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Mendeliome v0.8686 POLR1D Zornitza Stark Marked gene: POLR1D as ready
Mendeliome v0.8686 POLR1D Zornitza Stark Gene: polr1d has been classified as Green List (High Evidence).
Mendeliome v0.8686 POLR1D Zornitza Stark Phenotypes for gene: POLR1D were changed from to Treacher Collins syndrome 2, MIM# 613717
Mendeliome v0.8685 POLR1D Zornitza Stark Publications for gene: POLR1D were set to
Mendeliome v0.8684 POLR1D Zornitza Stark Mode of inheritance for gene: POLR1D was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.75 POLR1D Zornitza Stark edited their review of gene: POLR1D: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8683 POLR1D Zornitza Stark reviewed gene: POLR1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131976, 24603435, 27448281, 25790162; Phenotypes: Treacher Collins syndrome 2, MIM# 613717; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.75 POLR1D Zornitza Stark Mode of inheritance for gene: POLR1D was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.74 POLR1D Zornitza Stark Marked gene: POLR1D as ready
Mandibulofacial Acrofacial dysostosis v0.74 POLR1D Zornitza Stark Gene: polr1d has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.74 POLR1D Zornitza Stark Phenotypes for gene: POLR1D were changed from to Treacher Collins syndrome 2, MIM# 613717
Mandibulofacial Acrofacial dysostosis v0.73 POLR1D Zornitza Stark Publications for gene: POLR1D were set to
Mandibulofacial Acrofacial dysostosis v0.72 POLR1D Zornitza Stark Mode of inheritance for gene: POLR1D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.71 POLR1D Zornitza Stark reviewed gene: POLR1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131976, 24603435, 27448281, 25790162; Phenotypes: Treacher Collins syndrome 2, MIM# 613717; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.71 RPL11 Zornitza Stark Marked gene: RPL11 as ready
Mandibulofacial Acrofacial dysostosis v0.71 RPL11 Zornitza Stark Gene: rpl11 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.71 RPL11 Zornitza Stark Phenotypes for gene: RPL11 were changed from to Diamond-Blackfan anemia 7, MIM# 612562; MONDO:0012938
Mandibulofacial Acrofacial dysostosis v0.70 RPL11 Zornitza Stark Publications for gene: RPL11 were set to
Mandibulofacial Acrofacial dysostosis v0.69 RPL11 Zornitza Stark Mode of inheritance for gene: RPL11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.68 RPL11 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Craniofacial and limb abnormalities are common.
Ciliary Dyskinesia v1.12 TP73 Zornitza Stark Marked gene: TP73 as ready
Ciliary Dyskinesia v1.12 TP73 Zornitza Stark Gene: tp73 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.12 TP73 Zornitza Stark Classified gene: TP73 as Green List (high evidence)
Ciliary Dyskinesia v1.12 TP73 Zornitza Stark Gene: tp73 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.11 TP73 Zornitza Stark gene: TP73 was added
gene: TP73 was added to Ciliary Dyskinesia. Sources: Literature
Mode of inheritance for gene: TP73 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TP73 were set to 31130284; 34077761
Phenotypes for gene: TP73 were set to Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466
Review for gene: TP73 was set to GREEN
Added comment: 7 unrelated families reported. In vitro ciliogenesis experiments demonstrated that epithelial cells from TP73 variant carriers had reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controls.

Clinical features included recurrent respiratory infections and respiratory dysfunction caused by defective mucociliary clearance in early childhood. Affected individuals also had neurologic features, such as impaired intellectual development and central hypotonia, associated with structural brain abnormalities, most notably lissencephaly and thin or absent corpus callosum.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4030 TP73 Zornitza Stark Phenotypes for gene: TP73 were changed from Intellectual disability; lissencephaly to Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466; Intellectual disability; lissencephaly
Intellectual disability syndromic and non-syndromic v0.4029 TP73 Zornitza Stark edited their review of gene: TP73: Added comment: Additional 5 families reported in PMID 34077761; Changed rating: GREEN; Changed publications: 31130284, 34077761; Changed phenotypes: Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466, Intellectual disability, lissencephaly
Mendeliome v0.8683 TP73 Zornitza Stark Phenotypes for gene: TP73 were changed from Cortical malformation; Lissencephaly to Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466; Cortical malformation; Lissencephaly
Mendeliome v0.8682 TP73 Zornitza Stark reviewed gene: TP73: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466; Mode of inheritance: None
Lissencephaly and Band Heterotopia v1.4 TP73 Zornitza Stark Phenotypes for gene: TP73 were changed from brain malformation; lissencephaly to Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466; brain malformation; lissencephaly
Lissencephaly and Band Heterotopia v1.3 TP73 Zornitza Stark reviewed gene: TP73: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466; Mode of inheritance: None
Mendeliome v0.8682 SYT2 Zornitza Stark Phenotypes for gene: SYT2 were changed from Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040 to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Mendeliome v0.8681 SYT2 Zornitza Stark edited their review of gene: SYT2: Changed phenotypes: Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040, Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Congenital Myasthenia v1.3 SYT2 Zornitza Stark Phenotypes for gene: SYT2 were changed from Myasthenic syndrome, congenital, 7, presynaptic, 616040 to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Congenital Myasthenia v1.2 SYT2 Zornitza Stark edited their review of gene: SYT2: Changed phenotypes: Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040, Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive OMIM#619461
Mendeliome v0.8681 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Mendeliome v0.8681 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Mendeliome v0.8681 POLR1C Zornitza Stark Phenotypes for gene: POLR1C were changed from to Treacher Collins syndrome 3, MIM# 248390; Leukodystrophy, hypomyelinating, 11, MIM# 616494
Mendeliome v0.8680 POLR1C Zornitza Stark Publications for gene: POLR1C were set to
Mendeliome v0.8679 POLR1C Zornitza Stark Mode of inheritance for gene: POLR1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8678 POLR1C Zornitza Stark reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131976, 30957429, 26151409, 32042905; Phenotypes: Treacher Collins syndrome 3, MIM# 248390, Leukodystrophy, hypomyelinating, 11, MIM# 616494; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.68 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Mandibulofacial Acrofacial dysostosis v0.68 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.68 POLR1C Zornitza Stark Phenotypes for gene: POLR1C were changed from to Treacher Collins syndrome 3, MIM# 248390
Mandibulofacial Acrofacial dysostosis v0.67 POLR1C Zornitza Stark Publications for gene: POLR1C were set to
Mandibulofacial Acrofacial dysostosis v0.66 POLR1C Zornitza Stark Mode of inheritance for gene: POLR1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.65 POLR1C Zornitza Stark reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131976, 30957429; Phenotypes: Treacher Collins syndrome 3, MIM# 248390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8678 SF3B4 Zornitza Stark Marked gene: SF3B4 as ready
Mendeliome v0.8678 SF3B4 Zornitza Stark Gene: sf3b4 has been classified as Green List (High Evidence).
Mendeliome v0.8678 SF3B4 Zornitza Stark Phenotypes for gene: SF3B4 were changed from to Acrofacial dysostosis 1, Nager type, MIM# 154400
Mendeliome v0.8677 SF3B4 Zornitza Stark Publications for gene: SF3B4 were set to
Mendeliome v0.8676 SF3B4 Zornitza Stark Mode of inheritance for gene: SF3B4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8675 SF3B4 Zornitza Stark reviewed gene: SF3B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22541558, 23568615, 24003905; Phenotypes: Acrofacial dysostosis 1, Nager type, MIM# 154400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.65 SF3B4 Zornitza Stark Marked gene: SF3B4 as ready
Mandibulofacial Acrofacial dysostosis v0.65 SF3B4 Zornitza Stark Gene: sf3b4 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.65 SF3B4 Zornitza Stark Phenotypes for gene: SF3B4 were changed from to Acrofacial dysostosis 1, Nager type, MIM# 154400
Mandibulofacial Acrofacial dysostosis v0.64 SF3B4 Zornitza Stark Publications for gene: SF3B4 were set to
Mandibulofacial Acrofacial dysostosis v0.63 SF3B4 Zornitza Stark Mode of inheritance for gene: SF3B4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.62 SF3B4 Zornitza Stark reviewed gene: SF3B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22541558, 23568615, 24003905; Phenotypes: Acrofacial dysostosis 1, Nager type, MIM# 154400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8675 TMCO1 Zornitza Stark Marked gene: TMCO1 as ready
Mendeliome v0.8675 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Green List (High Evidence).
Mendeliome v0.8675 TMCO1 Zornitza Stark Phenotypes for gene: TMCO1 were changed from to Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980
Mendeliome v0.8674 TMCO1 Zornitza Stark Publications for gene: TMCO1 were set to
Mendeliome v0.8673 TMCO1 Zornitza Stark Mode of inheritance for gene: TMCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8672 TMCO1 Zornitza Stark reviewed gene: TMCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20018682, 23320496, 17351359, 30556256, 31102500; Phenotypes: Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.62 TMCO1 Zornitza Stark Marked gene: TMCO1 as ready
Mandibulofacial Acrofacial dysostosis v0.62 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.62 TMCO1 Zornitza Stark Phenotypes for gene: TMCO1 were changed from to Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980
Mandibulofacial Acrofacial dysostosis v0.61 TMCO1 Zornitza Stark Publications for gene: TMCO1 were set to
Mandibulofacial Acrofacial dysostosis v0.60 TMCO1 Zornitza Stark Mode of inheritance for gene: TMCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.59 TMCO1 Zornitza Stark changed review comment from: Clinical features include severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion.

More than 20 individuals reported.; to: Clinical features include severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion.

More than 20 individuals reported. c.292_293del (p.Ser98*) variant has been identified in multiple individuals from different ethnicities.
Mandibulofacial Acrofacial dysostosis v0.59 TMCO1 Zornitza Stark reviewed gene: TMCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20018682, 23320496, 17351359, 30556256, 31102500; Phenotypes: Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting disorders v0.136 SF3B2 Zornitza Stark Marked gene: SF3B2 as ready
Clefting disorders v0.136 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Clefting disorders v0.136 SF3B2 Zornitza Stark Classified gene: SF3B2 as Green List (high evidence)
Clefting disorders v0.136 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Clefting disorders v0.135 SF3B2 Zornitza Stark gene: SF3B2 was added
gene: SF3B2 was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: SF3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SF3B2 were set to 34344887
Phenotypes for gene: SF3B2 were set to Craniofacial microsomia
Review for gene: SF3B2 was set to GREEN
Added comment: Twenty individuals from seven families reported with de novo or transmitted haploinsufficient variants in SF3B2. Affected individuals had mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities.

Targeted morpholino knockdown of SF3B2 in Xenopus resulted in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease.

The families were ascertained from a cohort and the authors suggest that haploinsufficient variants in SF3B2 are the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases.
Sources: Literature
Mendeliome v0.8672 SEMA3D Zornitza Stark Phenotypes for gene: SEMA3D were changed from Hand and foot malformations to Hand and foot malformations; Hirschsprung disease
Mendeliome v0.8671 SPTBN4 Zornitza Stark reviewed gene: SPTBN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33772159, 29861105; Phenotypes: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, MIM# 617519; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8671 RGS10 Zornitza Stark Marked gene: RGS10 as ready
Mendeliome v0.8671 RGS10 Zornitza Stark Gene: rgs10 has been classified as Red List (Low Evidence).
Mendeliome v0.8671 RGS10 Zornitza Stark gene: RGS10 was added
gene: RGS10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RGS10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS10 were set to 34315806; 34339853
Phenotypes for gene: RGS10 were set to Immunodeficiency; short stature
Review for gene: RGS10 was set to RED
Added comment: Three affected siblings with short stature and immunodeficiency and segregating biallelic variants in RGS10 (c.489_491del:p.E163del and c.G511T:p.A171S). The affected individuals had recurrent infections, hypergammaglobulinaemia, profoundly reduced lymphocyte chemotaxis, abnormal lymph node architecture, and short stature due to growth hormone deficiency. Limited functional data presented. Further experimental data linking RGS10 to immune function presented in PMID 34339853.
Sources: Literature
Combined Immunodeficiency v0.291 RGS10 Zornitza Stark Marked gene: RGS10 as ready
Combined Immunodeficiency v0.291 RGS10 Zornitza Stark Gene: rgs10 has been classified as Red List (Low Evidence).
Combined Immunodeficiency v0.291 RGS10 Zornitza Stark Publications for gene: RGS10 were set to 34315806
Combined Immunodeficiency v0.290 RGS10 Zornitza Stark changed review comment from: Three affected siblings with short stature and immunodeficiency and segregating biallelic variants in RGS10 (c.489_491del:p.E163del and c.G511T:p.A171S). The affected individuals had recurrent infections, hypergammaglobulinaemia, profoundly reduced lymphocyte chemotaxis, abnormal lymph node architecture, and short stature due to growth hormone deficiency. Limited functional data presented.
Sources: Literature; to: Three affected siblings with short stature and immunodeficiency and segregating biallelic variants in RGS10 (c.489_491del:p.E163del and c.G511T:p.A171S). The affected individuals had recurrent infections, hypergammaglobulinaemia, profoundly reduced lymphocyte chemotaxis, abnormal lymph node architecture, and short stature due to growth hormone deficiency. Limited functional data presented. Further experimental data linking RGS10 to immune function presented in PMID 34339853.
Sources: Literature
Combined Immunodeficiency v0.290 RGS10 Zornitza Stark edited their review of gene: RGS10: Changed publications: 34315806, 34339853
Combined Immunodeficiency v0.290 RGS10 Zornitza Stark gene: RGS10 was added
gene: RGS10 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: RGS10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS10 were set to 34315806
Phenotypes for gene: RGS10 were set to Immunodeficiency; short stature
Review for gene: RGS10 was set to RED
Added comment: Three affected siblings with short stature and immunodeficiency and segregating biallelic variants in RGS10 (c.489_491del:p.E163del and c.G511T:p.A171S). The affected individuals had recurrent infections, hypergammaglobulinaemia, profoundly reduced lymphocyte chemotaxis, abnormal lymph node architecture, and short stature due to growth hormone deficiency. Limited functional data presented.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4029 MAST3 Zornitza Stark Marked gene: MAST3 as ready
Intellectual disability syndromic and non-syndromic v0.4029 MAST3 Zornitza Stark Gene: mast3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4029 MAST3 Zornitza Stark Classified gene: MAST3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4029 MAST3 Zornitza Stark Gene: mast3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4028 MAST3 Zornitza Stark gene: MAST3 was added
gene: MAST3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST3 were set to 34185323
Phenotypes for gene: MAST3 were set to Developmental and epileptic encephalopathy
Review for gene: MAST3 was set to GREEN
Added comment: Eleven individuals reported with de novo missense variants in the STK domain, including two recurrent variants p.G510S (n = 5) and p.G515S (n = 3). All 11 individuals had developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at <2 years of age. All patients developed multiple seizure types, 9 of 11 patients had seizures triggered by fever and 9 of 11 patients had drug-resistant seizures. Limited functional data.
Sources: Literature
Mendeliome v0.8670 MAST3 Zornitza Stark Marked gene: MAST3 as ready
Mendeliome v0.8670 MAST3 Zornitza Stark Gene: mast3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1161 MAST3 Zornitza Stark Marked gene: MAST3 as ready
Genetic Epilepsy v0.1161 MAST3 Zornitza Stark Gene: mast3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1161 MAST3 Zornitza Stark Phenotypes for gene: MAST3 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy
Mendeliome v0.8670 MAST3 Zornitza Stark Classified gene: MAST3 as Green List (high evidence)
Mendeliome v0.8670 MAST3 Zornitza Stark Gene: mast3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1160 MAST3 Zornitza Stark Phenotypes for gene: MAST3 were changed from Epilepsy to Developmental and epileptic encephalopathy
Mendeliome v0.8669 MAST3 Zornitza Stark gene: MAST3 was added
gene: MAST3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST3 were set to 34185323
Phenotypes for gene: MAST3 were set to Developmental and epileptic encephalopathy
Review for gene: MAST3 was set to GREEN
Added comment: Eleven individuals reported with de novo missense variants in the STK domain, including two recurrent variants p.G510S (n = 5) and p.G515S (n = 3). All 11 individuals had developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at <2 years of age. All patients developed multiple seizure types, 9 of 11 patients had seizures triggered by fever and 9 of 11 patients had drug-resistant seizures. Limited functional data.
Sources: Literature
Genetic Epilepsy v0.1159 MAST3 Zornitza Stark Classified gene: MAST3 as Green List (high evidence)
Genetic Epilepsy v0.1159 MAST3 Zornitza Stark Gene: mast3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1158 MAST3 Zornitza Stark gene: MAST3 was added
gene: MAST3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST3 were set to 34185323
Phenotypes for gene: MAST3 were set to Epilepsy
Review for gene: MAST3 was set to GREEN
Added comment: Eleven individuals reported with de novo missense variants in the STK domain, including two recurrent variants p.G510S (n = 5) and p.G515S (n = 3). All 11 individuals had developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at <2 years of age. All patients developed multiple seizure types, 9 of 11 patients had seizures triggered by fever and 9 of 11 patients had drug-resistant seizures. Limited functional data.
Sources: Literature
Mandibulofacial Acrofacial dysostosis v0.59 SF3B2 Zornitza Stark Marked gene: SF3B2 as ready
Mandibulofacial Acrofacial dysostosis v0.59 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.59 SF3B2 Zornitza Stark Classified gene: SF3B2 as Green List (high evidence)
Mandibulofacial Acrofacial dysostosis v0.59 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.58 SF3B2 Zornitza Stark gene: SF3B2 was added
gene: SF3B2 was added to Mandibulofacial Acrofacial dysostosis. Sources: Literature
Mode of inheritance for gene: SF3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SF3B2 were set to 34344887
Phenotypes for gene: SF3B2 were set to Craniofacial microsomia
Review for gene: SF3B2 was set to GREEN
Added comment: Twenty individuals from seven families reported with de novo or transmitted haploinsufficient variants in SF3B2. Affected individuals had mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities.

Targeted morpholino knockdown of SF3B2 in Xenopus resulted in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease.

The families were ascertained from a cohort and the authors suggest that haploinsufficient variants in SF3B2 are the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases.
Sources: Literature
Mendeliome v0.8668 SF3B2 Zornitza Stark Marked gene: SF3B2 as ready
Mendeliome v0.8668 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Mendeliome v0.8668 SF3B2 Zornitza Stark Classified gene: SF3B2 as Green List (high evidence)
Mendeliome v0.8668 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Mendeliome v0.8667 SF3B2 Zornitza Stark gene: SF3B2 was added
gene: SF3B2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SF3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SF3B2 were set to 34344887
Phenotypes for gene: SF3B2 were set to Craniofacial microsomia
Review for gene: SF3B2 was set to GREEN
Added comment: Twenty individuals from seven families reported with de novo or transmitted haploinsufficient variants in SF3B2. Affected individuals had mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities.

Targeted morpholino knockdown of SF3B2 in Xenopus resulted in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease.

The families were ascertained from a cohort and the authors suggest that haploinsufficient variants in SF3B2 are the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases.
Sources: Literature
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.99 IMPG1 Zornitza Stark Marked gene: IMPG1 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.99 IMPG1 Zornitza Stark Gene: impg1 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.99 IMPG1 Zornitza Stark Classified gene: IMPG1 as Amber List (moderate evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.99 IMPG1 Zornitza Stark Gene: impg1 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.98 IMPG1 Zornitza Stark gene: IMPG1 was added
gene: IMPG1 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: IMPG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IMPG1 were set to 32817297
Phenotypes for gene: IMPG1 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: IMPG1 was set to AMBER
Added comment: Variants in this gene are classically associated with macular dystrophy.

However note recent paper by Olivier et al. 2021 (PMID: 32817297) who identified seven variants in IMPG1 (including five novel) in 11 families with VMD or retinitis pigmentosa (RP).

4 families were diagnosed with autosomal dominant RP, 2 families had autosomal recessive RP, while 5 families developed VMD in association with heterozygous IMPG1 variants. Notably, inter- and intrafamilial phenotypic variation was evident with some individuals presenting RP while others had VMD, despite harbouring the same IMPG1 variant.

Knockdown of Impg1 in medaka fish resulted in a phenotype consistent with that observed in human patients, including a decreased length of rod and cone photoreceptor outer segments.
Sources: Literature
Retinitis pigmentosa_Autosomal Dominant v0.29 IMPG1 Zornitza Stark Marked gene: IMPG1 as ready
Retinitis pigmentosa_Autosomal Dominant v0.29 IMPG1 Zornitza Stark Gene: impg1 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Dominant v0.29 IMPG1 Zornitza Stark Classified gene: IMPG1 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Dominant v0.29 IMPG1 Zornitza Stark Gene: impg1 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Dominant v0.28 IMPG1 Zornitza Stark gene: IMPG1 was added
gene: IMPG1 was added to Retinitis pigmentosa_Autosomal Dominant. Sources: Literature
Mode of inheritance for gene: IMPG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IMPG1 were set to 32817297
Phenotypes for gene: IMPG1 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: IMPG1 was set to GREEN
Added comment: Variants in this gene are classically associated with macular dystrophy.

However note recent paper by Olivier et al. 2021 (PMID: 32817297) who identified seven variants in IMPG1 (including five novel) in 11 families with VMD or retinitis pigmentosa (RP).

4 families were diagnosed with autosomal dominant RP, 2 families had autosomal recessive RP, while 5 families developed VMD in association with heterozygous IMPG1 variants. Notably, inter- and intrafamilial phenotypic variation was evident with some individuals presenting RP while others had VMD, despite harbouring the same IMPG1 variant.

Knockdown of Impg1 in medaka fish resulted in a phenotype consistent with that observed in human patients, including a decreased length of rod and cone photoreceptor outer segments.
Sources: Literature
Macular Dystrophy/Stargardt Disease v0.30 IMPG1 Zornitza Stark Marked gene: IMPG1 as ready
Macular Dystrophy/Stargardt Disease v0.30 IMPG1 Zornitza Stark Gene: impg1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.30 IMPG1 Zornitza Stark Phenotypes for gene: IMPG1 were changed from Macular dystrophy, vitelliform, 4 to Macular dystrophy, vitelliform, 4, OMIM:616151; Retinitis pigmentosa, MONDO:0019200
Macular Dystrophy/Stargardt Disease v0.29 IMPG1 Zornitza Stark Publications for gene: IMPG1 were set to
Macular Dystrophy/Stargardt Disease v0.28 IMPG1 Zornitza Stark Mode of inheritance for gene: IMPG1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Macular Dystrophy/Stargardt Disease v0.27 IMPG1 Zornitza Stark reviewed gene: IMPG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23993198, 28644393, 30589393, 30688845, 32817297; Phenotypes: Macular dystrophy, vitelliform, 4, OMIM:616151, Retinitis pigmentosa, MONDO:0019200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8666 IMPG1 Zornitza Stark Marked gene: IMPG1 as ready
Mendeliome v0.8666 IMPG1 Zornitza Stark Gene: impg1 has been classified as Green List (High Evidence).
Mendeliome v0.8666 IMPG1 Zornitza Stark Phenotypes for gene: IMPG1 were changed from to Macular dystrophy, vitelliform, 4, OMIM:616151; Retinitis pigmentosa, MONDO:0019200
Mendeliome v0.8665 IMPG1 Zornitza Stark Publications for gene: IMPG1 were set to
Mendeliome v0.8664 IMPG1 Zornitza Stark Mode of inheritance for gene: IMPG1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8663 IMPG1 Arina Puzriakova reviewed gene: IMPG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23993198, 28644393, 30589393, 30688845, 32817297; Phenotypes: Macular dystrophy, vitelliform, 4, OMIM:616151, Retinitis pigmentosa, MONDO:0019200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Growth failure v0.74 Zornitza Stark removed gene:SPRED1 from the panel
Growth failure v0.73 XRCC4 Zornitza Stark Marked gene: XRCC4 as ready
Growth failure v0.73 XRCC4 Zornitza Stark Gene: xrcc4 has been classified as Green List (High Evidence).
Growth failure v0.73 XRCC4 Zornitza Stark Phenotypes for gene: XRCC4 were changed from short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism to Short stature, microcephaly, and endocrine dysfunction, MIM# 616541; MONDO:0014686
Growth failure v0.72 XRCC4 Zornitza Stark Publications for gene: XRCC4 were set to 25728776
Growth failure v0.71 XRCC4 Zornitza Stark Classified gene: XRCC4 as Green List (high evidence)
Growth failure v0.71 XRCC4 Zornitza Stark Gene: xrcc4 has been classified as Green List (High Evidence).
Growth failure v0.70 XRCC4 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Growth failure is an early and prominent feature.
Growth failure v0.70 RIT1 Zornitza Stark Marked gene: RIT1 as ready
Growth failure v0.70 RIT1 Zornitza Stark Gene: rit1 has been classified as Green List (High Evidence).
Growth failure v0.70 RIT1 Zornitza Stark Phenotypes for gene: RIT1 were changed from Rasopathy; Noonan syndrome type 8; Noonan syndrome 8 to Noonan syndrome 8, MIM# 615355
Growth failure v0.69 RIT1 Zornitza Stark Publications for gene: RIT1 were set to 24939608; 25124994; 23791108
Growth failure v0.68 RAF1 Zornitza Stark Marked gene: RAF1 as ready
Growth failure v0.68 RAF1 Zornitza Stark Gene: raf1 has been classified as Green List (High Evidence).
Growth failure v0.68 RAF1 Zornitza Stark Phenotypes for gene: RAF1 were changed from Noonan syndrome 5; Noonan syndrome; LEOPARD syndrome 2; Rasopathy; LEOPARD syndrome to Noonan syndrome 5, MIM# 611553
Growth failure v0.67 RAF1 Zornitza Stark Publications for gene: RAF1 were set to 17603483; 17603482
Growth failure v0.66 RAF1 Zornitza Stark changed review comment from: Over 20 affected individuals reported.; to: Over 20 affected individuals reported. Short stature is a key feature.
Growth failure v0.66 PTPN11 Zornitza Stark Marked gene: PTPN11 as ready
Growth failure v0.66 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Green List (High Evidence).
Growth failure v0.66 PTPN11 Zornitza Stark Phenotypes for gene: PTPN11 were changed from Noonan syndrome; LEOPARD syndrome 1; Noonan syndrome 1; LEOPARD syndrome to LEOPARD syndrome 1, 151100 AD (for reporting use Noonan syndrome with multiple lentigines); Noonan syndrome 1, MIM#163950
Growth failure v0.65 PTPN11 Zornitza Stark Mode of pathogenicity for gene: PTPN11 was changed from Other - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.64 ZPR1 Zornitza Stark Marked gene: ZPR1 as ready
Growth failure v0.64 ZPR1 Zornitza Stark Gene: zpr1 has been classified as Red List (Low Evidence).
Growth failure v0.64 ZPR1 Zornitza Stark Phenotypes for gene: ZPR1 were changed from ?Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies, OMIM:619321 to Growth restriction, hypoplastic kidneys, alpecia, and distinctive facies, MIM# 619321
Growth failure v0.63 ZPR1 Zornitza Stark Tag founder tag was added to gene: ZPR1.
Growth failure v0.63 ZPR1 Zornitza Stark reviewed gene: ZPR1: Rating: RED; Mode of pathogenicity: None; Publications: 29851065; Phenotypes: Growth restriction, hypoplastic kidneys, alpecia, and distinctive facies, MIM# 619321; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v0.63 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Growth failure v0.63 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Growth failure v0.63 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from Noonan syndrome-like disorder with loose anagen hair 2, 617506; Rasopathy with developmental delay, short stature and sparse slow-growing hair to Noonan syndrome-like disorder with loose anagen hair 2; OMIM # 617506
Growth failure v0.62 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to 27264673; 27681385; 28211982
Growth failure v0.61 PPP1CB Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Growth failure v0.60 PALB2 Zornitza Stark Marked gene: PALB2 as ready
Growth failure v0.60 PALB2 Zornitza Stark Gene: palb2 has been classified as Green List (High Evidence).
Growth failure v0.60 PALB2 Zornitza Stark Phenotypes for gene: PALB2 were changed from Fanconi anemia, complementation group N, 610832; 610832 Fanconi anemia, complementation group N to Fanconi anaemia, complementation group N, MIM# 610832
Growth failure v0.59 PALB2 Zornitza Stark changed review comment from: Established gene-disease association.; to: Established gene-disease association. Short stature is a key feature of FA.
Growth failure v0.59 NRAS Zornitza Stark Marked gene: NRAS as ready
Growth failure v0.59 NRAS Zornitza Stark Gene: nras has been classified as Green List (High Evidence).
Growth failure v0.59 NRAS Zornitza Stark Phenotypes for gene: NRAS were changed from Cardio-Facio-cutanenous syndrome; A restricted spectrum of NRAS mutations causes Noonan syndrome. (Nat Genet. 42: 27-29, 2010.); Noonan syndrome; CFC Syndrome; Noonan syndrome 6 to Noonan syndrome 6, MIM# 613224
Growth failure v0.58 NRAS Zornitza Stark Publications for gene: NRAS were set to 19966803; 19775298
Growth failure v0.57 NRAS Zornitza Stark changed review comment from: Over 20 affected individuals reported, well established gene-disease association.; to: Over 20 affected individuals reported, well established gene-disease association. Short stature is a key feature.
Growth failure v0.57 NBN Zornitza Stark Marked gene: NBN as ready
Growth failure v0.57 NBN Zornitza Stark Gene: nbn has been classified as Green List (High Evidence).
Growth failure v0.57 NBN Zornitza Stark Phenotypes for gene: NBN were changed from Nijmegen; Nijmegen breakage syndrome, 251260 to Nijmegen breakage syndrome, MIM# 251260; MONDO:0009623
Growth failure v0.56 NBN Zornitza Stark Publications for gene: NBN were set to
Growth failure v0.55 MAP2K2 Zornitza Stark Marked gene: MAP2K2 as ready
Growth failure v0.55 MAP2K2 Zornitza Stark Gene: map2k2 has been classified as Green List (High Evidence).
Growth failure v0.55 MAP2K2 Zornitza Stark Phenotypes for gene: MAP2K2 were changed from CFC syndrome; Cardiofaciocutaneous Syndrome; Cardiofaciocutaneous syndrome; Cardiofaciocutaneous syndrome 4; Cardio-Facio-Cutaneous syndrome; Cardio-Facio-Cutaneous syndrome type 4 to Cardiofaciocutaneous syndrome 4, MIM# 615280
Growth failure v0.54 MAP2K2 Zornitza Stark Publications for gene: MAP2K2 were set to 16439621; 21396583; 23379592
Growth failure v0.53 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Growth failure v0.53 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Growth failure v0.53 MAP2K1 Zornitza Stark Phenotypes for gene: MAP2K1 were changed from Cardiofaciocutaneous syndrome 3; CFC syndrome; ?Noonan syndrome; Cardiofaciocutaneous Syndrome; Cardiofaciocutaneous syndrome; Cardio-Facio-Cutaneous syndrome; LEOPARD syndrome to Cardiofaciocutaneous syndrome 3, MIM# 615279
Growth failure v0.52 MAP2K1 Zornitza Stark Publications for gene: MAP2K1 were set to 23321623; 16439621; 21396583; 16825433
Growth failure v0.51 LZTR1 Zornitza Stark Marked gene: LZTR1 as ready
Growth failure v0.51 LZTR1 Zornitza Stark Gene: lztr1 has been classified as Green List (High Evidence).
Growth failure v0.51 LZTR1 Zornitza Stark Phenotypes for gene: LZTR1 were changed from increased nuchal translucency; Prenatal hydrops; cardiac findings; Noonan syndrome 10 to Noonan syndrome 10; Noonan syndrome 2
Growth failure v0.50 LZTR1 Zornitza Stark Publications for gene: LZTR1 were set to 29469822; 25795793
Growth failure v0.49 KRAS Zornitza Stark Marked gene: KRAS as ready
Growth failure v0.49 KRAS Zornitza Stark Gene: kras has been classified as Green List (High Evidence).
Growth failure v0.49 KRAS Zornitza Stark Phenotypes for gene: KRAS were changed from Noonan syndrome 3; CFC syndrome; Cardiofaciocutaneous syndrome 2; Cardiofaciocutaneous Syndrome; Noonan syndrome; Rasopathy; Cardio-Facio-Cutaneous syndrome to Noonan syndrome 3, MIM# 609942; Cardiofaciocutaneous syndrome 2, MIM# 615278
Growth failure v0.48 KRAS Zornitza Stark Publications for gene: KRAS were set to 21396583
Growth failure v0.47 KRAS Zornitza Stark changed review comment from: Well established gene-disease association in individuals with Noonan syndrome, CFC and overlapping Noonan-CFC.; to: Well established gene-disease association in individuals with Noonan syndrome, CFC and overlapping Noonan-CFC. Short stature is a key feature.
Growth failure v0.47 HRAS Zornitza Stark Marked gene: HRAS as ready
Growth failure v0.47 HRAS Zornitza Stark Gene: hras has been classified as Green List (High Evidence).
Growth failure v0.47 HRAS Zornitza Stark Phenotypes for gene: HRAS were changed from Costello syndrome, 218040; Costello; Costello syndrome to Costello syndrome, MIM# 218040
Growth failure v0.46 HRAS Zornitza Stark Publications for gene: HRAS were set to 16969868; 16443854; 21396583; 16170316
Growth failure v0.45 HMGA2 Zornitza Stark Marked gene: HMGA2 as ready
Growth failure v0.45 HMGA2 Zornitza Stark Gene: hmga2 has been classified as Green List (High Evidence).
Growth failure v0.45 HMGA2 Zornitza Stark Phenotypes for gene: HMGA2 were changed from Silver-Russell syndrome 5, MONDO:0020795; Silver-Russell syndrome 5, OMIM:618908 to Silver-Russell syndrome 5, MIM# 618908; MONDO:0020795
Growth failure v0.44 HMGA2 Zornitza Stark Publications for gene: HMGA2 were set to 29655892
Growth failure v0.43 HMGA2 Zornitza Stark reviewed gene: HMGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25809938, 29453418, 29655892, 33482836; Phenotypes: Silver-Russell syndrome 5, MIM# 618908; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Growth failure v0.43 FGFR3 Zornitza Stark Marked gene: FGFR3 as ready
Growth failure v0.43 FGFR3 Zornitza Stark Gene: fgfr3 has been classified as Green List (High Evidence).
Growth failure v0.43 FGFR3 Zornitza Stark Phenotypes for gene: FGFR3 were changed from Hypochondroplasia, 146000 to Hypochondroplasia, MIM#146000
Growth failure v0.42 FGFR3 Zornitza Stark Mode of inheritance for gene: FGFR3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Growth failure v0.41 FGFR3 Zornitza Stark reviewed gene: FGFR3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypochondroplasia, MIM# 146000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Growth failure v0.41 FANCL Zornitza Stark Marked gene: FANCL as ready
Growth failure v0.41 FANCL Zornitza Stark Gene: fancl has been classified as Green List (High Evidence).
Growth failure v0.41 FANCL Zornitza Stark Phenotypes for gene: FANCL were changed from Fanconi anemia; 614083Fanconi anemia, complementation group L; Fanconi anemia, complementation group L, 614083; Fanconi Anemia to Fanconi anemia, complementation group L, MIM# 614083; MONDO:0013566
Growth failure v0.40 FANCL Zornitza Stark Publications for gene: FANCL were set to 25754594; 12724401; 19405097; 12973351; 16474160
Growth failure v0.39 FANCL Zornitza Stark changed review comment from: Established gene-disease association. Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer.; to: Established gene-disease association. Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer. Poor growth is a key feature.
Growth failure v0.39 FANCI Zornitza Stark Marked gene: FANCI as ready
Growth failure v0.39 FANCI Zornitza Stark Gene: fanci has been classified as Green List (High Evidence).
Growth failure v0.39 FANCI Zornitza Stark Phenotypes for gene: FANCI were changed from 609053 Fanconi anemia, complementation group I; Fanconi anemia; Fanconi anemia, complementation group I, 609053; Fanconi Anemia to Fanconi anemia, complementation group I, MIM# 609053; MONDO:0012186
Growth failure v0.38 FANCI Zornitza Stark changed review comment from: Established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer.; to: Established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer. Poor growth is a key feature.
Growth failure v0.38 FANCG Zornitza Stark Marked gene: FANCG as ready
Growth failure v0.38 FANCG Zornitza Stark Gene: fancg has been classified as Green List (High Evidence).
Growth failure v0.38 FANCG Zornitza Stark Phenotypes for gene: FANCG were changed from 614082 Fanconi anemia, complementation group G; hypogonadism and reduced fertility; Fanconi Anemia; bone marrow failure; a typical facial appearance with small head, eyes, and mouth; cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots); hearing loss; Fanconi anemia; and susceptibility to cancer, predominantly acute myeloid leukemia.; Fanconi anemia, complementation group G, 614082; Fanconi anemia complementation group G; malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii); pre- and postnatal growth retardation to Fanconi anaemia, complementation group G, MIM# 614082; MONDO:0013565
Growth failure v0.37 FANCG Zornitza Stark Publications for gene: FANCG were set to 16493006; 9806548
Growth failure v0.36 FANCG Zornitza Stark changed review comment from: Established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer.; to: Established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer. Poor growth is a key feature.
Growth failure v0.36 FANCF Zornitza Stark Marked gene: FANCF as ready
Growth failure v0.36 FANCF Zornitza Stark Gene: fancf has been classified as Green List (High Evidence).
Growth failure v0.36 FANCF Zornitza Stark Phenotypes for gene: FANCF were changed from Fanconi anemia, complementation group F, 603467; Fanconi anemia; 603467 Fanconi anemia, complementation group F; Fanconi Anemia to Fanconi anaemia, complementation group F 603467; MONDO:0011325
Growth failure v0.35 FANCF Zornitza Stark Publications for gene: FANCF were set to 10615118
Growth failure v0.34 FANCF Zornitza Stark changed review comment from: Established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer.; to: Established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer. Poor growth is a key feature.
Growth failure v0.34 FANCE Zornitza Stark Marked gene: FANCE as ready
Growth failure v0.34 FANCE Zornitza Stark Gene: fance has been classified as Green List (High Evidence).
Growth failure v0.34 FANCE Zornitza Stark Phenotypes for gene: FANCE were changed from Fanconi anemia; Fanconi anemia, complementation group E, 600901; 600901 Fanconi anemia, complementation group E; Fanconi Anemia to Fanconi anaemia, complementation group E, MIM# 600901; MONDO:0010953
Growth failure v0.33 FANCE Zornitza Stark Publications for gene: FANCE were set to 7662964; 10205272; 9147877; 9382107
Growth failure v0.32 FANCE Zornitza Stark changed review comment from: Established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer.; to: Established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer. Poor growth is a key feature.
Growth failure v0.32 FANCD2 Zornitza Stark Marked gene: FANCD2 as ready
Growth failure v0.32 FANCD2 Zornitza Stark Gene: fancd2 has been classified as Green List (High Evidence).
Growth failure v0.32 FANCD2 Zornitza Stark Phenotypes for gene: FANCD2 were changed from Fanconi anemia; 227646 Fanconi anemia, complementation group D2; Fanconi anemia, complementation group D2, 227646; Fanconi Anemia to Fanconi anaemia, complementation group D2, MIM# 227646
Growth failure v0.31 FANCD2 Zornitza Stark changed review comment from: Well established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer.; to: Well established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer. Poor growth is a key feature.
Growth failure v0.31 FANCC Zornitza Stark Marked gene: FANCC as ready
Growth failure v0.31 FANCC Zornitza Stark Gene: fancc has been classified as Green List (High Evidence).
Growth failure v0.31 FANCC Zornitza Stark Phenotypes for gene: FANCC were changed from hypogonadism and reduced fertility; Fanconi Anemia; bone marrow failure; a typical facial appearance with small head, eyes, and mouth; Fanconi anemia, complementation group C, 227645; cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots); hearing loss; Fanconi anemia; and susceptibility to cancer, predominantly acute myeloid leukemia.; 227645 Fanconi anemia, complementation group C; malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii); pre- and postnatal growth retardation to Fanconi anemia, complementation group C, MIM# 227645; MONDO:0009213
Growth failure v0.30 FANCC Zornitza Stark Publications for gene: FANCC were set to 16493006; 1574115
Growth failure v0.29 FANCC Zornitza Stark changed review comment from: Established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer.; to: Established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer. Poor growth is a key feature.
Growth failure v0.29 FANCB Zornitza Stark changed review comment from: Well established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, and early-onset bone marrow failure. Poor growth is a key feature.; to: Well established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, and early-onset bone marrow failure. Poor growth is a key feature.
Growth failure v0.29 FANCA Zornitza Stark Phenotypes for gene: FANCA were changed from Fanconi anaemia, complementation group A, MIM# 227650; MONDO:0009215 to Fanconi anaemia, complementation group A, MIM# 227650; MONDO:0009215
Growth failure v0.28 FANCB Zornitza Stark Marked gene: FANCB as ready
Growth failure v0.28 FANCB Zornitza Stark Gene: fancb has been classified as Green List (High Evidence).
Growth failure v0.28 FANCB Zornitza Stark Phenotypes for gene: FANCB were changed from Fanconi anemia, complementation group B, 300514; Falcon anemia; VACTERL Association with Hydrocephalus; Fanconi Anaemia; Fanconi Anemia Type B; 300514 Fanconi anemia, complementation group B; Fanconi anemia; Fanconi Anemia, X-Linked to Fanconi anaemia, complementation group B, MIM# 300514
Growth failure v0.27 FANCB Zornitza Stark Publications for gene: FANCB were set to
Growth failure v0.26 FANCB Zornitza Stark Mode of inheritance for gene: FANCB was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Growth failure v0.25 FANCB Zornitza Stark changed review comment from: Well established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, and early-onset bone marrow failure.; to: Well established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, and early-onset bone marrow failure. Poor growth is a key feature.
Growth failure v0.25 FANCA Zornitza Stark Marked gene: FANCA as ready
Growth failure v0.25 FANCA Zornitza Stark Gene: fanca has been classified as Green List (High Evidence).
Growth failure v0.25 FANCA Zornitza Stark Phenotypes for gene: FANCA were changed from hypogonadism and reduced fertility; Fanconi Anemia; bone marrow failure; a typical facial appearance with small head, eyes, and mouth; 227650 Fanconi anemia complementation group A; cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots); hearing loss; Fanconi anemia; and susceptibility to cancer, predominantly acute myeloid leukemia.; Fanconi anemia, complementation group A, 227650; malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii); pre- and postnatal growth retardation to Fanconi anaemia, complementation group A, MIM# 227650; MONDO:0009215
Growth failure v0.24 FANCA Zornitza Stark Publications for gene: FANCA were set to 16493006; 8896563
Growth failure v0.23 FANCA Zornitza Stark changed review comment from: Well established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer. ; to: Well established gene-disease association.

