cit has been classified as Green List (High Evidence).
Microcephaly v0.302 UBE3A Zornitza Stark Marked gene: UBE3A as ready
Microcephaly v0.302 UBE3A Zornitza Stark Gene: ube3a has been classified as Green List (High Evidence).
Microcephaly v0.302 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from to Angelman syndrome MIM#105830
Microcephaly v0.301 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.300 CHAMP1 Zornitza Stark Marked gene: CHAMP1 as ready
Microcephaly v0.300 CHAMP1 Zornitza Stark Gene: champ1 has been classified as Green List (High Evidence).
Microcephaly v0.300 CHAMP1 Zornitza Stark Publications for gene: CHAMP1 were set to
Microcephaly v0.299 CHAMP1 Zornitza Stark Mode of inheritance for gene: CHAMP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.298 CHAMP1 Zornitza Stark Phenotypes for gene: CHAMP1 were changed from to Mental retardation, autosomal dominant 40 (MIM#616579)
Microcephaly v0.297 CDKL5 Zornitza Stark Marked gene: CDKL5 as ready
Microcephaly v0.297 CDKL5 Zornitza Stark Gene: cdkl5 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.297 CENPF Zornitza Stark Classified gene: CENPF as Green List (high evidence)
Microcephaly v0.297 CENPF Zornitza Stark Gene: cenpf has been classified as Green List (High Evidence).
Microcephaly v0.296 CDKL5 Zornitza Stark Phenotypes for gene: CDKL5 were changed from to Epileptic encephalopathy, early infantile, 2 (MIM#300672)
Microcephaly v0.295 UFM1 Zornitza Stark Tag founder tag was added to gene: UFM1.
Microcephaly v0.295 UFM1 Zornitza Stark Marked gene: UFM1 as ready
Microcephaly v0.295 UFM1 Zornitza Stark Added comment: Comment when marking as ready: Green rating in view of the marked microcephaly, and large number of individuals reported with the founder variant. Rating is borderline but consistent across panels.
Microcephaly v0.295 UFM1 Zornitza Stark Gene: ufm1 has been classified as Green List (High Evidence).
Microcephaly v0.295 CENPE Seb Lunke Marked gene: CENPE as ready
Microcephaly v0.295 CENPE Seb Lunke Gene: cenpe has been classified as Red List (Low Evidence).
Microcephaly v0.295 UFM1 Zornitza Stark Classified gene: UFM1 as Green List (high evidence)
Microcephaly v0.295 UFM1 Zornitza Stark Gene: ufm1 has been classified as Green List (High Evidence).
Microcephaly v0.295 CENPE Seb Lunke Phenotypes for gene: CENPE were changed from to Microcephaly 13, primary, autosomal recessive (MIM#616051)
Microcephaly v0.294 CENPE Seb Lunke Publications for gene: CENPE were set to
Microcephaly v0.293 CENPE Seb Lunke Mode of inheritance for gene: CENPE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.292 CENPE Seb Lunke Classified gene: CENPE as Red List (low evidence)
Microcephaly v0.292 CENPE Seb Lunke Gene: cenpe has been classified as Red List (Low Evidence).
Microcephaly v0.291 CKAP2L Ain Roesley gene: CKAP2L was added
gene: CKAP2L was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CKAP2L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CKAP2L were set to 29473684; 25439729
Phenotypes for gene: CKAP2L were set to Filippi syndrome (MIM#272440)
Penetrance for gene: CKAP2L were set to unknown
Review for gene: CKAP2L was set to GREEN
Added comment: PMID: 29473684
- 1x proband with head circumference -3SD

PMID: 25439729
- 11 patients, 7 have OFCs <= -3SD
Sources: Literature
Microcephaly v0.291 TUBB2B Paul De Fazio reviewed gene: TUBB2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 19465910, 22333901; Phenotypes: Cortical dysplasia, complex, with other brain malformations 7 MIM#610031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Microcephaly v0.291 CDKL5 Zornitza Stark Publications for gene: CDKL5 were set to
Microcephaly v0.290 CDKL5 Zornitza Stark Mode of inheritance for gene: CDKL5 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Microcephaly v0.289 CDKL5 Zornitza Stark Classified gene: CDKL5 as Amber List (moderate evidence)
Microcephaly v0.289 CDKL5 Zornitza Stark Gene: cdkl5 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.288 CDK13 Seb Lunke Marked gene: CDK13 as ready
Microcephaly v0.288 CDK13 Seb Lunke Gene: cdk13 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.288 CDK13 Seb Lunke Phenotypes for gene: CDK13 were changed from to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (MIM#617360)
Microcephaly v0.287 UNC80 Zornitza Stark Marked gene: UNC80 as ready
Microcephaly v0.287 UNC80 Zornitza Stark Gene: unc80 has been classified as Green List (High Evidence).
Microcephaly v0.287 CDK13 Seb Lunke Publications for gene: CDK13 were set to
Microcephaly v0.287 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 MIM#616801
Microcephaly v0.286 CDK13 Seb Lunke Mode of inheritance for gene: CDK13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Microcephaly v0.286 UNC80 Zornitza Stark Publications for gene: UNC80 were set to
Microcephaly v0.285 UNC80 Zornitza Stark Mode of inheritance for gene: UNC80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.284 CDK13 Seb Lunke Classified gene: CDK13 as Amber List (moderate evidence)
Microcephaly v0.284 CDK13 Seb Lunke Gene: cdk13 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.283 DDX11 Zornitza Stark Marked gene: DDX11 as ready
Microcephaly v0.283 DDX11 Zornitza Stark Gene: ddx11 has been classified as Green List (High Evidence).
Microcephaly v0.283 DDX11 Zornitza Stark Classified gene: DDX11 as Green List (high evidence)
Microcephaly v0.283 DDX11 Zornitza Stark Gene: ddx11 has been classified as Green List (High Evidence).
Microcephaly v0.282 TUBGCP4 Paul De Fazio gene: TUBGCP4 was added
gene: TUBGCP4 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TUBGCP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP4 were set to 25817018
Phenotypes for gene: TUBGCP4 were set to Microcephaly and chorioretinopathy, autosomal recessive, MIM#616335
Review for gene: TUBGCP4 was set to GREEN
gene: TUBGCP4 was marked as current diagnostic
Added comment: 4 patients from 3 families with biallelic variants reported, all with microcephaly < -3SD. All had a synonymous splice variant on one allele.
Sources: Literature
Microcephaly v0.282 USP18 Zornitza Stark Marked gene: USP18 as ready
Microcephaly v0.282 USP18 Zornitza Stark Gene: usp18 has been classified as Red List (Low Evidence).
Microcephaly v0.282 USP18 Zornitza Stark Phenotypes for gene: USP18 were changed from to Pseudo-TORCH syndrome 2 MIM#617397
Microcephaly v0.281 USP18 Zornitza Stark Publications for gene: USP18 were set to
Microcephaly v0.280 CDC6 Seb Lunke Marked gene: CDC6 as ready
Microcephaly v0.280 CDC6 Seb Lunke Gene: cdc6 has been classified as Red List (Low Evidence).
Microcephaly v0.280 CDC6 Seb Lunke Classified gene: CDC6 as Red List (low evidence)
Microcephaly v0.280 CDC6 Seb Lunke Gene: cdc6 has been classified as Red List (Low Evidence).
Microcephaly v0.280 USP18 Zornitza Stark Mode of inheritance for gene: USP18 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.279 CDC6 Seb Lunke Classified gene: CDC6 as Red List (low evidence)
Microcephaly v0.279 CDC6 Seb Lunke Gene: cdc6 has been classified as Red List (Low Evidence).
Microcephaly v0.279 USP18 Zornitza Stark Classified gene: USP18 as Red List (low evidence)
Microcephaly v0.279 USP18 Zornitza Stark Gene: usp18 has been classified as Red List (Low Evidence).
Microcephaly v0.278 CCDC88A Zornitza Stark Classified gene: CCDC88A as Green List (high evidence)
Microcephaly v0.278 CCDC88A Zornitza Stark Gene: ccdc88a has been classified as Green List (High Evidence).
Microcephaly v0.277 CCDC88A Ain Roesley edited their review of gene: CCDC88A: Changed rating: GREEN; Changed phenotypes: PEHO syndrome-like (MIM#617507)
Microcephaly v0.277 BUB1B Seb Lunke Marked gene: BUB1B as ready
Microcephaly v0.277 BUB1B Seb Lunke Gene: bub1b has been classified as Green List (High Evidence).
Microcephaly v0.277 BUB1B Seb Lunke Phenotypes for gene: BUB1B were changed from to Mosaic variegated aneuploidy syndrome 1 (MIM#257300)
Microcephaly v0.276 CCDC88A Zornitza Stark Marked gene: CCDC88A as ready
Microcephaly v0.276 CCDC88A Zornitza Stark Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Microcephaly v0.276 BUB1B Seb Lunke Publications for gene: BUB1B were set to
Microcephaly v0.276 CCDC88A Zornitza Stark Classified gene: CCDC88A as Amber List (moderate evidence)
Microcephaly v0.276 CCDC88A Zornitza Stark Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Microcephaly v0.275 BUB1B Seb Lunke Mode of inheritance for gene: BUB1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.274 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Microcephaly v0.274 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Microcephaly v0.274 DHCR7 Zornitza Stark Classified gene: DHCR7 as Green List (high evidence)
Microcephaly v0.274 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Microcephaly v0.273 UBA5 Paul De Fazio gene: UBA5 was added
gene: UBA5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: UBA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBA5 were set to 27545674; 27545681
Phenotypes for gene: UBA5 were set to Epileptic encephalopathy, early infantile, 44 (MIM#617132)
Review for gene: UBA5 was set to GREEN
gene: UBA5 was marked as current diagnostic
Added comment: PMID 27545674: 8 patients from 5 unrelated families with biallelic variants reported. All had the same missense variant on one allele (517hets in gnomAD), which they referred to as a hypomorphic allele. 7 of the 8 were microcephalic (they used < -3SD as diagnostic criteria).

PMID 27545681: 5 patients from 4 families with biallelic variants reported. Head circumferences were cited as: -3.5SD, -2SD, 4th centile, -2.5SD, -2.4SD.
Sources: Literature
Microcephaly v0.273 DHCR7 Belinda Chong changed review comment from: 80%-84% of individuals have Microcephaly (https://www.ncbi.nlm.nih.gov/books/NBK1143/)

More than 200 mutations that cause Smith-Lemli-Opitz syndrome have been identified in the DHCR7 gene. (https://databases.lovd.nl/shared/genes/DHCR7)
Sources: Literature; to: 80%-84% of individuals have Microcephaly (https://www.ncbi.nlm.nih.gov/books/NBK1143/, ClinVar)

More than 200 mutations that cause Smith-Lemli-Opitz syndrome have been identified in the DHCR7 gene. (https://databases.lovd.nl/shared/genes/DHCR7)
Sources: Literature
Microcephaly v0.273 DNM1L Naomi Baker changed review comment from: Most individuals reported with variants in DNM1L do not have microcephaly listed as a phenotype.

PMID: 17460227 - Reports a newborn girl with microcephaly (head circumference below the 0.4 percentile), abnormal brain development, optic atrophy and hypoplasia, persistent lactic acidemia, and a mildly elevated plasma concentration of very-long-chain fatty acids. She died suddenly at the age of 37 days. A monoallelic missense variant was identified.

PMID: 26992161 - A monoallelic missense variant reported in a 2 year old boy with a chronic neurological disorder, characterized by postnatal microcephaly (OFC 45.5 cm (<3rd centile)), developmental delay, and pain insensitivity.

PMID: 30801875 - Five patients presenting with severe epileptic encephalopathy; microcephaly (<3rd percentile) reported in one patient. Five de novo dominant DNM1L variants were identified.
Loss-of-function and dominant negative; to: Most individuals reported with variants in DNM1L do not have microcephaly listed as a phenotype.

PMID: 17460227 - Reports a newborn girl with microcephaly (head circumference below the 0.4 percentile), abnormal brain development, optic atrophy and hypoplasia, persistent lactic acidemia, and a mildly elevated plasma concentration of very-long-chain fatty acids. She died suddenly at the age of 37 days. A monoallelic missense variant was identified.

PMID: 26992161 - A monoallelic missense variant reported in a 2 year old boy with a chronic neurological disorder, characterized by postnatal microcephaly (OFC 45.5 cm (<3rd centile)), developmental delay, and pain insensitivity.

PMID: 30801875 - Five patients presenting with severe epileptic encephalopathy; microcephaly (<3rd percentile) reported in one patient. Five de novo dominant DNM1L variants were identified.

Both loss-of-function (variants within the GTPase domain) and dominant negative (variants within the middle domain) mechanisms have been reported.
Microcephaly v0.273 DNM1L Naomi Baker reviewed gene: DNM1L: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 17460227, 26992161, 30801875; Phenotypes: Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MIM#614388; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Microcephaly v0.273 CIT Ain Roesley gene: CIT was added
gene: CIT was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CIT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIT were set to 27453578; 27503289; 27453579
Phenotypes for gene: CIT were set to Microcephaly 17, primary, autosomal recessive (MIM#617090)
Penetrance for gene: CIT were set to unknown
Review for gene: CIT was set to GREEN
Added comment: PMID: 27453578
- 3 consanguineous families with 7 affecteds and head circumferences ranging from -5.6 SD to -8.4 SD

PMID: 27503289
- 2 consanguineous families with 2 affecteds and OFCs of -9 and -10 SDs

PMID: 27453579
- 3 families (2 consanguineous) with 6 affecteds
- only 3 had OFCs records:: birth and last examined ranged from -3.5 to -12 SDs

*mix of missense and PTVs
Sources: Literature
Microcephaly v0.273 CHD4 Ain Roesley reviewed gene: CHD4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31388190; Phenotypes: Sifrim-Hitz-Weiss syndrome (MIM#617159); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Microcephaly v0.273 UBE3A Paul De Fazio reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angelman syndrome MIM#105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed); Current diagnostic: yes
Microcephaly v0.273 CHAMP1 Ain Roesley reviewed gene: CHAMP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27148580, 26340335; Phenotypes: Mental retardation, autosomal dominant 40 (MIM#616579); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Microcephaly v0.273 UFC1 Paul De Fazio gene: UFC1 was added
gene: UFC1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: UFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UFC1 were set to 29868776
Phenotypes for gene: UFC1 were set to Neurodevelopmental disorder with spasticity and poor growth (MIM#618076)
Review for gene: UFC1 was set to AMBER
gene: UFC1 was marked as current diagnostic
Added comment: PMID 29868776: 8 affected individuals from 4 families reported. 7 were described to be postnatally microcephalic (at or below 3rd percentile). One was -5.1SD and one was -3.6SD. SD values for the others weren't provided.

The following head circumference measurements were provided for 6 of the affecteds:

51cm at 16yo; 50cm at 19yo; 42.5cm at 12mo, 45cm at 28mo, 45.2cm at 7yo; 45cm at 4yo.

3 of the families were consanguineous Saudi families with the same homozygous missense variant.
Sources: Literature
Microcephaly v0.273 CENPF Ain Roesley gene: CENPF was added
gene: CENPF was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPF were set to 25564561; 28407396; 27300082; 31953238
Phenotypes for gene: CENPF were set to Stromme syndrome (MIM#243605)
Penetrance for gene: CENPF were set to unknown
Review for gene: CENPF was set to GREEN
Added comment: *Several Stromme syndrome patients reported with microcephaly however only the following were genetically confirmed.

PMID: 31953238
- 2 siblings from a consanguineous Saudi family
- Patient 1: head circumference -3.33 SD (44cm) at 3 years and -4.4 SD (45.5cm) at 6 years
- Patient 2: +5.07 SD (39.5cm) at birth and +8.99 SD (49cm) at 2 months
- homozygous splice variant

PMID: 28407396
- 1x proband with head circumference -6.29 SD (at birth) and -7.57 SD at 18 months
- homozygous fs variant

PMID: 25564561;
- 1x proband with OFC <0.4 centile (29.5cm) at birth and adult OFC of <0.4 centile (45.5cm)
- cHet for 2x nonsense variants

PMID: 27300082 ;
- 1x proband with OFC <3rd centile
- chet for PTVs
Sources: Literature
Microcephaly v0.273 UFM1 Paul De Fazio gene: UFM1 was added
gene: UFM1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: UFM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UFM1 were set to 28931644; 29868776; 31914610
Phenotypes for gene: UFM1 were set to Leukodystrophy, hypomyelinating, 14 MIM#617899
Review for gene: UFM1 was set to AMBER
gene: UFM1 was marked as current diagnostic
Added comment: Summary: Only 2 variants reported in this gene, one a founder promoter variant and one a missense variant found in 2 Sudanese families (3 hets in gnomAD). All affected individuals were reported with microcephaly but measurements only provided for two. A Drosophila model supports an association of this gene with microcephaly, but it's Drosophila.