Fanconi anaemia causes genomic instability and is characterised by multiple congenital anomalies including radial ray abnormalities and microcephaly, early-onset bone marrow failure, and a predisposition to cancer. Growth failure is a key feature.
Growth failure v0.23 ERCC4 Zornitza Stark Marked gene: ERCC4 as ready
Growth failure v0.23 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
Growth failure v0.23 ERCC4 Zornitza Stark Phenotypes for gene: ERCC4 were changed from 615272 Fanconi anemia, complementation group Q; Fanconi anemia, complementation group Q, 615272 to Fanconi anemia, complementation group Q, MIM# 615272; MONDO:0014108; XFE progeroid syndrome, MIM# 610965; MONDO:0012590
Growth failure v0.22 ERCC4 Zornitza Stark Publications for gene: ERCC4 were set to 23623386; 23623389; 24027083
Growth failure v0.21 ERCC4 Zornitza Stark changed review comment from: Excision repair defect resulting in a range of phenotypes. Growth failure is a key feature of FA.; to: Excision repair defect resulting in a range of phenotypes. Growth failure is a key feature of FA and of progeroid syndrome.
Growth failure v0.21 ERCC4 Zornitza Stark edited their review of gene: ERCC4: Changed phenotypes: Fanconi anemia, complementation group Q, MIM# 615272, MONDO:0014108, XFE progeroid syndrome, MIM# 610965, MONDO:0012590
Growth failure v0.21 ERCC4 Zornitza Stark changed review comment from: Excision repair defect resulting in a range of phenotypes.; to: Excision repair defect resulting in a range of phenotypes. Growth failure is a key feature of FA.
Renal Ciliopathies and Nephronophthisis v1.1 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from Bardet-Biedl syndrome; Short-rib thoracic dysplasia 10 with or without polydactyly, MIM# 615630 to Bardet-Biedl syndrome 20, MIM# 619471; Short-rib thoracic dysplasia 10 with or without polydactyly, MIM# 615630
Renal Ciliopathies and Nephronophthisis v1.0 IFT172 Zornitza Stark changed review comment from: Three families reported with a BBS phenotype, although this association is not listed in OMIM or MONDO. Gene is also associated with skeletal ciliopathy, with nephronophthisis reported.; to: Three families reported with a BBS phenotype. Gene is also associated with skeletal ciliopathy, with nephronophthisis reported.
Renal Ciliopathies and Nephronophthisis v1.0 IFT172 Zornitza Stark edited their review of gene: IFT172: Changed phenotypes: Bardet-Biedl syndrome 20, MIM# 619471, Short-rib thoracic dysplasia 10 with or without polydactyly, MIM# 615630
Mendeliome v0.8663 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from Retinitis pigmentosa 71 616394; Short-rib thoracic dysplasia 10 with or without polydactyly - 615630; Bardet-Biedl syndrome to Retinitis pigmentosa 71 616394; Short-rib thoracic dysplasia 10 with or without polydactyly - 615630; Bardet-Biedl syndrome 20, MIM# 619471
Ciliopathies v1.7 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from Bardet-Biedl syndrome; Retinitis pigmentosa 71, MIM# 616394; Short-rib thoracic dysplasia 10 with or without polydactyly, MIM# 615630 to Bardet-Biedl syndrome 20, MIM# 619471; Retinitis pigmentosa 71, MIM# 616394; Short-rib thoracic dysplasia 10 with or without polydactyly, MIM# 615630
Ciliopathies v1.6 IFT172 Zornitza Stark changed review comment from: Three families reported with a BBS phenotype, although this association is not listed in OMIM or MONDO.
More than 10 families reported with skeletal ciliopathy and 3 with RP. Supportive zebrafish models.; to: Three families reported with a BBS phenotype.
More than 10 families reported with skeletal ciliopathy and 3 with RP. Supportive zebrafish models.
Ciliopathies v1.6 IFT172 Zornitza Stark edited their review of gene: IFT172: Changed phenotypes: Bardet-Biedl syndrome 20, MIM# 619471, Retinitis pigmentosa 71, MIM# 616394, Short-rib thoracic dysplasia 10 with or without polydactyly, MIM# 615630
Bardet Biedl syndrome v1.10 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from Bardet-Biedl syndrome to Bardet-Biedl syndrome 20, MIM# 619471
Bardet Biedl syndrome v1.9 IFT172 Zornitza Stark changed review comment from: Three families reported with a BBS phenotype, although this association is not listed in OMIM or MONDO. Gene is associated with other ciliopathies as well.; to: Three families reported with a BBS phenotype. Gene is associated with other ciliopathies as well.
Bardet Biedl syndrome v1.9 IFT172 Zornitza Stark edited their review of gene: IFT172: Changed phenotypes: Bardet-Biedl syndrome 20, MIM# 619471
Intellectual disability syndromic and non-syndromic v0.4027 TRIM8 Zornitza Stark Phenotypes for gene: TRIM8 were changed from Intellectual disability; Seizures; FSGS to Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428; Intellectual disability; Seizures; FSGS
Intellectual disability syndromic and non-syndromic v0.4026 TRIM8 Zornitza Stark edited their review of gene: TRIM8: Changed phenotypes: Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428, Intellectual disability, Seizures, FSGS
Genetic Epilepsy v0.1157 TRIM8 Zornitza Stark Phenotypes for gene: TRIM8 were changed from Intellectual disability; Seizures to Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428; Intellectual disability; Seizures
Genetic Epilepsy v0.1156 TRIM8 Zornitza Stark edited their review of gene: TRIM8: Changed phenotypes: Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428, Intellectual disability, Seizures
Proteinuria v0.170 TRIM8 Zornitza Stark Phenotypes for gene: TRIM8 were changed from intellectual disability; epileptic encephalopathy; nephrotic syndrome; proteinuria to Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428; Intellectual disability; Seizures; nephrotic syndrome; proteinuria
Proteinuria v0.169 TRIM8 Zornitza Stark reviewed gene: TRIM8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428, Intellectual disability, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8662 TRIM8 Zornitza Stark Phenotypes for gene: TRIM8 were changed from Intellectual disability; Seizures to Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428; Intellectual disability; Seizures
Mendeliome v0.8661 TRIM8 Zornitza Stark edited their review of gene: TRIM8: Changed phenotypes: Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428, Intellectual disability, Seizures
Imprinting disorders v0.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Imprinting disorders v0.0 ZFP57 Zornitza Stark gene: ZFP57 was added
gene: ZFP57 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ZFP57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFP57 were set to 18622393; 23150280; 25848000
Phenotypes for gene: ZFP57 were set to IUGR; Diabetes mellitus, transient neonatal 1 OMIM:601410; Multi Locus Imprinting Disturbance; diabetes mellitus, transient neonatal, 1MONDO:0011073
Imprinting disorders v0.0 UBE3A Zornitza Stark gene: UBE3A was added
gene: UBE3A was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: UBE3A was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: UBE3A were set to 12545427; 8988172; http://igc.otago.ac.nz/home.html; 18500341]; 8988171; 21974935; 2309780; PMID: 9887341; [7795645; 30794780
Phenotypes for gene: UBE3A were set to Affected tissue: brain; Phenotype resulting from under expression: Angelman Syndrome
Imprinting disorders v0.0 SGCE Zornitza Stark gene: SGCE was added
gene: SGCE was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SGCE was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: SGCE were set to PMID: 25209853; 23237735; 23365103; http://igc.otago.ac.nz/home.html; 30794780
Phenotypes for gene: SGCE were set to Affected tissue: brain; Phenotype resulting from under expression: upper body myoclonus, dystonia
Imprinting disorders v0.0 PADI6 Zornitza Stark gene: PADI6 was added
gene: PADI6 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PADI6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PADI6 were set to 27545678; 33221824; 32928291
Phenotypes for gene: PADI6 were set to Preimplantation embryonic lethality 2 OMIM:617234; preimplantation embryonic lethality 2 MONDO:0014978; Multi Locus Imprinting Disturbance; Beckwith-Wiedemann syndrome
Imprinting disorders v0.0 NLRP7 Zornitza Stark gene: NLRP7 was added
gene: NLRP7 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: NLRP7 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP7 were set to 19246479; 28916717; 31201414; 16462743; 29574422
Phenotypes for gene: NLRP7 were set to Affected tissue: all (incompatible with life); hydatidiform mole, recurrent, 1 MONDO:0009273; Phenotype resulting from under expression: Biparental complete hydatidiform mole; Multi Locus Imprinting Disturbance
Imprinting disorders v0.0 NLRP5 Zornitza Stark gene: NLRP5 was added
gene: NLRP5 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: NLRP5 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP5 were set to 26323243; 31201414; 31829238
Phenotypes for gene: NLRP5 were set to Phenotype resulting from under expression: Biparental complete hydatidiform mole, Beckwith-Wiedemann Syndrome, Multi-locus imprinting disorder; Affected tissue: all
Imprinting disorders v0.0 NLRP2 Zornitza Stark gene: NLRP2 was added
gene: NLRP2 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: NLRP2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP2 were set to 26323243; 29574422; 32169557; 28317850; 30221575; 30877238; 33090377; 19300480; 28422141
Phenotypes for gene: NLRP2 were set to Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 MONDO:0016475
Mode of pathogenicity for gene: NLRP2 was set to Other
Imprinting disorders v0.0 MKRN3 Zornitza Stark gene: MKRN3 was added
gene: MKRN3 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: MKRN3 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: MKRN3 were set to PMID: 23738509; http://igc.otago.ac.nz/home.html; 30794780
Phenotypes for gene: MKRN3 were set to Phenotype resulting from under expression: Precocious Puberty Syndrome; Affected tissue: HPA axis
Imprinting disorders v0.0 L3MBTL1 Zornitza Stark gene: L3MBTL1 was added
gene: L3MBTL1 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: L3MBTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: L3MBTL1 were set to http://igc.otago.ac.nz/home.html; 23543057; PMID: 15123827; 30794780
Phenotypes for gene: L3MBTL1 were set to Affected tissue: myeloid lineages; Phenotype resulting from under expression: lymphoid malignancy
Imprinting disorders v0.0 KCNQ1OT1 Zornitza Stark gene: KCNQ1OT1 was added
gene: KCNQ1OT1 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KCNQ1OT1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: KCNQ1OT1 were set to 22205991; 15372379; 10220444; http://igc.otago.ac.nz/home.html; 23511928; 30794780
Phenotypes for gene: KCNQ1OT1 were set to Beckwith-Wiedemann syndrome OMIM:130650
Imprinting disorders v0.0 KCNK9 Zornitza Stark gene: KCNK9 was added
gene: KCNK9 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KCNK9 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: KCNK9 were set to http://igc.otago.ac.nz/home.html; PMID: 24667089; 18678320; 30794780
Phenotypes for gene: KCNK9 were set to Phenotype resulting from under expression: mental retardation, hypotonia, dysmprophism; Affected tissue: brain; Birk-Barel syndrome
Imprinting disorders v0.0 IGF2 Zornitza Stark gene: IGF2 was added
gene: IGF2 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: IGF2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: IGF2 were set to http://igc.otago.ac.nz/home.html; PMID: 26154720; 30794780
Phenotypes for gene: IGF2 were set to Affected tissue: all; Phenotypes resulting from gene over expression: Beckwith-Wiedemann Syndrome (proven effects of dosage alteration rather than gene muation). Phenotype resulting from under expression: Silver-Russell Syndrome
Imprinting disorders v0.0 H19 Zornitza Stark gene: H19 was added
gene: H19 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: H19 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: H19 were set to PMID: 20007505; 15743916; 23118352; [21863054; 21571108; 18245780]; 24916376; 25943194
Phenotypes for gene: H19 were set to Phenotypes resulting from gene over expression: Silver-Russell Syndrome (proven effects of dosage alteration rather than gene muation); Affected tissue: all; Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome
Imprinting disorders v0.0 GNAS Zornitza Stark gene: GNAS was added
gene: GNAS was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: GNAS were set to 10980525; [11406605; 12024005; 15800843]; 15181091; 9506752; 12024004; http://igc.otago.ac.nz/home.html; 15592469; [15592469; 11788646; 1944469; PMID: 2109828; 30794780
Phenotypes for gene: GNAS were set to Affected tissue: kidney, bone, brain; pseudopseudohypoparathyroidism; Phenotype resulting from under expression: Pseudohypoparathyroidism Type 1a
Imprinting disorders v0.0 CDKN1C Zornitza Stark gene: CDKN1C was added
gene: CDKN1C was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CDKN1C was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: CDKN1C were set to 10424811; PMID: 8841187; 22205991]; 20503313; 19843502; http://igc.otago.ac.nz/home.html; [15372379; 23511928; 30794780
Phenotypes for gene: CDKN1C were set to Affected tissue: all; Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome; Phenotypes resulting from gene over expression: IMAGE syndrome; Silver-Russell Syndrome
Imprinting disorders v0.0 Zornitza Stark Added panel Imprinting disorders
Skeletal dysplasia v0.112 CUL7 Zornitza Stark Marked gene: CUL7 as ready
Skeletal dysplasia v0.112 CUL7 Zornitza Stark Gene: cul7 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.112 CUL7 Zornitza Stark Phenotypes for gene: CUL7 were changed from 3-M syndrome 1 273750 to 3-M syndrome 1, MIM# 273750; Yakut short stature syndrome
Skeletal dysplasia v0.111 CUL7 Zornitza Stark Publications for gene: CUL7 were set to
Skeletal dysplasia v0.110 CUL7 Zornitza Stark reviewed gene: CUL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16142236, 19225462, 17675530; Phenotypes: 3-M syndrome 1, MIM# 273750, Yakut short stature syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8661 CUL7 Zornitza Stark Marked gene: CUL7 as ready
Mendeliome v0.8661 CUL7 Zornitza Stark Gene: cul7 has been classified as Green List (High Evidence).
Mendeliome v0.8661 CUL7 Zornitza Stark Phenotypes for gene: CUL7 were changed from to 3-M syndrome 1, MIM# 273750; Yakut short stature syndrome
Mendeliome v0.8660 CUL7 Zornitza Stark Publications for gene: CUL7 were set to
Mendeliome v0.8659 CUL7 Zornitza Stark Mode of inheritance for gene: CUL7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8658 CUL7 Zornitza Stark reviewed gene: CUL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16142236, 19225462, 17675530; Phenotypes: 3-M syndrome 1, MIM# 273750, Yakut short stature syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v0.21 CUL7 Zornitza Stark Marked gene: CUL7 as ready
Growth failure v0.21 CUL7 Zornitza Stark Gene: cul7 has been classified as Green List (High Evidence).
Growth failure v0.21 CUL7 Zornitza Stark Phenotypes for gene: CUL7 were changed from 3M; 3-M syndrome 1, 273750 to 3-M syndrome 1, MIM# 273750; Yakut short stature syndrome
Growth failure v0.20 CUL7 Zornitza Stark Publications for gene: CUL7 were set to
Growth failure v0.19 CUL7 Zornitza Stark reviewed gene: CUL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16142236, 19225462, 17675530; Phenotypes: 3-M syndrome 1, MIM# 273750, Yakut short stature syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v0.19 CDKN1C Zornitza Stark edited their review of gene: CDKN1C: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Growth failure v0.19 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
Growth failure v0.19 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Green List (High Evidence).
Growth failure v0.19 CDKN1C Zornitza Stark Phenotypes for gene: CDKN1C were changed from Beckwith-Wiedemann syndrome, 130650; Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies; SRS/BWS to IMAGe syndrome, MIM# 614732; Silver-Russell syndrome
Growth failure v0.18 CDKN1C Zornitza Stark Publications for gene: CDKN1C were set to
Growth failure v0.17 CDKN1C Zornitza Stark Mode of pathogenicity for gene: CDKN1C was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.16 CDKN1C Zornitza Stark edited their review of gene: CDKN1C: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.16 CDKN1C Zornitza Stark changed review comment from: IMAGe syndrome is a rare multisystem disorder characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and steroid replacement therapy commenced. Other reported features in this condition include hypercalciuria and/or hypocalcemia, craniosynostosis, cleft palate, and scoliosis.

Reported variants are gain-of-function missense on the maternal allele, and are located in a highly-conserved "hot-spot" within the PCNA-binding domain of CDKN1C between codons 272-279. Note 3 families reported with RSS phenotype without other IMAGE features, all with missense changes at amino acid positions 279 and 281.; to: IMAGe syndrome is a rare multisystem disorder characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and steroid replacement therapy commenced. Other reported features in this condition include hypercalciuria and/or hypocalcemia, craniosynostosis, cleft palate, and scoliosis.

Reported variants are gain-of-function missense on the maternal allele, and are located in a highly-conserved "hot-spot" within the PCNA-binding domain of CDKN1C between codons 272-279. Note 3 families reported with RSS phenotype without other IMAGE features, all with missense changes at amino acid positions 279 and 281.

Note LoF variants in this gene cause overgrowth and BWS.
Growth failure v0.16 CDKN1C Zornitza Stark reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 22634751, 33076988, 31976094, 31497289; Phenotypes: IMAGe syndrome, MIM# 614732, Silver-Russell syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Anophthalmia_Microphthalmia_Coloboma v1.7 PACS1 Chris Richmond gene: PACS1 was added
gene: PACS1 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: PACS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PACS1 were set to 32672908
Phenotypes for gene: PACS1 were set to 615009
Penetrance for gene: PACS1 were set to Complete
Review for gene: PACS1 was set to GREEN
gene: PACS1 was marked as current diagnostic
Added comment: Multiple papers reporting patients with colobomata - well described.
Sources: Literature
Growth failure v0.16 CCDC8 Zornitza Stark Marked gene: CCDC8 as ready
Growth failure v0.16 CCDC8 Zornitza Stark Gene: ccdc8 has been classified as Green List (High Evidence).
Growth failure v0.16 CCDC8 Zornitza Stark Phenotypes for gene: CCDC8 were changed from 3M; 3-M syndrome 3, 614205 to 3-M syndrome 3, MIM# 614205
Growth failure v0.15 CCDC8 Zornitza Stark Publications for gene: CCDC8 were set to 21737058
Growth failure v0.14 CCDC8 Zornitza Stark reviewed gene: CCDC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 21737058, 22325252, 28675896, 28675896; Phenotypes: 3-M syndrome 3, MIM# 614205; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v0.14 CBL Zornitza Stark Marked gene: CBL as ready
Growth failure v0.14 CBL Zornitza Stark Gene: cbl has been classified as Green List (High Evidence).
Growth failure v0.14 CBL Zornitza Stark Phenotypes for gene: CBL were changed from Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia; NOONAN SYNDROME-LIKE DISORDER WITH OR WITHOUT JUVENILE MEYLOMONOCYTIC LEUKEMIA to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukaemia, MIM# 613563; CBL-related disorder, MONDO:0013308
Growth failure v0.13 BRIP1 Zornitza Stark Marked gene: BRIP1 as ready
Growth failure v0.13 BRIP1 Zornitza Stark Gene: brip1 has been classified as Green List (High Evidence).
Growth failure v0.13 BRIP1 Zornitza Stark Phenotypes for gene: BRIP1 were changed from Fanconi anemia, complementation group J, 609054; 609054 Fanconi anemia, complementation group J to Fanconi anaemia, complementation group J, MIM# 609054
Growth failure v0.12 BRIP1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Prenatal and postnatal growth failure is a key feature of FA.
Growth failure v0.12 BRCA2 Zornitza Stark Marked gene: BRCA2 as ready
Growth failure v0.12 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
Growth failure v0.12 BRCA2 Zornitza Stark Phenotypes for gene: BRCA2 were changed from Fanconi anemia, complementation group D1, 605724; 605724 Fanconi anemia, complementation group D1 to Fanconi anaemia, complementation group D1, MIM# 605724
Growth failure v0.11 BRCA2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Pre-natal and post-natal growth failure is a key feature.
Growth failure v0.11 BRAF Zornitza Stark Marked gene: BRAF as ready
Growth failure v0.11 BRAF Zornitza Stark Gene: braf has been classified as Green List (High Evidence).
Growth failure v0.11 BRAF Zornitza Stark Phenotypes for gene: BRAF were changed from Noonan Syndrome; LEOPARD Syndrome; Cardiofaciocutaneous Syndrome; Cardiofaciocutaneous syndrome; Cardio-facio-cutaneous syndrome; LEOPARD syndrome 3 to Noonan syndrome 7, MIM# 613706; Cardiofaciocutaneous syndrome, MIM# 115150
Growth failure v0.10 BRAF Zornitza Stark Publications for gene: BRAF were set to 16474404; 21396583; 16825433; 19206169
Growth failure v0.9 BRAF Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Growth failure, feeding difficulties, short stature are prominent early presenting features.
Growth failure v0.9 BLM Zornitza Stark Marked gene: BLM as ready
Growth failure v0.9 BLM Zornitza Stark Gene: blm has been classified as Green List (High Evidence).
Growth failure v0.9 BLM Zornitza Stark Phenotypes for gene: BLM were changed from Bloom syndrome, 210900; 210900 Bloom syndrome; Bloom to Bloom syndrome, MIM# 210900
Growth failure v0.8 BLM Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Proportionate pre- and postnatal growth deficiency is a key feature.
Growth failure v0.8 ANKRD11 Zornitza Stark Marked gene: ANKRD11 as ready
Growth failure v0.8 ANKRD11 Zornitza Stark Gene: ankrd11 has been classified as Green List (High Evidence).
Growth failure v0.8 ANKRD11 Zornitza Stark Phenotypes for gene: ANKRD11 were changed from KBG syndrome, 148050; KBG to KBG syndrome, MIM# 148050
Growth failure v0.7 ANKRD11 Zornitza Stark Publications for gene: ANKRD11 were set to 21782149
Growth failure v0.6 ANKRD11 Zornitza Stark reviewed gene: ANKRD11: Rating: GREEN; Mode of pathogenicity: None; Publications: 33955014, 32258089, 32124548, 31191201, 29565525, 28449295; Phenotypes: KBG syndrome, MIM# 148050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8658 ACAN Zornitza Stark Publications for gene: ACAN were set to
Mendeliome v0.8657 ACAN Zornitza Stark edited their review of gene: ACAN: Added comment: Patients with SSOAD exhibit a broad phenotypic spectrum involving short stature associated with advanced bone maturation and early-onset osteoarthritis (OA), as well as mild dysmorphic features consisting of midface hypoplasia, brachydactyly, broad great toes, and lumbar lordosis. Other features include intervertebral disc disease and osteochondritis dissecans, which is characterized by separation of articular cartilage and subchondral bone from the articular surface. Phenotypes are highly variable even among patients within the same family, and there are no apparent genotype-phenotype correlations.

Well established gene-disease association, multiple families reported.

Note fewer families reported with bi-allelic variants in this gene and extreme short stature.; Changed publications: 24762113, 27870580, 19110214, 30124491, 28331218, 20137779; Changed phenotypes: Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM# 165800, Spondyloepimetaphyseal dysplasia, aggrecan type 612813
Growth failure v0.6 ACAN Zornitza Stark Marked gene: ACAN as ready
Growth failure v0.6 ACAN Zornitza Stark Gene: acan has been classified as Green List (High Evidence).
Growth failure v0.6 ACAN Zornitza Stark Phenotypes for gene: ACAN were changed from Spondyloepimetaphyseal dysplasia, aggrecan type (AR), 612813; ?Spondyloepiphyseal dysplasia, Kimberley type (AD), 608361; short stature, accelerated bone maturation, Spondyloepiphyseal dysplasia, early onset osteoarthritis; Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (AD), 165800 to Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, MIM# 165800; Spondyloepimetaphyseal dysplasia, aggrecan type, MIM# 612813
Growth failure v0.5 ACAN Zornitza Stark Publications for gene: ACAN were set to 24762113; 27870580
Growth failure v0.4 ACAN Zornitza Stark Mode of inheritance for gene: ACAN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Growth failure v0.3 ACAN Zornitza Stark reviewed gene: ACAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 28331218, 20137779, 24762113, 19110214, 30124491; Phenotypes: Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, MIM# 165800, Spondyloepimetaphyseal dysplasia, aggrecan type, MIM# 612813; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Combined Immunodeficiency v0.289 NFKBIA Zornitza Stark Marked gene: NFKBIA as ready
Combined Immunodeficiency v0.289 NFKBIA Zornitza Stark Gene: nfkbia has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.289 NFKBIA Zornitza Stark Phenotypes for gene: NFKBIA were changed from to Ectodermal dysplasia and immunodeficiency 2 MIM# 612132; Ectodermal dysplasia; TCR/ BCR activation impaired; low memory and isotype switched B cells; decreased IgG and IgA; elevated IgM; poor specific antibody responses; diarrhoea; agammaglobulinaemia; ectodermal dysplasia; recurrent respiratory and gastrointestinal infections; colitis; variable defects of skin, hair and teeth
Combined Immunodeficiency v0.288 NFKBIA Zornitza Stark Publications for gene: NFKBIA were set to
Combined Immunodeficiency v0.287 NFKBIA Zornitza Stark Mode of pathogenicity for gene: NFKBIA was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Combined Immunodeficiency v0.286 NFKBIA Zornitza Stark Mode of inheritance for gene: NFKBIA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8657 NFKBIA Zornitza Stark Marked gene: NFKBIA as ready
Mendeliome v0.8657 NFKBIA Zornitza Stark Gene: nfkbia has been classified as Green List (High Evidence).
Mendeliome v0.8657 NFKBIA Zornitza Stark Phenotypes for gene: NFKBIA were changed from to Ectodermal dysplasia and immunodeficiency 2 MIM# 612132; Ectodermal dysplasia; TCR/ BCR activation impaired; low memory and isotype switched B cells; decreased IgG and IgA; elevated IgM; poor specific antibody responses; diarrhoea; agammaglobulinaemia; ectodermal dysplasia; recurrent respiratory and gastrointestinal infections; colitis; variable defects of skin, hair and teeth
Mendeliome v0.8656 NFKBIA Zornitza Stark Mode of pathogenicity for gene: NFKBIA was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.8655 NFKBIA Zornitza Stark Mode of inheritance for gene: NFKBIA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Predominantly Antibody Deficiency v0.74 NFKB2 Zornitza Stark Marked gene: NFKB2 as ready
Predominantly Antibody Deficiency v0.74 NFKB2 Zornitza Stark Gene: nfkb2 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.74 NFKB2 Zornitza Stark Phenotypes for gene: NFKB2 were changed from to Immunodeficiency, common variable, 10 MIM# 615577; Low serum IgG, IgA, IgM; low B cell numbers; low switched memory B cells; Recurrent sinopulmonary infections, Alopecia; endocrinopathies; ACTH deficiency
Predominantly Antibody Deficiency v0.73 NFKB2 Zornitza Stark Publications for gene: NFKB2 were set to
Predominantly Antibody Deficiency v0.72 NFKB2 Zornitza Stark Mode of inheritance for gene: NFKB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Predominantly Antibody Deficiency v0.71 NFKB2 Zornitza Stark reviewed gene: NFKB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24140114, 24888602, 25524009, 31417880; Phenotypes: Immunodeficiency, common variable, 10 MIM# 615577, Low serum IgG, IgA, IgM, low B cell numbers, low switched memory B cells, Recurrent sinopulmonary infections, Alopecia, endocrinopathies, ACTH deficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.285 NFKB2 Zornitza Stark Marked gene: NFKB2 as ready
Combined Immunodeficiency v0.285 NFKB2 Zornitza Stark Gene: nfkb2 has been classified as Green List (High Evidence).
Mendeliome v0.8654 NFKB2 Zornitza Stark Marked gene: NFKB2 as ready
Mendeliome v0.8654 NFKB2 Zornitza Stark Gene: nfkb2 has been classified as Green List (High Evidence).
Mendeliome v0.8654 NFKB2 Zornitza Stark Phenotypes for gene: NFKB2 were changed from to Immunodeficiency, common variable, 10 MIM# 615577; Low serum IgG, IgA, IgM; low B cell numbers; low switched memory B cells; Recurrent sinopulmonary infections, Alopecia; endocrinopathies; ACTH deficiency
Mendeliome v0.8653 NFKB2 Zornitza Stark Publications for gene: NFKB2 were set to
Mendeliome v0.8652 NFKB2 Zornitza Stark Mode of inheritance for gene: NFKB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.285 NFKB2 Zornitza Stark Phenotypes for gene: NFKB2 were changed from to Immunodeficiency, common variable, 10 MIM# 615577; Low serum IgG, IgA, IgM; low B cell numbers; low switched memory B cells; Recurrent sinopulmonary infections, Alopecia; endocrinopathies; ACTH deficiency
Combined Immunodeficiency v0.284 NFKB2 Zornitza Stark Publications for gene: NFKB2 were set to
Combined Immunodeficiency v0.283 NFKB2 Zornitza Stark Mode of inheritance for gene: NFKB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Predominantly Antibody Deficiency v0.71 NFKB1 Zornitza Stark Marked gene: NFKB1 as ready
Predominantly Antibody Deficiency v0.71 NFKB1 Zornitza Stark Gene: nfkb1 has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.71 NFKB1 Zornitza Stark Phenotypes for gene: NFKB1 were changed from to Immunodeficiency, common variable, 12 MIM# 616576; Normal-low IgG, IgA, IgM; low-normal B cells; low switched memory B cells; hypogammaglobulinaemia; recurrent respiratory and gastrointestinal infections; Chronic obstructive pulmonary disease COPD; EBV proliferation; autoimmunity; alopecia
Predominantly Antibody Deficiency v0.70 NFKB1 Zornitza Stark Publications for gene: NFKB1 were set to
Predominantly Antibody Deficiency v0.69 NFKB1 Zornitza Stark Mode of inheritance for gene: NFKB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Predominantly Antibody Deficiency v0.68 NFKB1 Zornitza Stark reviewed gene: NFKB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26279205, 32278790, 27022143, 7834752; Phenotypes: Immunodeficiency, common variable, 12 MIM# 616576, Normal-low IgG, IgA, IgM, low-normal B cells, low switched memory B cells, hypogammaglobulinaemia, recurrent respiratory and gastrointestinal infections, Chronic obstructive pulmonary disease COPD, EBV proliferation, autoimmunity, alopecia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8651 NFKB1 Zornitza Stark Marked gene: NFKB1 as ready
Mendeliome v0.8651 NFKB1 Zornitza Stark Gene: nfkb1 has been classified as Green List (High Evidence).
Mendeliome v0.8651 NFKB1 Zornitza Stark Phenotypes for gene: NFKB1 were changed from to Immunodeficiency, common variable, 12 MIM# 616576; Normal-low IgG, IgA, IgM; low-normal B cells; low switched memory B cells; hypogammaglobulinaemia; recurrent respiratory and gastrointestinal infections; Chronic obstructive pulmonary disease COPD; EBV proliferation; autoimmunity; alopecia
Mendeliome v0.8650 NFKB1 Zornitza Stark Publications for gene: NFKB1 were set to
Mendeliome v0.8649 NFKB1 Zornitza Stark Mode of inheritance for gene: NFKB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.282 NFKB1 Zornitza Stark Marked gene: NFKB1 as ready
Combined Immunodeficiency v0.282 NFKB1 Zornitza Stark Gene: nfkb1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.282 NFKB1 Zornitza Stark Phenotypes for gene: NFKB1 were changed from to Immunodeficiency, common variable, 12 MIM# 616576; Normal-low IgG, IgA, IgM; low-normal B cells; low switched memory B cells; hypogammaglobulinaemia; recurrent respiratory and gastrointestinal infections; Chronic obstructive pulmonary disease COPD; EBV proliferation; autoimmunity; alopecia
Combined Immunodeficiency v0.281 NFKB1 Zornitza Stark Publications for gene: NFKB1 were set to
Combined Immunodeficiency v0.280 NFKB1 Zornitza Stark Mode of inheritance for gene: NFKB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mackenzie's Mission_Reproductive Carrier Screening v0.102 MCM4 Zornitza Stark reviewed gene: MCM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22354167, 22354170, 22499342; Phenotypes: Immunodeficiency 54, MIM# 609981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8648 MCM4 Zornitza Stark Marked gene: MCM4 as ready
Mendeliome v0.8648 MCM4 Zornitza Stark Gene: mcm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8648 MCM4 Zornitza Stark Phenotypes for gene: MCM4 were changed from to Immunodeficiency 54 MIM# 609981; Decreased NK cell number and function; Viral infections (EBV, HSV, VZV); Short stature; B cell lymphoma; Adrenal failure; Failure to thrive; Microcephaly; Increased chromosomal breakage; Hyperpigmentation; Lymphadenopathy
Mendeliome v0.8647 MCM4 Zornitza Stark Publications for gene: MCM4 were set to
Mendeliome v0.8646 MCM4 Zornitza Stark Mode of inheritance for gene: MCM4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8645 MCM4 Zornitza Stark Classified gene: MCM4 as Amber List (moderate evidence)
Mendeliome v0.8645 MCM4 Zornitza Stark Gene: mcm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8644 MCM4 Zornitza Stark Tag founder tag was added to gene: MCM4.
Mendeliome v0.8644 MCM4 Zornitza Stark reviewed gene: MCM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22354167, 22354170, 22499342; Phenotypes: Immunodeficiency 54 MIM# 609981, Decreased NK cell number and function, Viral infections (EBV, HSV, VZV), Short stature, B cell lymphoma, Adrenal failure, Failure to thrive, Microcephaly, Increased chromosomal breakage, Hyperpigmentation, Lymphadenopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.279 MCM4 Zornitza Stark Tag founder tag was added to gene: MCM4.
Combined Immunodeficiency v0.279 MCM4 Zornitza Stark Marked gene: MCM4 as ready
Combined Immunodeficiency v0.279 MCM4 Zornitza Stark Gene: mcm4 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v0.279 MCM4 Zornitza Stark Phenotypes for gene: MCM4 were changed from to Immunodeficiency 54 MIM# 609981; Decreased NK cell number and function; Viral infections (EBV, HSV, VZV); Short stature; B cell lymphoma; Adrenal failure; Failure to thrive; Microcephaly; Increased chromosomal breakage; Hyperpigmentation; Lymphadenopathy
Combined Immunodeficiency v0.278 MCM4 Zornitza Stark Publications for gene: MCM4 were set to
Combined Immunodeficiency v0.277 MCM4 Zornitza Stark Mode of inheritance for gene: MCM4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.276 MCM4 Zornitza Stark Classified gene: MCM4 as Amber List (moderate evidence)
Combined Immunodeficiency v0.276 MCM4 Zornitza Stark Gene: mcm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8644 MAP3K14 Zornitza Stark Marked gene: MAP3K14 as ready
Mendeliome v0.8644 MAP3K14 Zornitza Stark Gene: map3k14 has been classified as Green List (High Evidence).
Mendeliome v0.8644 MAP3K14 Zornitza Stark Phenotypes for gene: MAP3K14 were changed from to NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels
Mendeliome v0.8643 MAP3K14 Zornitza Stark Publications for gene: MAP3K14 were set to
Mendeliome v0.8642 MAP3K14 Zornitza Stark Mode of inheritance for gene: MAP3K14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8641 MAP3K14 Zornitza Stark reviewed gene: MAP3K14: Rating: GREEN; Mode of pathogenicity: None; Publications: 10319865, 11238593, 12352969; Phenotypes: NIK deficiency, Poor T cell proliferation to antigen, Low B-cell numbers, Low NK number and function, recurrent bacterial/viral/ cryptosporidium infections, hypogammaglobulinaemia, decreased immunoglobulin levels; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.275 MAP3K14 Zornitza Stark Marked gene: MAP3K14 as ready
Combined Immunodeficiency v0.275 MAP3K14 Zornitza Stark Added comment: Comment when marking as ready: Extensive functional characterisation in mouse models, see also PMIDs 10319865; 11238593; 12352969, hence Green rating with two families reported only.
Combined Immunodeficiency v0.275 MAP3K14 Zornitza Stark Gene: map3k14 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.275 MAP3K14 Zornitza Stark Publications for gene: MAP3K14 were set to 25406581; 29230214; 11251123
Combined Immunodeficiency v0.274 MAP3K14 Zornitza Stark Phenotypes for gene: MAP3K14 were changed from to NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels
Combined Immunodeficiency v0.273 MAP3K14 Zornitza Stark Publications for gene: MAP3K14 were set to
Combined Immunodeficiency v0.272 MAP3K14 Zornitza Stark Mode of inheritance for gene: MAP3K14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8641 LRBA Zornitza Stark Marked gene: LRBA as ready
Mendeliome v0.8641 LRBA Zornitza Stark Gene: lrba has been classified as Green List (High Evidence).
Mendeliome v0.8641 LRBA Zornitza Stark Phenotypes for gene: LRBA were changed from to Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700; Normal-decreased CD4 numbers; T cell dysregulation; Low-normal B cells; Reduced IgG and IgA; Recurrent infections; chronic diarrhoea; inflammatory bowel disease; hypogammaglobulinaemia; pneumonitis; autoimmune disorders; thrombocytopaenia
Mendeliome v0.8640 LRBA Zornitza Stark Publications for gene: LRBA were set to
Mendeliome v0.8639 LRBA Zornitza Stark Mode of inheritance for gene: LRBA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8638 LRBA Zornitza Stark reviewed gene: LRBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 22608502, 22721650, 25468195, 26206937, 33155142; Phenotypes: Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700, Normal-decreased CD4 numbers, T cell dysregulation, Low-normal B cells, Reduced IgG and IgA, Recurrent infections, chronic diarrhoea, inflammatory bowel disease, hypogammaglobulinaemia, pneumonitis, autoimmune disorders, thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.271 LRBA Zornitza Stark Marked gene: LRBA as ready
Combined Immunodeficiency v0.271 LRBA Zornitza Stark Gene: lrba has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.271 LRBA Zornitza Stark Phenotypes for gene: LRBA were changed from to Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700; Normal-decreased CD4 numbers; T cell dysregulation; Low-normal B cells; Reduced IgG and IgA; Recurrent infections; chronic diarrhoea; inflammatory bowel disease; hypogammaglobulinaemia; pneumonitis; autoimmune disorders; thrombocytopaenia
Combined Immunodeficiency v0.270 LRBA Zornitza Stark Publications for gene: LRBA were set to
Combined Immunodeficiency v0.269 LRBA Zornitza Stark Mode of inheritance for gene: LRBA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8638 NFKBIA Danielle Ariti reviewed gene: NFKBIA: 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: 28597146, 23864385, 23708964; Phenotypes: Ectodermal dysplasia and immunodeficiency 2 MIM# 612132, Ectodermal dysplasia, TCR/ BCR activation impaired, low memory and isotype switched B cells, decreased IgG and IgA, elevated IgM, poor specific antibody responses, diarrhoea, agammaglobulinaemia, ectodermal dysplasia, recurrent respiratory and gastrointestinal infections, colitis, variable defects of skin, hair and teeth; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8638 NFKB2 Danielle Ariti reviewed gene: NFKB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24140114, 24888602, 25524009, 31417880; Phenotypes: Immunodeficiency, common variable, 10 MIM# 615577, Low serum IgG, IgA, IgM, low B cell numbers, low switched memory B cells, Recurrent sinopulmonary infections, Alopecia, endocrinopathies, ACTH deficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8638 NFKB1 Danielle Ariti reviewed gene: NFKB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26279205, 32278790, 27022143, 7834752; Phenotypes: Immunodeficiency, common variable, 12 MIM# 616576, Normal-low IgG, IgA, IgM, low-normal B cells, low switched memory B cells, hypogammaglobulinaemia, recurrent respiratory and gastrointestinal infections, Chronic obstructive pulmonary disease COPD, EBV proliferation, autoimmunity, alopecia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.268 NFKBIA Danielle Ariti changed review comment from: 12 heterozygous variants were identified in 15 unrelated individuals (de novo in 14 individuals and somatic mosaicism in 1 individual).

Functional studies & two mouse models; demonstrate reported NFKBIA
gain-of-function variants resulting in impaired NFKB1 activity.

The majority of individuals displayed recurrent infections, chronic diarrhoea, agammaglobulinaemia, increased IgM, and defects in teeth (hair, nail, sweat glands).; to: 12 heterozygous variants were identified in 15 unrelated individuals (de novo in 14 individuals and somatic mosaicism in 1 individual).

Functional studies & two mouse models; demonstrate reported NFKBIA gain-of-function variants resulting in impaired NFKB1 activity.

The majority of individuals displayed recurrent infections, chronic diarrhoea, agammaglobulinaemia, increased IgM, and defects in teeth (hair, nail, sweat glands).
Combined Immunodeficiency v0.268 NFKBIA Danielle Ariti reviewed gene: NFKBIA: 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: 28597146, 23864385, 23708964; Phenotypes: Ectodermal dysplasia and immunodeficiency 2 MIM# 612132, Ectodermal dysplasia, TCR/ BCR activation impaired, low memory and isotype switched B cells, decreased IgG and IgA, elevated IgM, poor specific antibody responses, diarrhoea, agammaglobulinaemia, ectodermal dysplasia, recurrent respiratory and gastrointestinal infections, colitis, variable defects of skin, hair and teeth; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.268 NFKB2 Danielle Ariti reviewed gene: NFKB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24140114, 24888602, 25524009, 31417880; Phenotypes: Immunodeficiency, common variable, 10 MIM# 615577, Low serum IgG, IgA, IgM, low B cell numbers, low switched memory B cells, Recurrent sinopulmonary infections, Alopecia, endocrinopathies, ACTH deficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.268 NFKB1 Danielle Ariti reviewed gene: NFKB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26279205, 32278790, 27022143, 7834752; Phenotypes: Immunodeficiency, common variable, 12 MIM# 616576, Normal-low IgG, IgA, IgM, low-normal B cells, low switched memory B cells, hypogammaglobulinaemia, recurrent respiratory and gastrointestinal infections, Chronic obstructive pulmonary disease COPD, EBV proliferation, autoimmunity, alopecia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.268 MCM4 Danielle Ariti reviewed gene: MCM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22354167, 22354170, 22499342; Phenotypes: Immunodeficiency 54 MIM# 609981, Decreased NK cell number and function, Viral infections (EBV, HSV, VZV), Short stature, B cell lymphoma, Adrenal failure, Failure to thrive, Microcephaly, Increased chromosomal breakage, Hyperpigmentation, Lymphadenopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertension and Aldosterone disorders v1.4 WNK1 Zornitza Stark Phenotypes for gene: WNK1 were changed from to Pseudohypoaldosteronism 2C (PHA2C), MIM#614492
Hypertension and Aldosterone disorders v1.3 WNK1 Zornitza Stark Publications for gene: WNK1 were set to
Hypertension and Aldosterone disorders v1.2 WNK1 Zornitza Stark Mode of pathogenicity for gene: WNK1 was changed from to Other
Hypertension and Aldosterone disorders v1.1 WNK1 Zornitza Stark Mode of inheritance for gene: WNK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.268 MAP3K14 Danielle Ariti reviewed gene: MAP3K14: Rating: AMBER; Mode of pathogenicity: None; Publications: 25406581, 29230214, 11251123; Phenotypes: NIK deficiency, Poor T cell proliferation to antigen, Low B-cell numbers, Low NK number and function, recurrent bacterial/viral/ cryptosporidium infections, hypogammaglobulinaemia, decreased immunoglobulin levels; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.268 LRBA Danielle Ariti changed review comment from: Over 10 unrelated individuals with LRBA variants displaying immunodeficiency phenotype; one mouse model.

Reported homozygous truncating variants (missense/ nonsense).

Most reported individuals displayed reduced IgG and IgA, autoimmune disorders, hypogammaglobulinemia and recurrent infections.; to: Over 10 unrelated individuals with LRBA variants displaying immunodeficiency phenotype; one mouse model.

Reported homozygous truncating variants (missense/ nonsense).

Most reported individuals displayed reduced IgG and IgA, autoimmune disorders, hypogammaglobulinaemia and recurrent infections.
Combined Immunodeficiency v0.268 LRBA Danielle Ariti reviewed gene: LRBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 22608502, 22721650, 25468195, 26206937, 33155142; Phenotypes: Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700, Normal-decreased CD4 numbers, T cell dysregulation, Low-normal B cells, Reduced IgG and IgA, Recurrent infections, chronic diarrhoea, inflammatory bowel disease, hypogammaglobulinaemia, pneumonitis, autoimmune disorders, thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertension and Aldosterone disorders v1.0 WNK1 Chirag Patel reviewed gene: WNK1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 11498583, 11498583; Phenotypes: Pseudohypoaldosteronism 2C (PHA2C); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.8638 AQP2 Zornitza Stark Marked gene: AQP2 as ready
Mendeliome v0.8638 AQP2 Zornitza Stark Gene: aqp2 has been classified as Green List (High Evidence).
Mendeliome v0.8638 AQP2 Zornitza Stark Phenotypes for gene: AQP2 were changed from to Diabetes insipidus, nephrogenic, MIM#125800
Mendeliome v0.8637 AQP2 Zornitza Stark Publications for gene: AQP2 were set to
Mendeliome v0.8636 AQP2 Zornitza Stark Mode of inheritance for gene: AQP2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8635 AQP2 Zornitza Stark reviewed gene: AQP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7537761, 11536078; Phenotypes: Diabetes insipidus, nephrogenic, MIM#125800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4026 RNF2 Zornitza Stark Phenotypes for gene: RNF2 were changed from epilepsy; intellectual disability; intrauterine growth retardation to Lou-Schoch-Yamamoto syndrome , MIM#619460; epilepsy; intellectual disability; intrauterine growth retardation
Intellectual disability syndromic and non-syndromic v0.4025 RNF2 Zornitza Stark edited their review of gene: RNF2: Changed phenotypes: Lou-Schoch-Yamamoto syndrome , MIM#619460, epilepsy, intellectual disability, intrauterine growth retardation
Genetic Epilepsy v0.1156 RNF2 Zornitza Stark Phenotypes for gene: RNF2 were changed from epilepsy; intellectual disability; intrauterine growth retardation to Lou-Schoch-Yamamoto syndrome , MIM#619460; epilepsy; intellectual disability; intrauterine growth retardation
Genetic Epilepsy v0.1155 RNF2 Zornitza Stark edited their review of gene: RNF2: Changed phenotypes: Lou-Schoch-Yamamoto syndrome , MIM#619460, epilepsy, intellectual disability, intrauterine growth retardation
Mendeliome v0.8635 RNF2 Zornitza Stark Phenotypes for gene: RNF2 were changed from epilepsy; intellectual disability; intrauterine growth retardation to Lou-Schoch-Yamamoto syndrome , MIM#619460; epilepsy; intellectual disability; intrauterine growth retardation
Mendeliome v0.8634 RNF2 Zornitza Stark reviewed gene: RNF2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Lou-Schoch-Yamamoto syndrome , MIM#619460; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.4025 USP7 Zornitza Stark Phenotypes for gene: USP7 were changed from Hao-Fountain syndrome, MIM# 616863; ID; Autism to Hao-Fountain syndrome, MIM# 616863; MONDO:0014805; Intellectual disability; Autism
Intellectual disability syndromic and non-syndromic v0.4024 USP7 Zornitza Stark edited their review of gene: USP7: Changed phenotypes: Hao-Fountain syndrome, MIM# 616863, MONDO:0014805, Intellectual disability, Autism
Mendeliome v0.8634 USP7 Zornitza Stark Phenotypes for gene: USP7 were changed from Hao-Fountain syndrome, MIM# 616863; Intellectual disability; Autism to Hao-Fountain syndrome, MIM# 616863; MONDO:0014805; Intellectual disability; Autism
Mendeliome v0.8633 USP7 Zornitza Stark edited their review of gene: USP7: Changed phenotypes: Hao-Fountain syndrome, MIM# 616863, MONDO:0014805, Intellectual disability, Autism
Autism v0.167 USP7 Zornitza Stark Phenotypes for gene: USP7 were changed from Hao-Fountain syndrome, MIM# 616863; Intellectual disability; Autism to Hao-Fountain syndrome, MIM# 616863; MONDO:0014805; Intellectual disability; Autism
Autism v0.166 USP7 Zornitza Stark edited their review of gene: USP7: Changed phenotypes: Hao-Fountain syndrome, MIM# 616863, MONDO:0014805, Intellectual disability, Autism
Bone Marrow Failure v1.6 GIMAP5 Zornitza Stark Marked gene: GIMAP5 as ready
Bone Marrow Failure v1.6 GIMAP5 Zornitza Stark Gene: gimap5 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.6 GIMAP5 Zornitza Stark Classified gene: GIMAP5 as Green List (high evidence)
Bone Marrow Failure v1.6 GIMAP5 Zornitza Stark Gene: gimap5 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.5 GIMAP5 Zornitza Stark gene: GIMAP5 was added
gene: GIMAP5 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: GIMAP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIMAP5 were set to 33956074
Phenotypes for gene: GIMAP5 were set to Portal hypertension, noncirrhotic, 2, MIM# 619463
Review for gene: GIMAP5 was set to GREEN
Added comment: 8 individuals from 4 unrelated families reported with onset of disease in the first decade of life. Clinical features included jaundice, hyperbilirubinaemia, pancytopaenia, including neutropaenia, lymphopaenia, and thrombocytopaenia, hepatosplenomegaly, and oesophageal varices. Some individuals had recurrent infections or features suggestive of an immunodeficiency. Liver biopsy was notable for the absence of cirrhosis and the presence of nodular regeneration.
Sources: Expert list
Mendeliome v0.8633 GIMAP5 Zornitza Stark Marked gene: GIMAP5 as ready
Mendeliome v0.8633 GIMAP5 Zornitza Stark Gene: gimap5 has been classified as Green List (High Evidence).
Mendeliome v0.8633 GIMAP5 Zornitza Stark Classified gene: GIMAP5 as Green List (high evidence)
Mendeliome v0.8633 GIMAP5 Zornitza Stark Gene: gimap5 has been classified as Green List (High Evidence).
Mendeliome v0.8632 GIMAP5 Zornitza Stark gene: GIMAP5 was added
gene: GIMAP5 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GIMAP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIMAP5 were set to 33956074
Phenotypes for gene: GIMAP5 were set to Portal hypertension, noncirrhotic, 2, MIM# 619463
Review for gene: GIMAP5 was set to GREEN
Added comment: 8 individuals from 4 unrelated families reported with onset of disease in the first decade of life. Clinical features included jaundice, hyperbilirubinaemia, pancytopaenia, including neutropaenia, lymphopaenia, and thrombocytopaenia, hepatosplenomegaly, and oesophageal varices. Some individuals had recurrent infections or features suggestive of an immunodeficiency. Liver biopsy was notable for the absence of cirrhosis and the presence of nodular regeneration.
Sources: Expert list
Mendeliome v0.8631 ERBB2 Zornitza Stark Phenotypes for gene: ERBB2 were changed from to Visceral neuropathy, familial, 2, autosomal recessive, MIM# 619465
Gastrointestinal neuromuscular disease v1.15 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Gastrointestinal neuromuscular disease v1.14 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180, Complex neurocristinopathy
Mendeliome v0.8630 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy to Lethal congenital contractural syndrome 2, MIM# 607598; Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy
Mendeliome v0.8629 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598, Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180, Complex neurocristinopathy
Hirschsprung disease v0.18 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Complex neurocristinopathy to Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Complex neurocristinopathy
Hirschsprung disease v0.17 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180, Complex neurocristinopathy
Mendeliome v0.8629 IL7R Zornitza Stark Marked gene: IL7R as ready
Mendeliome v0.8629 IL7R Zornitza Stark Gene: il7r has been classified as Green List (High Evidence).
Mendeliome v0.8629 IL7R Zornitza Stark Phenotypes for gene: IL7R were changed from to Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; fever; rash; failure to thrive; recurrent respiratory and gastric infections; diarrhoea; lymphadenopathy; pneumonitis; Pancytopaenia; low T-cell numbers; decreased immunoglobulins; normal-high B/NK-cell numbers.
Mendeliome v0.8628 IL7R Zornitza Stark Publications for gene: IL7R were set to
Mendeliome v0.8627 IL7R Zornitza Stark Mode of inheritance for gene: IL7R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.268 ITK Zornitza Stark Marked gene: ITK as ready
Combined Immunodeficiency v0.268 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.268 ITK Zornitza Stark Phenotypes for gene: ITK were changed from to Lymphoproliferative syndrome 1 MIM# 613011; Lymphadenopathy; Recurrent infections; Hypogammaglobulinaemia; Evidence of EBV infection; EBV associated B cell Lymphoproliferation; High EBV viral load; Normal-low serum Ig; Depleted CD4+ T cells; Anaemia; Thrombocytopaenia; Hepatosplenomegaly
Combined Immunodeficiency v0.267 ITK Zornitza Stark Publications for gene: ITK were set to
Combined Immunodeficiency v0.266 ITK Zornitza Stark Mode of inheritance for gene: ITK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8626 MALT1 Zornitza Stark Marked gene: MALT1 as ready
Mendeliome v0.8626 MALT1 Zornitza Stark Gene: malt1 has been classified as Green List (High Evidence).
Mendeliome v0.8626 MALT1 Zornitza Stark Phenotypes for gene: MALT1 were changed from to Immunodeficiency 12 MIM# 615468; poor T-cell proliferation; normal T/B cell numbers; poor specific antibody response; recurrent bacterial/fungal/viral infections; bronchiectasis; failure to thrive
Mendeliome v0.8625 MALT1 Zornitza Stark Publications for gene: MALT1 were set to
Mendeliome v0.8624 MALT1 Zornitza Stark Mode of inheritance for gene: MALT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency (absent T present B cells) v0.28 IL2RG Zornitza Stark Marked gene: IL2RG as ready
Severe Combined Immunodeficiency (absent T present B cells) v0.28 IL2RG Zornitza Stark Gene: il2rg has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T present B cells) v0.28 IL2RG Zornitza Stark Phenotypes for gene: IL2RG were changed from to Combined immunodeficiency, X-linked, moderate MIM# 312863; Severe combined immunodeficiency, X-linked MIM# 300400; recurrent viral/fungal/bacterial infections; Low T/NK cells; Low Ig levels; lymphocytopaenia; hypogammaglobulinaemia; failure to thrive; diarrhoea; Pneumonia; Thymic hypoplasia
Severe Combined Immunodeficiency (absent T present B cells) v0.27 IL2RG Zornitza Stark Publications for gene: IL2RG were set to
Severe Combined Immunodeficiency (absent T present B cells) v0.26 IL2RG Zornitza Stark Mode of inheritance for gene: IL2RG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Severe Combined Immunodeficiency (absent T present B cells) v0.25 IL2RG Zornitza Stark reviewed gene: IL2RG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301584, 8462096, 8401490, 7883965, 9399950; Phenotypes: Combined immunodeficiency, X-linked, moderate MIM# 312863, Severe combined immunodeficiency, X-linked MIM# 300400, recurrent viral/fungal/bacterial infections, Low T/NK cells, Low Ig levels, lymphocytopaenia, hypogammaglobulinaemia, failure to thrive, diarrhoea, Pneumonia, Thymic hypoplasia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8623 IL2RG Zornitza Stark Marked gene: IL2RG as ready
Mendeliome v0.8623 IL2RG Zornitza Stark Gene: il2rg has been classified as Green List (High Evidence).
Mendeliome v0.8623 IL2RG Zornitza Stark Phenotypes for gene: IL2RG were changed from to Combined immunodeficiency, X-linked, moderate MIM# 312863; Severe combined immunodeficiency, X-linked MIM# 300400; recurrent viral/fungal/bacterial infections; Low T/NK cells; Low Ig levels; lymphocytopaenia; hypogammaglobulinaemia; failure to thrive; diarrhoea; Pneumonia; Thymic hypoplasia
Mendeliome v0.8622 IL2RG Zornitza Stark Publications for gene: IL2RG were set to
Mendeliome v0.8621 IL2RG Zornitza Stark Mode of inheritance for gene: IL2RG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8620 IL2RG Zornitza Stark reviewed gene: IL2RG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301584, 8462096, 8401490, 7883965, 9399950; Phenotypes: Combined immunodeficiency, X-linked, moderate MIM# 312863, Severe combined immunodeficiency, X-linked MIM# 300400, recurrent viral/fungal/bacterial infections, Low T/NK cells, Low Ig levels, lymphocytopaenia, hypogammaglobulinaemia, failure to thrive, diarrhoea, Pneumonia, Thymic hypoplasia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8620 IKZF1 Zornitza Stark Marked gene: IKZF1 as ready
Mendeliome v0.8620 IKZF1 Zornitza Stark Gene: ikzf1 has been classified as Green List (High Evidence).
Mendeliome v0.8620 IKZF1 Zornitza Stark Phenotypes for gene: IKZF1 were changed from to Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset
Mendeliome v0.8619 IKZF1 Zornitza Stark Publications for gene: IKZF1 were set to
Mendeliome v0.8618 IKZF1 Zornitza Stark Mode of inheritance for gene: IKZF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8617 IKZF1 Zornitza Stark reviewed gene: IKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21548011, 26981933, 29889099, 31057532, 7923373, 11805317; Phenotypes: Immunodeficiency, common variable, 13 MIM# 616873, recurrent bacterial respiratory infections, Thrombocytopaenia, immunodeficiency, Hypogammaglobulinaemia, decrease B-cells, decrease B-cell differentiation, decrease memory B/T cells, Low Ig, pneumocystis early CID onset; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.265 LIG4 Zornitza Stark Marked gene: LIG4 as ready
Combined Immunodeficiency v0.265 LIG4 Zornitza Stark Gene: lig4 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.265 LIG4 Zornitza Stark Phenotypes for gene: LIG4 were changed from to LIG4 syndrome MIM# 606593; T-/B- lymphocytopaenia; Normal NK, radiation sensitivity; Microcephaly; low B/C cells; low Ig; raised IgM; failure to thrive; bacterial/viral/fungal infections; hypogammaglobulinaemia; neurodevelopmental delay; microcephaly; pancytopaenia
Combined Immunodeficiency v0.264 LIG4 Zornitza Stark Publications for gene: LIG4 were set to
Combined Immunodeficiency v0.263 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8617 ITK Zornitza Stark Marked gene: ITK as ready
Mendeliome v0.8617 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.262 IL7R Zornitza Stark Marked gene: IL7R as ready
Combined Immunodeficiency v0.262 IL7R Zornitza Stark Gene: il7r has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.262 IL7R Zornitza Stark Phenotypes for gene: IL7R were changed from to Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; fever; rash; failure to thrive; recurrent respiratory and gastric infections; diarrhoea; lymphadenopathy; pneumonitis; Pancytopaenia; low T-cell numbers; decreased immunoglobulins; normal-high B/NK-cell numbers.
Combined Immunodeficiency v0.261 IL7R Zornitza Stark Publications for gene: IL7R were set to
Mendeliome v0.8617 ITK Zornitza Stark Phenotypes for gene: ITK were changed from to Lymphoproliferative syndrome 1 MIM# 613011; Lymphadenopathy; Recurrent infections; Hypogammaglobulinaemia; Evidence of EBV infection; EBV associated B cell Lymphoproliferation; High EBV viral load; Normal-low serum Ig; Depleted CD4+ T cells; Anaemia; Thrombocytopaenia; Hepatosplenomegaly
Combined Immunodeficiency v0.260 IL7R Zornitza Stark Mode of inheritance for gene: IL7R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8616 ITK Zornitza Stark Publications for gene: ITK were set to
Mendeliome v0.8615 ITK Zornitza Stark Mode of inheritance for gene: ITK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.259 MALT1 Danielle Ariti Deleted their comment
Combined Immunodeficiency v0.259 MALT1 Danielle Ariti edited their review of gene: MALT1: Added comment: 5 individuals from 3 unrelated families with immunodeficiency phenotype have reported variants in MALT1; two MALT1-knockout mouse models displaying primary T- and B-cell lymphocyte deficiency.