PMID 28931644: Found a 3bp deletion in the promoter region of UFM1 in 16 Roma individuals with hypomyelination with atrophy of the basal ganglia and cerebellum who were negative for TUBB4A mutations. Functional studies showed an effect on gene expressin in neuronal cell lines but not other cell lines. All affected individuals had microcephaly but no measurements were provided.

PMID 29868776: 4 affected individuals from 2 Sudanese families reported with the same missense variant. All four were said to have microcephaly but measurments only provided for two: Proband from family 1 had a head circumference of 40cm at 2yo; proband from family 2 had head circumference of < -4SD at 13mo.

PMID 31914610: Used Drosophila embryos to show that UFM1 knockdown was associated with developmental processes that lead to microcephaly.
Sources: Literature
Microcephaly v0.273 CENPE Ain Roesley reviewed gene: CENPE: Rating: RED; Mode of pathogenicity: None; Publications: 24748105, 30086807; Phenotypes: Microcephaly 13, primary, autosomal recessive (MIM#616051); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.273 CDKL5 Ain Roesley reviewed gene: CDKL5: Rating: AMBER; Mode of pathogenicity: None; Publications: 15689447, 19396824, 22678952, 31122804, 30928302; Phenotypes: Epileptic encephalopathy, early infantile, 2 (MIM#300672); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Microcephaly v0.273 UNC80 Paul De Fazio reviewed gene: UNC80: Rating: GREEN; Mode of pathogenicity: None; Publications: 26708751, 26708753, 26545877, 29572195; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 MIM#616801; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v0.273 DDX11 Naomi Baker gene: DDX11 was added
gene: DDX11 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DDX11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX11 were set to PMID: 31824187; 20137776; 23033317.
Phenotypes for gene: DDX11 were set to Warsaw breakage syndrome, MIM#613398
Penetrance for gene: DDX11 were set to Complete
Review for gene: DDX11 was set to GREEN
Added comment: The cardinal clinical features observed in Warsaw breakage syndrome (WABS) patients include severe pre- and post-natal growth retardation, microcephaly, sensorineural hearing loss, cochlear anomalies, facial dysmorphia and sister chromatid cohesion defects (PMID: 31824187).

A male patient with biallelic DDX11 variants (splice site and in-frame deletion) presented with several congenital abnormalities, including microcephaly, facial dysmorphy, high arched palate, coloboma of the right optic disc, deafness, small ventricular septal defect, bilateral clinodactyly of the fifth fingers, syndactyly of the second and third toes, cutis marmorata, and one hypo- and three hyperpigmented patches on the skin. Authors proposed to name the syndrome associated with defective DDX11 “Warsaw breakage syndrome” (WABS) (PMID: 20137776).

Three siblings carrying a biallelic DDX11 missense variant with clinical presentation of WABS: ID, growth retardation, and severe congenital abnormalities including microcephaly, facial dysmorphism, deafness due to cochlear abnormalities (in two of the sibs), and cardiac malformations (in one of the sibs) (PMID: 23033317).
Sources: Literature
Microcephaly v0.273 CDK13 Ain Roesley changed review comment from: Mild microcephaly in some patients (OMIM)

PMID: 29021403;
- 15 patients, all de novo missense
- OFC ranges from 50th to <0.4th centile. Only 4 patients have <0.4 centiles
(includes patients reported in PMID: 27479907)

PMID: 31238879;
- 7 patients with likely path variants in CDK13 (ACMG was used in classifications)
- 2 with microcephaly but measurements not provided; to: Mild microcephaly in some patients (OMIM)

PMID: 29021403;
- 15 patients, all de novo missense
- OFC ranges from 50th to <0.4th centile. Only 4 patients have <0.4 centiles and 2 with 1st centile
(includes patients reported in PMID: 27479907)

PMID: 31238879;
- 7 patients with likely path variants in CDK13 (ACMG was used in classifications)
- 2 with microcephaly but measurements not provided
Microcephaly v0.273 CDK13 Ain Roesley reviewed gene: CDK13: Rating: AMBER; Mode of pathogenicity: None; Publications: 27479907, 29021403, 31238879; Phenotypes: Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (MIM#617360); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Microcephaly v0.273 USP18 Paul De Fazio reviewed gene: USP18: Rating: RED; Mode of pathogenicity: None; Publications: 27325888, 31940699; Phenotypes: Pseudo-TORCH syndrome 2 MIM#617397; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v0.273 CDC6 Ain Roesley gene: CDC6 was added
gene: CDC6 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CDC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC6 were set to 21358632
Phenotypes for gene: CDC6 were set to Meier-Gorlin syndrome 5 (MIM#613805)
Penetrance for gene: CDC6 were set to unknown
Review for gene: CDC6 was set to RED
Added comment: PMID: 21358632;
- 1x proband with OFC -3.3SD
- homozygous for a missense

*no new reports since
Sources: Literature
Microcephaly v0.273 CCDC88A Ain Roesley gene: CCDC88A was added
gene: CCDC88A was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CCDC88A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC88A were set to 30392057; 26917597
Phenotypes for gene: CCDC88A were set to PEHO syndrome-like (MIM#617507)
Penetrance for gene: CCDC88A were set to unknown
Review for gene: CCDC88A was set to AMBER
Added comment: PMID: 30392057
- consanguineous Saudi family with 2 affecteds. Homozygous for a nonsense variant
- microcephaly, dev delay, ID, epilepsy, dysmorphism and brain atropy
- no measurements provided

PMID: 26917597
- consanguineous family with 3 affecteds. Homozygous fs variant
- infantile hypotonia, dev delay, optic and brain atrophy, seizures and microcephaly (measurements not provided)
- functional studies on KO mice
Sources: Literature
Microcephaly v0.273 GMNN Zornitza Stark Marked gene: GMNN as ready
Microcephaly v0.273 GMNN Zornitza Stark Gene: gmnn has been classified as Green List (High Evidence).
Microcephaly v0.273 GMNN Zornitza Stark Mode of inheritance for gene: GMNN was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.272 GMNN Zornitza Stark Classified gene: GMNN as Green List (high evidence)
Microcephaly v0.272 GMNN Zornitza Stark Gene: gmnn has been classified as Green List (High Evidence).
Microcephaly v0.271 GMNN Zornitza Stark edited their review of gene: GMNN: Changed phenotypes: Meier-Gorlin syndrome 6, MIM# 616835; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.271 GMNN Zornitza Stark gene: GMNN was added
gene: GMNN was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: GMNN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMNN were set to 26637980
Phenotypes for gene: GMNN were set to Meier-Gorlin syndrome 6, MIM# 616835
Review for gene: GMNN was set to GREEN
Added comment: Three unrelated individuals reported with variants in exon 2 (first coding exon) and primordial dwarfism (including microcephaly), microtia, and absent patellae.
Sources: Expert list
Microcephaly v0.270 BUB1B Ain Roesley reviewed gene: BUB1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18548531; Phenotypes: Mosaic variegated aneuploidy syndrome 1 (MIM#257300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.270 KIF21B Zornitza Stark Marked gene: KIF21B as ready
Microcephaly v0.270 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Microcephaly v0.270 KIF21B Zornitza Stark Classified gene: KIF21B as Green List (high evidence)
Microcephaly v0.270 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Microcephaly v0.269 KIF21B Zornitza Stark gene: KIF21B was added
gene: KIF21B was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF21B were set to 32415109
Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Mode of pathogenicity for gene: KIF21B 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: KIF21B was set to GREEN
Added comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors).
Sources: Literature
Microcephaly v0.268 DHCR7 Belinda Chong edited their review of gene: DHCR7: Changed rating: GREEN; Changed phenotypes: Smith-Lemli-Opitz syndrome 270400
Microcephaly v0.268 DHCR7 Belinda Chong gene: DHCR7 was added
gene: DHCR7 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to 9634533; 12949967; 15670717; 14981719
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome 270400
Added comment: 80%-84% of individuals have Microcephaly (https://www.ncbi.nlm.nih.gov/books/NBK1143/)

More than 200 mutations that cause Smith-Lemli-Opitz syndrome have been identified in the DHCR7 gene. (https://databases.lovd.nl/shared/genes/DHCR7)
Sources: Literature
Microcephaly v0.268 BRIP1 Ain Roesley gene: BRIP1 was added
gene: BRIP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: BRIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BRIP1 were set to Fanconi anemia, complementation group J (MIM#609054)
Penetrance for gene: BRIP1 were set to unknown
Review for gene: BRIP1 was set to GREEN
Added comment: 75% of Fanconi anemia (FA) patients present with microcephaly and BRIP1 contributes to approx 2% of FA diagnosis (gene reviews)
Sources: Literature
Microcephaly v0.268 ADARB1 Zornitza Stark Marked gene: ADARB1 as ready
Microcephaly v0.268 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Green List (High Evidence).
Microcephaly v0.268 ADARB1 Zornitza Stark Phenotypes for gene: ADARB1 were changed from Intellectual disability; microcephaly; seizures to Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862; Intellectual disability; microcephaly; seizures
Microcephaly v0.267 ADARB1 Zornitza Stark Publications for gene: ADARB1 were set to 32220291
Microcephaly v0.266 ADARB1 Arina Puzriakova reviewed gene: ADARB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32220291, 32719099; Phenotypes: Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.266 HDAC8 Zornitza Stark Marked gene: HDAC8 as ready
Microcephaly v0.266 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Green List (High Evidence).
Microcephaly v0.266 HDAC8 Zornitza Stark Classified gene: HDAC8 as Green List (high evidence)
Microcephaly v0.266 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Green List (High Evidence).
Microcephaly v0.265 HDAC8 Zornitza Stark gene: HDAC8 was added
gene: HDAC8 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: HDAC8 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: HDAC8 were set to 24403048
Phenotypes for gene: HDAC8 were set to Cornelia de Lange syndrome 5, MIM# 300882
Review for gene: HDAC8 was set to GREEN
Added comment: Over 35 individuals reported, ~30% had microcephaly.
Sources: Expert list
Microcephaly v0.264 IARS Zornitza Stark Marked gene: IARS as ready
Microcephaly v0.264 IARS Zornitza Stark Gene: iars has been classified as Green List (High Evidence).
Microcephaly v0.264 IARS Zornitza Stark Tag new gene name tag was added to gene: IARS.
Microcephaly v0.264 IARS Zornitza Stark Classified gene: IARS as Green List (high evidence)
Microcephaly v0.264 IARS Zornitza Stark Gene: iars has been classified as Green List (High Evidence).
Microcephaly v0.263 IARS Zornitza Stark gene: IARS was added
gene: IARS was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS were set to 27426735; 27891590
Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM# 617093
Review for gene: IARS was set to GREEN
Added comment: Microcephaly -3 to -5SD is part of the phenotype of this autosomal recessive multisystem disorder characterised by poor overall growth, impaired intellectual development, hypotonia, and variable liver dysfunction. Additional features, such as seizures and hearing loss, may also be present. At least 4 families reported. Note HGNC approved name is IARS1.
Sources: Expert list
Microcephaly v0.262 IGF1 Zornitza Stark Marked gene: IGF1 as ready
Microcephaly v0.262 IGF1 Zornitza Stark Gene: igf1 has been classified as Green List (High Evidence).
Microcephaly v0.262 IGF1 Zornitza Stark Classified gene: IGF1 as Green List (high evidence)
Microcephaly v0.262 IGF1 Zornitza Stark Gene: igf1 has been classified as Green List (High Evidence).
Microcephaly v0.261 IGF1 Zornitza Stark gene: IGF1 was added
gene: IGF1 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: IGF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGF1 were set to 15769976; 14684690; 8857020
Phenotypes for gene: IGF1 were set to Growth retardation with deafness and mental retardation due to IGF1 deficiency, MIM# 608747
Review for gene: IGF1 was set to GREEN
Added comment: Severe growth retardation including significant microcephaly.
Sources: Expert list
Microcephaly v0.260 IGF1R Zornitza Stark Marked gene: IGF1R as ready
Microcephaly v0.260 IGF1R Zornitza Stark Gene: igf1r has been classified as Green List (High Evidence).
Microcephaly v0.260 IGF1R Zornitza Stark Classified gene: IGF1R as Green List (high evidence)
Microcephaly v0.260 IGF1R Zornitza Stark Gene: igf1r has been classified as Green List (High Evidence).
Microcephaly v0.259 IGF1R Zornitza Stark gene: IGF1R was added
gene: IGF1R was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: IGF1R was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: IGF1R were set to 14657428; 25040157; 23045302; 26252249; 15928254
Phenotypes for gene: IGF1R were set to Insulin-like growth factor I, resistance to, MIM# 270450
Review for gene: IGF1R was set to GREEN
Added comment: Severe IUGR including significant microcephaly, both mono-allelic and bi-allelic variants reported.
Sources: Expert list
Microcephaly v0.258 KIF14 Zornitza Stark Marked gene: KIF14 as ready
Microcephaly v0.258 KIF14 Zornitza Stark Gene: kif14 has been classified as Green List (High Evidence).
Microcephaly v0.258 KIF14 Zornitza Stark Phenotypes for gene: KIF14 were changed from to Microcephaly 20, primary, autosomal recessive, MIM# 617914
Microcephaly v0.257 KIF14 Zornitza Stark Publications for gene: KIF14 were set to
Microcephaly v0.256 KIF14 Zornitza Stark Mode of inheritance for gene: KIF14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.255 KIF14 Zornitza Stark reviewed gene: KIF14: Rating: GREEN; Mode of pathogenicity: None; Publications: 28892560, 29343805; Phenotypes: Microcephaly 20, primary, autosomal recessive, MIM# 617914; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.255 KIF1BP Zornitza Stark Marked gene: KIF1BP as ready
Microcephaly v0.255 KIF1BP Zornitza Stark Gene: kif1bp has been classified as Green List (High Evidence).
Microcephaly v0.255 KIF1BP Zornitza Stark Classified gene: KIF1BP as Green List (high evidence)
Microcephaly v0.255 KIF1BP Zornitza Stark Gene: kif1bp has been classified as Green List (High Evidence).
Microcephaly v0.254 KIF1BP Zornitza Stark Tag new gene name tag was added to gene: KIF1BP.
Microcephaly v0.254 KIF1BP Zornitza Stark gene: KIF1BP was added
gene: KIF1BP was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: KIF1BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF1BP were set to 23427148
Phenotypes for gene: KIF1BP were set to Goldberg-Shprintzen megacolon syndrome, MIM# 609460
Review for gene: KIF1BP was set to GREEN
Added comment: Autosomal recessive multiple congenital anomaly syndrome characterised by intellectual disability, microcephaly, and dysmorphic facial features. Most individuals also have Hirschsprung disease and/or gyral abnormalities of the brain, consistent with defects in migration of neural crest cells and neurons. Other features, such as megalocornea or urogenital anomalies, may also be present. Well established gene-disease association, multiple families reported. Note HGNC approved name is KIAA1279.
Sources: Expert list
Microcephaly v0.253 KLHL7 Zornitza Stark Marked gene: KLHL7 as ready
Microcephaly v0.253 KLHL7 Zornitza Stark Gene: klhl7 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.253 KLHL7 Zornitza Stark Phenotypes for gene: KLHL7 were changed from to PERCHING syndrome, MIM# 617055
Microcephaly v0.252 KLHL7 Zornitza Stark Publications for gene: KLHL7 were set to
Microcephaly v0.251 KLHL7 Zornitza Stark Mode of inheritance for gene: KLHL7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.250 KLHL7 Zornitza Stark Classified gene: KLHL7 as Amber List (moderate evidence)
Microcephaly v0.250 KLHL7 Zornitza Stark Gene: klhl7 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.249 KLHL7 Zornitza Stark reviewed gene: KLHL7: Rating: AMBER; Mode of pathogenicity: None; Publications: 27392078, 29074562; Phenotypes: PERCHING syndrome, MIM# 617055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.249 GON7 Zornitza Stark Tag founder tag was added to gene: GON7.
Microcephaly v0.249 YRDC Zornitza Stark Marked gene: YRDC as ready
Microcephaly v0.249 YRDC Zornitza Stark Gene: yrdc has been classified as Green List (High Evidence).
Microcephaly v0.249 YRDC Zornitza Stark Classified gene: YRDC as Green List (high evidence)
Microcephaly v0.249 YRDC Zornitza Stark Gene: yrdc has been classified as Green List (High Evidence).
Microcephaly v0.248 YRDC Zornitza Stark gene: YRDC was added
gene: YRDC was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: YRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YRDC were set to 31481669
Phenotypes for gene: YRDC were set to Galloway-Mowat syndrome
Review for gene: YRDC was set to GREEN
Added comment: Three individuals from two unrelated families with typical features of Galloway-Mowat syndrome including proteinuria, microcephaly, developmental delay and brain malformations. Supportive functional data.
Sources: Literature
Microcephaly v0.247 GON7 Zornitza Stark Marked gene: GON7 as ready
Microcephaly v0.247 GON7 Zornitza Stark Gene: gon7 has been classified as Green List (High Evidence).
Microcephaly v0.247 GON7 Zornitza Stark Classified gene: GON7 as Green List (high evidence)
Microcephaly v0.247 GON7 Zornitza Stark Gene: gon7 has been classified as Green List (High Evidence).
Microcephaly v0.246 GON7 Zornitza Stark gene: GON7 was added
gene: GON7 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GON7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GON7 were set to 31481669
Phenotypes for gene: GON7 were set to Galloway-Mowat syndrome
Review for gene: GON7 was set to GREEN
Added comment: 11 individuals from 5 families. Four of the families had the same homozygous variant, shared haplotype suggestive of founder effect. Clinical features included proteinuria, microcephaly, brain malformations and developmental delay. Supportive functional data.
Sources: Literature
Microcephaly v0.245 LAGE3 Zornitza Stark Marked gene: LAGE3 as ready
Microcephaly v0.245 LAGE3 Zornitza Stark Gene: lage3 has been classified as Green List (High Evidence).
Microcephaly v0.245 LAGE3 Zornitza Stark Phenotypes for gene: LAGE3 were changed from to Galloway-Mowat syndrome 2, X-linked, MIM# 301006
Microcephaly v0.244 LAGE3 Zornitza Stark Publications for gene: LAGE3 were set to
Microcephaly v0.243 LAGE3 Zornitza Stark Mode of inheritance for gene: LAGE3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v0.242 LAGE3 Zornitza Stark reviewed gene: LAGE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828; Phenotypes: Galloway-Mowat syndrome 2, X-linked, MIM# 301006; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v0.242 LINGO1 Zornitza Stark Marked gene: LINGO1 as ready
Microcephaly v0.242 LINGO1 Zornitza Stark Gene: lingo1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.242 LINGO1 Zornitza Stark Phenotypes for gene: LINGO1 were changed from to Mental retardation, autosomal recessive 64, MIM# 618103
Microcephaly v0.241 LINGO1 Zornitza Stark Publications for gene: LINGO1 were set to
Microcephaly v0.240 LINGO1 Zornitza Stark Mode of inheritance for gene: LINGO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.239 LINGO1 Zornitza Stark Classified gene: LINGO1 as Amber List (moderate evidence)
Microcephaly v0.239 LINGO1 Zornitza Stark Gene: lingo1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.238 LINGO1 Zornitza Stark edited their review of gene: LINGO1: Changed rating: AMBER
Microcephaly v0.238 LINGO1 Zornitza Stark reviewed gene: LINGO1: Rating: ; Mode of pathogenicity: None; Publications: 31668702; Phenotypes: Mental retardation, autosomal recessive 64, MIM# 618103; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.238 OSGEP Zornitza Stark Marked gene: OSGEP as ready
Microcephaly v0.238 OSGEP Zornitza Stark Gene: osgep has been classified as Green List (High Evidence).
Microcephaly v0.238 OSGEP Zornitza Stark Phenotypes for gene: OSGEP were changed from to Galloway-Mowat syndrome 3, MIM# 617729
Microcephaly v0.237 OSGEP Zornitza Stark Publications for gene: OSGEP were set to
Microcephaly v0.236 OSGEP Zornitza Stark Mode of inheritance for gene: OSGEP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.235 OSGEP Zornitza Stark reviewed gene: OSGEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 28272532; Phenotypes: Galloway-Mowat syndrome 3, MIM# 617729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.235 NUP107 Zornitza Stark Marked gene: NUP107 as ready
Microcephaly v0.235 NUP107 Zornitza Stark Gene: nup107 has been classified as Green List (High Evidence).
Microcephaly v0.235 NUP107 Zornitza Stark Tag founder tag was added to gene: NUP107.
Microcephaly v0.235 NUP107 Zornitza Stark Phenotypes for gene: NUP107 were changed from to Galloway-Mowat syndrome 7, MIM# 618348
Microcephaly v0.234 NUP107 Zornitza Stark Publications for gene: NUP107 were set to
Microcephaly v0.233 NUP107 Zornitza Stark Mode of inheritance for gene: NUP107 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.232 NUP107 Zornitza Stark reviewed gene: NUP107: Rating: GREEN; Mode of pathogenicity: None; Publications: 28280135, 28117080, 30179222, 25558065; Phenotypes: Galloway-Mowat syndrome 7, MIM# 618348; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.232 VRK1 Zornitza Stark Marked gene: VRK1 as ready
Microcephaly v0.232 VRK1 Zornitza Stark Gene: vrk1 has been classified as Green List (High Evidence).
Microcephaly v0.232 VRK1 Zornitza Stark Phenotypes for gene: VRK1 were changed from to Pontocerebellar hypoplasia type 1A MIM#607596
Microcephaly v0.231 VRK1 Zornitza Stark Publications for gene: VRK1 were set to
Microcephaly v0.230 VRK1 Zornitza Stark Mode of inheritance for gene: VRK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.229 BRD4 Zornitza Stark Marked gene: BRD4 as ready
Microcephaly v0.229 BRD4 Zornitza Stark Gene: brd4 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.229 BRD4 Zornitza Stark Tag SV/CNV tag was added to gene: BRD4.
Microcephaly v0.229 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from to Cornelia de Lange-like syndrome
Microcephaly v0.228 BRD4 Zornitza Stark Publications for gene: BRD4 were set to
Microcephaly v0.227 BRD4 Zornitza Stark Mode of inheritance for gene: BRD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.226 BRD4 Zornitza Stark Classified gene: BRD4 as Amber List (moderate evidence)
Microcephaly v0.226 BRD4 Zornitza Stark Gene: brd4 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.225 WDR4 Zornitza Stark Marked gene: WDR4 as ready
Microcephaly v0.225 WDR4 Zornitza Stark Gene: wdr4 has been classified as Green List (High Evidence).
Microcephaly v0.225 WDR4 Zornitza Stark Phenotypes for gene: WDR4 were changed from to Galloway-Mowat syndrome 6 MIM#618347
Microcephaly v0.224 WDR4 Zornitza Stark Publications for gene: WDR4 were set to
Microcephaly v0.223 WDR4 Zornitza Stark Mode of inheritance for gene: WDR4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.222 NSD2 Zornitza Stark Marked gene: NSD2 as ready
Microcephaly v0.222 NSD2 Zornitza Stark Gene: nsd2 has been classified as Green List (High Evidence).
Microcephaly v0.222 NSD2 Zornitza Stark Phenotypes for gene: NSD2 were changed from to Microcephaly; intellectual disability
Microcephaly v0.221 NSD2 Zornitza Stark Publications for gene: NSD2 were set to
Microcephaly v0.220 NSD2 Zornitza Stark Mode of inheritance for gene: NSD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.219 NSD2 Zornitza Stark reviewed gene: NSD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30345613, 31171569; Phenotypes: Microcephaly, intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.219 NIPBL Zornitza Stark Marked gene: NIPBL as ready
Microcephaly v0.219 NIPBL Zornitza Stark Gene: nipbl has been classified as Green List (High Evidence).
Microcephaly v0.219 NIPBL Zornitza Stark Classified gene: NIPBL as Green List (high evidence)
Microcephaly v0.219 NIPBL Zornitza Stark Gene: nipbl has been classified as Green List (High Evidence).
Microcephaly v0.218 VRK1 Paul De Fazio reviewed gene: VRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19646678, 24126608, 27281532, 31560180; Phenotypes: Pontocerebellar hypoplasia type 1A MIM#607596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v0.218 NIPBL Zornitza Stark gene: NIPBL was added
gene: NIPBL was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: NIPBL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NIPBL were set to Cornelia de Lange syndrome 1, MIM# 122470
Review for gene: NIPBL was set to GREEN
Added comment: Well established gene-disease association, microcephaly is a prominent feature of the phenotype.
Sources: Expert list
Microcephaly v0.217 NCAPH Zornitza Stark Marked gene: NCAPH as ready
Microcephaly v0.217 NCAPH Zornitza Stark Gene: ncaph has been classified as Red List (Low Evidence).
Microcephaly v0.217 NCAPH Zornitza Stark Phenotypes for gene: NCAPH were changed from to Microcephaly 23, primary, autosomal recessive 617985
Microcephaly v0.216 NCAPH Zornitza Stark Publications for gene: NCAPH were set to
Microcephaly v0.215 NCAPH Zornitza Stark Mode of inheritance for gene: NCAPH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.214 NCAPH Zornitza Stark Classified gene: NCAPH as Red List (low evidence)
Microcephaly v0.214 NCAPH Zornitza Stark Gene: ncaph has been classified as Red List (Low Evidence).
Microcephaly v0.213 NCAPH Zornitza Stark reviewed gene: NCAPH: Rating: RED; Mode of pathogenicity: None; Publications: 27737959; Phenotypes: Microcephaly 23, primary, autosomal recessive 617985; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.213 BRD4 Ain Roesley reviewed gene: BRD4: Rating: AMBER; Mode of pathogenicity: None; Publications: 29379197, 30302754; Phenotypes: Cornelia de Lange-like syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Microcephaly v0.213 WDR4 Paul De Fazio reviewed gene: WDR4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26416026, 28617965, 30079490, 29597095; Phenotypes: Galloway-Mowat syndrome 6 MIM#618347; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v0.213 NCAPD3 Zornitza Stark Marked gene: NCAPD3 as ready
Microcephaly v0.213 NCAPD3 Zornitza Stark Gene: ncapd3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.213 NCAPD3 Zornitza Stark Phenotypes for gene: NCAPD3 were changed from to Microcephaly 22, primary, autosomal recessive, MIM# 617984
Microcephaly v0.212 NCAPD3 Zornitza Stark Publications for gene: NCAPD3 were set to 27737959
Microcephaly v0.211 BRCA2 Zornitza Stark Marked gene: BRCA2 as ready
Microcephaly v0.211 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
Microcephaly v0.211 BRCA2 Zornitza Stark Classified gene: BRCA2 as Green List (high evidence)
Microcephaly v0.211 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
Microcephaly v0.210 BRCA2 Ain Roesley gene: BRCA2 was added
gene: BRCA2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: BRCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BRCA2 were set to Fanconi anemia, complementation group D1 (MIM#605724)
Penetrance for gene: BRCA2 were set to unknown
Review for gene: BRCA2 was set to GREEN
Added comment: Approx 75% of FA patients present with microcephaly and approx 3% of FA patients have variants in BRCA2 (GeneReviews)
Sources: Literature
Microcephaly v0.210 WDR73 Zornitza Stark Marked gene: WDR73 as ready
Microcephaly v0.210 WDR73 Zornitza Stark Gene: wdr73 has been classified as Green List (High Evidence).
Microcephaly v0.210 WDR73 Zornitza Stark Classified gene: WDR73 as Green List (high evidence)
Microcephaly v0.210 WDR73 Zornitza Stark Gene: wdr73 has been classified as Green List (High Evidence).
Microcephaly v0.209 BLM Zornitza Stark Marked gene: BLM as ready
Microcephaly v0.209 BLM Zornitza Stark Gene: blm has been classified as Green List (High Evidence).
Microcephaly v0.209 BLM Zornitza Stark Publications for gene: BLM were set to 30214071
Microcephaly v0.208 BLM Zornitza Stark Classified gene: BLM as Green List (high evidence)
Microcephaly v0.208 BLM Zornitza Stark Gene: blm has been classified as Green List (High Evidence).
Microcephaly v0.207 WDR37 Zornitza Stark Marked gene: WDR37 as ready
Microcephaly v0.207 WDR37 Zornitza Stark Gene: wdr37 has been classified as Green List (High Evidence).
Microcephaly v0.207 WDR37 Zornitza Stark Phenotypes for gene: WDR37 were changed from to Neurooculocardiogenitourinary syndrome MIM#618652
Microcephaly v0.206 WDR37 Zornitza Stark Publications for gene: WDR37 were set to
Microcephaly v0.205 WDR37 Zornitza Stark Mode of inheritance for gene: WDR37 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.204 ZNF335 Zornitza Stark Marked gene: ZNF335 as ready
Microcephaly v0.204 ZNF335 Zornitza Stark Gene: znf335 has been classified as Green List (High Evidence).
Microcephaly v0.204 ZNF335 Zornitza Stark Phenotypes for gene: ZNF335 were changed from to Microcephaly 10, primary, autosomal recessive (MIM#615095)
Microcephaly v0.204 WDR37 Paul De Fazio reviewed gene: WDR37: Rating: GREEN; Mode of pathogenicity: None; Publications: 31327508, 31327510; Phenotypes: Neurooculocardiogenitourinary syndrome MIM#618652; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Microcephaly v0.204 ZNF335 Zornitza Stark Publications for gene: ZNF335 were set to 23178126; 27540107; 29652087
Microcephaly v0.203 BLM Ain Roesley edited their review of gene: BLM: Added comment: Microcephaly is a feature of Bloom Syndrome

PMID: 30214071;
- in a cohort of microcephalic patients (<=-2SD), 1 family with 2 affecteds are homozygous for a nonsense variant

PMID: 29056561
- 1x proband. At 36 yrs of age her head circumference was 47.8cm (-6.2SD)

PMID: 23928670;
- 1x patient of a consanguineous Dutch family. At 4 years of age: head circumference 45.9 cm (3.2 SDS). Homozygous nonsense
- 1x patient of a consanguineous Turkish family. At 5 years of age: head circumference 46.3 cm (2.7 SDS). Homozygous nonsense