Variants identified were homozygous missense variants resulting in the alteration of highly conserved residue domains.

All individuals reported onset in infancy of recurrent bacterial/ fungal/ viral infections leading to bronchiectasis and poor T-cell proliferation.; Changed rating: GREEN
Combined Immunodeficiency v0.259 MALT1 Zornitza Stark Phenotypes for gene: MALT1 were changed from Immunodeficiency 12 MIM# 615468; poor T-cell proliferation; normal T/B cell numbers; poor specific antibody response; recurrent bacterial/fungal/viral infections; bronchiectasis; failure to thrive to Immunodeficiency 12 MIM# 615468; poor T-cell proliferation; normal T/B cell numbers; poor specific antibody response; recurrent bacterial/fungal/viral infections; bronchiectasis; failure to thrive
Combined Immunodeficiency v0.259 MALT1 Zornitza Stark Marked gene: MALT1 as ready
Combined Immunodeficiency v0.259 MALT1 Zornitza Stark Gene: malt1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.259 MALT1 Zornitza Stark Phenotypes for gene: MALT1 were changed from to Immunodeficiency 12 MIM# 615468; poor T-cell proliferation; normal T/B cell numbers; poor specific antibody response; recurrent bacterial/fungal/viral infections; bronchiectasis; failure to thrive
Mendeliome v0.8614 MALT1 Danielle Ariti Deleted their comment
Combined Immunodeficiency v0.258 IL2RG Zornitza Stark Marked gene: IL2RG as ready
Combined Immunodeficiency v0.258 IL2RG Zornitza Stark Gene: il2rg has been classified as Green List (High Evidence).
Mendeliome v0.8614 MALT1 Danielle Ariti edited their review of gene: MALT1: Added comment: 5 individuals from 3 unrelated families with immunodeficiency phenotype have reported variants in MALT1; two MALT1-knockout mouse models displaying primary T- and B-cell lymphocyte deficiency.

Variants identified were homozygous missense variants resulting in the alteration of highly conserved residue domains.

All individuals reported onset in infancy of recurrent bacterial/ fungal/ viral infections leading to bronchiectasis and poor T-cell proliferation.; Changed rating: GREEN
Combined Immunodeficiency v0.258 MALT1 Zornitza Stark Publications for gene: MALT1 were set to
Combined Immunodeficiency v0.257 MALT1 Zornitza Stark Mode of inheritance for gene: MALT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.256 IL2RG Zornitza Stark Phenotypes for gene: IL2RG were changed from to Combined immunodeficiency, X-linked, moderate MIM# 312863; Severe combined immunodeficiency, X-linked MIM# 300400; recurrent viral/fungal/bacterial infections; Low T/NK cells; Low Ig levels; lymphocytopaenia; hypogammaglobulinaemia; failure to thrive; diarrhoea; Pneumonia; Thymic hypoplasia
Combined Immunodeficiency v0.255 IL2RG Zornitza Stark Publications for gene: IL2RG were set to 20301584; 8462096; 8401490; 7883965; 9399950
Combined Immunodeficiency v0.255 IKZF1 Zornitza Stark Marked gene: IKZF1 as ready
Combined Immunodeficiency v0.255 IKZF1 Zornitza Stark Gene: ikzf1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.255 IKZF1 Zornitza Stark Phenotypes for gene: IKZF1 were changed from to Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset
Combined Immunodeficiency v0.254 IL2RG Zornitza Stark Publications for gene: IL2RG were set to
Combined Immunodeficiency v0.254 IKZF1 Zornitza Stark Publications for gene: IKZF1 were set to 21548011; 26981933; 29889099; 31057532; 7923373; 11805317
Combined Immunodeficiency v0.253 IL2RG Zornitza Stark Mode of inheritance for gene: IL2RG was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Combined Immunodeficiency v0.253 IKZF1 Zornitza Stark Publications for gene: IKZF1 were set to
Combined Immunodeficiency v0.253 IL2RG Zornitza Stark Mode of inheritance for gene: IL2RG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Combined Immunodeficiency v0.252 IKZF1 Zornitza Stark Mode of inheritance for gene: IKZF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.252 IKZF1 Zornitza Stark Mode of inheritance for gene: IKZF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1155 AP1G1 Zornitza Stark Marked gene: AP1G1 as ready
Genetic Epilepsy v0.1155 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1155 AP1G1 Zornitza Stark Classified gene: AP1G1 as Green List (high evidence)
Genetic Epilepsy v0.1155 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4024 AP1G1 Zornitza Stark Marked gene: AP1G1 as ready
Intellectual disability syndromic and non-syndromic v0.4024 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4024 AP1G1 Zornitza Stark Marked gene: AP1G1 as ready
Intellectual disability syndromic and non-syndromic v0.4024 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4024 AP1G1 Zornitza Stark Classified gene: AP1G1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4024 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4023 AP1G1 Zornitza Stark changed review comment from: Two bi-allelic homozygous missense variants were found in two distinct families with Italian and Pakistani origins; homozygous missense variants.

Eight de novo heterozygous variants were identified in nine isolated affected individuals from nine families; including five missense, two frameshift, and one intronic variant that disrupts the canonical splice acceptor site.

Knocking out AP1G1 Zebrafish model resulted in severe developmental abnormalities and increased lethality.

All individuals had neurodevelopmental disorder (NDD) including global developmental delay and ID, which varied in severity from mild to severe.
Sources: Literature; to: Two bi-allelic homozygous missense variants were found in two distinct families with Italian and Pakistani origins; homozygous missense variants.

Eight de novo heterozygous variants were identified in nine isolated affected individuals from nine families; including five missense, two frameshift, and one intronic variant that disrupts the canonical splice acceptor site.

Knocking out AP1G1 Zebrafish model resulted in severe developmental abnormalities and increased lethality.

All individuals had neurodevelopmental disorder (NDD) including global developmental delay and ID, which varied in severity from mild to severe.

GREEN for mono-allelic, AMBER for bi-allelic.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4023 AP1G1 Zornitza Stark gene: AP1G1 was added
gene: AP1G1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AP1G1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AP1G1 were set to 34102099
Phenotypes for gene: AP1G1 were set to Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy
Review for gene: AP1G1 was set to GREEN
Added comment: Two bi-allelic homozygous missense variants were found in two distinct families with Italian and Pakistani origins; homozygous missense variants.

Eight de novo heterozygous variants were identified in nine isolated affected individuals from nine families; including five missense, two frameshift, and one intronic variant that disrupts the canonical splice acceptor site.

Knocking out AP1G1 Zebrafish model resulted in severe developmental abnormalities and increased lethality.

All individuals had neurodevelopmental disorder (NDD) including global developmental delay and ID, which varied in severity from mild to severe.
Sources: Literature
Genetic Epilepsy v0.1154 AP1G1 Danielle Ariti gene: AP1G1 was added
gene: AP1G1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: AP1G1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AP1G1 were set to 34102099
Phenotypes for gene: AP1G1 were set to Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy
Review for gene: AP1G1 was set to GREEN
Added comment: Two bi-allelic homozygous missense variants were found in two distinct families with Italian and Pakistani origins; homozygous missense variants.

Eight de novo heterozygous variants were identified in nine isolated affected individuals from nine families; including five missense, two frameshift, and one intronic variant that disrupts the canonical splice acceptor site.

Knocking out AP1G1 Zebrafish model resulted in severe developmental abnormalities and increased lethality.

All individuals had neurodevelopmental disorder (NDD) including global developmental delay and ID, which varied in severity from mild to severe.
Sources: Literature
Combined Immunodeficiency v0.251 LIG4 Danielle Ariti reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27717373, 10911993; Phenotypes: LIG4 syndrome MIM# 606593, T-/B- lymphocytopaenia, Normal NK, radiation sensitivity, Microcephaly, low B/C cells, low Ig, raised IgM, failure to thrive, bacterial/viral/fungal infections, hypogammaglobulinaemia, neurodevelopmental delay, microcephaly, pancytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 IL7R Danielle Ariti reviewed gene: IL7R: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843216, 19890784, 26123418, 11023514, 7964471; Phenotypes: Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971, fever, rash, failure to thrive, recurrent respiratory and gastric infections, diarrhoea, lymphadenopathy, pneumonitis, Pancytopaenia, low T-cell numbers, decreased immunoglobulins, normal-high B/NK-cell numbers.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.251 IL7R Danielle Ariti changed review comment from: 6 unrelated individuals with 9 unique variants (missense, splicing, nonsense, and frameshift) have been reported).

Two IL7R null mice models demonstrating a phenotype consistent with T cell Lymphopaenia

Typical patient immunological phenotype consisted of Low B-cells, decreased immunoglobulins with normal-high B/NK cell numbers.; to: 6 unrelated individuals with 9 unique variants (missense, splicing, nonsense, and frameshift) have been reported.

Two IL7R null mice models demonstrating a phenotype consistent with T cell Lymphopaenia

Typical patient immunological phenotype consisted of Low B-cells, decreased immunoglobulins with normal-high B/NK cell numbers.
Combined Immunodeficiency v0.251 IL7R Danielle Ariti reviewed gene: IL7R: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843216, 19890784, 26123418, 11023514, 7964471; Phenotypes: Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971, fever, rash, failure to thrive, recurrent respiratory and gastric infections, diarrhoea, lymphadenopathy, pneumonitis, Pancytopaenia, low T-cell numbers, decreased immunoglobulins, normal-high B/NK-cell numbers.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 ITK Danielle Ariti reviewed gene: ITK: Rating: GREEN; Mode of pathogenicity: None; Publications: 19425169, 22289921, 25061172, 26056787, 9311799, 10213685; Phenotypes: Lymphoproliferative syndrome 1 MIM# 613011, Lymphadenopathy, Recurrent infections, Hypogammaglobulinaemia, Evidence of EBV infection, EBV associated B cell Lymphoproliferation, High EBV viral load, Normal-low serum Ig, Depleted CD4+ T cells, Anaemia, Thrombocytopaenia, Hepatosplenomegaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 MALT1 Danielle Ariti reviewed gene: MALT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23727036, 24332264, 14576442, 31037583; Phenotypes: Immunodeficiency 12 MIM# 615468, poor T-cell proliferation, normal T/B cell numbers, poor specific antibody response, recurrent bacterial/fungal/viral infections, bronchiectasis, failure to thrive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.251 ITK Danielle Ariti reviewed gene: ITK: Rating: GREEN; Mode of pathogenicity: None; Publications: 19425169, 22289921, 25061172, 26056787, 9311799, 10213685; Phenotypes: Lymphoproliferative syndrome 1 MIM# 613011, Lymphadenopathy, Recurrent infections, Hypogammaglobulinaemia, Evidence of EBV infection, EBV associated B cell Lymphoproliferation, High EBV viral load, Normal-low serum Ig, Depleted CD4+ T cells, Anaemia, Thrombocytopaenia, Hepatosplenomegaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.251 MALT1 Danielle Ariti reviewed gene: MALT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23727036, 24332264, 14576442, 31037583; Phenotypes: Immunodeficiency 12 MIM# 615468, poor T-cell proliferation, normal T/B cell numbers, poor specific antibody response, recurrent bacterial/fungal/viral infections, bronchiectasis, failure to thrive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.251 IL2RG Danielle Ariti reviewed gene: IL2RG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301584, 8462096, 8401490, 7883965, 9399950; Phenotypes: Combined immunodeficiency, X-linked, moderate MIM# 312863, Severe combined immunodeficiency, X-linked MIM# 300400, recurrent viral/fungal/bacterial infections, Low T/NK cells, Low Ig levels, lymphocytopaenia, hypogammaglobulinaemia, failure to thrive, diarrhoea, Pneumonia, Thymic hypoplasia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Combined Immunodeficiency v0.251 IKZF1 Danielle Ariti reviewed gene: IKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21548011, 26981933, 29889099, 31057532, 7923373, 11805317; Phenotypes: Immunodeficiency, common variable, 13 MIM# 616873, recurrent bacterial respiratory infections, Thrombocytopaenia, immunodeficiency, Hypogammaglobulinaemia, decrease B-cells, decrease B-cell differentiation, decrease memory B/T cells, Low Ig, pneumocystis early CID onset; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pierre Robin Sequence v0.38 PLCB4 Zornitza Stark Marked gene: PLCB4 as ready
Pierre Robin Sequence v0.38 PLCB4 Zornitza Stark Gene: plcb4 has been classified as Green List (High Evidence).
Pierre Robin Sequence v0.38 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from to Auriculocondylar syndrome 2, MIM# 614669
Pierre Robin Sequence v0.37 PLCB4 Zornitza Stark Publications for gene: PLCB4 were set to
Pierre Robin Sequence v0.36 PLCB4 Zornitza Stark Mode of inheritance for gene: PLCB4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pierre Robin Sequence v0.35 PLCB4 Zornitza Stark reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22560091, 23315542, 33131036, 32201334, 28328130, 27007857, 23913798; Phenotypes: Auriculocondylar syndrome 2, MIM# 614669; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8614 PLCB4 Zornitza Stark Marked gene: PLCB4 as ready
Mendeliome v0.8614 PLCB4 Zornitza Stark Gene: plcb4 has been classified as Green List (High Evidence).
Mendeliome v0.8614 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from to Auriculocondylar syndrome 2, MIM# 614669
Mendeliome v0.8613 PLCB4 Zornitza Stark Publications for gene: PLCB4 were set to
Mendeliome v0.8612 PLCB4 Zornitza Stark Mode of inheritance for gene: PLCB4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8611 PLCB4 Zornitza Stark reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22560091, 23315542, 33131036, 32201334, 28328130, 27007857, 23913798; Phenotypes: Auriculocondylar syndrome 2, MIM# 614669; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.57 PLCB4 Zornitza Stark Marked gene: PLCB4 as ready
Mandibulofacial Acrofacial dysostosis v0.57 PLCB4 Zornitza Stark Gene: plcb4 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.57 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from to Auriculocondylar syndrome 2, MIM# 614669
Mandibulofacial Acrofacial dysostosis v0.56 PLCB4 Zornitza Stark Publications for gene: PLCB4 were set to
Mandibulofacial Acrofacial dysostosis v0.55 PLCB4 Zornitza Stark Mode of pathogenicity for gene: PLCB4 was changed from to Other
Mandibulofacial Acrofacial dysostosis v0.54 PLCB4 Zornitza Stark Mode of inheritance for gene: PLCB4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.53 PLCB4 Zornitza Stark reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22560091, 23315542, 33131036, 32201334, 28328130, 27007857, 23913798; Phenotypes: Auriculocondylar syndrome 2, MIM# 614669; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8611 PBX1 Zornitza Stark Marked gene: PBX1 as ready
Mendeliome v0.8611 PBX1 Zornitza Stark Gene: pbx1 has been classified as Green List (High Evidence).
Mendeliome v0.8611 PBX1 Zornitza Stark Phenotypes for gene: PBX1 were changed from to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MIM# 617641
Mendeliome v0.8610 PBX1 Zornitza Stark Publications for gene: PBX1 were set to
Mendeliome v0.8609 PBX1 Zornitza Stark Mode of inheritance for gene: PBX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8608 PBX1 Zornitza Stark reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28566479, 29036646; Phenotypes: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MIM# 617641; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.53 PBX1 Zornitza Stark Marked gene: PBX1 as ready
Mandibulofacial Acrofacial dysostosis v0.53 PBX1 Zornitza Stark Gene: pbx1 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.53 PBX1 Zornitza Stark Phenotypes for gene: PBX1 were changed from to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MIM# 617641
Mandibulofacial Acrofacial dysostosis v0.52 PBX1 Zornitza Stark Publications for gene: PBX1 were set to
Mandibulofacial Acrofacial dysostosis v0.51 PBX1 Zornitza Stark Mode of inheritance for gene: PBX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.50 PBX1 Zornitza Stark reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28566479, 29036646; Phenotypes: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MIM# 617641; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1154 SPTBN1 Zornitza Stark Marked gene: SPTBN1 as ready
Genetic Epilepsy v0.1154 SPTBN1 Zornitza Stark Gene: sptbn1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1154 SPTBN1 Zornitza Stark Classified gene: SPTBN1 as Green List (high evidence)
Genetic Epilepsy v0.1154 SPTBN1 Zornitza Stark Gene: sptbn1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4022 SPTBN1 Zornitza Stark Marked gene: SPTBN1 as ready
Intellectual disability syndromic and non-syndromic v0.4022 SPTBN1 Zornitza Stark Gene: sptbn1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4022 SPTBN1 Zornitza Stark Classified gene: SPTBN1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4022 SPTBN1 Zornitza Stark Gene: sptbn1 has been classified as Green List (High Evidence).
Polydactyly v0.236 HMGB1 Zornitza Stark Marked gene: HMGB1 as ready
Polydactyly v0.236 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Red List (Low Evidence).
Polydactyly v0.236 HMGB1 Zornitza Stark Classified gene: HMGB1 as Red List (low evidence)
Polydactyly v0.236 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.110 UBA2 Zornitza Stark Classified gene: UBA2 as Green List (high evidence)
Skeletal dysplasia v0.110 UBA2 Zornitza Stark Gene: uba2 has been classified as Green List (High Evidence).
Mendeliome v0.8608 VRK1 Zornitza Stark Phenotypes for gene: VRK1 were changed from Pontocerebellar hypoplasia type 1A, MIM# 607596; SMA to Pontocerebellar hypoplasia type 1A, MIM# 607596; Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia
Mendeliome v0.8607 VRK1 Zornitza Stark Publications for gene: VRK1 were set to 19646678; 21937992; 25609612; 24126608; 27281532
Mendeliome v0.8606 VRK1 Zornitza Stark changed review comment from: Complex phenotype with mixed peripheral and central neurological features. Two families reported where PCH was prominent and accompanied by ataxia. At least three families also reported where peripheral neuropathy dominated the clinical picture without PCH/ataxia.; to: Complex phenotype with mixed peripheral and central neurological features. Two families reported where PCH was prominent and accompanied by ataxia. At least three families also reported where peripheral neuropathy dominated the clinical picture without PCH/ataxia.

Further delineation of phenotype 2021:
PMID 34169149: expanding spectrum of neurologic disorders associated with VRK1. Two Hispanic individuals, one homozygous (R321C: VUS and LP/P in ClinVar) and one cHet (R321C+V236M, latter P and more recently VUS in ClinVar), with slowly progressive weakness and a clinical syndrome consistent with adult-onset spinal muscular atrophy WITHOUT pontocerebellar atrophy. No hom in gnomAD and both have been reported in cHet individuals with other features: R321C in association with adult-onset amyotrophic lateral sclerosis and V236M with rapidly progressive sensorimotor polyneuropathy and microcephaly. Authors suggest PMID 26583493 and 31837156 have similar reports. PMID 26583493 reports a 32yo Hispanic individual, cHet H119R+R321C, with early-onset amyotrophic lateral sclerosis, 5 years progressive weakness. PMID 31837156 reports two patients with adult-onset length-dependent motor neuropathy from unrelated consanguineous families of Moroccan Jewish descent, both hom for R387H.
Mendeliome v0.8606 VRK1 Zornitza Stark edited their review of gene: VRK1: Changed publications: 19646678, 21937992, 25609612, 24126608, 27281532, 34169149, 26583493; Changed phenotypes: Pontocerebellar hypoplasia type 1A, MIM# 607596, Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia
Motor Neurone Disease v0.126 VRK1 Zornitza Stark Phenotypes for gene: VRK1 were changed from Distal hereditary motor neuropathy; dHMN/dSMA to Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia; Distal hereditary motor neuropathy; dHMN/dSMA
Motor Neurone Disease v0.125 VRK1 Zornitza Stark Publications for gene: VRK1 were set to 31560180; 32242460; 31178479; 31837156; 30847374
Motor Neurone Disease v0.124 VRK1 Zornitza Stark Classified gene: VRK1 as Amber List (moderate evidence)
Motor Neurone Disease v0.124 VRK1 Zornitza Stark Gene: vrk1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1153 CLCN3 Zornitza Stark Marked gene: CLCN3 as ready
Genetic Epilepsy v0.1153 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1153 CLCN3 Zornitza Stark Classified gene: CLCN3 as Green List (high evidence)
Genetic Epilepsy v0.1153 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Callosome v0.309 CLCN3 Zornitza Stark Marked gene: CLCN3 as ready
Callosome v0.309 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Callosome v0.309 CLCN3 Zornitza Stark Classified gene: CLCN3 as Green List (high evidence)
Callosome v0.309 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1152 CLCN3 Zornitza Stark gene: CLCN3 was added
gene: CLCN3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CLCN3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CLCN3 were set to 34186028
Phenotypes for gene: CLCN3 were set to Neurodevelopmental disorder
Mode of pathogenicity for gene: CLCN3 was set to Other
Review for gene: CLCN3 was set to GREEN
Added comment: 11 individuals reported, 9 that carried 8 different rare heterozygous missense variants in CLCN3, and 2 siblings that were homozygous for an NMD-predicted frameshift variant likely abolishing ClC-3 function. All missense variants were confirmed to be de novo in eight individuals for whom parental data was available.

The 11 individuals in the cohort share clinical features of variable severity. All 11 have GDD or ID and dysmorphic features, and a majority has mood or behavioural disorders and structural brain abnormalities:
- Structural brain abnormalities on MRI (9/11) included partial or full agenesis of the corpus callosum (6/9), disorganized cerebellar folia (4/9), delayed myelination (3/9), decreased white matter volume (3/9), pons hypoplasia (3/9), and dysmorphic dentate nuclei (3/9). Six of those with brain abnormalities also presented with seizures.
- Nine have abnormal vision, including strabismus in four and inability to fix or follow in the two with homozygous loss-of-function variants.
- Hypotonia ranging from mild to severe was reported in 7 of the 11 individuals.
- Six have mood or behavioural disorders, particularly anxiety (3/6).
- Consistent dysmorphic facial features included microcephaly, prominent forehead, hypertelorism, down-slanting palpebral fissures, full cheeks, and micrognathia.

The severity of disease in the two siblings with homozygous disruption of ClC-3 is consistent with the drastic phenotype seen in Clcn3 KO mice. The disease was more severe in two siblings carrying homozygous loss-of-function variants with the presence of GDD, absent speech, seizures, and salt and pepper fundal pigmentation in both individuals, with one deceased at 14 months of age. The siblings also had significant neuroanatomical findings including diffusely decreased white matter volume, thin corpora callosa, small hippocampi, and disorganized cerebellar folia. Supporting biallelic inheritance for LoF variants, disruption of mouse Clcn3 results in drastic neurodegeneration with loss of the hippocampus a few months after birth and early retinal degeneration. Clcn3−/− mice display severe neurodegeneration, whereas heterozygous Clcn3+/− mice appear normal.

Patch-clamp studies were used to investigate four of the missense variants. These suggested a gain of function in two variants with increased current in HEK cells, however they also showed reduced rectification of voltage and a loss of transient current, plus decreased current amplitude, glycosylation and surface expression when expressed in oocytes, and were suspected to interfere with channel gating and a negative feedback mechanism. These effects were also shown to vary depending on pH levels. The current of the remaining two variants did not differ from WT. For heterozygous missense variants, the disruption induced may be at least partially conferred to mutant/WT homodimers and mutant/ClC-4 heterodimers.

Both loss and gain of function in this gene resulted in the same phenotype.
Sources: Literature
Callosome v0.308 CLCN3 Zornitza Stark gene: CLCN3 was added
gene: CLCN3 was added to Callosome. Sources: Literature
Mode of inheritance for gene: CLCN3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CLCN3 were set to 34186028
Phenotypes for gene: CLCN3 were set to Neurodevelopmental disorder
Mode of pathogenicity for gene: CLCN3 was set to Other
Review for gene: CLCN3 was set to GREEN
Added comment: 11 individuals reported, 9 that carried 8 different rare heterozygous missense variants in CLCN3, and 2 siblings that were homozygous for an NMD-predicted frameshift variant likely abolishing ClC-3 function. All missense variants were confirmed to be de novo in eight individuals for whom parental data was available.

The 11 individuals in the cohort share clinical features of variable severity. All 11 have GDD or ID and dysmorphic features, and a majority has mood or behavioural disorders and structural brain abnormalities:
- Structural brain abnormalities on MRI (9/11) included partial or full agenesis of the corpus callosum (6/9), disorganized cerebellar folia (4/9), delayed myelination (3/9), decreased white matter volume (3/9), pons hypoplasia (3/9), and dysmorphic dentate nuclei (3/9). Six of those with brain abnormalities also presented with seizures.
- Nine have abnormal vision, including strabismus in four and inability to fix or follow in the two with homozygous loss-of-function variants.
- Hypotonia ranging from mild to severe was reported in 7 of the 11 individuals.
- Six have mood or behavioural disorders, particularly anxiety (3/6).
- Consistent dysmorphic facial features included microcephaly, prominent forehead, hypertelorism, down-slanting palpebral fissures, full cheeks, and micrognathia.

The severity of disease in the two siblings with homozygous disruption of ClC-3 is consistent with the drastic phenotype seen in Clcn3 KO mice. The disease was more severe in two siblings carrying homozygous loss-of-function variants with the presence of GDD, absent speech, seizures, and salt and pepper fundal pigmentation in both individuals, with one deceased at 14 months of age. The siblings also had significant neuroanatomical findings including diffusely decreased white matter volume, thin corpora callosa, small hippocampi, and disorganized cerebellar folia. Supporting biallelic inheritance for LoF variants, disruption of mouse Clcn3 results in drastic neurodegeneration with loss of the hippocampus a few months after birth and early retinal degeneration. Clcn3−/− mice display severe neurodegeneration, whereas heterozygous Clcn3+/− mice appear normal.

Patch-clamp studies were used to investigate four of the missense variants. These suggested a gain of function in two variants with increased current in HEK cells, however they also showed reduced rectification of voltage and a loss of transient current, plus decreased current amplitude, glycosylation and surface expression when expressed in oocytes, and were suspected to interfere with channel gating and a negative feedback mechanism. These effects were also shown to vary depending on pH levels. The current of the remaining two variants did not differ from WT. For heterozygous missense variants, the disruption induced may be at least partially conferred to mutant/WT homodimers and mutant/ClC-4 heterodimers.

Both loss and gain of function in this gene resulted in the same phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4021 CLCN3 Zornitza Stark Marked gene: CLCN3 as ready
Intellectual disability syndromic and non-syndromic v0.4021 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4021 CLCN3 Zornitza Stark Classified gene: CLCN3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4021 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4020 CLCN3 Zornitza Stark gene: CLCN3 was added
gene: CLCN3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CLCN3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CLCN3 were set to 34186028
Phenotypes for gene: CLCN3 were set to Neurodevelopmental disorder
Mode of pathogenicity for gene: CLCN3 was set to Other
Review for gene: CLCN3 was set to GREEN
Added comment: 11 individuals reported, 9 that carried 8 different rare heterozygous missense variants in CLCN3, and 2 siblings that were homozygous for an NMD-predicted frameshift variant likely abolishing ClC-3 function. All missense variants were confirmed to be de novo in eight individuals for whom parental data was available.

The 11 individuals in the cohort share clinical features of variable severity. All 11 have GDD or ID and dysmorphic features, and a majority has mood or behavioural disorders and structural brain abnormalities:
- Structural brain abnormalities on MRI (9/11) included partial or full agenesis of the corpus callosum (6/9), disorganized cerebellar folia (4/9), delayed myelination (3/9), decreased white matter volume (3/9), pons hypoplasia (3/9), and dysmorphic dentate nuclei (3/9). Six of those with brain abnormalities also presented with seizures.
- Nine have abnormal vision, including strabismus in four and inability to fix or follow in the two with homozygous loss-of-function variants.
- Hypotonia ranging from mild to severe was reported in 7 of the 11 individuals.
- Six have mood or behavioural disorders, particularly anxiety (3/6).
- Consistent dysmorphic facial features included microcephaly, prominent forehead, hypertelorism, down-slanting palpebral fissures, full cheeks, and micrognathia.