PMID: 25129257;
- 1 family with 3 affecteds. 1 had a head circumference of -4SD. Homozygous fs; Changed rating: GREEN; Changed publications: 30214071, 29056561, 23928670; Changed phenotypes: Bloom syndrome (MIM#210900)
Microcephaly v0.203 ZNF335 Zornitza Stark Publications for gene: ZNF335 were set to
Microcephaly v0.203 NCAPD3 Zornitza Stark Publications for gene: NCAPD3 were set to
Microcephaly v0.202 ZNF335 Zornitza Stark Mode of inheritance for gene: ZNF335 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.201 NCAPD3 Zornitza Stark Mode of inheritance for gene: NCAPD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.200 NCAPD3 Zornitza Stark Classified gene: NCAPD3 as Amber List (moderate evidence)
Microcephaly v0.200 NCAPD3 Zornitza Stark Gene: ncapd3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.199 NCAPD3 Zornitza Stark reviewed gene: NCAPD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 27737959; Phenotypes: Microcephaly 22, primary, autosomal recessive, MIM# 617984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.199 NACC1 Zornitza Stark Marked gene: NACC1 as ready
Microcephaly v0.199 NACC1 Zornitza Stark Gene: nacc1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.199 NACC1 Zornitza Stark Phenotypes for gene: NACC1 were changed from to Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination , MIM#617393
Microcephaly v0.198 NACC1 Zornitza Stark Publications for gene: NACC1 were set to
Microcephaly v0.197 NACC1 Zornitza Stark Mode of inheritance for gene: NACC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.196 NACC1 Zornitza Stark Classified gene: NACC1 as Amber List (moderate evidence)
Microcephaly v0.196 NACC1 Zornitza Stark Gene: nacc1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.195 NACC1 Zornitza Stark reviewed gene: NACC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28132692; Phenotypes: Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination , MIM#617393; Mode of inheritance: None
Microcephaly v0.195 MYCN Zornitza Stark edited their review of gene: MYCN: Changed rating: GREEN; Changed phenotypes: Feingold syndrome 1, MIM# 164280
Microcephaly v0.195 MYCN Zornitza Stark Marked gene: MYCN as ready
Microcephaly v0.195 MYCN Zornitza Stark Gene: mycn has been classified as Green List (High Evidence).
Microcephaly v0.195 MYCN Zornitza Stark Classified gene: MYCN as Green List (high evidence)
Microcephaly v0.195 MYCN Zornitza Stark Gene: mycn has been classified as Green List (High Evidence).
Microcephaly v0.194 MYCN Zornitza Stark gene: MYCN was added
gene: MYCN was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: MYCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYCN were set to 18470948
Phenotypes for gene: MYCN were set to Feingold syndrome 1, MIM# 164280
Added comment: Well established gene-disease association, microcephaly is a key feature.
Sources: Expert list
Microcephaly v0.193 MRE11 Zornitza Stark Marked gene: MRE11 as ready
Microcephaly v0.193 MRE11 Zornitza Stark Gene: mre11 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.193 MRE11 Zornitza Stark Phenotypes for gene: MRE11 were changed from to Nijmegen breakage syndrome-like severe microcephaly
Microcephaly v0.192 MRE11 Zornitza Stark Publications for gene: MRE11 were set to
Microcephaly v0.191 ZNF335 Paul De Fazio reviewed gene: ZNF335: Rating: GREEN; Mode of pathogenicity: None; Publications: 23178126, 27540107, 29652087; Phenotypes: Microcephaly 10, primary, autosomal recessive (MIM#615095); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v0.191 MRE11 Zornitza Stark Mode of inheritance for gene: MRE11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.190 MRE11 Zornitza Stark Classified gene: MRE11 as Amber List (moderate evidence)
Microcephaly v0.190 MRE11 Zornitza Stark Gene: mre11 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.189 MRE11 Zornitza Stark reviewed gene: MRE11: Rating: AMBER; Mode of pathogenicity: None; Publications: 21227757; Phenotypes: Nijmegen breakage syndrome-like severe microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.189 BLM Ain Roesley Deleted their comment
Microcephaly v0.189 MED17 Zornitza Stark Marked gene: MED17 as ready
Microcephaly v0.189 MED17 Zornitza Stark Gene: med17 has been classified as Green List (High Evidence).
Microcephaly v0.189 MED17 Zornitza Stark Phenotypes for gene: MED17 were changed from to Microcephaly, postnatal progressive, with seizures and brain atrophy, MIM# 613668
Microcephaly v0.188 WDR73 Paul De Fazio gene: WDR73 was added
gene: WDR73 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WDR73 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR73 were set to 25466283; 26123727; 25873735; 26070982; 30315938
Phenotypes for gene: WDR73 were set to Galloway-Mowat syndrome 1 MIM#251300
Review for gene: WDR73 was set to GREEN
gene: WDR73 was marked as current diagnostic
Added comment: Summary: many individuals with progressive microcephaly reported, though only a few (4
families) with head circumference -3SD.

PMID 25466283: Three affected children from two families with LoF variants. All had progressive microcephaly among other phenotypes (e.g. facial dysmorphisms, brain MRI anomalies). Head circumferences were -3SD at 5yo, -2.5SD at 2yo, -3SD at 10yo.

PMID 26123727: 9 individuals from 4 families with "Microcephaly (< 3rd centile)" and biallelic variants, ranging in age from 2.5yo to 31yo.

PMID 26070982: describes 30 Amish individuals with the same homozygous LoF variant, 80% of whom (24 individuals) had head circumference <-2SD.

PMID 25873735: 2 sibs with biallelic LoF variants and head circumference -1.8SD at 12yo and −1.15SD at 5yo respectively.

PMID 30315938: 2 families with homozygous missense variants. All had postnatal microcephaly: -2.5SD, -4,5SD, -3,8SD from 1 family and -3 SD from the other.
Sources: Literature
Microcephaly v0.188 MED17 Zornitza Stark Publications for gene: MED17 were set to
Microcephaly v0.187 MED17 Zornitza Stark Mode of inheritance for gene: MED17 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.186 MED17 Zornitza Stark reviewed gene: MED17: Rating: GREEN; Mode of pathogenicity: None; Publications: 20950787, 30345598, 26004231; Phenotypes: Microcephaly, postnatal progressive, with seizures and brain atrophy, MIM# 613668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.186 MECP2 Zornitza Stark Marked gene: MECP2 as ready
Microcephaly v0.186 MECP2 Zornitza Stark Gene: mecp2 has been classified as Green List (High Evidence).
Microcephaly v0.186 MECP2 Zornitza Stark Phenotypes for gene: MECP2 were changed from to Rett syndrome, MIM# 312750; Encephalopathy, neonatal severe 300673
Microcephaly v0.185 MECP2 Zornitza Stark Mode of inheritance for gene: MECP2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Microcephaly v0.184 MECP2 Zornitza Stark reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rett syndrome, MIM# 312750, Encephalopathy, neonatal severe 300673; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Microcephaly v0.184 ATRIP Zornitza Stark Marked gene: ATRIP as ready
Microcephaly v0.184 ATRIP Zornitza Stark Gene: atrip has been classified as Red List (Low Evidence).
Microcephaly v0.184 ATRIP Zornitza Stark Classified gene: ATRIP as Red List (low evidence)
Microcephaly v0.184 ATRIP Zornitza Stark Gene: atrip has been classified as Red List (Low Evidence).
Microcephaly v0.183 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Microcephaly v0.183 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Green List (High Evidence).
Microcephaly v0.183 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from to hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations
Microcephaly v0.182 ATP1A2 Zornitza Stark Publications for gene: ATP1A2 were set to
Microcephaly v0.181 ATP1A2 Zornitza Stark Mode of inheritance for gene: ATP1A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.180 ARCN1 Zornitza Stark Marked gene: ARCN1 as ready
Microcephaly v0.180 ARCN1 Zornitza Stark Added comment: Comment when marking as ready: Borderline Amber/Green. Microcephaly is a key part of the phenotype but few measurements actually reported.
Microcephaly v0.180 ARCN1 Zornitza Stark Gene: arcn1 has been classified as Green List (High Evidence).
Microcephaly v0.180 ARCN1 Zornitza Stark Phenotypes for gene: ARCN1 were changed from to Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (MIM#617164)
Microcephaly v0.179 ARCN1 Zornitza Stark Publications for gene: ARCN1 were set to
Microcephaly v0.178 ARCN1 Zornitza Stark Mode of inheritance for gene: ARCN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.177 AP4S1 Zornitza Stark Marked gene: AP4S1 as ready
Microcephaly v0.177 AP4S1 Zornitza Stark Added comment: Comment when marking as ready: Borderline Amber/Green as only one affected individual <-3SD; however, part of same gene family as other spastic paraplegias with microcephaly.
Microcephaly v0.177 AP4S1 Zornitza Stark Gene: ap4s1 has been classified as Green List (High Evidence).
Microcephaly v0.177 AP4S1 Zornitza Stark Phenotypes for gene: AP4S1 were changed from to Spastic paraplegia 52, autosomal recessive (MIM#614067)
Microcephaly v0.176 AP4S1 Zornitza Stark Publications for gene: AP4S1 were set to
Microcephaly v0.175 AP4S1 Zornitza Stark Mode of inheritance for gene: AP4S1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.174 AP4M1 Zornitza Stark Marked gene: AP4M1 as ready
Microcephaly v0.174 AP4M1 Zornitza Stark Gene: ap4m1 has been classified as Green List (High Evidence).
Microcephaly v0.174 AP4M1 Zornitza Stark Phenotypes for gene: AP4M1 were changed from to Spastic paraplegia 50, autosomal recessive (MIM#612936)
Microcephaly v0.173 AP4M1 Zornitza Stark Publications for gene: AP4M1 were set to
Microcephaly v0.172 AP4M1 Zornitza Stark Mode of inheritance for gene: AP4M1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.171 BLM Ain Roesley gene: BLM was added
gene: BLM was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: BLM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLM were set to 30214071
Phenotypes for gene: BLM were set to Bloom syndrome (MIM#210900)
Penetrance for gene: BLM were set to unknown
Review for gene: BLM was set to RED
Added comment: Microcephaly is a feature of Bloom Syndrome, however there is limited evidence for the association of microcephaly with BLM gene specifically.

PMID: 30214071;
in a cohort of microcephalic patients (<=-2SD), 1 family with 2 affecteds are homozygous for a nonsense variant
Sources: Literature
Microcephaly v0.171 ATRIP Ain Roesley gene: ATRIP was added
gene: ATRIP was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ATRIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATRIP were set to 23144622
Phenotypes for gene: ATRIP were set to Seckel Syndrome
Penetrance for gene: ATRIP were set to unknown
Review for gene: ATRIP was set to RED
Added comment: PMID: 23144622;
- 1x proband from a consanguineous family
- progressive severe microcephaly (-9 to -10SD)
- cHet for a nonsense and a splice
Sources: Literature
Microcephaly v0.171 ATP1A2 Ain Roesley reviewed gene: ATP1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30690204, 31608932; Phenotypes: hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.171 ARCN1 Ain Roesley reviewed gene: ARCN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27476655; Phenotypes: Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (MIM#617164); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Microcephaly v0.171 AP4S1 Ain Roesley reviewed gene: AP4S1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21620353, 25552650, 27444738; Phenotypes: Spastic paraplegia 52, autosomal recessive (MIM#614067); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.171 AP4M1 Ain Roesley edited their review of gene: AP4M1: Changed publications: 28464862, 24700674
Microcephaly v0.171 AP4M1 Ain Roesley changed review comment from: PMID: 28464862;
- 1x with severe progressive microcephaly (< - 4 SD)
- homozygous nonsense

PMID: 24700674;
- 2x unrelated patients (1 and 3) < -3 SD head circumference
- 2x homozygous nonsense

PMID: 21620353 ;
- 3 families with 4 affecteds ( < -3 SD)
- all PTVs; to: PMID: 28464862;
- 1x with severe progressive microcephaly (< - 4 SD)
- homozygous nonsense

PMID: 24700674;
- 2x unrelated patients (1 and 3) < -3 SD head circumference
- 2x homozygous nonsense
Microcephaly v0.171 AP4M1 Ain Roesley reviewed gene: AP4M1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28464862, 24700674, 21620353; Phenotypes: Spastic paraplegia 50, autosomal recessive (MIM#612936); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.171 AKT3 Zornitza Stark changed review comment from: Activating variants in AKT2 and micro duplications are associated with macrocephaly/megalencephaly. Note that deletions involving AKT3 have consistently been associated with microcephaly. However, most involve at least one other gene apart from AKT3. One family reported with only AKT3 deleted: deletion was inherited from a phenotypically normal parent, suggesting either additional effects in bigger deletions or incomplete penetrance.; to: Activating variants in AKT3 and micro duplications are associated with macrocephaly/megalencephaly. Note that deletions involving AKT3 have consistently been associated with microcephaly. However, most involve at least one other gene apart from AKT3. One family reported with only AKT3 deleted: deletion was inherited from a phenotypically normal parent, suggesting either additional effects in bigger deletions or incomplete penetrance.
Microcephaly v0.171 AKT3 Zornitza Stark Marked gene: AKT3 as ready
Microcephaly v0.171 AKT3 Zornitza Stark Gene: akt3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.171 AKT3 Zornitza Stark Phenotypes for gene: AKT3 were changed from to Microcephaly
Microcephaly v0.170 AKT3 Zornitza Stark Publications for gene: AKT3 were set to
Microcephaly v0.169 AKT3 Zornitza Stark Mode of inheritance for gene: AKT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.168 AKT3 Zornitza Stark Classified gene: AKT3 as Amber List (moderate evidence)
Microcephaly v0.168 AKT3 Zornitza Stark Gene: akt3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.167 AKT3 Zornitza Stark Tag SV/CNV tag was added to gene: AKT3.
Microcephaly v0.167 AKT3 Zornitza Stark reviewed gene: AKT3: Rating: AMBER; Mode of pathogenicity: None; Publications: 32827175, 31929334, 30853971, 30053339, 25424989; Phenotypes: Microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.167 AP4E1 Zornitza Stark Marked gene: AP4E1 as ready
Microcephaly v0.167 AP4E1 Zornitza Stark Gene: ap4e1 has been classified as Green List (High Evidence).
Microcephaly v0.167 AP4E1 Zornitza Stark Phenotypes for gene: AP4E1 were changed from to Spastic paraplegia 51, autosomal recessive, MIM# 613744
Microcephaly v0.166 AP4E1 Zornitza Stark Publications for gene: AP4E1 were set to
Microcephaly v0.165 AP4E1 Zornitza Stark Mode of inheritance for gene: AP4E1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.164 AP4E1 Zornitza Stark reviewed gene: AP4E1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20972249, 21620353, 21937992; Phenotypes: Spastic paraplegia 51, autosomal recessive, MIM# 613744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.164 AP4B1 Zornitza Stark Marked gene: AP4B1 as ready
Microcephaly v0.164 AP4B1 Zornitza Stark Gene: ap4b1 has been classified as Green List (High Evidence).
Microcephaly v0.164 AP4B1 Zornitza Stark Phenotypes for gene: AP4B1 were changed from to Spastic paraplegia 47, autosomal recessive, MIM# 614066
Microcephaly v0.163 AP4B1 Zornitza Stark Publications for gene: AP4B1 were set to
Microcephaly v0.162 AP4B1 Zornitza Stark Mode of inheritance for gene: AP4B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.161 AP4B1 Zornitza Stark reviewed gene: AP4B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21620353, 22290197, 24700674, 24781758; Phenotypes: Spastic paraplegia 47, autosomal recessive, MIM# 614066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.161 ANKLE2 Zornitza Stark Marked gene: ANKLE2 as ready
Microcephaly v0.161 ANKLE2 Zornitza Stark Gene: ankle2 has been classified as Green List (High Evidence).
Microcephaly v0.161 ANKLE2 Zornitza Stark Phenotypes for gene: ANKLE2 were changed from to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Microcephaly v0.160 ANKLE2 Zornitza Stark Publications for gene: ANKLE2 were set to
Microcephaly v0.159 ANKLE2 Zornitza Stark Mode of inheritance for gene: ANKLE2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.158 ANKLE2 Zornitza Stark reviewed gene: ANKLE2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25259927, 30214071, 31735666; Phenotypes: Microcephaly 16, primary, autosomal recessive, MIM# 616681; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.158 AARS Zornitza Stark Marked gene: AARS as ready
Microcephaly v0.158 AARS Zornitza Stark Gene: aars has been classified as Green List (High Evidence).
Microcephaly v0.158 AARS Zornitza Stark Classified gene: AARS as Green List (high evidence)
Microcephaly v0.158 AARS Zornitza Stark Gene: aars has been classified as Green List (High Evidence).
Microcephaly v0.157 AARS Zornitza Stark gene: AARS was added
gene: AARS was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: AARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS were set to 28493438; 25817015
Phenotypes for gene: AARS were set to Epileptic encephalopathy, early infantile, 29, MIM# 616339
Review for gene: AARS was set to GREEN
Added comment: Bi-allelic variants associated with a severe phenotype comprising leukodystrophy, epilepsy, microcephaly and neurodevelopmental delay reported in three families.
Sources: Expert Review
Microcephaly v0.156 PAFAH1B1 Zornitza Stark Marked gene: PAFAH1B1 as ready
Microcephaly v0.156 PAFAH1B1 Zornitza Stark Gene: pafah1b1 has been classified as Green List (High Evidence).
Microcephaly v0.156 PAFAH1B1 Zornitza Stark Phenotypes for gene: PAFAH1B1 were changed from to Lissencephaly 1, MIM# 607432; Subcortical laminar heterotopia, MIM# 607432; MONDO:0011830
Microcephaly v0.155 PAFAH1B1 Zornitza Stark Publications for gene: PAFAH1B1 were set to
Microcephaly v0.154 PAFAH1B1 Zornitza Stark Mode of inheritance for gene: PAFAH1B1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.153 PAFAH1B1 Zornitza Stark Tag SV/CNV tag was added to gene: PAFAH1B1.
Microcephaly v0.153 PAFAH1B1 Zornitza Stark reviewed gene: PAFAH1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11754098, 18285425; Phenotypes: Lissencephaly 1, MIM# 607432, Subcortical laminar heterotopia, MIM# 607432, MONDO:0011830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.153 KIF2A Zornitza Stark Marked gene: KIF2A as ready
Microcephaly v0.153 KIF2A Zornitza Stark Gene: kif2a has been classified as Green List (High Evidence).
Microcephaly v0.153 KIF2A Zornitza Stark Classified gene: KIF2A as Green List (high evidence)
Microcephaly v0.153 KIF2A Zornitza Stark Gene: kif2a has been classified as Green List (High Evidence).
Microcephaly v0.152 KIF2A Zornitza Stark gene: KIF2A was added
gene: KIF2A was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: KIF2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF2A were set to 23603762; 27896282; 27747449; 29077851; 31919497
Phenotypes for gene: KIF2A were set to Cortical dysplasia, complex, with other brain malformations 3, MIM# 615411
Review for gene: KIF2A was set to GREEN
Added comment: At least five unrelated families reported, with various malformations of cortical development including lissencephaly, agyria, posterior or frontal pachygyria, subcortical band heterotopia, and thin corpus callosum; microcephaly, intellectual disability and seizures. Microcephaly is in the range of -2SD -4.5SD, described as progressive in at least one individual. Some normocephalic but lower end of normal range. Some recurrent missense at p.Ser317 and p.His321. Functional data supports gene-disease association.
Sources: Expert Review
Microcephaly v0.151 ARFGEF2 Zornitza Stark Marked gene: ARFGEF2 as ready
Microcephaly v0.151 ARFGEF2 Zornitza Stark Gene: arfgef2 has been classified as Green List (High Evidence).
Microcephaly v0.151 ARFGEF2 Zornitza Stark Phenotypes for gene: ARFGEF2 were changed from to Periventricular heterotopia with microcephaly (MIM#608097)
Microcephaly v0.150 ARFGEF2 Zornitza Stark Publications for gene: ARFGEF2 were set to
Microcephaly v0.149 ARFGEF2 Zornitza Stark Mode of inheritance for gene: ARFGEF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.148 ARFGEF2 Zornitza Stark reviewed gene: ARFGEF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25160555, 26126837, 23812912; Phenotypes: Periventricular heterotopia with microcephaly (MIM#608097); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.148 SMO Zornitza Stark Phenotypes for gene: SMO were changed from Microcephaly, congenital heart disease, polydactyly, aganglionosis to Microcephaly, congenital heart disease, polydactyly, aganglionosis; Pallister-Hall-like syndrome , MIM#241800
Microcephaly v0.147 RAC1 Zornitza Stark Marked gene: RAC1 as ready
Microcephaly v0.147 RAC1 Zornitza Stark Gene: rac1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.147 RAC1 Zornitza Stark Phenotypes for gene: RAC1 were changed from to Mental retardation, autosomal dominant 48, MIM# 617751
Microcephaly v0.146 RAC1 Zornitza Stark Publications for gene: RAC1 were set to
Microcephaly v0.145 RAC1 Zornitza Stark Mode of inheritance for gene: RAC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.144 RAC1 Zornitza Stark Classified gene: RAC1 as Amber List (moderate evidence)
Microcephaly v0.144 RAC1 Zornitza Stark Gene: rac1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.143 RAC1 Zornitza Stark reviewed gene: RAC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30042656, 29276006, 30293988; Phenotypes: Mental retardation, autosomal dominant 48, MIM# 617751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.143 ASPM Zornitza Stark Marked gene: ASPM as ready
Microcephaly v0.143 ASPM Zornitza Stark Gene: aspm has been classified as Green List (High Evidence).
Microcephaly v0.143 ASPM Zornitza Stark Phenotypes for gene: ASPM were changed from to Microcephaly 5, primary, autosomal recessive, MIM#608716
Microcephaly v0.142 ASPM Zornitza Stark Publications for gene: ASPM were set to
Microcephaly v0.141 ASPM Zornitza Stark Mode of inheritance for gene: ASPM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.140 ASPM Zornitza Stark reviewed gene: ASPM: Rating: GREEN; Mode of pathogenicity: None; Publications: 29243349, 19028728; Phenotypes: Microcephaly 5, primary, autosomal recessive, MIM#608716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.140 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Microcephaly v0.139 GRM7 Zornitza Stark edited their review of gene: GRM7: Changed phenotypes: Epilepsy, microcephaly, developmental delay, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Microcephaly v0.139 HIST1H4C Zornitza Stark Marked gene: HIST1H4C as ready
Microcephaly v0.139 HIST1H4C Zornitza Stark Gene: hist1h4c has been classified as Green List (High Evidence).
Microcephaly v0.139 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from to Growth delay, microcephaly and intellectual disability
Microcephaly v0.138 HIST1H4C Zornitza Stark Publications for gene: HIST1H4C were set to
Microcephaly v0.137 HIST1H4C Zornitza Stark Mode of inheritance for gene: HIST1H4C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.136 HIST1H4C Zornitza Stark reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 28920961; Phenotypes: Growth delay, microcephaly and intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.136 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Microcephaly v0.136 ADD3 Zornitza Stark Added comment: Comment when marking as ready: Microcephaly is borderline.
Microcephaly v0.136 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.136 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Microcephaly v0.136 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.136 ADD3 Zornitza Stark Classified gene: ADD3 as Amber List (moderate evidence)
Microcephaly v0.136 ADD3 Zornitza Stark Gene: add3 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.135 ADD3 Elena Savva gene: ADD3 was added
gene: ADD3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to PMID: 23836506; 29768408
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3 617008
Review for gene: ADD3 was set to GREEN
Added comment: PMID: 29768408;23836506 - 9/10 patients (4 families) with borderline microcephaly
Sources: Literature
Microcephaly v0.135 EXOC7 Zornitza Stark Marked gene: EXOC7 as ready
Microcephaly v0.135 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Microcephaly v0.135 PDCD6IP Zornitza Stark Marked gene: PDCD6IP as ready
Microcephaly v0.135 PDCD6IP Zornitza Stark Added comment: Comment when marking as ready: Single family and animal models, upgrade to Amber.
Microcephaly v0.135 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Microcephaly v0.135 PDCD6IP Zornitza Stark Classified gene: PDCD6IP as Amber List (moderate evidence)
Microcephaly v0.135 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Microcephaly v0.134 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Microcephaly v0.134 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Microcephaly v0.133 EXOC7 Chirag Patel gene: EXOC7 was added
gene: EXOC7 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to PMID: 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Microcephaly v0.132 PDCD6IP Chirag Patel gene: PDCD6IP was added
gene: PDCD6IP was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to PMID: 32286682
Phenotypes for gene: PDCD6IP were set to Primary microcephaly
Review for gene: PDCD6IP was set to RED
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Microcephaly v0.131 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Microcephaly v0.131 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Microcephaly v0.131 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Microcephaly v0.131 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Microcephaly v0.130 DPM1 Zornitza Stark Marked gene: DPM1 as ready
Microcephaly v0.130 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Microcephaly v0.130 DPM1 Zornitza Stark Classified gene: DPM1 as Green List (high evidence)
Microcephaly v0.130 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Microcephaly v0.129 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Neuromuscular disorder
Review for gene: GOLGA2 was set to GREEN
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients + animal model
Sources: Literature
Microcephaly v0.129 DPM1 Elena Savva gene: DPM1 was added
gene: DPM1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DPM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPM1 were set to PMID:16641202; 10642602; 10642597
Phenotypes for gene: DPM1 were set to Congenital disorder of glycosylation, type Ie 608799
Added comment: PMID: 16641202 - 2 siblings of consanguineous parents. One patient showed retarded motor skills at 1, 2 and 4 years old, with distal myopathy present at 3 years of age. The younger sister presented at 7 weeks of age with generalized hypotonia. Both had normal CK levels. Both siblings were progressively microcephalic.

PMID: 10642602 - 2 chet siblings with hypotonia within the first year of life. Both had elevated CK. Both siblings were progressively microcephalic