The severity of disease in the two siblings with homozygous disruption of ClC-3 is consistent with the drastic phenotype seen in Clcn3 KO mice. The disease was more severe in two siblings carrying homozygous loss-of-function variants with the presence of GDD, absent speech, seizures, and salt and pepper fundal pigmentation in both individuals, with one deceased at 14 months of age. The siblings also had significant neuroanatomical findings including diffusely decreased white matter volume, thin corpora callosa, small hippocampi, and disorganized cerebellar folia. Supporting biallelic inheritance for LoF variants, disruption of mouse Clcn3 results in drastic neurodegeneration with loss of the hippocampus a few months after birth and early retinal degeneration. Clcn3−/− mice display severe neurodegeneration, whereas heterozygous Clcn3+/− mice appear normal.

Patch-clamp studies were used to investigate four of the missense variants. These suggested a gain of function in two variants with increased current in HEK cells, however they also showed reduced rectification of voltage and a loss of transient current, plus decreased current amplitude, glycosylation and surface expression when expressed in oocytes, and were suspected to interfere with channel gating and a negative feedback mechanism. These effects were also shown to vary depending on pH levels. The current of the remaining two variants did not differ from WT. For heterozygous missense variants, the disruption induced may be at least partially conferred to mutant/WT homodimers and mutant/ClC-4 heterodimers.

Both loss and gain of function in this gene resulted in the same phenotype.
Sources: Literature
Mendeliome v0.8606 CLCN3 Zornitza Stark Marked gene: CLCN3 as ready
Mendeliome v0.8606 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Mendeliome v0.8606 CLCN3 Zornitza Stark Mode of inheritance for gene: CLCN3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.8605 CLCN3 Zornitza Stark Classified gene: CLCN3 as Green List (high evidence)
Mendeliome v0.8605 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
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
Genetic Epilepsy v0.1151 TNPO2 Zornitza Stark Marked gene: TNPO2 as ready
Genetic Epilepsy v0.1151 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1151 TNPO2 Zornitza Stark Classified gene: TNPO2 as Green List (high evidence)
Genetic Epilepsy v0.1151 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1150 TNPO2 Zornitza Stark gene: TNPO2 was added
gene: TNPO2 was added to Genetic Epilepsy. 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
Intellectual disability syndromic and non-syndromic v0.4019 TNPO2 Zornitza Stark Marked gene: TNPO2 as ready
Intellectual disability syndromic and non-syndromic v0.4019 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4019 TNPO2 Zornitza Stark Phenotypes for gene: TNPO2 were changed from Developmental delays, neurologic deficits and dysmorphic features to Intellectual disability, neurologic deficits and dysmorphic features
Intellectual disability syndromic and non-syndromic v0.4018 TNPO2 Zornitza Stark Classified gene: TNPO2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4018 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Mendeliome v0.8604 TNPO2 Zornitza Stark Marked gene: TNPO2 as ready
Mendeliome v0.8604 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Mendeliome v0.8604 TNPO2 Zornitza Stark Phenotypes for gene: TNPO2 were changed from Developmental delays, neurologic deficits and dysmorphic features to Intellectual disability, neurologic deficits and dysmorphic features
Mendeliome v0.8603 TNPO2 Zornitza Stark Classified gene: TNPO2 as Green List (high evidence)
Mendeliome v0.8603 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Mendeliome v0.8602 ZDHHC15 Daniel Flanagan reviewed gene: ZDHHC15: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: cerebral palsy, intellectual disability, autism spectrum disorder, epilepsy; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8602 DNAH10 Zornitza Stark Marked gene: DNAH10 as ready
Mendeliome v0.8602 DNAH10 Zornitza Stark Gene: dnah10 has been classified as Green List (High Evidence).
Mendeliome v0.8602 DNAH10 Zornitza Stark Classified gene: DNAH10 as Green List (high evidence)
Mendeliome v0.8602 DNAH10 Zornitza Stark Gene: dnah10 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.123 VRK1 Michelle Torres reviewed gene: VRK1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34169149, 26583493, 31837156; Phenotypes: Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8601 CLCN3 Kristin Rigbye gene: CLCN3 was added
gene: CLCN3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLCN3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CLCN3 were set to PMID: 34186028
Phenotypes for gene: CLCN3 were set to Neurodevelopmental disorder
Mode of pathogenicity for gene: CLCN3 was set to Other
Review for gene: CLCN3 was set to GREEN
Added comment: 11 individuals reported, 9 that carried 8 different rare heterozygous missense variants in CLCN3, and 2 siblings that were homozygous for an NMD-predicted frameshift variant likely abolishing ClC-3 function. All missense variants were confirmed to be de novo in eight individuals for whom parental data was available.

The 11 individuals in the cohort share clinical features of variable severity. All 11 have GDD or ID and dysmorphic features, and a majority has mood or behavioural disorders and structural brain abnormalities:
- Structural brain abnormalities on MRI (9/11) included partial or full agenesis of the corpus callosum (6/9), disorganized cerebellar folia (4/9), delayed myelination (3/9), decreased white matter volume (3/9), pons hypoplasia (3/9), and dysmorphic dentate nuclei (3/9). Six of those with brain abnormalities also presented with seizures.
- Nine have abnormal vision, including strabismus in four and inability to fix or follow in the two with homozygous loss-of-function variants.
- Hypotonia ranging from mild to severe was reported in 7 of the 11 individuals.
- Six have mood or behavioural disorders, particularly anxiety (3/6).
- Consistent dysmorphic facial features included microcephaly, prominent forehead, hypertelorism, down-slanting palpebral fissures, full cheeks, and micrognathia.

The severity of disease in the two siblings with homozygous disruption of ClC-3 is consistent with the drastic phenotype seen in Clcn3 KO mice. The disease was more severe in two siblings carrying homozygous loss-of-function variants with the presence of GDD, absent speech, seizures, and salt and pepper fundal pigmentation in both individuals, with one deceased at 14 months of age. The siblings also had significant neuroanatomical findings including diffusely decreased white matter volume, thin corpora callosa, small hippocampi, and disorganized cerebellar folia. Supporting biallelic inheritance for LoF variants, disruption of mouse Clcn3 results in drastic neurodegeneration with loss of the hippocampus a few months after birth and early retinal degeneration. Clcn3−/− mice display severe neurodegeneration, whereas heterozygous Clcn3+/− mice appear normal.

Patch-clamp studies were used to investigate four of the missense variants. These suggested a gain of function in two variants with increased current in HEK cells, however they also showed reduced rectification of voltage and a loss of transient current, plus decreased current amplitude, glycosylation and surface expression when expressed in oocytes, and were suspected to interfere with channel gating and a negative feedback mechanism. These effects were also shown to vary depending on pH levels. The current of the remaining two variants did not differ from WT. For heterozygous missense variants, the disruption induced may be at least partially conferred to mutant/WT homodimers and mutant/ClC-4 heterodimers.

Both loss and gain of function in this gene resulted in the same phenotype.
Sources: Literature
Motor Neurone Disease v0.123 VRK1 Michelle Torres Deleted their review
Motor Neurone Disease v0.123 VRK1 Michelle Torres commented on gene: VRK1
Intellectual disability syndromic and non-syndromic v0.4017 TNPO2 Elena Savva gene: TNPO2 was added
gene: TNPO2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TNPO2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNPO2 were set to PMID: 34314705
Phenotypes for gene: TNPO2 were set to Developmental delays, 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
Mendeliome v0.8601 TNPO2 Elena Savva gene: TNPO2 was added
gene: TNPO2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNPO2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNPO2 were set to PMID: 34314705
Phenotypes for gene: TNPO2 were set to Developmental delays, 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
Mendeliome v0.8601 SPTBN4 Melanie Marty Deleted their review
Mendeliome v0.8601 DNAH10 Ain Roesley gene: DNAH10 was added
gene: DNAH10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAH10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH10 were set to 34237282
Phenotypes for gene: DNAH10 were set to primary male infertility with asthenoteratozoospermia
Penetrance for gene: DNAH10 were set to unknown
Review for gene: DNAH10 was set to GREEN
Added comment: 4x families with 5 affecteds (chets and homs - 4 missense and 2 fs). Knockout mouse models were infertile and showed significant reduction in count and motility compared to heterozygous mice
Sources: Literature
Lissencephaly and Band Heterotopia v1.3 TP73 Seb Lunke Marked gene: TP73 as ready
Lissencephaly and Band Heterotopia v1.3 TP73 Seb Lunke Gene: tp73 has been classified as Green List (High Evidence).
Lissencephaly and Band Heterotopia v1.3 TP73 Seb Lunke Phenotypes for gene: TP73 were changed from chronic airway disease; brain malformation; lissencephaly to brain malformation; lissencephaly
Lissencephaly and Band Heterotopia v1.2 TP73 Seb Lunke Classified gene: TP73 as Green List (high evidence)
Lissencephaly and Band Heterotopia v1.2 TP73 Seb Lunke Gene: tp73 has been classified as Green List (High Evidence).
Mendeliome v0.8601 AP1G1 Zornitza Stark Marked gene: AP1G1 as ready
Mendeliome v0.8601 AP1G1 Zornitza Stark Added comment: Comment when marking as ready: Good evidence for association between mono-allelic variants and NDD, moderate evidence for bi-allelic variants causing disease.
Mendeliome v0.8601 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Mendeliome v0.8601 ALDH1A2 Seb Lunke commented on gene: ALDH1A2
Lissencephaly and Band Heterotopia v1.1 TP73 Ee Ming Wong gene: TP73 was added
gene: TP73 was added to Lissencephaly and Band Heterotopia. Sources: Literature
Mode of inheritance for gene: TP73 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TP73 were set to 34077761
Phenotypes for gene: TP73 were set to chronic airway disease; brain malformation; lissencephaly
Review for gene: TP73 was set to GREEN
gene: TP73 was marked as current diagnostic
Added comment: - Seven individuals from five unrelated families homozygous for TP73 variants (includes 1x large deletion, 1x splice variant, 1x frameshift and 2x nonsense variants)
- In vitro ciliogenesis experiments demonstrated that epithelial cells from TP73 variant carriers had reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controls
Sources: Literature
Mendeliome v0.8601 AP1G1 Zornitza Stark Classified gene: AP1G1 as Green List (high evidence)
Mendeliome v0.8601 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Mendeliome v0.8600 SEMA3D Ain Roesley edited their review of gene: SEMA3D: Added comment: Reported as a common susceptibility loci. No reported evidence for an association with Mendelian disease. Sema3d null heterozygote and homozygote mouse model had normal intestinal innervation.; Changed publications: 28334784, 25839327; Changed phenotypes: Hirschsprung disease
Mendeliome v0.8600 AP1G1 Danielle Ariti gene: AP1G1 was added
gene: AP1G1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AP1G1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AP1G1 were set to 34102099
Phenotypes for gene: AP1G1 were set to Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy
Mode of pathogenicity for gene: AP1G1 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: AP1G1 was set to GREEN
Added comment: Two bi-allelic homozygous missense variants were found in two distinct families with Italian and Pakistani origins; homozygous missense variants.

Eight de novo heterozygous variants were identified in nine isolated affected individuals from nine families; including five missense, two frameshift, and one intronic variant that disrupts the canonical splice acceptor site.

Knocking out AP1G1 Zebrafish model resulted in severe developmental abnormalities and increased lethality.

All individuals had neurodevelopmental disorder (NDD) including global developmental delay and ID, which varied in severity from mild to severe.
Sources: Literature
Mendeliome v0.8600 SEMA3D Zornitza Stark Marked gene: SEMA3D as ready
Mendeliome v0.8600 SEMA3D Zornitza Stark Gene: sema3d has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4017 TP73 Seb Lunke Publications for gene: TP73 were set to 31130284
Mendeliome v0.8600 SEMA3D Zornitza Stark Phenotypes for gene: SEMA3D were changed from to Hand and foot malformations
Mendeliome v0.8599 SEMA3D Zornitza Stark Classified gene: SEMA3D as Red List (low evidence)
Mendeliome v0.8599 SEMA3D Zornitza Stark Gene: sema3d has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4016 SPTBN1 Belinda Chong changed review comment from: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature
Sources: Literature; to: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures (9/29); behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4016 TP73 Seb Lunke Classified gene: TP73 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4016 TP73 Seb Lunke Gene: tp73 has been classified as Green List (High Evidence).
Mendeliome v0.8598 SPTBN1 Belinda Chong changed review comment from: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature; to: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures (9/29); behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature
Mendeliome v0.8598 SPTBN4 Zornitza Stark Marked gene: SPTBN4 as ready
Mendeliome v0.8598 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1149 SPTBN1 Belinda Chong gene: SPTBN1 was added
gene: SPTBN1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SPTBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPTBN1 were set to PMID: 34211179 PMID: 33847457
Phenotypes for gene: SPTBN1 were set to Neurodevelopmental Syndrome
Added comment: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures (9/29) ; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature
Sources: Literature
Mendeliome v0.8598 SPTBN4 Zornitza Stark Phenotypes for gene: SPTBN4 were changed from to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND, OMIM #617519)
Mendeliome v0.8597 TP73 Seb Lunke Classified gene: TP73 as Green List (high evidence)
Mendeliome v0.8597 TP73 Seb Lunke Gene: tp73 has been classified as Green List (High Evidence).
Mendeliome v0.8597 SPTBN4 Zornitza Stark Publications for gene: SPTBN4 were set to
Mendeliome v0.8596 SPTBN4 Zornitza Stark Mode of inheritance for gene: SPTBN4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8595 TP73 Seb Lunke Publications for gene: TP73 were set to PMID: 31130284
Intellectual disability syndromic and non-syndromic v0.4015 SPTBN1 Belinda Chong gene: SPTBN1 was added
gene: SPTBN1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SPTBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPTBN1 were set to PMID: 34211179 PMID: 33847457
Phenotypes for gene: SPTBN1 were set to Neurodevelopmental Syndrome
Review for gene: SPTBN1 was set to GREEN
Added comment: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature
Sources: Literature
Polydactyly v0.235 HMGB1 Ain Roesley gene: HMGB1 was added
gene: HMGB1 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: HMGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HMGB1 were set to 34159400
Phenotypes for gene: HMGB1 were set to Mirror image foot polydactyly
Penetrance for gene: HMGB1 were set to unknown
Review for gene: HMGB1 was set to RED
Added comment: 1x de novo fs in a proband with severe mirror image foot polydactyly. No functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4015 EDEM3 Seb Lunke Marked gene: EDEM3 as ready
Intellectual disability syndromic and non-syndromic v0.4015 EDEM3 Seb Lunke Gene: edem3 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.16 EDEM3 Seb Lunke Phenotypes for gene: EDEM3 were changed from EDEM3-congenital disorder of glycosylation to Congenital disorder of glycosylation; Developmental delay
Congenital Disorders of Glycosylation v1.15 EDEM3 Seb Lunke Marked gene: EDEM3 as ready
Congenital Disorders of Glycosylation v1.15 EDEM3 Seb Lunke Gene: edem3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4015 EDEM3 Seb Lunke Phenotypes for gene: EDEM3 were changed from EDEM3-congenital disorder of glycosylation to Congenital disorder of glycosylation; Developmental delay
Mendeliome v0.8594 HMGB1 Zornitza Stark Marked gene: HMGB1 as ready
Mendeliome v0.8594 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4014 EDEM3 Seb Lunke Classified gene: EDEM3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4014 EDEM3 Seb Lunke Gene: edem3 has been classified as Green List (High Evidence).
Mendeliome v0.8594 HMGB1 Zornitza Stark Classified gene: HMGB1 as Red List (low evidence)
Mendeliome v0.8594 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v1.15 EDEM3 Seb Lunke Classified gene: EDEM3 as Green List (high evidence)
Congenital Disorders of Glycosylation v1.15 EDEM3 Seb Lunke Gene: edem3 has been classified as Green List (High Evidence).
Mendeliome v0.8593 SPTBN1 Zornitza Stark Marked gene: SPTBN1 as ready
Mendeliome v0.8593 SPTBN1 Zornitza Stark Gene: sptbn1 has been classified as Green List (High Evidence).
Mendeliome v0.8593 SPTBN1 Zornitza Stark Phenotypes for gene: SPTBN1 were changed from Neurodevelopmental Syndrome to Neurodevelopmental Syndrome; Intellectual disability; Seizures
Mendeliome v0.8592 EDEM3 Seb Lunke Marked gene: EDEM3 as ready
Mendeliome v0.8592 EDEM3 Seb Lunke Gene: edem3 has been classified as Green List (High Evidence).
Mendeliome v0.8592 EDEM3 Seb Lunke Phenotypes for gene: EDEM3 were changed from EDEM3-congenital disorder of glycosylation to Congenital disorder of glycosylation; Developmental delay
Skeletal dysplasia v0.109 UBA2 Ain Roesley reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34159400; Phenotypes: isolated split hand malformation; Mode of inheritance: None
Mendeliome v0.8591 UBA2 Ain Roesley changed review comment from: 2x unrelated probands with isolated split hand malformation. fs variants - 1x de novo and 1x inherited from apparent unaffected mother (no radiographs of her hand available)

1x proband with unilateral split-hand malformation. Her daughter and grandson reported to have ectrofactyly but were unavailable for testing; to: 2x unrelated probands with isolated split hand malformation. fs variants - 1x de novo and 1x inherited from apparent unaffected mother (no radiographs of her hand available)

1x proband with unilateral split-hand malformation (missense). Her daughter and grandson reported to have ectrofactyly but were unavailable for testing
Mendeliome v0.8591 SPTBN1 Zornitza Stark Classified gene: SPTBN1 as Green List (high evidence)
Mendeliome v0.8591 SPTBN1 Zornitza Stark Gene: sptbn1 has been classified as Green List (High Evidence).
Mendeliome v0.8590 EDEM3 Seb Lunke Classified gene: EDEM3 as Green List (high evidence)
Mendeliome v0.8590 EDEM3 Seb Lunke Gene: edem3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4013 EDEM3 Michelle Torres gene: EDEM3 was added
gene: EDEM3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EDEM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EDEM3 were set to 34143952
Phenotypes for gene: EDEM3 were set to EDEM3-congenital disorder of glycosylation
Review for gene: EDEM3 was set to GREEN
Added comment: PMID: 34143952: 7 families (11 individuals) with 6x PTV and 2x missense variants with neurodevelopmental delay and variable facial dysmorphisms. The unaffected parents were all heterozygous carriers. Functional show LoF of EDEM3 enzymatic activity.
Sources: Literature
Mendeliome v0.8589 UBA2 Zornitza Stark Publications for gene: UBA2 were set to PMID: 31332306; 31587267
Mendeliome v0.8588 UBA2 Zornitza Stark Classified gene: UBA2 as Green List (high evidence)
Mendeliome v0.8588 UBA2 Zornitza Stark Gene: uba2 has been classified as Green List (High Evidence).
Mendeliome v0.8587 ALDH1A2 Ain Roesley reviewed gene: ALDH1A2: Rating: RED; Mode of pathogenicity: None; Publications: 34159400; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8587 GCNA Zornitza Stark Marked gene: GCNA as ready
Mendeliome v0.8587 GCNA Zornitza Stark Gene: gcna has been classified as Green List (High Evidence).
Mendeliome v0.8587 GCNA Zornitza Stark Classified gene: GCNA as Green List (high evidence)
Mendeliome v0.8587 GCNA Zornitza Stark Gene: gcna has been classified as Green List (High Evidence).
Mendeliome v0.8586 SEMA3D Ain Roesley gene: SEMA3D was added
gene: SEMA3D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEMA3D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SEMA3D were set to 34159400
Penetrance for gene: SEMA3D were set to unknown
Review for gene: SEMA3D was set to RED
Added comment: 1x de novo missense in a proband with short stature, absent distal phalanges of the 5th fingers and toes, and dysplastic middle phalanges of the toes.

However, there is 4 hets in gnomAD v2
Sources: Literature
Mendeliome v0.8586 SPTBN4 Melanie Marty reviewed gene: SPTBN4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33772159; Phenotypes: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND, OMIM #617519); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8586 TP73 Ee Ming Wong changed review comment from: - Seven individuals from five unrelated families homozygous for TP73 variants (includes 1x large deletion, 1x splice variant, 1x frameshift and 2x nonsense variants)
- Epithelial cells from TP73 variant carriers showed reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controls; to: - Seven individuals from five unrelated families homozygous for TP73 variants (includes 1x large deletion, 1x splice variant, 1x frameshift and 2x nonsense variants)
- In vitro ciliogenesis experiments demonstrated that epithelial cells from TP73 variant carriers had reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controls
Mendeliome v0.8586 TP73 Ee Ming Wong reviewed gene: TP73: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34077761; Phenotypes: chronic airway disease, brain malformation, lissencephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8586 HMGB1 Ain Roesley changed review comment from: 1x de novo fs, no functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development
Sources: Literature; to: 1x de novo fs in a proband with severe mirror image foot polydactyly. No functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development
Sources: Literature
Mendeliome v0.8586 HMGB1 Ain Roesley gene: HMGB1 was added
gene: HMGB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HMGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HMGB1 were set to 34159400
Phenotypes for gene: HMGB1 were set to Mirror image foot polydactyly
Penetrance for gene: HMGB1 were set to unknown
Review for gene: HMGB1 was set to RED
Added comment: 1x de novo fs, no functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development
Sources: Literature
Mendeliome v0.8586 SPTBN1 Belinda Chong gene: SPTBN1 was added
gene: SPTBN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPTBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPTBN1 were set to PMID: 34211179; PMID: 33847457
Phenotypes for gene: SPTBN1 were set to Neurodevelopmental Syndrome
Review for gene: SPTBN1 was set to GREEN
Added comment: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature
Mendeliome v0.8586 UBA2 Ain Roesley reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34159400; Phenotypes: isolated split hand malformation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital Disorders of Glycosylation v1.14 EDEM3 Michelle Torres gene: EDEM3 was added
gene: EDEM3 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: EDEM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EDEM3 were set to 34143952
Phenotypes for gene: EDEM3 were set to EDEM3-congenital disorder of glycosylation
Review for gene: EDEM3 was set to GREEN
Added comment: PMID: 34143952: 7 families (11 individuals) with 6x PTV and 2x missense variants with neurodevelopmental delay and variable facial dysmorphisms. The unaffected parents were all heterozygous carriers. Functional show LoF of EDEM3 enzymatic activity.
Sources: Literature
Sources: Literature
Mendeliome v0.8586 EDEM3 Michelle Torres gene: EDEM3 was added
gene: EDEM3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EDEM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EDEM3 were set to 34143952
Phenotypes for gene: EDEM3 were set to EDEM3-congenital disorder of glycosylation
Review for gene: EDEM3 was set to GREEN
Added comment: PMID: 34143952: 7 families (11 individuals) with 6x PTV and 2x missense variants with neurodevelopmental delay and variable facial dysmorphisms. The unaffected parents were all heterozygous carriers. Functional show LoF of EDEM3 enzymatic activity.
Sources: Literature
Mendeliome v0.8586 GCNA Ain Roesley gene: GCNA was added
gene: GCNA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GCNA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GCNA were set to 33963445
Phenotypes for gene: GCNA were set to primary spermatogenic failure
Penetrance for gene: GCNA were set to unknown
Review for gene: GCNA was set to GREEN
Added comment: 7x probands all missense except 1 fs. Variants had <0.0005 MAF in gnomad v2 male cohort and absent in 5784 Dutch control cohort
no functional studies were done except for histology of Ser659Trp, revealing a Sertoli-cell only
Sources: Literature
Additional findings_Paediatric v0.253 ANK2 Zornitza Stark Phenotypes for gene: ANK2 were changed from Long QT syndrome to Complex neurodevelopmental disorder, MONDO:0100038
Additional findings_Paediatric v0.252 ANK2 Zornitza Stark Classified gene: ANK2 as Green List (high evidence)
Additional findings_Paediatric v0.252 ANK2 Zornitza Stark Gene: ank2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.251 ANK2 Zornitza Stark reviewed gene: ANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22542183, 25363768, 27479843, 28554332, 30564305, 30755392, 31981491, 33004838, 33057194; Phenotypes: Complex neurodevelopmental disorder, MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.60 ANK2 Zornitza Stark Mode of inheritance for gene: ANK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8586 ANK2 Zornitza Stark Marked gene: ANK2 as ready
Mendeliome v0.8586 ANK2 Zornitza Stark Gene: ank2 has been classified as Green List (High Evidence).
Mendeliome v0.8586 ANK2 Zornitza Stark Classified gene: ANK2 as Green List (high evidence)
Mendeliome v0.8586 ANK2 Zornitza Stark Gene: ank2 has been classified as Green List (High Evidence).
Mendeliome v0.8585 ANK2 Zornitza Stark gene: ANK2 was added
gene: ANK2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANK2 were set to 31983240; 22542183; 25363768; 27479843; 28554332; 30564305; 30755392; 31981491; 33004838; 33057194
Phenotypes for gene: ANK2 were set to Long QT syndrome 4, MIM# 600919; Complex neurodevelopmental disorder, MONDO:0100038
Review for gene: ANK2 was set to GREEN
Added comment: Link with cardiac abnormalities such as LongQT is DISPUTED. More than 10 unrelated individuals reported with neurodevelopmental phenotype, comprising autism/ID and de novo truncating variants, in addition to many other individuals as part of large NDD cohorts. This association has been assessed as DEFINITIVE by ClinGen.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4013 ANK2 Zornitza Stark Marked gene: ANK2 as ready
Intellectual disability syndromic and non-syndromic v0.4013 ANK2 Zornitza Stark Gene: ank2 has been classified as Green List (High Evidence).
Incidentalome v0.75 ANK2 Zornitza Stark Marked gene: ANK2 as ready
Incidentalome v0.75 ANK2 Zornitza Stark Gene: ank2 has been classified as Red List (Low Evidence).
Incidentalome v0.75 ANK2 Zornitza Stark Phenotypes for gene: ANK2 were changed from to Long QT syndrome 4, MIM# 600919
Incidentalome v0.74 ANK2 Zornitza Stark Publications for gene: ANK2 were set to
Incidentalome v0.73 ANK2 Zornitza Stark Mode of inheritance for gene: ANK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.72 ANK2 Zornitza Stark Classified gene: ANK2 as Red List (low evidence)
Incidentalome v0.72 ANK2 Zornitza Stark Gene: ank2 has been classified as Red List (Low Evidence).
Incidentalome v0.71 ANK2 Zornitza Stark reviewed gene: ANK2: Rating: RED; Mode of pathogenicity: None; Publications: 31983240; Phenotypes: Long QT syndrome 4, MIM# 600919; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.166 ANK2 Zornitza Stark Marked gene: ANK2 as ready
Autism v0.166 ANK2 Zornitza Stark Gene: ank2 has been classified as Green List (High Evidence).
Autism v0.166 ANK2 Zornitza Stark Phenotypes for gene: ANK2 were changed from to Complex neurodevelopmental disorder, MONDO:0100038
Autism v0.165 ANK2 Zornitza Stark Publications for gene: ANK2 were set to
Autism v0.164 ANK2 Zornitza Stark Mode of inheritance for gene: ANK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.163 ANK2 Zornitza Stark reviewed gene: ANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22542183, 25363768, 27479843, 28554332, 30564305, 30755392, 31981491, 33004838, 33057194; Phenotypes: Complex neurodevelopmental disorder, MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4013 ANK2 Zornitza Stark Phenotypes for gene: ANK2 were changed from Complex neurodevelopmental disorder, MONDO:0100038 to Complex neurodevelopmental disorder, MONDO:0100038
Intellectual disability syndromic and non-syndromic v0.4012 ANK2 Zornitza Stark Publications for gene: ANK2 were set to 22542183; 25363768; 27479843; 28554332; 30564305; 30755392; 31981491; 33004838; 33057194
Intellectual disability syndromic and non-syndromic v0.4011 ANK2 Zornitza Stark Phenotypes for gene: ANK2 were changed from intellectual disability to Complex neurodevelopmental disorder, MONDO:0100038
Intellectual disability syndromic and non-syndromic v0.4010 ANK2 Zornitza Stark Publications for gene: ANK2 were set to 22542183, 25363768, 27479843, 28554332, 30564305, 30755392, 31981491
Intellectual disability syndromic and non-syndromic v0.4010 ANK2 Zornitza Stark Classified gene: ANK2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4010 ANK2 Zornitza Stark Gene: ank2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4009 ANK2 Zornitza Stark reviewed gene: ANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22542183, 25363768, 27479843, 28554332, 30564305, 30755392, 31981491, 33004838, 33057194; Phenotypes: Complex neurodevelopmental disorder, MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia - adult onset v0.137 PRDX3 Zornitza Stark Marked gene: PRDX3 as ready
Ataxia - adult onset v0.137 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.137 PRDX3 Zornitza Stark Classified gene: PRDX3 as Green List (high evidence)
Ataxia - adult onset v0.137 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.289 PRDX3 Zornitza Stark Marked gene: PRDX3 as ready
Ataxia - paediatric v0.289 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.289 PRDX3 Zornitza Stark Classified gene: PRDX3 as Green List (high evidence)
Ataxia - paediatric v0.289 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.136 PRDX3 Zornitza Stark gene: PRDX3 was added
gene: PRDX3 was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDX3 were set to 33889951
Phenotypes for gene: PRDX3 were set to Cerebellar ataxia (early onset, mild to moderate, progressive)
Review for gene: PRDX3 was set to GREEN
Added comment: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.

Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.

The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote with a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.

The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.

Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.

PRDX3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.

Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.

In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature
Ataxia - paediatric v0.288 PRDX3 Zornitza Stark gene: PRDX3 was added
gene: PRDX3 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDX3 were set to 33889951
Phenotypes for gene: PRDX3 were set to Cerebellar ataxia (early onset, mild to moderate, progressive)
Review for gene: PRDX3 was set to GREEN
Added comment: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.

Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.

The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote with a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.

The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.

Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.

PRDX3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.

Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.

In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature
Mitochondrial disease v0.645 PRDX3 Zornitza Stark Marked gene: PRDX3 as ready
Mitochondrial disease v0.645 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Mitochondrial disease v0.645 PRDX3 Zornitza Stark Classified gene: PRDX3 as Green List (high evidence)
Mitochondrial disease v0.645 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Mitochondrial disease v0.644 PRDX3 Zornitza Stark gene: PRDX3 was added
gene: PRDX3 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDX3 were set to 33889951
Phenotypes for gene: PRDX3 were set to Cerebellar ataxia (early onset, mild to moderate, progressive)
Review for gene: PRDX3 was set to GREEN
Added comment: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.

Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.

The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote with a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.

The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.

Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.

PRDX3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.

Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.