PMID: 10642597 - 2 unrelated patients. One had profound hypotonia at 3 years of age. The other patient was markedly hypotonic in infancy. Both were microcephalic and hd elevated CK levels.
Sources: Literature
Microcephaly v0.129 SMO Zornitza Stark Marked gene: SMO as ready
Microcephaly v0.129 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Microcephaly v0.129 SMO Zornitza Stark Classified gene: SMO as Green List (high evidence)
Microcephaly v0.129 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Microcephaly v0.128 SMO Zornitza Stark gene: SMO was added
gene: SMO was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMO were set to 32413283
Phenotypes for gene: SMO were set to Microcephaly, congenital heart disease, polydactyly, aganglionosis
Review for gene: SMO was set to GREEN
Added comment: Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Sources: Literature
Microcephaly v0.127 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Microcephaly v0.127 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Microcephaly v0.127 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Microcephaly v0.127 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Microcephaly v0.126 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model.
Sources: Literature
Microcephaly v0.125 CSNK2A1 Zornitza Stark Marked gene: CSNK2A1 as ready
Microcephaly v0.125 CSNK2A1 Zornitza Stark Gene: csnk2a1 has been classified as Green List (High Evidence).
Microcephaly v0.125 CSNK2A1 Bryony Thompson Classified gene: CSNK2A1 as Green List (high evidence)
Microcephaly v0.125 CSNK2A1 Bryony Thompson Gene: csnk2a1 has been classified as Green List (High Evidence).
Microcephaly v0.124 CSNK2A1 Bryony Thompson gene: CSNK2A1 was added
gene: CSNK2A1 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: CSNK2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK2A1 were set to 29240241
Phenotypes for gene: CSNK2A1 were set to Okur-Chung neurodevelopmental syndrome MIM#617062
Review for gene: CSNK2A1 was set to GREEN
Added comment: Microcephaly is a feature of the condition in 8/14 cases with de novo variants.
Sources: Expert list
Microcephaly v0.123 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Microcephaly v0.123 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Microcephaly v0.123 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Microcephaly v0.123 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Microcephaly v0.122 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Literature
Microcephaly v0.121 VPS51 Zornitza Stark changed review comment from: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list; to: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable. Microcephaly -3/-4SD.
Sources: Expert list
Microcephaly v0.121 VPS51 Zornitza Stark gene: VPS51 was added
gene: VPS51 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list
Microcephaly v0.120 CEP55 Zornitza Stark Marked gene: CEP55 as ready
Microcephaly v0.120 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Microcephaly v0.120 CEP55 Zornitza Stark Classified gene: CEP55 as Green List (high evidence)
Microcephaly v0.120 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Microcephaly v0.119 CEP55 Zornitza Stark gene: CEP55 was added
gene: CEP55 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CEP55 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP55 were set to 32100459
Phenotypes for gene: CEP55 were set to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500; Microcephaly; Intellectual disability
Review for gene: CEP55 was set to GREEN
Added comment: Homozygous nonsense variants in CEP55 are associated with a lethal condition characterized by multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly (MARCH syndrome) also known as Meckel-like syndrome. New report of seven living individuals from five families with biallelic CEP55 variants. Four unrelated individuals with microcephaly, speech delays, and bilateral toe syndactyly all had a common CEP55 variant c.70G>A p.(Glu24Lys) in trans with nonsense variants. Three siblings were homozygous for a consensus splice site variant near the end of the gene. These affected girls all had severely delayed development, microcephaly, and varying degrees of lissencephaly/pachygyria. This series suggests that individuals with compound heterozygosity for nonsense and missense variants in CEP55 have a different viable phenotype.
Sources: Literature
Microcephaly v0.118 C7orf43 Zornitza Stark Marked gene: C7orf43 as ready
Microcephaly v0.118 C7orf43 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name: MAP11
Microcephaly v0.118 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.118 C7orf43 Zornitza Stark Classified gene: C7orf43 as Amber List (moderate evidence)
Microcephaly v0.118 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.117 C7orf43 Zornitza Stark gene: C7orf43 was added
gene: C7orf43 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: C7orf43 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C7orf43 were set to 30715179
Phenotypes for gene: C7orf43 were set to Microcephaly 25, primary, autosomal recessive, MIM# 618351
Review for gene: C7orf43 was set to AMBER
Added comment: Single family reported: three affected siblings with homozygous truncating variant. Supportive zebrafish model.
Sources: Literature
Microcephaly v0.116 TSEN34 Zornitza Stark Marked gene: TSEN34 as ready
Microcephaly v0.116 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Microcephaly v0.116 TSEN34 Zornitza Stark Phenotypes for gene: TSEN34 were changed from to Pontocerebellar hypoplasia type 2C, MIM# 612390
Microcephaly v0.115 TSEN34 Zornitza Stark Publications for gene: TSEN34 were set to
Microcephaly v0.114 TSEN34 Zornitza Stark Mode of inheritance for gene: TSEN34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.113 TSEN34 Zornitza Stark Classified gene: TSEN34 as Red List (low evidence)
Microcephaly v0.113 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Microcephaly v0.112 TSEN34 Zornitza Stark reviewed gene: TSEN34: Rating: RED; Mode of pathogenicity: None; Publications: 18711368; Phenotypes: Pontocerebellar hypoplasia type 2C, MIM# 612390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.112 TRAPPC9 Zornitza Stark Marked gene: TRAPPC9 as ready
Microcephaly v0.112 TRAPPC9 Zornitza Stark Gene: trappc9 has been classified as Green List (High Evidence).
Microcephaly v0.112 TRAPPC9 Zornitza Stark Phenotypes for gene: TRAPPC9 were changed from to Mental retardation, autosomal recessive 13, MIM# 613192
Microcephaly v0.111 TRAPPC9 Zornitza Stark Publications for gene: TRAPPC9 were set to
Microcephaly v0.110 TRAPPC9 Zornitza Stark Mode of inheritance for gene: TRAPPC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.109 TRAPPC9 Zornitza Stark reviewed gene: TRAPPC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 22549410, 20004765, 20004763, 30853973; Phenotypes: Mental retardation, autosomal recessive 13, MIM# 613192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.109 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract to microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Microcephaly v0.108 NUP188 Zornitza Stark Publications for gene: NUP188 were set to https://doi.org/10.1159/000504818; 28726809
Microcephaly v0.107 NUP188 Zornitza Stark Classified gene: NUP188 as Green List (high evidence)
Microcephaly v0.107 NUP188 Zornitza Stark Gene: nup188 has been classified as Green List (High Evidence).
Microcephaly v0.106 NUP188 Zornitza Stark edited their review of gene: NUP188: Added comment: Additional 6 unrelated individuals with bi-allelic LoF variants reported, promoted to Green.; Changed rating: GREEN; Changed publications: 32021605, 28726809, 32275884; Changed phenotypes: microcephaly, ID, cataract, structural brain abnormalities, hypoventilation
Microcephaly v0.106 NSMCE2 Zornitza Stark Marked gene: NSMCE2 as ready
Microcephaly v0.106 NSMCE2 Zornitza Stark Gene: nsmce2 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.106 NSMCE2 Tiong Tan Classified gene: NSMCE2 as Amber List (moderate evidence)
Microcephaly v0.106 NSMCE2 Tiong Tan Gene: nsmce2 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.105 NSMCE2 Tiong Tan gene: NSMCE2 was added
gene: NSMCE2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: NSMCE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSMCE2 were set to 25105364
Phenotypes for gene: NSMCE2 were set to SECKEL SYNDROME 10
Penetrance for gene: NSMCE2 were set to Complete
Review for gene: NSMCE2 was set to AMBER
Added comment: Biallelic hypomorphic variants in two unrelated women with microcephalic primordial dwarfism, insulin-resistant diabetes, fatty liver, and hypertriglyceridemia developing in childhood; and primary gonadal failure. Good quality functional evidence. No additional confirmatory cases since 2014 publication
Sources: Literature
Microcephaly v0.104 FRMD4A Zornitza Stark Marked gene: FRMD4A as ready
Microcephaly v0.104 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Microcephaly v0.104 FRMD4A Zornitza Stark Classified gene: FRMD4A as Amber List (moderate evidence)
Microcephaly v0.104 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Microcephaly v0.103 FRMD4A Zornitza Stark gene: FRMD4A was added
gene: FRMD4A was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: FRMD4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRMD4A were set to 25388005; 30214071
Phenotypes for gene: FRMD4A were set to Intellectual disability; microcephaly; Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia, MIM# 616819
Review for gene: FRMD4A was set to AMBER
Added comment: Single Bedouin Israeli family reported with homozygous variant initially. Good segregation data. No functional data. Another family reported as part of a large consanguineous microcephaly cohort, different variant.
Sources: Expert Review
Microcephaly v0.102 ADARB1 Zornitza Stark Classified gene: ADARB1 as Green List (high evidence)
Microcephaly v0.102 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Green List (High Evidence).
Microcephaly v0.101 ADARB1 Zornitza Stark gene: ADARB1 was added
gene: ADARB1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ADARB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADARB1 were set to 32220291
Phenotypes for gene: ADARB1 were set to Intellectual disability; microcephaly; seizures
Review for gene: ADARB1 was set to GREEN
Added comment: Four unrelated individuals with bi-allelic variants in this gene.
Sources: Literature
Microcephaly v0.100 GPT2 Zornitza Stark Marked gene: GPT2 as ready
Microcephaly v0.100 GPT2 Zornitza Stark Gene: gpt2 has been classified as Green List (High Evidence).
Microcephaly v0.100 GPT2 Zornitza Stark Classified gene: GPT2 as Green List (high evidence)
Microcephaly v0.100 GPT2 Zornitza Stark Gene: gpt2 has been classified as Green List (High Evidence).
Microcephaly v0.99 GPT2 Zornitza Stark gene: GPT2 was added
gene: GPT2 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: GPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPT2 were set to 27601654; 25758935
Phenotypes for gene: GPT2 were set to Mental retardation, autosomal recessive 49, MIM#616281
Review for gene: GPT2 was set to GREEN
Added comment: Two missense and 1 truncating variants reported, in 3 unrelated consanguineous families with intellectual and developmental disabilities and microcephaly. Functional studies showed loss of enzyme activity.
Sources: Expert list
Microcephaly v0.98 MFSD2A Zornitza Stark Marked gene: MFSD2A as ready
Microcephaly v0.98 MFSD2A Zornitza Stark Gene: mfsd2a has been classified as Green List (High Evidence).
Microcephaly v0.98 MFSD2A Zornitza Stark Phenotypes for gene: MFSD2A were changed from to Microcephaly 15, primary, autosomal recessive, MIM# 616486
Microcephaly v0.97 MFSD2A Zornitza Stark Publications for gene: MFSD2A were set to
Microcephaly v0.96 MFSD2A Zornitza Stark Mode of inheritance for gene: MFSD2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.95 MFSD2A Zornitza Stark reviewed gene: MFSD2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 26005865, 26005868, 24828044; Phenotypes: Microcephaly 15, primary, autosomal recessive, MIM# 616486; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.95 BPTF Zornitza Stark Marked gene: BPTF as ready
Microcephaly v0.95 BPTF Zornitza Stark Gene: bptf has been classified as Green List (High Evidence).
Microcephaly v0.95 BPTF Zornitza Stark Phenotypes for gene: BPTF were changed from to Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, MIM# 617755
Microcephaly v0.94 BPTF Zornitza Stark Publications for gene: BPTF were set to
Microcephaly v0.93 BPTF Zornitza Stark Mode of inheritance for gene: BPTF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.92 BPTF Zornitza Stark reviewed gene: BPTF: Rating: GREEN; Mode of pathogenicity: None; Publications: 28942966; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, MIM# 617755; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.92 TRIO Zornitza Stark Marked gene: TRIO as ready
Microcephaly v0.92 TRIO Zornitza Stark Gene: trio has been classified as Green List (High Evidence).
Microcephaly v0.92 TRIO Zornitza Stark Phenotypes for gene: TRIO were changed from to Mental retardation, autosomal dominant 44, MIM# 617061
Microcephaly v0.91 TRIO Zornitza Stark Publications for gene: TRIO were set to
Microcephaly v0.90 TRIO Zornitza Stark Mode of inheritance for gene: TRIO was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.89 TRIO Zornitza Stark reviewed gene: TRIO: Rating: GREEN; Mode of pathogenicity: None; Publications: 26721934, 32109419; Phenotypes: Mental retardation, autosomal dominant 44, MIM# 617061; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.89 TAF2 Zornitza Stark Marked gene: TAF2 as ready
Microcephaly v0.89 TAF2 Zornitza Stark Gene: taf2 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.89 TAF2 Zornitza Stark Phenotypes for gene: TAF2 were changed from to Mental retardation, autosomal recessive 40, MIM# 615599
Microcephaly v0.88 TAF2 Zornitza Stark Publications for gene: TAF2 were set to
Microcephaly v0.87 TAF2 Zornitza Stark Mode of inheritance for gene: TAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.86 TAF2 Zornitza Stark Classified gene: TAF2 as Amber List (moderate evidence)
Microcephaly v0.86 TAF2 Zornitza Stark Gene: taf2 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.85 TAF2 Zornitza Stark reviewed gene: TAF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21937992, 22633631, 26350204; Phenotypes: Mental retardation, autosomal recessive 40, MIM# 615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.85 CEP135 Zornitza Stark Marked gene: CEP135 as ready
Microcephaly v0.85 CEP135 Zornitza Stark Gene: cep135 has been classified as Green List (High Evidence).
Microcephaly v0.85 CEP135 Zornitza Stark Phenotypes for gene: CEP135 were changed from to Microcephalic primordial dwarfism; Microcephaly 8, primary, autosomal recessive, 614673
Microcephaly v0.84 CEP135 Zornitza Stark Publications for gene: CEP135 were set to
Microcephaly v0.83 CEP135 Zornitza Stark Mode of inheritance for gene: CEP135 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.82 CEP135 Zornitza Stark reviewed gene: CEP135: Rating: GREEN; Mode of pathogenicity: None; Publications: 30214071, 22521416; Phenotypes: Microcephalic primordial dwarfism, Microcephaly 8, primary, autosomal recessive, 614673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.82 SASS6 Zornitza Stark Marked gene: SASS6 as ready
Microcephaly v0.82 SASS6 Zornitza Stark Gene: sass6 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.82 SASS6 Zornitza Stark Mode of inheritance for gene: SASS6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.81 SASS6 Zornitza Stark Phenotypes for gene: SASS6 were changed from Microcephaly 14, primary, autosomal recessive, MIM# 616402 to Microcephaly 14, primary, autosomal recessive, MIM# 616402
Microcephaly v0.80 SASS6 Zornitza Stark Phenotypes for gene: SASS6 were changed from to Microcephaly 14, primary, autosomal recessive, MIM# 616402
Microcephaly v0.80 SASS6 Zornitza Stark Publications for gene: SASS6 were set to
Microcephaly v0.79 SASS6 Zornitza Stark Classified gene: SASS6 as Amber List (moderate evidence)
Microcephaly v0.79 SASS6 Zornitza Stark Gene: sass6 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.78 SASS6 Zornitza Stark reviewed gene: SASS6: Rating: AMBER; Mode of pathogenicity: None; Publications: 24951542, 30639237; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.78 TUBGCP6 Zornitza Stark Marked gene: TUBGCP6 as ready
Microcephaly v0.78 TUBGCP6 Zornitza Stark Added comment: Comment when marking as ready: Originally reported in Mennonite families (founder effect) but three unrelated families reported subsequently.
Microcephaly v0.78 TUBGCP6 Zornitza Stark Gene: tubgcp6 has been classified as Green List (High Evidence).
Microcephaly v0.78 TUBGCP6 Zornitza Stark Phenotypes for gene: TUBGCP6 were changed from to Microcephaly and chorioretinopathy, autosomal recessive, 1, MIM#251270
Microcephaly v0.77 TUBGCP6 Zornitza Stark Publications for gene: TUBGCP6 were set to
Microcephaly v0.76 TUBGCP6 Zornitza Stark Mode of inheritance for gene: TUBGCP6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.75 TUBGCP6 Michelle Torres reviewed gene: TUBGCP6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25344692; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.75 XRCC4 Zornitza Stark Marked gene: XRCC4 as ready
Microcephaly v0.75 XRCC4 Zornitza Stark Gene: xrcc4 has been classified as Green List (High Evidence).
Microcephaly v0.75 XRCC4 Zornitza Stark Classified gene: XRCC4 as Green List (high evidence)
Microcephaly v0.75 XRCC4 Zornitza Stark Gene: xrcc4 has been classified as Green List (High Evidence).
Microcephaly v0.74 XRCC4 Crystle Lee gene: XRCC4 was added
gene: XRCC4 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: XRCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XRCC4 were set to PMID: 25839420; 25728776
Phenotypes for gene: XRCC4 were set to Short stature, microcephaly, and endocrine dysfunction (MIM#616541)
Review for gene: XRCC4 was set to GREEN
Added comment: Biallelic variants reported in multiple affected families with microcephaly
Sources: Literature
Microcephaly v0.74 TUBGCP2 Zornitza Stark Marked gene: TUBGCP2 as ready
Microcephaly v0.74 TUBGCP2 Zornitza Stark Gene: tubgcp2 has been classified as Green List (High Evidence).
Microcephaly v0.74 TUBGCP2 Zornitza Stark Classified gene: TUBGCP2 as Green List (high evidence)
Microcephaly v0.74 TUBGCP2 Zornitza Stark Gene: tubgcp2 has been classified as Green List (High Evidence).
Microcephaly v0.73 TUBGCP2 Zornitza Stark gene: TUBGCP2 was added
gene: TUBGCP2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP2 were set to 31630790
Phenotypes for gene: TUBGCP2 were set to Lissencephaly; pachygyria; subcortical band heterotopia; microcephaly; intellectual disability
Review for gene: TUBGCP2 was set to GREEN
Added comment: Four unrelated families reported.
Sources: Literature
Microcephaly v0.72 PCDH12 Zornitza Stark Marked gene: PCDH12 as ready
Microcephaly v0.72 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Microcephaly v0.72 PCDH12 Tiong Tan Classified gene: PCDH12 as Green List (high evidence)
Microcephaly v0.72 PCDH12 Tiong Tan Gene: pcdh12 has been classified as Green List (High Evidence).
Microcephaly v0.71 PCDH12 Tiong Tan gene: PCDH12 was added
gene: PCDH12 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: PCDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDH12 were set to 27164683; 22822038
Phenotypes for gene: PCDH12 were set to DIENCEPHALIC-MESENCEPHALIC JUNCTION DYSPLASIA SYNDROME 1
Penetrance for gene: PCDH12 were set to Complete
Review for gene: PCDH12 was set to GREEN
Added comment: Sources: Literature
Microcephaly v0.70 Zornitza Stark Panel name changed from Microcephaly_VCGS to Microcephaly
Panel types changed to Victorian Clinical Genetics Services
Microcephaly v0.69 AGMO Zornitza Stark Publications for gene: AGMO were set to 31555905
Microcephaly v0.68 AGMO Sue White Classified gene: AGMO as Green List (high evidence)
Microcephaly v0.68 AGMO Sue White Gene: agmo has been classified as Green List (High Evidence).
Microcephaly v0.67 AGMO Sue White Classified gene: AGMO as Green List (high evidence)
Microcephaly v0.67 AGMO Sue White Gene: agmo has been classified as Green List (High Evidence).
Microcephaly v0.66 AGMO Sue White Marked gene: AGMO as ready
Microcephaly v0.66 AGMO Sue White Gene: agmo has been classified as Red List (Low Evidence).
Microcephaly v0.66 AGMO Sue White gene: AGMO was added
gene: AGMO was added to Microcephaly_VCGS. Sources: Literature
Mode of inheritance for gene: AGMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGMO were set to 31555905
Phenotypes for gene: AGMO were set to microcephaly; intellectual disability; epilepsy
Penetrance for gene: AGMO were set to Complete
Review for gene: AGMO was set to GREEN
Added comment: biallelic LOF and missense variants reported
Sources: Literature
Microcephaly v0.65 DNMT3A Zornitza Stark Marked gene: DNMT3A as ready
Microcephaly v0.65 DNMT3A Zornitza Stark Added comment: Comment when marking as ready: Three individuals reported, two with the same de novo missense variant. Postulated to be GOF as opposed to LOF variants in this gene which cause an overgrowth syndrome. Animal model supports pathogenicity.
Microcephaly v0.65 DNMT3A Zornitza Stark Gene: dnmt3a has been classified as Green List (High Evidence).
Microcephaly v0.65 DNMT3A Zornitza Stark Mode of pathogenicity for gene: DNMT3A was changed from None to Other
Microcephaly v0.64 DNMT3A Zornitza Stark Classified gene: DNMT3A as Green List (high evidence)
Microcephaly v0.64 DNMT3A Zornitza Stark Gene: dnmt3a has been classified as Green List (High Evidence).
Microcephaly v0.60 DNMT3A Sue White gene: DNMT3A was added
gene: DNMT3A was added to Microcephaly_VCGS. Sources: Literature
Mode of inheritance for gene: DNMT3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNMT3A were set to 30478443
Phenotypes for gene: DNMT3A were set to intellectual disability; microcephaly; short stature
Penetrance for gene: DNMT3A were set to Complete
Review for gene: DNMT3A was set to GREEN
gene: DNMT3A was marked as current diagnostic
Added comment: gain of function heterozygous variants cause an microcephaly-primordial short stature-type phenotype with intellectual disability
Sources: Literature
Microcephaly v0.60 DNMT3A Sue White gene: DNMT3A was added
gene: DNMT3A was added to Microcephaly_VCGS. Sources: Literature
Mode of inheritance for gene: DNMT3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNMT3A were set to 30478443
Phenotypes for gene: DNMT3A were set to intellectual disability; microcephaly; short stature
Penetrance for gene: DNMT3A were set to Complete
gene: DNMT3A was marked as current diagnostic
Added comment: gain of function heterozygous variants cause an microcephaly-primordial short stature-type phenotype with intellectual disability
Sources: Literature
Microcephaly v0.59 RUSC2 Zornitza Stark Marked gene: RUSC2 as ready
Microcephaly v0.59 RUSC2 Zornitza Stark Gene: rusc2 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.59 RUSC2 Zornitza Stark Publications for gene: RUSC2 were set to
Microcephaly v0.58 RUSC2 Zornitza Stark Phenotypes for gene: RUSC2 were changed from Mental retardation, autosomal recessive 61, MIM# 617773 to Mental retardation, autosomal recessive 61, MIM# 617773
Microcephaly v0.57 RUSC2 Zornitza Stark Phenotypes for gene: RUSC2 were changed from to Mental retardation, autosomal recessive 61, MIM# 617773
Microcephaly v0.56 RUSC2 Zornitza Stark Mode of inheritance for gene: RUSC2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.55 RUSC2 Zornitza Stark Mode of inheritance for gene: RUSC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.54 RUSC2 Zornitza Stark Classified gene: RUSC2 as Amber List (moderate evidence)
Microcephaly v0.54 RUSC2 Zornitza Stark Gene: rusc2 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.53 UGP2 Zornitza Stark Marked gene: UGP2 as ready
Microcephaly v0.53 UGP2 Zornitza Stark Gene: ugp2 has been classified as Green List (High Evidence).
Microcephaly v0.53 UGP2 Zornitza Stark Classified gene: UGP2 as Green List (high evidence)
Microcephaly v0.53 UGP2 Zornitza Stark Gene: ugp2 has been classified as Green List (High Evidence).
Microcephaly v0.52 UGP2 Zornitza Stark gene: UGP2 was added
gene: UGP2 was added to Microcephaly_VCGS. Sources: Literature
Mode of inheritance for gene: UGP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGP2 were set to 31820119
Phenotypes for gene: UGP2 were set to Epileptic encephalopathy; intellectual disability; microcephaly
Added comment: 22 individuals from 15 families reported with the same homozygous missense variant in this gene, chr2:64083454A > G, which causes a disruption of the start codon in the shorter isoform, which is expressed in brain.
Sources: Literature
Microcephaly v0.51 NUP188 Zornitza Stark Marked gene: NUP188 as ready
Microcephaly v0.51 NUP188 Zornitza Stark Gene: nup188 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.51 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from to microcephaly; ID; cataract
Microcephaly v0.50 NUP188 Zornitza Stark Publications for gene: NUP188 were set to
Microcephaly v0.49 NUP188 Zornitza Stark Mode of inheritance for gene: NUP188 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.48 NUP188 Zornitza Stark Classified gene: NUP188 as Amber List (moderate evidence)
Microcephaly v0.48 NUP188 Zornitza Stark Gene: nup188 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.47 NUP188 Zornitza Stark reviewed gene: NUP188: Rating: AMBER; Mode of pathogenicity: None; Publications: https://doi.org/10.1159/000504818, 28726809; Phenotypes: microcephaly, ID, cataract; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.47 DNA2 Zornitza Stark Marked gene: DNA2 as ready
Microcephaly v0.47 DNA2 Zornitza Stark Gene: dna2 has been classified as Green List (High Evidence).
Microcephaly v0.47 DNA2 Zornitza Stark Phenotypes for gene: DNA2 were changed from to Seckel syndrome 8, MIM#615807
Microcephaly v0.46 DNA2 Zornitza Stark Publications for gene: DNA2 were set to
Microcephaly v0.45 DNA2 Zornitza Stark Mode of inheritance for gene: DNA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.44 DNA2 Zornitza Stark reviewed gene: DNA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24389050, 31045292; Phenotypes: Seckel syndrome 8, MIM#615807; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.44 SEC31A Tiong Tan Marked gene: SEC31A as ready
Microcephaly v0.44 SEC31A Tiong Tan Gene: sec31a has been classified as Amber List (Moderate Evidence).
Microcephaly v0.44 SEC31A Tiong Tan Classified gene: SEC31A as Amber List (moderate evidence)
Microcephaly v0.44 SEC31A Tiong Tan Gene: sec31a has been classified as Amber List (Moderate Evidence).
Microcephaly v0.43 SEC31A Tiong Tan gene: SEC31A was added
gene: SEC31A was added to Microcephaly_VCGS. Sources: Literature
Mode of inheritance for gene: SEC31A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEC31A were set to 30464055
Phenotypes for gene: SEC31A were set to ?Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, OMIM #618651
Review for gene: SEC31A was set to AMBER
Added comment: Single family with two affected sibs with functional data (drosophila)
Sources: Literature
Microcephaly v0.42 SVBP Zornitza Stark Marked gene: SVBP as ready
Microcephaly v0.42 SVBP Zornitza Stark Gene: svbp has been classified as Green List (High Evidence).
Microcephaly v0.42 SVBP Zornitza Stark Classified gene: SVBP as Green List (high evidence)
Microcephaly v0.42 SVBP Zornitza Stark Gene: svbp has been classified as Green List (High Evidence).
Microcephaly v0.41 SVBP Zornitza Stark gene: SVBP was added
gene: SVBP was added to Microcephaly_VCGS. Sources: Literature
Mode of inheritance for gene: SVBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVBP were set to 31363758; 30607023
Phenotypes for gene: SVBP were set to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly; OMIM #618569
Review for gene: SVBP was set to GREEN
Added comment: 5 unrelated families with homozygous mutations in SVBP. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls.
Sources: Literature
Microcephaly v0.40 RNF113A Zornitza Stark Mode of inheritance for gene: RNF113A was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v0.39 NCAPD2 Zornitza Stark Phenotypes for gene: NCAPD2 were changed from Microcephaly 21, primary, autosomal recessive; OMIM #617983 to Microcephaly 21, primary, autosomal recessive; OMIM #617983
Microcephaly v0.39 NCAPD2 Zornitza Stark Marked gene: NCAPD2 as ready
Microcephaly v0.39 NCAPD2 Zornitza Stark Gene: ncapd2 has been classified as Green List (High Evidence).
Microcephaly v0.39 NCAPD2 Zornitza Stark Phenotypes for gene: NCAPD2 were changed from to Microcephaly 21, primary, autosomal recessive; OMIM #617983
Microcephaly v0.38 NCAPD2 Zornitza Stark Mode of inheritance for gene: NCAPD2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.37 NCAPD2 Zornitza Stark Publications for gene: NCAPD2 were set to
Microcephaly v0.37 NCAPD2 Zornitza Stark Mode of inheritance for gene: NCAPD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.36 NCAPD2 Zornitza Stark reviewed gene: NCAPD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31056748, 27737959, 28097321; Phenotypes: Microcephaly 21, primary, autosomal recessive, OMIM #617983; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.36 DYNC1I2 Zornitza Stark Marked gene: DYNC1I2 as ready
Microcephaly v0.36 DYNC1I2 Zornitza Stark Gene: dync1i2 has been classified as Green List (High Evidence).
Microcephaly v0.36 DYNC1I2 Zornitza Stark Classified gene: DYNC1I2 as Green List (high evidence)
Microcephaly v0.36 DYNC1I2 Zornitza Stark Gene: dync1i2 has been classified as Green List (High Evidence).
Microcephaly v0.35 DYNC1I2 Zornitza Stark gene: DYNC1I2 was added
gene: DYNC1I2 was added to Microcephaly_VCGS. Sources: Literature
Mode of inheritance for gene: DYNC1I2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DYNC1I2 were set to 31079899
Phenotypes for gene: DYNC1I2 were set to Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492
Review for gene: DYNC1I2 was set to GREEN
Added comment: Five individuals from three unrelated families reported.
Sources: Literature
Microcephaly v0.34 RNF113A Zornitza Stark Marked gene: RNF113A as ready
Microcephaly v0.34 RNF113A Zornitza Stark Gene: rnf113a has been classified as Amber List (Moderate Evidence).
Microcephaly v0.34 RNF113A Zornitza Stark Classified gene: RNF113A as Amber List (moderate evidence)
Microcephaly v0.34 RNF113A Zornitza Stark Gene: rnf113a has been classified as Amber List (Moderate Evidence).
Microcephaly v0.33 RNF113A Zornitza Stark gene: RNF113A was added
gene: RNF113A was added to Microcephaly_VCGS. Sources: Literature
Mode of inheritance for gene: RNF113A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF113A were set to 25612912; 31793730
Phenotypes for gene: RNF113A were set to Trichothiodystrophy 5, nonphotosensitive; OMIM #300953
Review for gene: RNF113A was set to AMBER
Added comment: 1 family of 2 male cousins with IUGR, progressive microcephaly, profound ID, genital anomalies, and severe linear growth failure, and nonsense Q301X mutation in RNF113A gene. Segregated with disease in the family. The mutation markedly reduced RNF113A protein expression in extracts from lymphoblastoid cell lines derived from the affected individuals.