In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4009 ANK2 Anna Le Fevre commented on gene: ANK2: Publications largely cover autism risk and discovery in large cohorts. ClinGen review mentions ID, seizures and microcephaly but phenotype and penetrance appear incompletely described.
Intellectual disability syndromic and non-syndromic v0.4009 ANK2 Anna Le Fevre edited their review of gene: ANK2: Changed phenotypes: intellectual disability, autism
Intellectual disability syndromic and non-syndromic v0.4009 ANK2 Anna Le Fevre gene: ANK2 was added
gene: ANK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANK2 were set to 22542183, 25363768, 27479843, 28554332, 30564305, 30755392, 31981491
Phenotypes for gene: ANK2 were set to intellectual disability
Penetrance for gene: ANK2 were set to unknown
Added comment: Curated by ClinGen 2020 as definitively associated
? consider taking gene off incidentalome gene list
Sources: Other
Mendeliome v0.8584 PRDX3 Zornitza Stark Marked gene: PRDX3 as ready
Mendeliome v0.8584 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Mendeliome v0.8584 PRDX3 Zornitza Stark Classified gene: PRDX3 as Green List (high evidence)
Mendeliome v0.8584 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Mendeliome v0.8583 PRDX3 Hazel Phillimore changed review comment from: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.
Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.
The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote of a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.
The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.
Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.
PRXD3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.
Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.
In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature; to: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.
Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.
The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote with a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.
The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.
Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.
PRDX3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.
Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.
In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature
Mendeliome v0.8583 PRDX3 Hazel Phillimore gene: PRDX3 was added
gene: PRDX3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDX3 were set to PMID: 33889951
Phenotypes for gene: PRDX3 were set to cerebellar ataxia (early onset, mild to moderate, progressive)
Penetrance for gene: PRDX3 were set to unknown
Review for gene: PRDX3 was set to GREEN
Added comment: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.
Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.
The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote of a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.
The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.
Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.
PRXD3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.
Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.
In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature
Mandibulofacial Acrofacial dysostosis v0.49 EDN1 Zornitza Stark Marked gene: EDN1 as ready
Mandibulofacial Acrofacial dysostosis v0.49 EDN1 Zornitza Stark Gene: edn1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.109 GSC Zornitza Stark Marked gene: GSC as ready
Skeletal dysplasia v0.109 GSC Zornitza Stark Gene: gsc has been classified as Green List (High Evidence).
Skeletal dysplasia v0.109 GSC Zornitza Stark Phenotypes for gene: GSC were changed from Foundation Trust) Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities 602471; Foundation Trust) Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities 602471 to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471
Skeletal dysplasia v0.108 GSC Zornitza Stark Publications for gene: GSC were set to
Skeletal dysplasia v0.107 GSC Zornitza Stark reviewed gene: GSC: Rating: GREEN; Mode of pathogenicity: None; Publications: 24290375; Phenotypes: Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8583 GSC Zornitza Stark Marked gene: GSC as ready
Mendeliome v0.8583 GSC Zornitza Stark Gene: gsc has been classified as Green List (High Evidence).
Mendeliome v0.8583 GSC Zornitza Stark Phenotypes for gene: GSC were changed from to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471
Mendeliome v0.8582 GSC Zornitza Stark Publications for gene: GSC were set to
Mendeliome v0.8581 GSC Zornitza Stark Mode of inheritance for gene: GSC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8580 GSC Zornitza Stark reviewed gene: GSC: Rating: GREEN; Mode of pathogenicity: None; Publications: 24290375; Phenotypes: Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.49 GSC Zornitza Stark Marked gene: GSC as ready
Mandibulofacial Acrofacial dysostosis v0.49 GSC Zornitza Stark Gene: gsc has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.49 GSC Zornitza Stark Phenotypes for gene: GSC were changed from to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471
Mandibulofacial Acrofacial dysostosis v0.48 GSC Zornitza Stark Publications for gene: GSC were set to
Mandibulofacial Acrofacial dysostosis v0.47 GSC Zornitza Stark Mode of inheritance for gene: GSC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.46 GSC Zornitza Stark reviewed gene: GSC: Rating: GREEN; Mode of pathogenicity: None; Publications: 24290375; Phenotypes: Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8580 GNAI3 Zornitza Stark Marked gene: GNAI3 as ready
Mendeliome v0.8580 GNAI3 Zornitza Stark Gene: gnai3 has been classified as Green List (High Evidence).
Mendeliome v0.8580 GNAI3 Zornitza Stark Phenotypes for gene: GNAI3 were changed from to Auriculocondylar syndrome 1, OMIM #602483
Mendeliome v0.8579 GNAI3 Zornitza Stark Publications for gene: GNAI3 were set to
Mendeliome v0.8578 GNAI3 Zornitza Stark Mode of inheritance for gene: GNAI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8577 GNAI3 Zornitza Stark reviewed gene: GNAI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22560091; Phenotypes: Auriculocondylar syndrome 1, OMIM #602483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.46 GNAI3 Zornitza Stark Marked gene: GNAI3 as ready
Mandibulofacial Acrofacial dysostosis v0.46 GNAI3 Zornitza Stark Gene: gnai3 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.46 GNAI3 Zornitza Stark Phenotypes for gene: GNAI3 were changed from to Auriculocondylar syndrome 1, OMIM #602483
Mandibulofacial Acrofacial dysostosis v0.45 GNAI3 Zornitza Stark Publications for gene: GNAI3 were set to
Mandibulofacial Acrofacial dysostosis v0.44 GNAI3 Zornitza Stark Mode of inheritance for gene: GNAI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.43 GNAI3 Zornitza Stark reviewed gene: GNAI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22560091; Phenotypes: Auriculocondylar syndrome 1, OMIM #602483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.134 EIF4A3 Zornitza Stark Marked gene: EIF4A3 as ready
Clefting disorders v0.134 EIF4A3 Zornitza Stark Gene: eif4a3 has been classified as Green List (High Evidence).
Clefting disorders v0.134 EIF4A3 Zornitza Stark Publications for gene: EIF4A3 were set to 10594883; 29112243; 29922329
Clefting disorders v0.133 EIF4A3 Zornitza Stark reviewed gene: EIF4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24360810; Phenotypes: Robin sequence with cleft mandible and limb anomalies, MIM# 268305, Richieri-Costa-Pereira syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4009 EIF4A3 Zornitza Stark Marked gene: EIF4A3 as ready
Intellectual disability syndromic and non-syndromic v0.4009 EIF4A3 Zornitza Stark Gene: eif4a3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4009 EIF4A3 Zornitza Stark Phenotypes for gene: EIF4A3 were changed from to Robin sequence with cleft mandible and limb anomalies, MIM# 268305; Richieri-Costa-Pereira syndrome
Intellectual disability syndromic and non-syndromic v0.4008 EIF4A3 Zornitza Stark Publications for gene: EIF4A3 were set to
Intellectual disability syndromic and non-syndromic v0.4007 EIF4A3 Zornitza Stark Mode of inheritance for gene: EIF4A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4006 EIF4A3 Zornitza Stark reviewed gene: EIF4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24360810; Phenotypes: Robin sequence with cleft mandible and limb anomalies, MIM# 268305, Richieri-Costa-Pereira syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pierre Robin Sequence v0.35 EIF4A3 Zornitza Stark Marked gene: EIF4A3 as ready
Pierre Robin Sequence v0.35 EIF4A3 Zornitza Stark Gene: eif4a3 has been classified as Green List (High Evidence).
Pierre Robin Sequence v0.35 EIF4A3 Zornitza Stark Phenotypes for gene: EIF4A3 were changed from to Robin sequence with cleft mandible and limb anomalies, MIM# 268305; Richieri-Costa-Pereira syndrome
Pierre Robin Sequence v0.34 EIF4A3 Zornitza Stark Publications for gene: EIF4A3 were set to
Pierre Robin Sequence v0.33 EIF4A3 Zornitza Stark Mode of inheritance for gene: EIF4A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Pierre Robin Sequence v0.32 EIF4A3 Zornitza Stark reviewed gene: EIF4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24360810; Phenotypes: Robin sequence with cleft mandible and limb anomalies, MIM# 268305, Richieri-Costa-Pereira syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8577 EIF4A3 Zornitza Stark Marked gene: EIF4A3 as ready
Mendeliome v0.8577 EIF4A3 Zornitza Stark Gene: eif4a3 has been classified as Green List (High Evidence).
Mendeliome v0.8577 EIF4A3 Zornitza Stark Phenotypes for gene: EIF4A3 were changed from to Robin sequence with cleft mandible and limb anomalies, MIM# 268305; Richieri-Costa-Pereira syndrome
Mendeliome v0.8576 EIF4A3 Zornitza Stark Publications for gene: EIF4A3 were set to
Mendeliome v0.8575 EIF4A3 Zornitza Stark Mode of inheritance for gene: EIF4A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8574 EIF4A3 Zornitza Stark reviewed gene: EIF4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24360810; Phenotypes: Robin sequence with cleft mandible and limb anomalies, MIM# 268305, Richieri-Costa-Pereira syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.43 EIF4A3 Zornitza Stark Marked gene: EIF4A3 as ready
Mandibulofacial Acrofacial dysostosis v0.43 EIF4A3 Zornitza Stark Gene: eif4a3 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.43 EIF4A3 Zornitza Stark Phenotypes for gene: EIF4A3 were changed from to Robin sequence with cleft mandible and limb anomalies, MIM# 268305; Richieri-Costa-Pereira syndrome
Mandibulofacial Acrofacial dysostosis v0.42 EIF4A3 Zornitza Stark Publications for gene: EIF4A3 were set to
Mandibulofacial Acrofacial dysostosis v0.41 EIF4A3 Zornitza Stark Mode of inheritance for gene: EIF4A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mandibulofacial Acrofacial dysostosis v0.40 EIF4A3 Zornitza Stark reviewed gene: EIF4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24360810; Phenotypes: Robin sequence with cleft mandible and limb anomalies, MIM# 268305, Richieri-Costa-Pereira syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v1.12 SCN11A Zornitza Stark Marked gene: SCN11A as ready
Gastrointestinal neuromuscular disease v1.12 SCN11A Zornitza Stark Gene: scn11a has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.12 SCN11A Zornitza Stark Classified gene: SCN11A as Green List (high evidence)
Gastrointestinal neuromuscular disease v1.12 SCN11A Zornitza Stark Gene: scn11a has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.11 SCN11A Zornitza Stark gene: SCN11A was added
gene: SCN11A was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: SCN11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN11A were set to 27503742; 25118027
Phenotypes for gene: SCN11A were set to Neuropathy, hereditary sensory and autonomic, type VII, MIM# 615548
Review for gene: SCN11A was set to GREEN
Added comment: Gastrointestinal dysmotility reported.
Sources: Expert list
Gastrointestinal neuromuscular disease v1.10 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
Gastrointestinal neuromuscular disease v1.10 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.10 SAMD9 Zornitza Stark Classified gene: SAMD9 as Green List (high evidence)
Gastrointestinal neuromuscular disease v1.10 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.9 SAMD9 Zornitza Stark gene: SAMD9 was added
gene: SAMD9 was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: SAMD9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SAMD9 were set to 27182967
Phenotypes for gene: SAMD9 were set to MIRAGE syndrome, MIM# 617053
Review for gene: SAMD9 was set to GREEN
Added comment: Chronic diarrhoea and colonic dilatation reported.
Sources: Expert list
Gastrointestinal neuromuscular disease v1.8 IDS Zornitza Stark Classified gene: IDS as Green List (high evidence)
Gastrointestinal neuromuscular disease v1.8 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.7 IDS Zornitza Stark gene: IDS was added
gene: IDS was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: IDS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: IDS were set to Mucopolysaccharidosis II, MIM# 309900
Review for gene: IDS was set to GREEN
Added comment: Intestinal pseudo-obstruction reported.
Sources: Expert list
Gastrointestinal neuromuscular disease v1.6 DMD Zornitza Stark Marked gene: DMD as ready
Gastrointestinal neuromuscular disease v1.6 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.6 DMD Zornitza Stark Classified gene: DMD as Green List (high evidence)
Gastrointestinal neuromuscular disease v1.6 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.5 DMD Zornitza Stark Tag SV/CNV tag was added to gene: DMD.
Gastrointestinal neuromuscular disease v1.5 DMD Zornitza Stark gene: DMD was added
gene: DMD was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: DMD was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DMD were set to 3380114
Phenotypes for gene: DMD were set to Duchenne muscular dystrophy, MIM# 310200
Review for gene: DMD was set to GREEN
Added comment: Can rarely present with gut dysmotility.
Sources: Expert list
Gastrointestinal neuromuscular disease v1.4 DES Zornitza Stark Marked gene: DES as ready
Gastrointestinal neuromuscular disease v1.4 DES Zornitza Stark Gene: des has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.4 DES Zornitza Stark Classified gene: DES as Green List (high evidence)
Gastrointestinal neuromuscular disease v1.4 DES Zornitza Stark Gene: des has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.3 DES Zornitza Stark gene: DES was added
gene: DES was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: DES was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: DES were set to Myopathy, myofibrillar, 1 , MIM#601419
Review for gene: DES was set to GREEN
Added comment: Well established gene-disease association. Primarily skeletal and cardiac involvement but gut involvement with constipation/diarrhoea reported.
Sources: Expert list
Gastrointestinal neuromuscular disease v1.2 CLMP Zornitza Stark Marked gene: CLMP as ready
Gastrointestinal neuromuscular disease v1.2 CLMP Zornitza Stark Gene: clmp has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.2 CLMP Zornitza Stark Classified gene: CLMP as Green List (high evidence)
Gastrointestinal neuromuscular disease v1.2 CLMP Zornitza Stark Gene: clmp has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.1 CLMP Zornitza Stark gene: CLMP was added
gene: CLMP was added to Gastrointestinal neuromuscular disease. Sources: Expert list
Mode of inheritance for gene: CLMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLMP were set to 22155368
Phenotypes for gene: CLMP were set to Congenital short bowel syndrome , MIM#615237
Review for gene: CLMP was set to GREEN
Added comment: Well established gene-disease association, phenotypic overlap.
Sources: Expert list
Gastrointestinal neuromuscular disease v1.0 Zornitza Stark promoted panel to version 1.0
Hirschsprung disease v0.17 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Hirschsprung disease; Arthrogryposis to Complex neurocristinopathy
Hirschsprung disease v0.16 ERBB3 Zornitza Stark Publications for gene: ERBB3 were set to 33720042
Hirschsprung disease v0.15 ERBB3 Zornitza Stark reviewed gene: ERBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33497358; Phenotypes: Complex neurocristinopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.69 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Neurodevelopmental disorder with gut dysmotility to Complex neurocristinopathy
Gastrointestinal neuromuscular disease v0.68 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Complex neurocristinopathy
Mendeliome v0.8574 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598, Complex neurocristinopathy
Mendeliome v0.8574 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Complex neurocristinopathy
Mendeliome v0.8574 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Neurodevelopmental disorder with gut dysmotility to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy
Mendeliome v0.8573 ERBB3 Zornitza Stark changed review comment from: PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and neurodevelopmental disorder. Note variants in this gene have also recently been linked to Hirschsprung's disease.; to: PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and other features of neurocristinopathy including short-segment HSCR, progressive axonal peripheral neuropathy, dysautonomia, hypopigmentation, deafness. Note variants in this gene have also recently been linked to Hirschsprung's disease.
Gastrointestinal neuromuscular disease v0.68 ERBB3 Zornitza Stark changed review comment from: 6 individuals from 4 unrelated families reported with severe gut dysmotility and neurodevelopmental disorder. Note variants in this gene have also recently been linked to Hirschsprung's disease.
Sources: Literature; to: 6 individuals from 4 unrelated families reported with severe gut dysmotility and other features of neurocristinopathy including short-segment HSCR, progressive axonal peripheral neuropathy, dysautonomia, hypopigmentation, deafness. Note variants in this gene have also recently been linked to Hirschsprung's disease.
Sources: Literature
Mendeliome v0.8573 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Neurodevelopmental disorder with gut dysmotility
Mendeliome v0.8572 ERBB3 Zornitza Stark Publications for gene: ERBB3 were set to 17701904; 31752936; 33720042
Mendeliome v0.8571 ERBB3 Zornitza Stark changed review comment from: Two families reported with contractures, positional approach used in gene discovery (2007). Another family reported more recently with a multi-system disorder but without contractures.; to: Lethal congenital contractual syndrome: Two families reported with contractures, positional approach used in gene discovery (2007). Another family reported more recently with a multi-system disorder but without contractures.
Mendeliome v0.8571 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Added comment: PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and neurodevelopmental disorder. Note variants in this gene have also recently been linked to Hirschsprung's disease.; Changed rating: GREEN; Changed publications: 17701904, 31752936, 33497358; Changed phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598, Neurodevelopmental disorder with gut dysmotility
Gastrointestinal neuromuscular disease v0.68 ERBB3 Zornitza Stark Marked gene: ERBB3 as ready
Gastrointestinal neuromuscular disease v0.68 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.68 ERBB3 Zornitza Stark Classified gene: ERBB3 as Green List (high evidence)
Gastrointestinal neuromuscular disease v0.68 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.67 ERBB3 Zornitza Stark gene: ERBB3 was added
gene: ERBB3 was added to Gastrointestinal neuromuscular disease. Sources: Literature
Mode of inheritance for gene: ERBB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERBB3 were set to 33497358
Phenotypes for gene: ERBB3 were set to Neurodevelopmental disorder with gut dysmotility
Review for gene: ERBB3 was set to GREEN
Added comment: 6 individuals from 4 unrelated families reported with severe gut dysmotility and neurodevelopmental disorder. Note variants in this gene have also recently been linked to Hirschsprung's disease.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.31 FLNA Zornitza Stark Marked gene: FLNA as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.31 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.66 POLG Zornitza Stark Marked gene: POLG as ready
Gastrointestinal neuromuscular disease v0.66 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.66 POLG Zornitza Stark Phenotypes for gene: POLG were changed from Mitochondrial DNA depletion syndrome 4B (MNGIE type), 613662 to Mitochondrial DNA depletion syndrome 4A (Alpers type), MIM# 203700
Gastrointestinal neuromuscular disease v0.65 POLG Zornitza Stark Publications for gene: POLG were set to
Gastrointestinal neuromuscular disease v0.64 POLG Zornitza Stark reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 22006280; Phenotypes: Mitochondrial DNA depletion syndrome 4A (Alpers type), MIM# 203700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.64 FLNA Zornitza Stark Publications for gene: FLNA were set to 17357080; 23037936; 33464596
Gastrointestinal neuromuscular disease v0.63 FLNA Zornitza Stark changed review comment from: Variants in FLNA cause a wide spectrum of disease including skeletal dysplasia, neuronal migration abnormality, cardiovascular malformation, and intellectual disability.

At least 4 families reported with predominantly intestinal phenotype with dysmotility and obstruction +/- short bowel.; to: Variants in FLNA cause a wide spectrum of disease including skeletal dysplasia, neuronal migration abnormality, cardiovascular malformation, and intellectual disability.

At least 6 families reported with predominantly intestinal phenotype with dysmotility and obstruction +/- short bowel.
Gastrointestinal neuromuscular disease v0.63 FLNA Zornitza Stark edited their review of gene: FLNA: Changed publications: 17357080, 23037936, 33464596, 20871226
Pulmonary Fibrosis_Interstitial Lung Disease v0.31 FLNA Zornitza Stark Classified gene: FLNA as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.31 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.30 FLNA Zornitza Stark gene: FLNA was added
gene: FLNA was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FLNA were set to 30547349
Phenotypes for gene: FLNA were set to Interstitial lung disease
Review for gene: FLNA was set to GREEN
Added comment: Variants in FLNA cause a wide spectrum of disease including skeletal dysplasia, neuronal migration abnormality, cardiovascular malformation, and intellectual disability.

PMID 30547349 reviews 18 individuals with significant interstitial lung disease +/- other cardiac/neurological features.
Sources: Literature
Gastrointestinal neuromuscular disease v0.63 FLNA Zornitza Stark Marked gene: FLNA as ready
Gastrointestinal neuromuscular disease v0.63 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.63 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from Periventricular heterotopia in males, seizures in females to Intestinal pseudoobstruction, neuronal, MIM# 300048; Congenital short bowel syndrome, MIM# 300048
Gastrointestinal neuromuscular disease v0.62 FLNA Zornitza Stark Publications for gene: FLNA were set to
Gastrointestinal neuromuscular disease v0.61 FLNA Zornitza Stark reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 17357080, 23037936, 33464596; Phenotypes: Intestinal pseudoobstruction, neuronal, MIM# 300048, Congenital short bowel syndrome, MIM# 300048; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Gastrointestinal neuromuscular disease v0.61 EDNRB Zornitza Stark Marked gene: EDNRB as ready
Gastrointestinal neuromuscular disease v0.61 EDNRB Zornitza Stark Gene: ednrb has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.61 EDNRB Zornitza Stark Phenotypes for gene: EDNRB were changed from Waardenburg syndrome w/pigmentary abnormalities to Waardenburg syndrome, type 4A, MIM# 277580
Gastrointestinal neuromuscular disease v0.60 EDNRB Zornitza Stark reviewed gene: EDNRB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Waardenburg syndrome, type 4A, MIM# 277580; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8571 PDCL3 Zornitza Stark Marked gene: PDCL3 as ready
Mendeliome v0.8571 PDCL3 Zornitza Stark Gene: pdcl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8571 PDCL3 Zornitza Stark Classified gene: PDCL3 as Amber List (moderate evidence)
Mendeliome v0.8571 PDCL3 Zornitza Stark Gene: pdcl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8570 PDCL3 Zornitza Stark gene: PDCL3 was added
gene: PDCL3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PDCL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCL3 were set to 32621347
Phenotypes for gene: PDCL3 were set to Megacystis-microcolon
Review for gene: PDCL3 was set to AMBER
Added comment: Single publication (PMID 32621347): one family with two affected fetuses - one with megacystis and microcolon, and the other with megacystisis and bilateral diaphragmatic hernia (prune-belly phenotype). Compound het LOF variants in PDCL3 (one frameshift and one missense). Complete absence of PDLC3 expression demonstrated in one of the affected fetuses. No homozygous LOF PDCL3 variants in gnomAD. PCDL3 negatively modulates actin folding and is strongly expressed in smooth muscle of bladder and colon.
Sources: Expert Review
Gastrointestinal neuromuscular disease v0.60 PDCL3 Zornitza Stark Marked gene: PDCL3 as ready
Gastrointestinal neuromuscular disease v0.60 PDCL3 Zornitza Stark Gene: pdcl3 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.60 PDCL3 Zornitza Stark Classified gene: PDCL3 as Amber List (moderate evidence)
Gastrointestinal neuromuscular disease v0.60 PDCL3 Zornitza Stark Gene: pdcl3 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.59 RET Zornitza Stark Marked gene: RET as ready
Gastrointestinal neuromuscular disease v0.59 RET Zornitza Stark Gene: ret has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.59 RET Zornitza Stark Phenotypes for gene: RET were changed from {Hirschsprung disease, susceptibility to, 1}, 142623 to Central hypoventilation syndrome, congenital, MIM# 209880; Multiple endocrine neoplasia IIA, MIM# 171400; Multiple endocrine neoplasia IIB, MIM# 162300
Gastrointestinal neuromuscular disease v0.58 RET Zornitza Stark Mode of inheritance for gene: RET was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gastrointestinal neuromuscular disease v0.57 RET Zornitza Stark reviewed gene: RET: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Central hypoventilation syndrome, congenital, MIM# 209880, Multiple endocrine neoplasia IIA, MIM# 171400, Multiple endocrine neoplasia IIB, MIM# 162300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8569 SGO1 Zornitza Stark Marked gene: SGO1 as ready
Mendeliome v0.8569 SGO1 Zornitza Stark Gene: sgo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8569 SGO1 Zornitza Stark Phenotypes for gene: SGO1 were changed from to Chronic atrial and intestinal dysrhythmia, MIM# 616201
Mendeliome v0.8568 SGO1 Zornitza Stark Publications for gene: SGO1 were set to
Mendeliome v0.8567 SGO1 Zornitza Stark Mode of inheritance for gene: SGO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8566 SGO1 Zornitza Stark Classified gene: SGO1 as Amber List (moderate evidence)
Mendeliome v0.8566 SGO1 Zornitza Stark Gene: sgo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8565 SGO1 Zornitza Stark reviewed gene: SGO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25282101; Phenotypes: Chronic atrial and intestinal dysrhythmia, MIM# 616201; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.102 SGO1 Zornitza Stark reviewed gene: SGO1: Rating: RED; Mode of pathogenicity: None; Publications: 25282101; Phenotypes: Chronic atrial and intestinal dysrhythmia, MIM# 616201; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.57 SGO1 Zornitza Stark Marked gene: SGO1 as ready
Gastrointestinal neuromuscular disease v0.57 SGO1 Zornitza Stark Gene: sgo1 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.57 SGO1 Zornitza Stark Phenotypes for gene: SGO1 were changed from Chronic atrial and intestinal dysrhythmia, 616201 to Chronic atrial and intestinal dysrhythmia, MIM# 616201
Gastrointestinal neuromuscular disease v0.56 SGO1 Zornitza Stark Publications for gene: SGO1 were set to
Gastrointestinal neuromuscular disease v0.55 SGO1 Zornitza Stark Classified gene: SGO1 as Amber List (moderate evidence)
Gastrointestinal neuromuscular disease v0.55 SGO1 Zornitza Stark Gene: sgo1 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.54 SGO1 Zornitza Stark Tag founder tag was added to gene: SGO1.
Gastrointestinal neuromuscular disease v0.54 SGO1 Zornitza Stark changed review comment from: Single homozygous missense identified in 3 families, founder effect demonstrated by haplotype analysis. Functional data supports gene-disease association.; to: Single homozygous missense identified in 15 individuals, founder effect demonstrated by haplotype analysis. Functional data supports gene-disease association.
Gastrointestinal neuromuscular disease v0.54 SGO1 Zornitza Stark reviewed gene: SGO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25282101; Phenotypes: Chronic atrial and intestinal dysrhythmia, MIM# 616201; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.54 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Gastrointestinal neuromuscular disease v0.54 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.54 SOX10 Zornitza Stark Mode of inheritance for gene: SOX10 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gastrointestinal neuromuscular disease v0.53 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from Waardenburg syndrome w/pigmentary abnormalities to PCWH syndrome, MIM# 609136
Gastrointestinal neuromuscular disease v0.52 SOX10 Zornitza Stark Publications for gene: SOX10 were set to
Gastrointestinal neuromuscular disease v0.51 SOX10 Zornitza Stark reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10762540, 10482261, 15004559; Phenotypes: PCWH syndrome, MIM# 609136; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8565 TYMP Zornitza Stark Marked gene: TYMP as ready
Mendeliome v0.8565 TYMP Zornitza Stark Gene: tymp has been classified as Green List (High Evidence).
Mendeliome v0.8565 TYMP Zornitza Stark Phenotypes for gene: TYMP were changed from to Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041; MNGIE: ptosis, ophthalmoplegia & ophthalmoparesis, hearing loss, neuropathy
Mendeliome v0.8564 TYMP Zornitza Stark Publications for gene: TYMP were set to
Mendeliome v0.8563 TYMP Zornitza Stark Mode of inheritance for gene: TYMP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8562 TYMP Zornitza Stark reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 9924029, 14757860; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041, MNGIE: ptosis, ophthalmoplegia & ophthalmoparesis, hearing loss, neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.51 TYMP Zornitza Stark Marked gene: TYMP as ready
Gastrointestinal neuromuscular disease v0.51 TYMP Zornitza Stark Gene: tymp has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.51 TYMP Zornitza Stark Phenotypes for gene: TYMP were changed from MNGIE: ptosis, ophthalmoplegia & ophthalmoparesis, hearing loss, neuropathy to Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041; MNGIE: ptosis, ophthalmoplegia & ophthalmoparesis, hearing loss, neuropathy
Gastrointestinal neuromuscular disease v0.50 TYMP Zornitza Stark Publications for gene: TYMP were set to
Gastrointestinal neuromuscular disease v0.49 TYMP Zornitza Stark reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 9924029, 14757860; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8562 ZNF687 Zornitza Stark Marked gene: ZNF687 as ready
Mendeliome v0.8562 ZNF687 Zornitza Stark Gene: znf687 has been classified as Green List (High Evidence).
Mendeliome v0.8562 ZNF687 Zornitza Stark Phenotypes for gene: ZNF687 were changed from to Paget disease of bone 6, MIM#616833
Mendeliome v0.8561 ZNF687 Zornitza Stark Publications for gene: ZNF687 were set to
Mendeliome v0.8560 ZNF687 Zornitza Stark Mode of inheritance for gene: ZNF687 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8559 ZNF687 Zornitza Stark Tag founder tag was added to gene: ZNF687.
Mendeliome v0.8559 ZNF687 Zornitza Stark reviewed gene: ZNF687: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Paget disease of bone 6, MIM#616833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8559 GRHPR Zornitza Stark Marked gene: GRHPR as ready
Mendeliome v0.8559 GRHPR Zornitza Stark Gene: grhpr has been classified as Green List (High Evidence).
Mendeliome v0.8559 GRHPR Zornitza Stark Phenotypes for gene: GRHPR were changed from to Hyperoxaluria, primary, type II, MIM# 260000; MONDO:0009824
Mendeliome v0.8558 GRHPR Zornitza Stark Publications for gene: GRHPR were set to
Mendeliome v0.8557 GRHPR Zornitza Stark Mode of inheritance for gene: GRHPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8556 GRHPR Zornitza Stark reviewed gene: GRHPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 10484776, 11030416, 24116921; Phenotypes: Hyperoxaluria, primary, type II, MIM# 260000, MONDO:0009824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8556 AGXT Zornitza Stark Marked gene: AGXT as ready
Mendeliome v0.8556 AGXT Zornitza Stark Gene: agxt has been classified as Green List (High Evidence).
Mendeliome v0.8556 AGXT Zornitza Stark Phenotypes for gene: AGXT were changed from to Hyperoxaluria, primary, type 1, MIM# 259900; MONDO:0009823
Mendeliome v0.8555 AGXT Zornitza Stark Publications for gene: AGXT were set to
Mendeliome v0.8554 AGXT Zornitza Stark Mode of inheritance for gene: AGXT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8553 AGXT Zornitza Stark reviewed gene: AGXT: Rating: GREEN; Mode of pathogenicity: None; Publications: 2039493, 19479957; Phenotypes: Hyperoxaluria, primary, type 1, MIM# 259900, MONDO:0009823; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8553 HOGA1 Zornitza Stark Marked gene: HOGA1 as ready
Mendeliome v0.8553 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Mendeliome v0.8553 HOGA1 Zornitza Stark Phenotypes for gene: HOGA1 were changed from to Hyperoxaluria, primary, type III MIM#613616
Mendeliome v0.8552 HOGA1 Zornitza Stark Publications for gene: HOGA1 were set to
Mendeliome v0.8551 HOGA1 Zornitza Stark Mode of inheritance for gene: HOGA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8550 ZNF687 Ain Roesley reviewed gene: ZNF687: Rating: AMBER; Mode of pathogenicity: None; Publications: 26849110, 29493781, 32106343; Phenotypes: Paget disease of bone 6, MIM#616833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8550 HOGA1 Paul De Fazio reviewed gene: HOGA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20797690, 21896830, 22391140; Phenotypes: Hyperoxaluria, primary, type III MIM#613616; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Desmosomal disorders v0.8 DSC2 Zornitza Stark Marked gene: DSC2 as ready
Desmosomal disorders v0.8 DSC2 Zornitza Stark Gene: dsc2 has been classified as Green List (High Evidence).
Desmosomal disorders v0.8 DSC2 Zornitza Stark Phenotypes for gene: DSC2 were changed from to Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476
Desmosomal disorders v0.7 DSC2 Zornitza Stark Publications for gene: DSC2 were set to
Desmosomal disorders v0.6 DSC2 Zornitza Stark Mode of inheritance for gene: DSC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Desmosomal disorders v0.5 DSC2 Zornitza Stark reviewed gene: DSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18957847, 23863954; Phenotypes: Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phagocyte Defects v1.0 Zornitza Stark promoted panel to version 1.0
Phagocyte Defects v0.136 SEC61A1 Zornitza Stark Marked gene: SEC61A1 as ready
Phagocyte Defects v0.136 SEC61A1 Zornitza Stark Gene: sec61a1 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v0.136 MKL1 Zornitza Stark Marked gene: MKL1 as ready
Phagocyte Defects v0.136 MKL1 Zornitza Stark Gene: mkl1 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v0.136 CXCR4 Zornitza Stark Marked gene: CXCR4 as ready
Phagocyte Defects v0.136 CXCR4 Zornitza Stark Gene: cxcr4 has been classified as Green List (High Evidence).
Phagocyte Defects v0.136 CXCR4 Zornitza Stark Phenotypes for gene: CXCR4 were changed from to WHIM syndrome 1, MIM# 193670
Phagocyte Defects v0.135 CXCR4 Zornitza Stark Publications for gene: CXCR4 were set to
Phagocyte Defects v0.134 CXCR4 Zornitza Stark Mode of inheritance for gene: CXCR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phagocyte Defects v0.133 CXCR4 Zornitza Stark reviewed gene: CXCR4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12692554, 15536153, 23009155; Phenotypes: WHIM syndrome 1, MIM# 193670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phagocyte Defects v0.133 WAS Zornitza Stark Marked gene: WAS as ready
Phagocyte Defects v0.133 WAS Zornitza Stark Gene: was has been classified as Green List (High Evidence).
Phagocyte Defects v0.133 WAS Zornitza Stark Phenotypes for gene: WAS were changed from to Neutropaenia, severe congenital, X-linked, MIM# 300299
Phagocyte Defects v0.132 WAS Zornitza Stark Publications for gene: WAS were set to
Phagocyte Defects v0.131 WAS Zornitza Stark Mode of inheritance for gene: WAS was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phagocyte Defects v0.130 WAS Zornitza Stark reviewed gene: WAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 11242115, 16804117, 19006568; Phenotypes: Neutropaenia, severe congenital, X-linked, MIM# 300299; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phagocyte Defects v0.130 WIPF1 Zornitza Stark changed review comment from: Neutropaenia is not a prominent feature. Mostly experimental data linking to macrophage defects.; to: Neutropaenia is not a prominent feature. Mostly experimental data linking to macrophage defects. Gene is on multiple other, more appropriate immunology panels.
Phagocyte Defects v0.130 WIPF1 Zornitza Stark Marked gene: WIPF1 as ready
Phagocyte Defects v0.130 WIPF1 Zornitza Stark Gene: wipf1 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v0.130 WIPF1 Zornitza Stark Phenotypes for gene: WIPF1 were changed from to Wiskott-Aldrich syndrome 2, MIM# 614493
Phagocyte Defects v0.129 WIPF1 Zornitza Stark Publications for gene: WIPF1 were set to
Phagocyte Defects v0.128 WIPF1 Zornitza Stark Mode of inheritance for gene: WIPF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.127 WIPF1 Zornitza Stark Classified gene: WIPF1 as Amber List (moderate evidence)
Phagocyte Defects v0.127 WIPF1 Zornitza Stark Gene: wipf1 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v0.126 WIPF1 Zornitza Stark reviewed gene: WIPF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 17312144, 17890224; Phenotypes: Wiskott-Aldrich syndrome 2, MIM# 614493; Mode of inheritance: None
Mendeliome v0.8550 VPS45 Zornitza Stark Marked gene: VPS45 as ready
Mendeliome v0.8550 VPS45 Zornitza Stark Gene: vps45 has been classified as Green List (High Evidence).
Mendeliome v0.8550 VPS45 Zornitza Stark Phenotypes for gene: VPS45 were changed from to Neutropaenia, severe congenital, 5, autosomal recessive, MIM# 615285
Mendeliome v0.8549 VPS45 Zornitza Stark Publications for gene: VPS45 were set to
Mendeliome v0.8548 VPS45 Zornitza Stark Mode of inheritance for gene: VPS45 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8547 VPS45 Zornitza Stark reviewed gene: VPS45: Rating: GREEN; Mode of pathogenicity: None; Publications: 23738510, 23599270, 33623350, 32037586, 30294941; Phenotypes: Neutropaenia, severe congenital, 5, autosomal recessive, MIM# 615285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.126 VPS45 Zornitza Stark Marked gene: VPS45 as ready
Phagocyte Defects v0.126 VPS45 Zornitza Stark Gene: vps45 has been classified as Green List (High Evidence).
Phagocyte Defects v0.126 VPS45 Zornitza Stark Phenotypes for gene: VPS45 were changed from to Neutropaenia, severe congenital, 5, autosomal recessive, MIM# 615285
Phagocyte Defects v0.125 VPS45 Zornitza Stark Publications for gene: VPS45 were set to
Phagocyte Defects v0.124 VPS45 Zornitza Stark Mode of inheritance for gene: VPS45 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.123 VPS45 Zornitza Stark reviewed gene: VPS45: Rating: GREEN; Mode of pathogenicity: None; Publications: 23738510, 23599270, 33623350, 32037586, 30294941; Phenotypes: Neutropaenia, severe congenital, 5, autosomal recessive, MIM# 615285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.123 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Phagocyte Defects v0.123 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Phagocyte Defects v0.123 VPS13B Zornitza Stark Phenotypes for gene: VPS13B were changed from to Cohen syndrome, MIM# 216550
Phagocyte Defects v0.122 VPS13B Zornitza Stark Mode of inheritance for gene: VPS13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.121 VPS13B Zornitza Stark reviewed gene: VPS13B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cohen syndrome, MIM# 216550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.121 TAZ Zornitza Stark Marked gene: TAZ as ready
Phagocyte Defects v0.121 TAZ Zornitza Stark Gene: taz has been classified as Green List (High Evidence).
Phagocyte Defects v0.121 TAZ Zornitza Stark Phenotypes for gene: TAZ were changed from to Barth syndrome, MIM# 302060
Phagocyte Defects v0.120 TAZ Zornitza Stark Mode of inheritance for gene: TAZ was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phagocyte Defects v0.119 TAZ Zornitza Stark reviewed gene: TAZ: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Barth syndrome, MIM# 302060; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phagocyte Defects v0.119 SLC37A4 Zornitza Stark Marked gene: SLC37A4 as ready
Phagocyte Defects v0.119 SLC37A4 Zornitza Stark Gene: slc37a4 has been classified as Green List (High Evidence).
Phagocyte Defects v0.119 SLC37A4 Zornitza Stark Phenotypes for gene: SLC37A4 were changed from to Glycogen storage disease Ib, MIM# 232220
Phagocyte Defects v0.118 SLC37A4 Zornitza Stark Mode of inheritance for gene: SLC37A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.117 SLC37A4 Zornitza Stark reviewed gene: SLC37A4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycogen storage disease Ib, MIM# 232220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.117 NCF4 Zornitza Stark Marked gene: NCF4 as ready
Phagocyte Defects v0.117 NCF4 Zornitza Stark Gene: ncf4 has been classified as Green List (High Evidence).
Phagocyte Defects v0.117 NCF4 Zornitza Stark Phenotypes for gene: NCF4 were changed from to Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960
Phagocyte Defects v0.116 NCF4 Zornitza Stark Publications for gene: NCF4 were set to
Phagocyte Defects v0.115 NCF4 Zornitza Stark Mode of inheritance for gene: NCF4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.114 NCF2 Zornitza Stark Marked gene: NCF2 as ready
Phagocyte Defects v0.114 NCF2 Zornitza Stark Gene: ncf2 has been classified as Green List (High Evidence).
Phagocyte Defects v0.114 NCF2 Zornitza Stark Phenotypes for gene: NCF2 were changed from to Chronic granulomatous disease 2, autosomal recessive, MIM# 233710
Phagocyte Defects v0.113 NCF2 Zornitza Stark Publications for gene: NCF2 were set to
Phagocyte Defects v0.112 NCF2 Zornitza Stark Mode of inheritance for gene: NCF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.111 SLC35C1 Zornitza Stark Marked gene: SLC35C1 as ready
Phagocyte Defects v0.111 SLC35C1 Zornitza Stark Gene: slc35c1 has been classified as Green List (High Evidence).
Phagocyte Defects v0.111 SLC35C1 Zornitza Stark Phenotypes for gene: SLC35C1 were changed from to Congenital disorder of glycosylation, type IIc, MIM# 266265, MONDO:0009953
Phagocyte Defects v0.110 SLC35C1 Zornitza Stark Publications for gene: SLC35C1 were set to
Phagocyte Defects v0.109 SLC35C1 Zornitza Stark Mode of inheritance for gene: SLC35C1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.108 SBDS Zornitza Stark Marked gene: SBDS as ready
Phagocyte Defects v0.108 SBDS Zornitza Stark Gene: sbds has been classified as Green List (High Evidence).
Phagocyte Defects v0.108 SBDS Zornitza Stark Phenotypes for gene: SBDS were changed from to Shwachman-Diamond syndrome, MIM# 260400
Phagocyte Defects v0.107 SBDS Zornitza Stark Mode of inheritance for gene: SBDS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.106 SBDS Zornitza Stark reviewed gene: SBDS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Shwachman-Diamond syndrome, MIM# 260400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8547 LAMTOR2 Zornitza Stark Marked gene: LAMTOR2 as ready
Mendeliome v0.8547 LAMTOR2 Zornitza Stark Gene: lamtor2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8547 LAMTOR2 Zornitza Stark Phenotypes for gene: LAMTOR2 were changed from to Immunodeficiency due to defect in MAPBP-interacting protein, MIM# 610798
Mendeliome v0.8546 LAMTOR2 Zornitza Stark Publications for gene: LAMTOR2 were set to
Mendeliome v0.8545 LAMTOR2 Zornitza Stark Mode of inheritance for gene: LAMTOR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8544 LAMTOR2 Zornitza Stark Classified gene: LAMTOR2 as Amber List (moderate evidence)
Mendeliome v0.8544 LAMTOR2 Zornitza Stark Gene: lamtor2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8543 LAMTOR2 Zornitza Stark reviewed gene: LAMTOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 17195838, 24092934; Phenotypes: Immunodeficiency due to defect in MAPBP-interacting protein, MIM# 610798; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.106 LAMTOR2 Zornitza Stark Marked gene: LAMTOR2 as ready
Phagocyte Defects v0.106 LAMTOR2 Zornitza Stark Gene: lamtor2 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v0.106 LAMTOR2 Zornitza Stark Phenotypes for gene: LAMTOR2 were changed from to Immunodeficiency due to defect in MAPBP-interacting protein, MIM# 610798
Phagocyte Defects v0.105 LAMTOR2 Zornitza Stark Publications for gene: LAMTOR2 were set to
Phagocyte Defects v0.104 LAMTOR2 Zornitza Stark Mode of inheritance for gene: LAMTOR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.103 LAMTOR2 Zornitza Stark Classified gene: LAMTOR2 as Amber List (moderate evidence)
Phagocyte Defects v0.103 LAMTOR2 Zornitza Stark Gene: lamtor2 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v0.102 LAMTOR2 Zornitza Stark reviewed gene: LAMTOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 17195838, 24092934; Phenotypes: Immunodeficiency due to defect in MAPBP-interacting protein, MIM# 610798; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8543 IKZF3 Zornitza Stark Marked gene: IKZF3 as ready
Mendeliome v0.8543 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8543 IKZF3 Zornitza Stark Classified gene: IKZF3 as Amber List (moderate evidence)
Mendeliome v0.8543 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v0.251 IKZF3 Zornitza Stark Marked gene: IKZF3 as ready
Combined Immunodeficiency v0.251 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8542 IKZF3 Zornitza Stark gene: IKZF3 was added
gene: IKZF3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: IKZF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF3 were set to 34155405
Phenotypes for gene: IKZF3 were set to Immunodeficiency 84, MIM# 619437
Review for gene: IKZF3 was set to AMBER
Added comment: Single family reported where heterozygous missense variant in this gene segregated with immunodeficiency in a mother and two children. Findings included low levels of B cells and impaired early B-cell development, variable T-cell abnormalities, hypogammaglobulinaemia, increased susceptibility to infection with Epstein-Barr virus (EBV). One individual developed lymphoma in adulthood. Mouse model recapitulated phenotype.
Sources: Expert Review
Combined Immunodeficiency v0.251 IKZF3 Zornitza Stark Classified gene: IKZF3 as Amber List (moderate evidence)
Combined Immunodeficiency v0.251 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v0.250 IKZF3 Zornitza Stark Classified gene: IKZF3 as Amber List (moderate evidence)
Combined Immunodeficiency v0.250 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v0.249 IKZF3 Zornitza Stark gene: IKZF3 was added
gene: IKZF3 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: IKZF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF3 were set to 34155405
Phenotypes for gene: IKZF3 were set to Immunodeficiency 84, MIM# 619437
Review for gene: IKZF3 was set to AMBER
Added comment: Single family reported where heterozygous missense variant in this gene segregated with immunodeficiency in a mother and two children. Findings included low levels of B cells and impaired early B-cell development, variable T-cell abnormalities, hypogammaglobulinaemia, increased susceptibility to infection with Epstein-Barr virus (EBV). One individual developed lymphoma in adulthood.

Mouse model recapitulated phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4006 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Intellectual disability syndromic and non-syndromic v0.4006 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4006 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to D-bifunctional protein deficiency, AR (MIM#261515); Perrault syndrome 1, AR (MIM#233400)
Intellectual disability syndromic and non-syndromic v0.4005 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Intellectual disability syndromic and non-syndromic v0.4004 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4003 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27790638; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515), Perrault syndrome 1, AR (MIM#233400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Peroxisomal Disorders v0.23 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Peroxisomal Disorders v0.23 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Peroxisomal Disorders v0.23 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to D-bifunctional protein deficiency, AR (MIM#261515); Perrault syndrome 1, AR (MIM#233400)
Peroxisomal Disorders v0.22 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Peroxisomal Disorders v0.21 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Peroxisomal Disorders v0.20 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27790638; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515), Perrault syndrome 1, AR (MIM#233400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8541 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Mendeliome v0.8541 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Mendeliome v0.8541 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to D-bifunctional protein deficiency, AR (MIM#261515); Perrault syndrome 1, AR (MIM#233400)
Mendeliome v0.8540 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Mendeliome v0.8539 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8538 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515), Perrault syndrome 1, AR (MIM#233400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8538 HSD17B4 Michelle Torres reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27790638; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515), Perrault syndrome 1, AR (MIM#233400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8538 LCK Zornitza Stark Marked gene: LCK as ready
Mendeliome v0.8538 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v0.248 ICOS Zornitza Stark Marked gene: ICOS as ready
Combined Immunodeficiency v0.248 ICOS Zornitza Stark Gene: icos has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.248 ICOS Zornitza Stark Phenotypes for gene: ICOS were changed from to Immunodeficiency, common variable, 1 MIM# 607594; recurrent bacterial respiratory/gastrointestinal infections; autoimmunity; gastroenteritis; low IgG/IgA; normal-low IgM; hypogammaglobulinaemia; low-normal B-cells; normal T-cells; Bronchitis; Lymphadenopathy; Hepatomegaly; Diarrhoea
Combined Immunodeficiency v0.247 ICOS Zornitza Stark Publications for gene: ICOS were set to
Combined Immunodeficiency v0.246 ICOS Zornitza Stark Mode of inheritance for gene: ICOS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.245 ICOS Zornitza Stark Tag SV/CNV tag was added to gene: ICOS.
Mendeliome v0.8538 LCK Zornitza Stark Phenotypes for gene: LCK were changed from to Immunodeficiency 22 MIM# 615758; Recurrent infections; Immune dysregulation; autoimmunity; Low CD4+; low CD8+; restricted T cell repertoire; poor TCR signaling; Normal IgG/IgA; high IgM; failure to thrive; diarrhoea; lymphopaenia; hypogammaglobulinaemia; anaemia; thrombocytopaenia; CD4+ T-cell lymphopaenia
Mendeliome v0.8537 LCK Zornitza Stark Publications for gene: LCK were set to
Mendeliome v0.8536 LCK Zornitza Stark Mode of inheritance for gene: LCK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8535 LCK Zornitza Stark Classified gene: LCK as Amber List (moderate evidence)
Mendeliome v0.8535 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8534 LCK Zornitza Stark Classified gene: LCK as Amber List (moderate evidence)
Mendeliome v0.8534 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v0.245 LCK Zornitza Stark Marked gene: LCK as ready
Combined Immunodeficiency v0.245 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8533 LCK Zornitza Stark reviewed gene: LCK: Rating: AMBER; Mode of pathogenicity: None; Publications: 22985903, 1579166, 11021796; Phenotypes: Immunodeficiency 22 MIM# 615758, Recurrent infections, Immune dysregulation, autoimmunity, Low CD4+, low CD8+, restricted T cell repertoire, poor TCR signaling, Normal IgG/IgA, high IgM, failure to thrive, diarrhoea, lymphopenia, hypogammaglobulinemia, anaemia, thrombocytopaenia, CD4+ T-cell lymphopenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.245 LCK Zornitza Stark Phenotypes for gene: LCK were changed from to Immunodeficiency 22 MIM# 615758; Recurrent infections; Immune dysregulation; autoimmunity; Low CD4+; low CD8+; restricted T cell repertoire; poor TCR signaling; Normal IgG/IgA; high IgM; failure to thrive; diarrhoea; lymphopenia; hypogammaglobulinemia; anaemia; thrombocytopaenia; CD4+ T-cell lymphopenia
Combined Immunodeficiency v0.244 LCK Zornitza Stark Publications for gene: LCK were set to
Combined Immunodeficiency v0.243 LCK Zornitza Stark Mode of inheritance for gene: LCK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8533 DOCK8 Zornitza Stark Marked gene: DOCK8 as ready
Mendeliome v0.8533 DOCK8 Zornitza Stark Gene: dock8 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.242 LCK Zornitza Stark Classified gene: LCK as Amber List (moderate evidence)
Combined Immunodeficiency v0.242 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8533 DOCK8 Zornitza Stark Phenotypes for gene: DOCK8 were changed from to Hyper-IgE recurrent infection syndrome, autosomal recessive MIM# 243700; T cell Lymphopaenia; decraese T/B/NK cells; Eosinophilia; low IgM; elevated IgE; recurrent cutaneous/ viral/ bacterial/ fungal/ infections; severe atopy/allergic disease; autoimmune haemolytic anaemia; eczema; cancer diathesis
Mendeliome v0.8532 DOCK8 Zornitza Stark Publications for gene: DOCK8 were set to
Combined Immunodeficiency v0.241 DOCK8 Zornitza Stark Marked gene: DOCK8 as ready
Combined Immunodeficiency v0.241 DOCK8 Zornitza Stark Gene: dock8 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.241 DOCK8 Zornitza Stark Phenotypes for gene: DOCK8 were changed from to Hyper-IgE recurrent infection syndrome, autosomal recessive MIM# 243700; T cell Lymphopaenia; decraese T/B/NK cells; Eosinophilia; low IgM; elevated IgE; recurrent cutaneous/ viral/ bacterial/ fungal/ infections; severe atopy/allergic disease; autoimmune haemolytic anaemia; eczema; cancer diathesis
Mendeliome v0.8531 DOCK8 Zornitza Stark Mode of inheritance for gene: DOCK8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.240 DOCK8 Zornitza Stark Publications for gene: DOCK8 were set to
Mendeliome v0.8530 DOCK2 Zornitza Stark Marked gene: DOCK2 as ready
Mendeliome v0.8530 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.239 DOCK8 Zornitza Stark Mode of inheritance for gene: DOCK8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8530 DOCK2 Zornitza Stark Phenotypes for gene: DOCK2 were changed from to Immunodeficiency 40 MIM# 616433; T/B-cell lymphopaenia; early-onset invasive herpes/viral/bacterial Infections; function defects in T/B/NK cells; immunodeficiency; defective IFN-mediated immunity; elevated IgM; normal IgG/IgA levels
Mendeliome v0.8529 DOCK2 Zornitza Stark Publications for gene: DOCK2 were set to
Mendeliome v0.8528 DOCK2 Zornitza Stark Mode of inheritance for gene: DOCK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8527 DOCK2 Zornitza Stark reviewed gene: DOCK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26083206, 29204803, 33928462, 30826364, 30838481, 11518968; Phenotypes: Immunodeficiency 40 MIM# 616433, T/B-cell lymphopaenia, early-onset invasive herpes/viral/bacterial Infections, function defects in T/B/NK cells, immunodeficiency, defective IFN-mediated immunity, elevated IgM, normal IgG/IgA levels; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8527 DOCK8 Danielle Ariti reviewed gene: DOCK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 19776401, 20622910, 21931011, 26659092, 19898472, 25422492; Phenotypes: Hyper-IgE recurrent infection syndrome, autosomal recessive MIM# 243700, T cell Lymphopaenia, decraese T/B/NK cells, Eosinophilia, low IgM, elevated IgE, recurrent cutaneous/ viral/ bacterial/ fungal/ infections, severe atopy/allergic disease, autoimmune haemolytic anaemia, eczema, cancer diathesisc; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.238 DOCK2 Zornitza Stark Marked gene: DOCK2 as ready
Combined Immunodeficiency v0.238 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.238 DOCK2 Zornitza Stark Phenotypes for gene: DOCK2 were changed from to Immunodeficiency 40 MIM# 616433; T/B-cell lymphopaenia; early-onset invasive herpes/viral/bacterial Infections; function defects in T/B/NK cells; immunodeficiency; defective IFN-mediated immunity; elevated IgM; normal IgG/IgA levels
Combined Immunodeficiency v0.237 DOCK2 Zornitza Stark Publications for gene: DOCK2 were set to
Combined Immunodeficiency v0.236 DOCK2 Zornitza Stark Mode of inheritance for gene: DOCK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8527 DNMT3B Zornitza Stark Marked gene: DNMT3B as ready
Mendeliome v0.8527 DNMT3B Zornitza Stark Gene: dnmt3b has been classified as Green List (High Evidence).
Mendeliome v0.8527 DNMT3B Zornitza Stark Phenotypes for gene: DNMT3B were changed from to Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860; facial dysmorphic features; flat nasal bridge; developmental delay; macroglossia; bacterial/opportunistic infections (recurrent); malabsorption; cytopaenia; malignancies; multiradial configurations of chromosomes 1, 9, 16; Hypogammaglobulinaemia; agammaglobulinaemia; variable antibody deficiency; decreased immunoglobulin production; low T/B/NK cells
Predominantly Antibody Deficiency v0.68 DNMT3B Danielle Ariti reviewed gene: DNMT3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20587527, 10555141, 17359920, 9718351, 10647011, 11102980, 12239717; Phenotypes: mmunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860, facial dysmorphic features, flat nasal bridge, developmental delay, macroglossia, bacterial/opportunistic infections (recurrent), malabsorption, cytopaenia, malignancies, multiradial configurations of chromosomes 1, 9, 16, Hypogammaglobulinaemia, agammaglobulinaemia, variable antibody deficiency, decreased immunoglobulin production, low T/B/NK cells; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8526 DNMT3B Zornitza Stark Publications for gene: DNMT3B were set to
Mendeliome v0.8525 DNMT3B Zornitza Stark Mode of inheritance for gene: DNMT3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8524 DNMT3B Zornitza Stark reviewed gene: DNMT3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20587527, 10555141, 17359920, 9718351, 10647011, 11102980, 12239717; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860, facial dysmorphic features, flat nasal bridge, developmental delay, macroglossia, bacterial/opportunistic infections (recurrent), malabsorption, cytopaenia, malignancies, multiradial configurations of chromosomes 1, 9, 16, Hypogammaglobulinaemia, agammaglobulinaemia, variable antibody deficiency, decreased immunoglobulin production, low T/B/NK cells; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.235 DNMT3B Zornitza Stark Marked gene: DNMT3B as ready
Combined Immunodeficiency v0.235 DNMT3B Zornitza Stark Gene: dnmt3b has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.235 DNMT3B Zornitza Stark Phenotypes for gene: DNMT3B were changed from to Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860; facial dysmorphic features; flat nasal bridge; developmental delay; macroglossia; bacterial/opportunistic infections (recurrent); malabsorption; cytopaenia; malignancies; multiradial configurations of chromosomes 1, 9, 16; Hypogammaglobulinaemia; agammaglobulinaemia; variable antibody deficiency; decreased immunoglobulin production; low T/B/NK cells
Combined Immunodeficiency v0.234 DNMT3B Zornitza Stark Publications for gene: DNMT3B were set to
Combined Immunodeficiency v0.233 DNMT3B Zornitza Stark Mode of inheritance for gene: DNMT3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.232 ICOS Danielle Ariti changed review comment from: 15 affected individuals from 8 unrelated families reported with ICOS variants and displayed immunodeficiency, common variable, 1 phenotype; three mouse models.

Homozygous and compound heterozygous deletion and missense variants, with the most frequent variant being a 442 nucleotide deletion.

Patients typically presented with recurrent bacterial respiratory & gastrointestinal infections and low IgG/IgA. However, phenotypic expression is highly variable, with some individuals only displaying immunological phenotypes.; to: 15 affected individuals from 8 unrelated families reported with ICOS variants and displayed immunodeficiency, common variable, 1 phenotype; three mouse models.

Homozygous and compound heterozygous deletion and missense variants, with the most frequent variant being a 442 nucleotide deletion.

Patients typically presented with recurrent bacterial respiratory & gastrointestinal infections and low IgG/IgA. However, phenotypic expression is highly variable, with some individuals only displaying immunological phenotypes.
Combined Immunodeficiency v0.232 ICOS Danielle Ariti reviewed gene: ICOS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12577056, 15507387, 19380800, 28861081, 31858365, 11343122, 16982935; Phenotypes: Immunodeficiency, common variable, 1 MIM# 607594, recurrent bacterial respiratory/gastrointestinal infections, autoimmunity, gastroenteritis, low IgG/IgA, normal-low IgM, hypogammaglobulinaemia, low-normal B-cells, normal T-cells, Bronchitis, Lymphadenopathy, Hepatomegaly, Diarrhoea; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.232 LCK Danielle Ariti reviewed gene: LCK: Rating: AMBER; Mode of pathogenicity: None; Publications: 22985903, 1579166, 11021796; Phenotypes: Immunodeficiency 22 MIM# 615758, Recurrent infections, Immune dysregulation, autoimmunity, Low CD4+, low CD8+, restricted T cell repertoire, poor TCR signaling, Normal IgG/IgA, high IgM, failure to thrive, diarrhoea, lymphopenia, hypogammaglobulinemia, anaemia, thrombocytopaenia, CD4+ T-cell lymphopenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.232 DOCK8 Danielle Ariti reviewed gene: DOCK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 19776401, 20622910, 21931011, 26659092, 19898472, 25422492; Phenotypes: Hyper-IgE recurrent infection syndrome, autosomal recessive MIM# 243700, T cell Lymphopaenia, decraese T/B/NK cells, Eosinophilia, low IgM, elevated IgE, recurrent cutaneous/ viral/ bacterial/ fungal/ infections, severe atopy/allergic disease, autoimmune haemolytic anaemia, eczema, cancer diathesis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.232 DOCK2 Danielle Ariti reviewed gene: DOCK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26083206, 29204803, 33928462, 30826364, 30838481, 11518968; Phenotypes: Immunodeficiency 40 MIM# 616433, T/B-cell lymphopaenia, early-onset invasive herpes/viral/bacterial Infections, function defects in T/B/NK cells, immunodeficiency, defective IFN-mediated immunity, elevated IgM, normal IgG/IgA levels; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8524 TMPO Bryony Thompson Marked gene: TMPO as ready
Mendeliome v0.8524 TMPO Bryony Thompson Gene: tmpo has been classified as Red List (Low Evidence).
Mendeliome v0.8524 TMPO Bryony Thompson Classified gene: TMPO as Red List (low evidence)
Mendeliome v0.8524 TMPO Bryony Thompson Gene: tmpo has been classified as Red List (Low Evidence).
Mendeliome v0.8523 TMPO Bryony Thompson reviewed gene: TMPO: Rating: RED; Mode of pathogenicity: None; Publications: 16247757; Phenotypes: Hypertrophic cardiomyopathy, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8523 SYNCRIP Zornitza Stark Marked gene: SYNCRIP as ready
Mendeliome v0.8523 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Green List (High Evidence).
Mendeliome v0.8523 SYNCRIP Zornitza Stark Classified gene: SYNCRIP as Green List (high evidence)
Mendeliome v0.8523 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Green List (High Evidence).
Mendeliome v0.8522 SYNCRIP Zornitza Stark gene: SYNCRIP was added
gene: SYNCRIP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SYNCRIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYNCRIP were set to 34157790; 30504930; 27479843; 23020937
Phenotypes for gene: SYNCRIP were set to Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology
Review for gene: SYNCRIP was set to GREEN
Added comment: Semino et al (2021 - PMID: 34157790) provide clinical details on 3 unrelated individuals with de novo SYNCRIP variants and provide a review of 5 additional subjects previously identified within large cohorts in the literature and databases.

Features included DD, ID (7/7 for whom this information was available), ASD or autistic features (4/7). MRI abnormalities were observed in 3 (widening of CSF spaces, periventricular nodular heterotopia, prominent lat. ventricles). Epilepsy (myoclonic-astatic epilepsy / Doose syndrome) was reported for 2(/8) individuals.

The 3 patients here reported were identified following trio/singleton exome with Sanger confirmation of the variants and their de novo occurrence.

Variants are in almost all cases de novo (7/7 for whom this was known) and in 5/8 cases were pLoF, in 2/8 missense SNVs while a case from DECIPHER had a 77.92 kb whole gene deletion not involving other genes with unknown inheritance.

Overall the variants reported to date include [NM_006372.5]:
1 - c.858_859del p.(Gly287Leufs*5)
2 - c.854dupA p.(Asn285Lysfs*8)
3 - c.734T>C p.(Leu245Pro)
4 - chr6:85605276-85683190 deletion (GRCh38)
5 - c.629T>C p.(Phe210Ser)
6 - c.1573_1574delinsTT p.(Gln525Leu)
7 - c.1247_1250del p.(Arg416Lysfs*145)
8 - c.1518_1519insC p.(Ala507Argfs*14)

[P1-3: this report, P4: DECIPHER 254774, P5-6: Guo et al 2019 - PMID: 30504930, P7: Lelieveld et al 2016 - PMID: 27479843, P8: Rauch et al 2012 - PMID: 23020937 / all other Refs not here reviewed, clinical details summarized by Semino et al in table 1]

SYNCRIP (also known as HNRNPQ) encodes synaptotagmin‐binding cytoplasmic RNA‐interacting protein. As the authors note, this RNA-binding protein is involved in multiple pathways associated with neuronal/muscular developmental disorders. Several references are provided for its involvement in regulation of RNA metabolism, among others sequence recognition, pre-mRNA splicing, translation, transport and degradation.

Mutations in other RNA-interacting proteins and hnRNP members (e.g. HNRNPU, HNRNPD) are associated with NDD.

The missense variant (p.Leu245Pro) is within RRM2 one of the 3 RNA recognition motif (RRM) domains of the protein. These 3 domains, corresponding to the central part of the protein (aa 150-400), are relatively intolerant to variation (based on in silico predictions and/or variation in gnomAD). Leu245 localizes within an RNA binding pocket and in silico modeling suggests alteration of the tertiary structure and RNA-binding capacity of RRM2.

There are no additional studies performed.

Overall haploinsufficiency appears to be the underlying disease mechanism based on the truncating variants and the gene deletion. [pLI in gnomAD : 1, %HI : 2.48%]

Animal models are not discussed.

There is no associated phenotype in OMIM. This gene is included in the DD panel of G2P (monoallelic LoF variants / SYNCRIP-related developmental disorder). SysID also lists SYNCRIP within the current primary ID genes.
Sources: Literature
Genetic Epilepsy v0.1149 SYNCRIP Zornitza Stark Marked gene: SYNCRIP as ready
Genetic Epilepsy v0.1149 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1149 SYNCRIP Zornitza Stark Classified gene: SYNCRIP as Amber List (moderate evidence)
Genetic Epilepsy v0.1149 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4003 SYNCRIP Zornitza Stark Marked gene: SYNCRIP as ready
Intellectual disability syndromic and non-syndromic v0.4003 SYNCRIP Zornitza Stark Added comment: Comment when marking as ready: Sufficient cases for Green rating on ID panel.
Intellectual disability syndromic and non-syndromic v0.4003 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4003 SYNCRIP Zornitza Stark Classified gene: SYNCRIP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4003 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.232 DNMT3B Danielle Ariti reviewed gene: DNMT3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20587527, 10555141, 17359920, 9718351, 10647011, 11102980, 12239717; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860, facial dysmorphic features, flat nasal bridge, developmental delay, macroglossia, bacterial/opportunistic infections (recurrent), malabsorption, cytopaenia, malignancies, multiradial configurations of chromosomes 1, 9, 16, Hypogammaglobulinaemia, agammaglobulinaemia, variable antibody deficiency, decreased immunoglobulin production, low T/B/NK cells; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.232 CD3G Danielle Ariti changed review comment from: 10 affected individuals from 5 unrelated families; homozygous and compound heterozygous variants (splicing, missense and small deletion variants) identified resulting in premature stop codons and truncated protein; multiple mouse models.

All individuals displayed immune deficiency and autoimmunity of variable severity. Some individuals presented at birth with failure to thrive due to lethal SCID features, whilst other CD3G-deficient individuals were in healthy condition decades into life. The most common immunologic profile includes partial T lymphocytopenia and low CD3, with normal B cells, NK cells, and immunoglobulins.; to: 10 affected individuals from 5 unrelated families; homozygous and compound heterozygous variants (splicing, missense and small deletion variants) identified resulting in premature stop codons and truncated protein; multiple mouse models.

All individuals displayed immune deficiency and autoimmunity of variable severity. Some individuals presented at birth with failure to thrive due to lethal SCID features, whilst other CD3G- deficient individuals only display immunological phenotype and no other features. The most common immunologic profile includes partial T lymphocytopenia and low CD3, with normal B cells, NK cells, and immunoglobulins.
Combined Immunodeficiency v0.232 CD27 Danielle Ariti changed review comment from: 17 affected individuals from 9 unrelated families; homozygous (missense) and compound heterozygous (missense/ nonsense) variants identified in CD27; one mouse model

Affected individuals present with varied phenotypes (even within the same families); most commonly with lymphadenopathy, fever, hepatosplenomegaly, EBV-related infections, and immunodeficiency associated with hypogammaglobulinaemia. However, some CD27-deficient individuals are asymptomatic or display borderline-low hypogammaglobulinaemia.; to: 17 affected individuals from 9 unrelated families; homozygous (missense) and compound heterozygous (missense/ nonsense) variants identified in CD27; one mouse model

Affected individuals present with varied phenotypes (even within the same families); most commonly with lymphadenopathy, fever, hepatosplenomegaly, EBV-related infections, and immunodeficiency associated with hypogammaglobulinaemia. However, some CD27-deficient individuals are asymptomatic-borderline low hypogammaglobulinaemia.
Intellectual disability syndromic and non-syndromic v0.4002 SYNCRIP Konstantinos Varvagiannis gene: SYNCRIP was added
gene: SYNCRIP was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SYNCRIP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SYNCRIP were set to 34157790; 30504930; 27479843; 23020937
Phenotypes for gene: SYNCRIP were set to Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology
Review for gene: SYNCRIP was set to AMBER
Added comment: Semino et al (2021 - PMID: 34157790) provide clinical details on 3 unrelated individuals with de novo SYNCRIP variants and provide a review of 5 additional subjects previously identified within large cohorts in the literature and databases.