2 fetuses affected with abnormalities similar to previous report, with the same nonsense Q301X mutation in RNF113A gene. ?Founder effect.
Sources: Literature
Microcephaly v0.32 PUS7 Zornitza Stark Marked gene: PUS7 as ready
Microcephaly v0.32 PUS7 Zornitza Stark Gene: pus7 has been classified as Green List (High Evidence).
Microcephaly v0.32 PUS7 Zornitza Stark Classified gene: PUS7 as Green List (high evidence)
Microcephaly v0.32 PUS7 Zornitza Stark Gene: pus7 has been classified as Green List (High Evidence).
Microcephaly v0.31 PUS7 Zornitza Stark gene: PUS7 was added
gene: PUS7 was added to Microcephaly_VCGS. Sources: Literature
Mode of inheritance for gene: PUS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS7 were set to 30526862; 30778726; 31583274
Phenotypes for gene: PUS7 were set to Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature; OMIM #618342
Added comment: 11 patients from 6 families with ID, speech delay, short stature, microcephaly, and aggressive behavior, with homozygous PUS7 mutations, which segregated with disease.
Sources: Literature
Microcephaly v0.30 SELENOI Zornitza Stark Marked gene: SELENOI as ready
Microcephaly v0.30 SELENOI Zornitza Stark Gene: selenoi has been classified as Amber List (Moderate Evidence).
Microcephaly v0.30 SELENOI Zornitza Stark Publications for gene: SELENOI were set to
Microcephaly v0.29 SELENOI Zornitza Stark Phenotypes for gene: SELENOI were changed from to developmental delay; spasticity; periventricular white mater abnormalities; peripheral neuropathy; seizures; microcephaly; bifid uvula in some affected individuals
Microcephaly v0.28 SELENOI Zornitza Stark Mode of inheritance for gene: SELENOI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.27 SELENOI Zornitza Stark Classified gene: SELENOI as Amber List (moderate evidence)
Microcephaly v0.27 SELENOI Zornitza Stark Gene: selenoi has been classified as Amber List (Moderate Evidence).
Microcephaly v0.26 SELENOI Zornitza Stark reviewed gene: SELENOI: Rating: AMBER; Mode of pathogenicity: None; Publications: 28052917; Phenotypes: developmental delay, spasticity, periventricular white mater abnormalities, peripheral neuropathy, seizures, bifid uvula in some affected individuals; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.26 PHC1 Zornitza Stark Marked gene: PHC1 as ready
Microcephaly v0.26 PHC1 Zornitza Stark Gene: phc1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.26 PHC1 Zornitza Stark Phenotypes for gene: PHC1 were changed from to Microcephaly 11, primary, autosomal recessive, MIM#615414
Microcephaly v0.25 PHC1 Zornitza Stark Classified gene: PHC1 as Amber List (moderate evidence)
Microcephaly v0.25 PHC1 Zornitza Stark Gene: phc1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.24 PHC1 Zornitza Stark Publications for gene: PHC1 were set to
Microcephaly v0.23 PHC1 Zornitza Stark Mode of inheritance for gene: PHC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.23 PHC1 Zornitza Stark Classified gene: PHC1 as Amber List (moderate evidence)
Microcephaly v0.23 PHC1 Zornitza Stark Gene: phc1 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.22 PHC1 Zornitza Stark reviewed gene: PHC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23418308; Phenotypes: Microcephaly 11, primary, autosomal recessive, MIM#615414; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.22 TMX2 Zornitza Stark Marked gene: TMX2 as ready
Microcephaly v0.22 TMX2 Zornitza Stark Gene: tmx2 has been classified as Green List (High Evidence).
Microcephaly v0.22 TMX2 Zornitza Stark Phenotypes for gene: TMX2 were changed from to Microcephaly; ID; brain malformations
Microcephaly v0.21 TMX2 Zornitza Stark Publications for gene: TMX2 were set to
Microcephaly v0.20 TMX2 Zornitza Stark Mode of inheritance for gene: TMX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.19 TMX2 Zornitza Stark reviewed gene: TMX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31735293, 31586943; Phenotypes: Microcephaly, ID, brain malformations; Mode of inheritance: None
Microcephaly v0.19 NIN Zornitza Stark Marked gene: NIN as ready
Microcephaly v0.19 NIN Zornitza Stark Gene: nin has been classified as Red List (Low Evidence).
Microcephaly v0.19 NIN Zornitza Stark Phenotypes for gene: NIN were changed from to Seckel syndrome 7, MIM#614851
Microcephaly v0.18 NIN Zornitza Stark Publications for gene: NIN were set to
Microcephaly v0.17 NIN Zornitza Stark Classified gene: NIN as Red List (low evidence)
Microcephaly v0.17 NIN Zornitza Stark Gene: nin has been classified as Red List (Low Evidence).
Microcephaly v0.16 NIN Zornitza Stark Mode of inheritance for gene: NIN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.16 NIN Zornitza Stark Classified gene: NIN as Red List (low evidence)
Microcephaly v0.16 NIN Zornitza Stark Gene: nin has been classified as Red List (Low Evidence).
Microcephaly v0.14 CTNNA2 Zornitza Stark Phenotypes for gene: CTNNA2 were changed from Cortical dysplasia, complex, with other brain malformations 9, MIM#618174 to Cortical dysplasia, complex, with other brain malformations 9, MIM#618174
Microcephaly v0.13 CTNNA2 Zornitza Stark Marked gene: CTNNA2 as ready
Microcephaly v0.13 CTNNA2 Zornitza Stark Gene: ctnna2 has been classified as Green List (High Evidence).
Microcephaly v0.13 CTNNA2 Zornitza Stark Phenotypes for gene: CTNNA2 were changed from Cortical dysplasia, complex, with other brain malformations 9, MIM#618174 to Cortical dysplasia, complex, with other brain malformations 9, MIM#618174
Microcephaly v0.13 CTNNA2 Zornitza Stark Phenotypes for gene: CTNNA2 were changed from to Cortical dysplasia, complex, with other brain malformations 9, MIM#618174
Microcephaly v0.12 CTNNA2 Zornitza Stark Publications for gene: CTNNA2 were set to
Microcephaly v0.11 CTNNA2 Zornitza Stark Mode of inheritance for gene: CTNNA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.9 CEP63 Zornitza Stark Marked gene: CEP63 as ready
Microcephaly v0.9 CEP63 Zornitza Stark Gene: cep63 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.9 CEP63 Zornitza Stark Phenotypes for gene: CEP63 were changed from to Seckel syndrome 6, MIM#614728
Microcephaly v0.8 CEP63 Zornitza Stark Publications for gene: CEP63 were set to 21983783; 26158450
Microcephaly v0.8 CEP63 Zornitza Stark Publications for gene: CEP63 were set to
Microcephaly v0.7 CEP63 Zornitza Stark Mode of inheritance for gene: CEP63 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.6 CEP63 Zornitza Stark Classified gene: CEP63 as Amber List (moderate evidence)
Microcephaly v0.6 CEP63 Zornitza Stark Gene: cep63 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.5 CEP63 Zornitza Stark reviewed gene: CEP63: Rating: AMBER; Mode of pathogenicity: None; Publications: 21983783, 26158450; Phenotypes: Seckel syndrome 6, MIM#614728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.5 CDK6 Zornitza Stark Marked gene: CDK6 as ready
Microcephaly v0.5 CDK6 Zornitza Stark Gene: cdk6 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.5 CDK6 Zornitza Stark Phenotypes for gene: CDK6 were changed from to Microcephaly 12, primary, autosomal recessive, MIM#616080
Microcephaly v0.4 CDK6 Zornitza Stark Publications for gene: CDK6 were set to
Microcephaly v0.3 CDK6 Zornitza Stark Mode of inheritance for gene: CDK6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.2 CDK6 Zornitza Stark Classified gene: CDK6 as Amber List (moderate evidence)
Microcephaly v0.2 CDK6 Zornitza Stark Gene: cdk6 has been classified as Amber List (Moderate Evidence).
Microcephaly v0.1 CDK6 Zornitza Stark reviewed gene: CDK6: Rating: AMBER; Mode of pathogenicity: None; Publications: 23918663; Phenotypes: Microcephaly 12, primary, autosomal recessive, MIM#616080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.0 ZNF335 Zornitza Stark gene: ZNF335 was added
gene: ZNF335 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ZNF335 was set to Unknown
Microcephaly v0.0 ZEB2 Zornitza Stark gene: ZEB2 was added
gene: ZEB2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ZEB2 was set to Unknown
Microcephaly v0.0 WDR62 Zornitza Stark gene: WDR62 was added
gene: WDR62 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: WDR62 was set to Unknown
Microcephaly v0.0 WDR4 Zornitza Stark gene: WDR4 was added
gene: WDR4 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: WDR4 was set to Unknown
Microcephaly v0.0 WDR37 Zornitza Stark gene: WDR37 was added
gene: WDR37 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: WDR37 was set to Unknown
Microcephaly v0.0 VRK1 Zornitza Stark gene: VRK1 was added
gene: VRK1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: VRK1 was set to Unknown
Microcephaly v0.0 USP18 Zornitza Stark gene: USP18 was added
gene: USP18 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: USP18 was set to Unknown
Microcephaly v0.0 UNC80 Zornitza Stark gene: UNC80 was added
gene: UNC80 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: UNC80 was set to Unknown
Microcephaly v0.0 UBE3A Zornitza Stark gene: UBE3A was added
gene: UBE3A was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: UBE3A was set to Unknown
Microcephaly v0.0 TUBGCP6 Zornitza Stark gene: TUBGCP6 was added
gene: TUBGCP6 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TUBGCP6 was set to Unknown
Microcephaly v0.0 TUBB2B Zornitza Stark gene: TUBB2B was added
gene: TUBB2B was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TUBB2B was set to Unknown
Microcephaly v0.0 TSEN54 Zornitza Stark gene: TSEN54 was added
gene: TSEN54 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TSEN54 was set to Unknown
Microcephaly v0.0 TSEN34 Zornitza Stark gene: TSEN34 was added
gene: TSEN34 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TSEN34 was set to Unknown
Microcephaly v0.0 TSEN2 Zornitza Stark gene: TSEN2 was added
gene: TSEN2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TSEN2 was set to Unknown
Microcephaly v0.0 TRMT10A Zornitza Stark gene: TRMT10A was added
gene: TRMT10A was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRMT10A was set to Unknown
Microcephaly v0.0 TRIT1 Zornitza Stark gene: TRIT1 was added
gene: TRIT1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRIT1 was set to Unknown
Microcephaly v0.0 TRIP13 Zornitza Stark gene: TRIP13 was added
gene: TRIP13 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRIP13 was set to Unknown
Microcephaly v0.0 TRIO Zornitza Stark gene: TRIO was added
gene: TRIO was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRIO was set to Unknown
Microcephaly v0.0 TRAPPC9 Zornitza Stark gene: TRAPPC9 was added
gene: TRAPPC9 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRAPPC9 was set to Unknown
Microcephaly v0.0 TRAPPC6B Zornitza Stark gene: TRAPPC6B was added
gene: TRAPPC6B was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRAPPC6B was set to Unknown
Microcephaly v0.0 TRAPPC12 Zornitza Stark gene: TRAPPC12 was added
gene: TRAPPC12 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRAPPC12 was set to Unknown
Microcephaly v0.0 TRAIP Zornitza Stark gene: TRAIP was added
gene: TRAIP was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRAIP was set to Unknown
Microcephaly v0.0 TPRKB Zornitza Stark gene: TPRKB was added
gene: TPRKB was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TPRKB was set to Unknown
Microcephaly v0.0 TP53RK Zornitza Stark gene: TP53RK was added
gene: TP53RK was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TP53RK was set to Unknown
Microcephaly v0.0 TOP3A Zornitza Stark gene: TOP3A was added
gene: TOP3A was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TOP3A was set to Unknown
Microcephaly v0.0 TMX2 Zornitza Stark gene: TMX2 was added
gene: TMX2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TMX2 was set to Unknown
Microcephaly v0.0 TCF4 Zornitza Stark gene: TCF4 was added
gene: TCF4 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TCF4 was set to Unknown
Microcephaly v0.0 TBCD Zornitza Stark gene: TBCD was added
gene: TBCD was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TBCD was set to Unknown
Microcephaly v0.0 TBC1D20 Zornitza Stark gene: TBC1D20 was added
gene: TBC1D20 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TBC1D20 was set to Unknown
Microcephaly v0.0 TAF2 Zornitza Stark gene: TAF2 was added
gene: TAF2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TAF2 was set to Unknown
Microcephaly v0.0 STIL Zornitza Stark gene: STIL was added
gene: STIL was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: STIL was set to Unknown
Microcephaly v0.0 STAMBP Zornitza Stark gene: STAMBP was added
gene: STAMBP was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: STAMBP was set to Unknown
Microcephaly v0.0 STAG1 Zornitza Stark gene: STAG1 was added
gene: STAG1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: STAG1 was set to Unknown
Microcephaly v0.0 SLC9A6 Zornitza Stark gene: SLC9A6 was added
gene: SLC9A6 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC9A6 was set to Unknown
Microcephaly v0.0 SLC2A1 Zornitza Stark gene: SLC2A1 was added
gene: SLC2A1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC2A1 was set to Unknown
Microcephaly v0.0 SLC25A19 Zornitza Stark gene: SLC25A19 was added
gene: SLC25A19 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A19 was set to Unknown
Microcephaly v0.0 SLC1A4 Zornitza Stark gene: SLC1A4 was added
gene: SLC1A4 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC1A4 was set to Unknown
Microcephaly v0.0 SELENOI Zornitza Stark gene: SELENOI was added
gene: SELENOI was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SELENOI was set to Unknown
Microcephaly v0.0 SASS6 Zornitza Stark gene: SASS6 was added
gene: SASS6 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SASS6 was set to Unknown
Microcephaly v0.0 RUSC2 Zornitza Stark gene: RUSC2 was added
gene: RUSC2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RUSC2 was set to Unknown
Microcephaly v0.0 RTTN Zornitza Stark gene: RTTN was added
gene: RTTN was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RTTN was set to Unknown
Microcephaly v0.0 RBBP8 Zornitza Stark gene: RBBP8 was added
gene: RBBP8 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RBBP8 was set to Unknown
Microcephaly v0.0 RARS2 Zornitza Stark gene: RARS2 was added
gene: RARS2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RARS2 was set to Unknown
Microcephaly v0.0 RAC1 Zornitza Stark gene: RAC1 was added
gene: RAC1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RAC1 was set to Unknown
Microcephaly v0.0 RAB3GAP2 Zornitza Stark gene: RAB3GAP2 was added
gene: RAB3GAP2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RAB3GAP2 was set to Unknown
Microcephaly v0.0 RAB3GAP1 Zornitza Stark gene: RAB3GAP1 was added
gene: RAB3GAP1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RAB3GAP1 was set to Unknown
Microcephaly v0.0 RAB18 Zornitza Stark gene: RAB18 was added
gene: RAB18 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RAB18 was set to Unknown
Microcephaly v0.0 PUF60 Zornitza Stark gene: PUF60 was added
gene: PUF60 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PUF60 was set to Unknown
Microcephaly v0.0 PTPN23 Zornitza Stark gene: PTPN23 was added
gene: PTPN23 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PTPN23 was set to Unknown
Microcephaly v0.0 PQBP1 Zornitza Stark gene: PQBP1 was added
gene: PQBP1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PQBP1 was set to Unknown
Microcephaly v0.0 PPP1R15B Zornitza Stark gene: PPP1R15B was added
gene: PPP1R15B was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PPP1R15B was set to Unknown
Microcephaly v0.0 POMT1 Zornitza Stark gene: POMT1 was added
gene: POMT1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POMT1 was set to Unknown
Microcephaly v0.0 POGZ Zornitza Stark gene: POGZ was added
gene: POGZ was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POGZ was set to Unknown
Microcephaly v0.0 PNKP Zornitza Stark gene: PNKP was added
gene: PNKP was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PNKP was set to Unknown
Microcephaly v0.0 PIGH Zornitza Stark gene: PIGH was added
gene: PIGH was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PIGH was set to Unknown
Microcephaly v0.0 PHC1 Zornitza Stark gene: PHC1 was added
gene: PHC1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PHC1 was set to Unknown
Microcephaly v0.0 PCYT2 Zornitza Stark gene: PCYT2 was added
gene: PCYT2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PCYT2 was set to Unknown
Microcephaly v0.0 PCNT Zornitza Stark gene: PCNT was added
gene: PCNT was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PCNT was set to Unknown
Microcephaly v0.0 PCGF2 Zornitza Stark gene: PCGF2 was added
gene: PCGF2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PCGF2 was set to Unknown
Microcephaly v0.0 PAFAH1B1 Zornitza Stark gene: PAFAH1B1 was added
gene: PAFAH1B1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PAFAH1B1 was set to Unknown
Microcephaly v0.0 OSGEP Zornitza Stark gene: OSGEP was added
gene: OSGEP was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: OSGEP was set to Unknown
Microcephaly v0.0 ORC6 Zornitza Stark gene: ORC6 was added
gene: ORC6 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ORC6 was set to Unknown
Microcephaly v0.0 ORC4 Zornitza Stark gene: ORC4 was added
gene: ORC4 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ORC4 was set to Unknown
Microcephaly v0.0 ORC1 Zornitza Stark gene: ORC1 was added
gene: ORC1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ORC1 was set to Unknown
Microcephaly v0.0 NUP188 Zornitza Stark gene: NUP188 was added
gene: NUP188 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NUP188 was set to Unknown
Microcephaly v0.0 NUP107 Zornitza Stark gene: NUP107 was added
gene: NUP107 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NUP107 was set to Unknown
Microcephaly v0.0 NSD2 Zornitza Stark gene: NSD2 was added
gene: NSD2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NSD2 was set to Unknown
Microcephaly v0.0 NIN Zornitza Stark gene: NIN was added
gene: NIN was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NIN was set to Unknown
Microcephaly v0.0 NHEJ1 Zornitza Stark gene: NHEJ1 was added
gene: NHEJ1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NHEJ1 was set to Unknown
Microcephaly v0.0 NDE1 Zornitza Stark gene: NDE1 was added
gene: NDE1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NDE1 was set to Unknown
Microcephaly v0.0 NCAPH Zornitza Stark gene: NCAPH was added
gene: NCAPH was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NCAPH was set to Unknown
Microcephaly v0.0 NCAPD3 Zornitza Stark gene: NCAPD3 was added
gene: NCAPD3 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NCAPD3 was set to Unknown
Microcephaly v0.0 NCAPD2 Zornitza Stark gene: NCAPD2 was added
gene: NCAPD2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NCAPD2 was set to Unknown
Microcephaly v0.0 NBN Zornitza Stark gene: NBN was added
gene: NBN was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NBN was set to Unknown
Microcephaly v0.0 NACC1 Zornitza Stark gene: NACC1 was added
gene: NACC1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NACC1 was set to Unknown
Microcephaly v0.0 MSMO1 Zornitza Stark gene: MSMO1 was added
gene: MSMO1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MSMO1 was set to Unknown
Microcephaly v0.0 MRE11 Zornitza Stark gene: MRE11 was added
gene: MRE11 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MRE11 was set to Unknown
Microcephaly v0.0 MFSD2A Zornitza Stark gene: MFSD2A was added
gene: MFSD2A was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MFSD2A was set to Unknown
Microcephaly v0.0 MED17 Zornitza Stark gene: MED17 was added
gene: MED17 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MED17 was set to Unknown
Microcephaly v0.0 MECP2 Zornitza Stark gene: MECP2 was added
gene: MECP2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MECP2 was set to Unknown
Microcephaly v0.0 MCPH1 Zornitza Stark gene: MCPH1 was added
gene: MCPH1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MCPH1 was set to Unknown
Microcephaly v0.0 LINGO1 Zornitza Stark gene: LINGO1 was added
gene: LINGO1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LINGO1 was set to Unknown
Microcephaly v0.0 LIG4 Zornitza Stark gene: LIG4 was added
gene: LIG4 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LIG4 was set to Unknown
Microcephaly v0.0 LARP7 Zornitza Stark gene: LARP7 was added
gene: LARP7 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LARP7 was set to Unknown
Microcephaly v0.0 LAGE3 Zornitza Stark gene: LAGE3 was added
gene: LAGE3 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LAGE3 was set to Unknown
Microcephaly v0.0 KNL1 Zornitza Stark gene: KNL1 was added
gene: KNL1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KNL1 was set to Unknown
Microcephaly v0.0 KLHL7 Zornitza Stark gene: KLHL7 was added
gene: KLHL7 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KLHL7 was set to Unknown
Microcephaly v0.0 KIF14 Zornitza Stark gene: KIF14 was added
gene: KIF14 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KIF14 was set to Unknown
Microcephaly v0.0 KIF11 Zornitza Stark gene: KIF11 was added
gene: KIF11 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KIF11 was set to Unknown
Microcephaly v0.0 IER3IP1 Zornitza Stark gene: IER3IP1 was added
gene: IER3IP1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: IER3IP1 was set to Unknown
Microcephaly v0.0 HIST1H4C Zornitza Stark gene: HIST1H4C was added
gene: HIST1H4C was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HIST1H4C was set to Unknown
Microcephaly v0.0 FOXG1 Zornitza Stark gene: FOXG1 was added
gene: FOXG1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FOXG1 was set to Unknown
Microcephaly v0.0 FDXR Zornitza Stark gene: FDXR was added
gene: FDXR was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FDXR was set to Unknown
Microcephaly v0.0 EIF2S3 Zornitza Stark gene: EIF2S3 was added
gene: EIF2S3 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EIF2S3 was set to Unknown
Microcephaly v0.0 EFTUD2 Zornitza Stark gene: EFTUD2 was added
gene: EFTUD2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EFTUD2 was set to Unknown
Microcephaly v0.0 DYRK1A Zornitza Stark gene: DYRK1A was added
gene: DYRK1A was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DYRK1A was set to Unknown
Microcephaly v0.0 DONSON Zornitza Stark gene: DONSON was added
gene: DONSON was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DONSON was set to Unknown
Microcephaly v0.0 DNM1L Zornitza Stark gene: DNM1L was added
gene: DNM1L was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DNM1L was set to Unknown
Microcephaly v0.0 DNA2 Zornitza Stark gene: DNA2 was added
gene: DNA2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DNA2 was set to Unknown
Microcephaly v0.0 CTU2 Zornitza Stark gene: CTU2 was added
gene: CTU2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CTU2 was set to Unknown
Microcephaly v0.0 CTNNA2 Zornitza Stark gene: CTNNA2 was added
gene: CTNNA2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CTNNA2 was set to Unknown
Microcephaly v0.0 CTCF Zornitza Stark gene: CTCF was added
gene: CTCF was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CTCF was set to Unknown
Microcephaly v0.0 CLTC Zornitza Stark gene: CLTC was added
gene: CLTC was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CLTC was set to Unknown
Microcephaly v0.0 CHD4 Zornitza Stark gene: CHD4 was added
gene: CHD4 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CHD4 was set to Unknown
Microcephaly v0.0 CHAMP1 Zornitza Stark gene: CHAMP1 was added
gene: CHAMP1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CHAMP1 was set to Unknown
Microcephaly v0.0 CEP63 Zornitza Stark gene: CEP63 was added
gene: CEP63 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CEP63 was set to Unknown
Microcephaly v0.0 CEP152 Zornitza Stark gene: CEP152 was added
gene: CEP152 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CEP152 was set to Unknown
Microcephaly v0.0 CEP135 Zornitza Stark gene: CEP135 was added
gene: CEP135 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CEP135 was set to Unknown
Microcephaly v0.0 CENPJ Zornitza Stark gene: CENPJ was added
gene: CENPJ was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CENPJ was set to Unknown
Microcephaly v0.0 CENPE Zornitza Stark gene: CENPE was added
gene: CENPE was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CENPE was set to Unknown
Microcephaly v0.0 CDT1 Zornitza Stark gene: CDT1 was added
gene: CDT1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CDT1 was set to Unknown
Microcephaly v0.0 CDKL5 Zornitza Stark gene: CDKL5 was added
gene: CDKL5 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CDKL5 was set to Unknown
Microcephaly v0.0 CDK6 Zornitza Stark gene: CDK6 was added
gene: CDK6 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CDK6 was set to Unknown
Microcephaly v0.0 CDK5RAP2 Zornitza Stark gene: CDK5RAP2 was added
gene: CDK5RAP2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CDK5RAP2 was set to Unknown
Microcephaly v0.0 CDK13 Zornitza Stark gene: CDK13 was added
gene: CDK13 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CDK13 was set to Unknown
Microcephaly v0.0 CASK Zornitza Stark gene: CASK was added
gene: CASK was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CASK was set to Unknown
Microcephaly v0.0 BUB1B Zornitza Stark gene: BUB1B was added
gene: BUB1B was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: BUB1B was set to Unknown
Microcephaly v0.0 BRD4 Zornitza Stark gene: BRD4 was added
gene: BRD4 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: BRD4 was set to Unknown
Microcephaly v0.0 BPTF Zornitza Stark gene: BPTF was added
gene: BPTF was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: BPTF was set to Unknown
Microcephaly v0.0 ATRX Zornitza Stark gene: ATRX was added
gene: ATRX was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ATRX was set to Unknown
Microcephaly v0.0 ATR Zornitza Stark gene: ATR was added
gene: ATR was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ATR was set to Unknown
Microcephaly v0.0 ATP1A2 Zornitza Stark gene: ATP1A2 was added
gene: ATP1A2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ATP1A2 was set to Unknown
Microcephaly v0.0 ASPM Zornitza Stark gene: ASPM was added
gene: ASPM was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ASPM was set to Unknown
Microcephaly v0.0 ARFGEF2 Zornitza Stark gene: ARFGEF2 was added
gene: ARFGEF2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ARFGEF2 was set to Unknown
Microcephaly v0.0 ARCN1 Zornitza Stark gene: ARCN1 was added
gene: ARCN1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ARCN1 was set to Unknown
Microcephaly v0.0 AP4S1 Zornitza Stark gene: AP4S1 was added
gene: AP4S1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AP4S1 was set to Unknown
Microcephaly v0.0 AP4M1 Zornitza Stark gene: AP4M1 was added
gene: AP4M1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AP4M1 was set to Unknown
Microcephaly v0.0 AP4E1 Zornitza Stark gene: AP4E1 was added
gene: AP4E1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AP4E1 was set to Unknown
Microcephaly v0.0 AP4B1 Zornitza Stark gene: AP4B1 was added
gene: AP4B1 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AP4B1 was set to Unknown
Microcephaly v0.0 ANKLE2 Zornitza Stark gene: ANKLE2 was added
gene: ANKLE2 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ANKLE2 was set to Unknown
Microcephaly v0.0 AKT3 Zornitza Stark gene: AKT3 was added
gene: AKT3 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AKT3 was set to Unknown
Microcephaly v0.0 Zornitza Stark Added panel Microcephaly_VCGS