Features included DD, ID (7/7 for whom this information was available), ASD or autistic features (4/7). MRI abnormalities were observed in 3 (widening of CSF spaces, periventricular nodular heterotopia, prominent lat. ventricles). Epilepsy (myoclonic-astatic epilepsy / Doose syndrome) was reported for 2(/8) individuals.

The 3 patients here reported were identified following trio/singleton exome with Sanger confirmation of the variants and their de novo occurrence.

Variants are in almost all cases de novo (7/7 for whom this was known) and in 5/8 cases were pLoF, in 2/8 missense SNVs while a case from DECIPHER had a 77.92 kb whole gene deletion not involving other genes with unknown inheritance.

Overall the variants reported to date include [NM_006372.5]:
1 - c.858_859del p.(Gly287Leufs*5)
2 - c.854dupA p.(Asn285Lysfs*8)
3 - c.734T>C p.(Leu245Pro)
4 - chr6:85605276-85683190 deletion (GRCh38)
5 - c.629T>C p.(Phe210Ser)
6 - c.1573_1574delinsTT p.(Gln525Leu)
7 - c.1247_1250del p.(Arg416Lysfs*145)
8 - c.1518_1519insC p.(Ala507Argfs*14)

[P1-3: this report, P4: DECIPHER 254774, P5-6: Guo et al 2019 - PMID: 30504930, P7: Lelieveld et al 2016 - PMID: 27479843, P8: Rauch et al 2012 - PMID: 23020937 / all other Refs not here reviewed, clinical details summarized by Semino et al in table 1]

SYNCRIP (also known as HNRNPQ) encodes synaptotagmin‐binding cytoplasmic RNA‐interacting protein. As the authors note, this RNA-binding protein is involved in multiple pathways associated with neuronal/muscular developmental disorders. Several references are provided for its involvement in regulation of RNA metabolism, among others sequence recognition, pre-mRNA splicing, translation, transport and degradation.

Mutations in other RNA-interacting proteins and hnRNP members (e.g. HNRNPU, HNRNPD) are associated with NDD.

The missense variant (p.Leu245Pro) is within RRM2 one of the 3 RNA recognition motif (RRM) domains of the protein. These 3 domains, corresponding to the central part of the protein (aa 150-400), are relatively intolerant to variation (based on in silico predictions and/or variation in gnomAD). Leu245 localizes within an RNA binding pocket and in silico modeling suggests alteration of the tertiary structure and RNA-binding capacity of RRM2.

There are no additional studies performed.

Overall haploinsufficiency appears to be the underlying disease mechanism based on the truncating variants and the gene deletion. [pLI in gnomAD : 1, %HI : 2.48%]

Animal models are not discussed.

There is no associated phenotype in OMIM. This gene is included in the DD panel of G2P (monoallelic LoF variants / SYNCRIP-related developmental disorder). SysID also lists SYNCRIP within the current primary ID genes.
Sources: Literature
Genetic Epilepsy v0.1148 SYNCRIP Konstantinos Varvagiannis gene: SYNCRIP was added
gene: SYNCRIP was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SYNCRIP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SYNCRIP were set to 34157790; 30504930; 27479843; 23020937
Phenotypes for gene: SYNCRIP were set to Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology
Review for gene: SYNCRIP was set to AMBER
Added comment: Semino et al (2021 - PMID: 34157790) provide clinical details on 3 unrelated individuals with de novo SYNCRIP variants and provide a review of 5 additional subjects previously identified within large cohorts in the literature and databases.

Features included DD, ID (7/7 for whom this information was available), ASD or autistic features (4/7). MRI abnormalities were observed in 3 (widening of CSF spaces, periventricular nodular heterotopia, prominent lat. ventricles). Epilepsy (myoclonic-astatic epilepsy / Doose syndrome) was reported for 2(/8) individuals.

The 3 patients here reported were identified following trio/singleton exome with Sanger confirmation of the variants and their de novo occurrence.

Variants are in almost all cases de novo (7/7 for whom this was known) and in 5/8 cases were pLoF, in 2/8 missense SNVs while a case from DECIPHER had a 77.92 kb whole gene deletion not involving other genes with unknown inheritance.

Overall the variants reported to date include [NM_006372.5]:
1 - c.858_859del p.(Gly287Leufs*5)
2 - c.854dupA p.(Asn285Lysfs*8)
3 - c.734T>C p.(Leu245Pro)
4 - chr6:85605276-85683190 deletion (GRCh38)
5 - c.629T>C p.(Phe210Ser)
6 - c.1573_1574delinsTT p.(Gln525Leu)
7 - c.1247_1250del p.(Arg416Lysfs*145)
8 - c.1518_1519insC p.(Ala507Argfs*14)

[P1-3: this report, P4: DECIPHER 254774, P5-6: Guo et al 2019 - PMID: 30504930, P7: Lelieveld et al 2016 - PMID: 27479843, P8: Rauch et al 2012 - PMID: 23020937 / all other Refs not here reviewed, clinical details summarized by Semino et al in table 1]

SYNCRIP (also known as HNRNPQ) encodes synaptotagmin‐binding cytoplasmic RNA‐interacting protein. As the authors note, this RNA-binding protein is involved in multiple pathways associated with neuronal/muscular developmental disorders. Several references are provided for its involvement in regulation of RNA metabolism, among others sequence recognition, pre-mRNA splicing, translation, transport and degradation.

Mutations in other RNA-interacting proteins and hnRNP members (e.g. HNRNPU, HNRNPD) are associated with NDD.

The missense variant (p.Leu245Pro) is within RRM2 one of the 3 RNA recognition motif (RRM) domains of the protein. These 3 domains, corresponding to the central part of the protein (aa 150-400), are relatively intolerant to variation (based on in silico predictions and/or variation in gnomAD). Leu245 localizes within an RNA binding pocket and in silico modeling suggests alteration of the tertiary structure and RNA-binding capacity of RRM2.

There are no additional studies performed.

Overall haploinsufficiency appears to be the underlying disease mechanism based on the truncating variants and the gene deletion. [pLI in gnomAD : 1, %HI : 2.48%]

Animal models are not discussed.

There is no associated phenotype in OMIM. This gene is included in the DD panel of G2P (monoallelic LoF variants / SYNCRIP-related developmental disorder). SysID also lists SYNCRIP within the current primary ID genes.
Sources: Literature
Phagocyte Defects v0.102 NCF1 Zornitza Stark Marked gene: NCF1 as ready
Phagocyte Defects v0.102 NCF1 Zornitza Stark Gene: ncf1 has been classified as Green List (High Evidence).
Phagocyte Defects v0.102 NCF1 Zornitza Stark Phenotypes for gene: NCF1 were changed from to Chronic granulomatous disease 1, autosomal recessive, MIM# 233700
Phagocyte Defects v0.101 NCF1 Zornitza Stark Publications for gene: NCF1 were set to
Phagocyte Defects v0.100 NCF1 Zornitza Stark Mode of inheritance for gene: NCF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8521 MSN Zornitza Stark Marked gene: MSN as ready
Mendeliome v0.8521 MSN Zornitza Stark Gene: msn has been classified as Green List (High Evidence).
Mendeliome v0.8521 MSN Zornitza Stark Phenotypes for gene: MSN were changed from to Immunodeficiency 50, MIM# 300988
Mendeliome v0.8520 MSN Zornitza Stark Publications for gene: MSN were set to
Mendeliome v0.8519 MSN Zornitza Stark Mode of inheritance for gene: MSN was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8518 MSN Zornitza Stark reviewed gene: MSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 27405666; Phenotypes: Immunodeficiency 50, MIM# 300988; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phagocyte Defects v0.99 MSN Zornitza Stark Marked gene: MSN as ready
Phagocyte Defects v0.99 MSN Zornitza Stark Gene: msn has been classified as Green List (High Evidence).
Phagocyte Defects v0.99 MSN Zornitza Stark changed review comment from: Seven males from five unrelated families reported.
Sources: Expert list; to: Seven males from five unrelated families reported. Profound lymphopaenia, fluctuating neutropaenia.
Sources: Expert list
Mendeliome v0.8518 JAGN1 Zornitza Stark Marked gene: JAGN1 as ready
Mendeliome v0.8518 JAGN1 Zornitza Stark Gene: jagn1 has been classified as Green List (High Evidence).
Mendeliome v0.8518 JAGN1 Zornitza Stark Phenotypes for gene: JAGN1 were changed from to Neutropaenia, severe congenital, 6, autosomal recessive, MIM# 616022
Mendeliome v0.8517 JAGN1 Zornitza Stark Publications for gene: JAGN1 were set to
Mendeliome v0.8516 JAGN1 Zornitza Stark Mode of inheritance for gene: JAGN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8515 JAGN1 Zornitza Stark reviewed gene: JAGN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25129144; Phenotypes: Neutropaenia, severe congenital, 6, autosomal recessive, MIM# 616022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.99 JAGN1 Zornitza Stark Marked gene: JAGN1 as ready
Phagocyte Defects v0.99 JAGN1 Zornitza Stark Gene: jagn1 has been classified as Green List (High Evidence).
Phagocyte Defects v0.99 JAGN1 Zornitza Stark Phenotypes for gene: JAGN1 were changed from to Neutropaenia, severe congenital, 6, autosomal recessive, MIM# 616022
Phagocyte Defects v0.98 JAGN1 Zornitza Stark Publications for gene: JAGN1 were set to
Phagocyte Defects v0.97 JAGN1 Zornitza Stark Mode of inheritance for gene: JAGN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.96 JAGN1 Zornitza Stark reviewed gene: JAGN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25129144; Phenotypes: Neutropaenia, severe congenital, 6, autosomal recessive, MIM# 616022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8515 ITGB2 Zornitza Stark Marked gene: ITGB2 as ready
Mendeliome v0.8515 ITGB2 Zornitza Stark Gene: itgb2 has been classified as Green List (High Evidence).
Mendeliome v0.8515 ITGB2 Zornitza Stark Phenotypes for gene: ITGB2 were changed from to Leukocyte adhesion deficiency, MIM# 116920
Mendeliome v0.8514 ITGB2 Zornitza Stark Publications for gene: ITGB2 were set to
Mendeliome v0.8513 ITGB2 Zornitza Stark Mode of inheritance for gene: ITGB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8512 ITGB2 Zornitza Stark reviewed gene: ITGB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1968911, 1694220, 33957747, 32279896, 31374327; Phenotypes: Leukocyte adhesion deficiency, MIM# 116920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.96 ITGB2 Zornitza Stark Marked gene: ITGB2 as ready
Phagocyte Defects v0.96 ITGB2 Zornitza Stark Gene: itgb2 has been classified as Green List (High Evidence).
Phagocyte Defects v0.96 ITGB2 Zornitza Stark Phenotypes for gene: ITGB2 were changed from to Leukocyte adhesion deficiency, MIM# 116920
Phagocyte Defects v0.95 ITGB2 Zornitza Stark Publications for gene: ITGB2 were set to
Phagocyte Defects v0.94 ITGB2 Zornitza Stark Mode of inheritance for gene: ITGB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.93 ITGB2 Zornitza Stark reviewed gene: ITGB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1968911, 1694220, 33957747, 32279896, 31374327; Phenotypes: Leukocyte adhesion deficiency, MIM# 116920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8512 NLRP2 Melanie Marty commented on gene: NLRP2
Phagocyte Defects v0.93 GATA2 Zornitza Stark Marked gene: GATA2 as ready
Phagocyte Defects v0.93 GATA2 Zornitza Stark Gene: gata2 has been classified as Green List (High Evidence).
Phagocyte Defects v0.93 GATA2 Zornitza Stark Phenotypes for gene: GATA2 were changed from to Emberger syndrome, MIM# 614038
Phagocyte Defects v0.92 GATA2 Zornitza Stark Publications for gene: GATA2 were set to
Phagocyte Defects v0.91 GATA2 Zornitza Stark Mode of inheritance for gene: GATA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phagocyte Defects v0.90 GATA2 Zornitza Stark edited their review of gene: GATA2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phagocyte Defects v0.90 GATA2 Zornitza Stark reviewed gene: GATA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26710799; Phenotypes: Emberger syndrome, MIM# 614038; Mode of inheritance: None
Dystonia - complex v0.188 CAMK4 Zornitza Stark edited their review of gene: CAMK4: Changed phenotypes: Intellectual disability, Autism, Behavioral abnormality, Abnormality of movement, Dystonia, Ataxia, Chorea, Myoclonus
Dystonia - complex v0.188 CAMK4 Zornitza Stark Marked gene: CAMK4 as ready
Dystonia - complex v0.188 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Dystonia - complex v0.188 CAMK4 Zornitza Stark Phenotypes for gene: CAMK4 were changed from 30262571; 33098801; 33211350 to Intellectual disability; Autism; Behavioral abnormality; Abnormality of movement; Dystonia; Ataxia; Chorea; Myoclonus
Dystonia - complex v0.187 CAMK4 Zornitza Stark Classified gene: CAMK4 as Green List (high evidence)
Dystonia - complex v0.187 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Dystonia - complex v0.186 CAMK4 Zornitza Stark gene: CAMK4 was added
gene: CAMK4 was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: CAMK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350
Phenotypes for gene: CAMK4 were set to 30262571; 33098801; 33211350
Review for gene: CAMK4 was set to GREEN
Added comment: 3 publications by Zech et al (2018, 2020 - PMIDs : 30262571, 33098801, 33211350) provide clinical details on 3 individuals, each harboring a private de novo CAMK4 variant.

Overlapping features included DD, ID, behavoral issues, autism and abnormal hyperkinetic movements. Dystonia and chorea in all 3 appeared 3-20 years after initial symptoms.

CAMK4 encodes Calcium/Calmodulin-dependent protein kinase IV, an important mediator of calcium-mediated activity and dynamics, particularly in the brain. It is involved in neuronal transmission, synaptic plasticity, and neuronal gene expression required for brain development and neuronal homeostasis (summary by OMIM based on Zech et al, 2018).

The 473 aa enzyme has a protein kinase domain (aa 46-300) and a C-terminal autoregulatory domain (aa 305-341) the latter comprising an autoinhibitory domain (AID / aa 305-321) and a calmodulin-binding domain (CBD / aa 322-341) [NP_001735.1 / NM_001744.4 - also used below].

Variants in all 3 subjects were identified following trio-WES and were in all cases protein-truncating, mapping to exon 10 or exon 10-intron 10 junction, expected to escape NMD and cause selective abrogation of the autoinhibitory domain (aa 305-321) leading overall to gain-of-function.

Variation databases include pLoF CAMK4 variants albeit in all cases usptream or downstream of this region (pLI of this gene in gnomAD: 0.51). Variants leading to selective abrogation of the autoregulatory domain have not been reported.

Extensive evidence for the GoF effect of the variant has been provided in the first publication. Several previous studies have demonstrated that abrogation of the AID domain leads to consitutive activation (details below).

Mouse models - though corresponding to homozygous loss of function - support a role for CAMKIV in cognitive and motor symptoms. Null mice display tremulous and ataxic movements, deficiencies in balance and sensorimotor performance associated with reduced number of Purkinje neurons (Ribar et al 2000, PMID: 11069976 - not reviewed). Wei et al (2002, PMID: 12006982 - not reviewed) provided evidence for alteration in hippocampal physiology and memory function.

Heterozygous mutations in other genes for calcium/calmodulin-dependent protein kinases (CAMKs) e.g. CAMK2A/CAMK2B (encoding subunits of CAMKII) have been reported in individuals with ID.

---

The proband in the first publication (PMID: 30262571) was a male with DD, ID, behavioral difficulties (ASD, autoaggression, stereotypies) and hyperkinetic movement disorder (myoclonus, chorea, ataxia) with severe generalized dystonia (onset at the age of 13y). Brain MRI demonstrated cerebellar atrophy.

Extensive work-up incl. karyotyping, CMA, DYT-TOR1A, THAP1, GCH1, SCA1/2/3/6/7/8/12/17, Friedreich's ataxia and FMR1 analysis was negative.F

Trio WES identified a dn splice site variant (c.981+1G>A) in the last exon-intron junction. RT-PCR followed by gel electrophoresis and Sanger in fibroblasts from an affected and control subject revealed that the proband had - as predicted by the type/location of the variant - in equal amount 2 cDNA products, a normal as well as a truncated one.

Sequencing of the shortest revealed utilization of a cryptic donor splice site upstream of the mutated donor leading to a 77bp out-of-frame deletion and introduction of a premature stop codon in the last codon (p.Lys303Serfs*28). Western blot in fibroblast cell lines revealed 2 bands corresponding to the normal protein product as well as to the p.Lys303Serfs*28 although expression of the latter was lower than that of the full length protein.

Several previous studies have shown that mutant CAMKIV species that lack the autoinhibitory domain are consitutively active (several Refs provided). Among others Chatila et al (1996, PMID: 8702940) studied an in vitro-engineered truncation mutant (Δ1-317 - truncation at position 317 of the protein) with functionally validated gain-of-function effect.

To prove enhanced activity of the splicing variant, Zech et al assessed phosphorylation of CREB (cyclic AMP-responsive element binding protein), a downstream substrate of CAMKIV. Immunobloting revealed significant increase of CREB phosphorylation in patient fibroblasts compared to controls. Overactivation of CAMKIV signaling was reversed when cells were treated with STO-609 an inhibitor of CAMKK, the ustream activator of CAMKIV.

Overall the authors demonstrated that loss of CAMKIV autoregulatory domain due to this splice variant had a gain-of-function effect.

----

Following trio-WES, Zech et al (2020 - PMID: 33098801) identified another relevant subject within cohort of 764 individuals with dystonia. This 12-y.o. male, harboring a different variant affecting the same donor site (c.981+1G>T), presented DD, ID, dystonia (onset at 3y) and additional movement disorders (myoclonus, ataxia) as well as similar behavior (ASD, autoaggression, stereotypies). [Details in suppl. p20].

----

Finally Zech et al (2020 - PMID: 33211350) reported on a 24-y.o. woman with adolescence onset choreodystonia. Other features included DD, moderate ID, absence seizures in infancy, OCD with anxiety and later diagnosis of ASD. Trio WES revealed a dn stopgain variant (c.940C>T; p.Gln314*).
Sources: Expert Review
Mendeliome v0.8512 CAMK4 Zornitza Stark Marked gene: CAMK4 as ready
Mendeliome v0.8512 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Mendeliome v0.8512 CAMK4 Zornitza Stark Classified gene: CAMK4 as Green List (high evidence)
Mendeliome v0.8512 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Mendeliome v0.8511 CAMK4 Zornitza Stark gene: CAMK4 was added
gene: CAMK4 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CAMK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350
Phenotypes for gene: CAMK4 were set to Intellectual disability; Autism; Behavioral abnormality; Abnormality of movement; Dystonia; Ataxia; Chorea; Myoclonus
Review for gene: CAMK4 was set to GREEN
Added comment: 3 publications by Zech et al (2018, 2020 - PMIDs : 30262571, 33098801, 33211350) provide clinical details on 3 individuals, each harboring a private de novo CAMK4 variant.

Overlapping features included DD, ID, behavoral issues, autism and abnormal hyperkinetic movements. Dystonia and chorea in all 3 appeared 3-20 years after initial symptoms.

CAMK4 encodes Calcium/Calmodulin-dependent protein kinase IV, an important mediator of calcium-mediated activity and dynamics, particularly in the brain. It is involved in neuronal transmission, synaptic plasticity, and neuronal gene expression required for brain development and neuronal homeostasis (summary by OMIM based on Zech et al, 2018).

The 473 aa enzyme has a protein kinase domain (aa 46-300) and a C-terminal autoregulatory domain (aa 305-341) the latter comprising an autoinhibitory domain (AID / aa 305-321) and a calmodulin-binding domain (CBD / aa 322-341) [NP_001735.1 / NM_001744.4 - also used below].

Variants in all 3 subjects were identified following trio-WES and were in all cases protein-truncating, mapping to exon 10 or exon 10-intron 10 junction, expected to escape NMD and cause selective abrogation of the autoinhibitory domain (aa 305-321) leading overall to gain-of-function.

Variation databases include pLoF CAMK4 variants albeit in all cases usptream or downstream of this region (pLI of this gene in gnomAD: 0.51). Variants leading to selective abrogation of the autoregulatory domain have not been reported.

Extensive evidence for the GoF effect of the variant has been provided in the first publication. Several previous studies have demonstrated that abrogation of the AID domain leads to consitutive activation (details below).

Mouse models - though corresponding to homozygous loss of function - support a role for CAMKIV in cognitive and motor symptoms. Null mice display tremulous and ataxic movements, deficiencies in balance and sensorimotor performance associated with reduced number of Purkinje neurons (Ribar et al 2000, PMID: 11069976 - not reviewed). Wei et al (2002, PMID: 12006982 - not reviewed) provided evidence for alteration in hippocampal physiology and memory function.

Heterozygous mutations in other genes for calcium/calmodulin-dependent protein kinases (CAMKs) e.g. CAMK2A/CAMK2B (encoding subunits of CAMKII) have been reported in individuals with ID.

---

The proband in the first publication (PMID: 30262571) was a male with DD, ID, behavioral difficulties (ASD, autoaggression, stereotypies) and hyperkinetic movement disorder (myoclonus, chorea, ataxia) with severe generalized dystonia (onset at the age of 13y). Brain MRI demonstrated cerebellar atrophy.

Extensive work-up incl. karyotyping, CMA, DYT-TOR1A, THAP1, GCH1, SCA1/2/3/6/7/8/12/17, Friedreich's ataxia and FMR1 analysis was negative.F

Trio WES identified a dn splice site variant (c.981+1G>A) in the last exon-intron junction. RT-PCR followed by gel electrophoresis and Sanger in fibroblasts from an affected and control subject revealed that the proband had - as predicted by the type/location of the variant - in equal amount 2 cDNA products, a normal as well as a truncated one.

Sequencing of the shortest revealed utilization of a cryptic donor splice site upstream of the mutated donor leading to a 77bp out-of-frame deletion and introduction of a premature stop codon in the last codon (p.Lys303Serfs*28). Western blot in fibroblast cell lines revealed 2 bands corresponding to the normal protein product as well as to the p.Lys303Serfs*28 although expression of the latter was lower than that of the full length protein.

Several previous studies have shown that mutant CAMKIV species that lack the autoinhibitory domain are consitutively active (several Refs provided). Among others Chatila et al (1996, PMID: 8702940) studied an in vitro-engineered truncation mutant (Δ1-317 - truncation at position 317 of the protein) with functionally validated gain-of-function effect.

To prove enhanced activity of the splicing variant, Zech et al assessed phosphorylation of CREB (cyclic AMP-responsive element binding protein), a downstream substrate of CAMKIV. Immunobloting revealed significant increase of CREB phosphorylation in patient fibroblasts compared to controls. Overactivation of CAMKIV signaling was reversed when cells were treated with STO-609 an inhibitor of CAMKK, the ustream activator of CAMKIV.

Overall the authors demonstrated that loss of CAMKIV autoregulatory domain due to this splice variant had a gain-of-function effect.

----

Following trio-WES, Zech et al (2020 - PMID: 33098801) identified another relevant subject within cohort of 764 individuals with dystonia. This 12-y.o. male, harboring a different variant affecting the same donor site (c.981+1G>T), presented DD, ID, dystonia (onset at 3y) and additional movement disorders (myoclonus, ataxia) as well as similar behavior (ASD, autoaggression, stereotypies). [Details in suppl. p20].

----

Finally Zech et al (2020 - PMID: 33211350) reported on a 24-y.o. woman with adolescence onset choreodystonia. Other features included DD, moderate ID, absence seizures in infancy, OCD with anxiety and later diagnosis of ASD. Trio WES revealed a dn stopgain variant (c.940C>T; p.Gln314*).
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4002 CAMK4 Zornitza Stark Marked gene: CAMK4 as ready
Intellectual disability syndromic and non-syndromic v0.4002 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4002 CAMK4 Zornitza Stark Classified gene: CAMK4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4002 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4001 CAMK4 Konstantinos Varvagiannis gene: CAMK4 was added
gene: CAMK4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature,Other
Mode of inheritance for gene: CAMK4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350
Phenotypes for gene: CAMK4 were set to Global developmental delay; Intellectual disability; Autism; Behavioral abnormality; Abnormality of movement; Dystonia; Ataxia; Chorea; Myoclonus
Penetrance for gene: CAMK4 were set to Complete
Review for gene: CAMK4 was set to GREEN
Added comment: 3 publications by Zech et al (2018, 2020 - PMIDs : 30262571, 33098801, 33211350) provide clinical details on 3 individuals, each harboring a private de novo CAMK4 variant.

Overlapping features included DD, ID, behavoral issues, autism and abnormal hyperkinetic movements. Dystonia and chorea in all 3 appeared 3-20 years after initial symptoms.

CAMK4 encodes Calcium/Calmodulin-dependent protein kinase IV, an important mediator of calcium-mediated activity and dynamics, particularly in the brain. It is involved in neuronal transmission, synaptic plasticity, and neuronal gene expression required for brain development and neuronal homeostasis (summary by OMIM based on Zech et al, 2018).

The 473 aa enzyme has a protein kinase domain (aa 46-300) and a C-terminal autoregulatory domain (aa 305-341) the latter comprising an autoinhibitory domain (AID / aa 305-321) and a calmodulin-binding domain (CBD / aa 322-341) [NP_001735.1 / NM_001744.4 - also used below].

Variants in all 3 subjects were identified following trio-WES and were in all cases protein-truncating, mapping to exon 10 or exon 10-intron 10 junction, expected to escape NMD and cause selective abrogation of the autoinhibitory domain (aa 305-321) leading overall to gain-of-function.

Variation databases include pLoF CAMK4 variants albeit in all cases usptream or downstream of this region (pLI of this gene in gnomAD: 0.51). Variants leading to selective abrogation of the autoregulatory domain have not been reported.

Extensive evidence for the GoF effect of the variant has been provided in the first publication. Several previous studies have demonstrated that abrogation of the AID domain leads to consitutive activation (details below).

Mouse models - though corresponding to homozygous loss of function - support a role for CAMKIV in cognitive and motor symptoms. Null mice display tremulous and ataxic movements, deficiencies in balance and sensorimotor performance associated with reduced number of Purkinje neurons (Ribar et al 2000, PMID: 11069976 - not reviewed). Wei et al (2002, PMID: 12006982 - not reviewed) provided evidence for alteration in hippocampal physiology and memory function.

Heterozygous mutations in other genes for calcium/calmodulin-dependent protein kinases (CAMKs) e.g. CAMK2A/CAMK2B (encoding subunits of CAMKII) have been reported in individuals with ID.

---

The proband in the first publication (PMID: 30262571) was a male with DD, ID, behavioral difficulties (ASD, autoaggression, stereotypies) and hyperkinetic movement disorder (myoclonus, chorea, ataxia) with severe generalized dystonia (onset at the age of 13y). Brain MRI demonstrated cerebellar atrophy.

Extensive work-up incl. karyotyping, CMA, DYT-TOR1A, THAP1, GCH1, SCA1/2/3/6/7/8/12/17, Friedreich's ataxia and FMR1 analysis was negative.F

Trio WES identified a dn splice site variant (c.981+1G>A) in the last exon-intron junction. RT-PCR followed by gel electrophoresis and Sanger in fibroblasts from an affected and control subject revealed that the proband had - as predicted by the type/location of the variant - in equal amount 2 cDNA products, a normal as well as a truncated one.

Sequencing of the shortest revealed utilization of a cryptic donor splice site upstream of the mutated donor leading to a 77bp out-of-frame deletion and introduction of a premature stop codon in the last codon (p.Lys303Serfs*28). Western blot in fibroblast cell lines revealed 2 bands corresponding to the normal protein product as well as to the p.Lys303Serfs*28 although expression of the latter was lower than that of the full length protein.

Several previous studies have shown that mutant CAMKIV species that lack the autoinhibitory domain are consitutively active (several Refs provided). Among others Chatila et al (1996, PMID: 8702940) studied an in vitro-engineered truncation mutant (Δ1-317 - truncation at position 317 of the protein) with functionally validated gain-of-function effect.

To prove enhanced activity of the splicing variant, Zech et al assessed phosphorylation of CREB (cyclic AMP-responsive element binding protein), a downstream substrate of CAMKIV. Immunobloting revealed significant increase of CREB phosphorylation in patient fibroblasts compared to controls. Overactivation of CAMKIV signaling was reversed when cells were treated with STO-609 an inhibitor of CAMKK, the ustream activator of CAMKIV.

Overall the authors demonstrated that loss of CAMKIV autoregulatory domain due to this splice variant had a gain-of-function effect.

----

Following trio-WES, Zech et al (2020 - PMID: 33098801) identified another relevant subject within cohort of 764 individuals with dystonia. This 12-y.o. male, harboring a different variant affecting the same donor site (c.981+1G>T), presented DD, ID, dystonia (onset at 3y) and additional movement disorders (myoclonus, ataxia) as well as similar behavior (ASD, autoaggression, stereotypies). [Details in suppl. p20].

----

Finally Zech et al (2020 - PMID: 33211350) reported on a 24-y.o. woman with adolescence onset choreodystonia. Other features included DD, moderate ID, absence seizures in infancy, OCD with anxiety and later diagnosis of ASD. Trio WES revealed a dn stopgain variant (c.940C>T; p.Gln314*).

----

There is no associated phenotype in OMIM, G2P.

In SysID CAMK4 is listed among the current primary ID genes.

----

Please consider inclusion in other relevant panels.
Sources: Literature, Other
Mendeliome v0.8510 FERMT3 Zornitza Stark Marked gene: FERMT3 as ready
Mendeliome v0.8510 FERMT3 Zornitza Stark Gene: fermt3 has been classified as Green List (High Evidence).
Mendeliome v0.8510 FERMT3 Zornitza Stark Phenotypes for gene: FERMT3 were changed from to Leukocyte adhesion deficiency, type III, MIM# 612840
Mendeliome v0.8509 FERMT3 Zornitza Stark Publications for gene: FERMT3 were set to
Mendeliome v0.8508 FERMT3 Zornitza Stark Mode of inheritance for gene: FERMT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8507 FERMT3 Zornitza Stark reviewed gene: FERMT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234460, 19064721; Phenotypes: Leukocyte adhesion deficiency, type III, MIM# 612840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.90 FERMT3 Zornitza Stark Marked gene: FERMT3 as ready
Phagocyte Defects v0.90 FERMT3 Zornitza Stark Gene: fermt3 has been classified as Green List (High Evidence).
Phagocyte Defects v0.90 FERMT3 Zornitza Stark Phenotypes for gene: FERMT3 were changed from to Leukocyte adhesion deficiency, type III, MIM# 612840
Phagocyte Defects v0.89 FERMT3 Zornitza Stark Publications for gene: FERMT3 were set to
Phagocyte Defects v0.88 FERMT3 Zornitza Stark Mode of inheritance for gene: FERMT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.87 FERMT3 Zornitza Stark reviewed gene: FERMT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234460, 19064721; Phenotypes: Leukocyte adhesion deficiency, type III, MIM# 612840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8507 ELANE Zornitza Stark Phenotypes for gene: ELANE were changed from Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700 to Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700; Neutropaenia, cyclic, MIM# 162800
Mendeliome v0.8506 ELANE Zornitza Stark edited their review of gene: ELANE: Changed phenotypes: Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700, Neutropaenia, cyclic, MIM# 162800
Phagocyte Defects v0.87 ELANE Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association.

Severe congenital neutropaenia is a heterogeneous disorder of haematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. About 60% of affected individuals of European and Middle Eastern ancestry have dominant ELANE mutations.
Phagocyte Defects v0.87 ELANE Zornitza Stark Marked gene: ELANE as ready
Phagocyte Defects v0.87 ELANE Zornitza Stark Gene: elane has been classified as Green List (High Evidence).
Phagocyte Defects v0.87 ELANE Zornitza Stark Phenotypes for gene: ELANE were changed from to Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700; Neutropaenia, cyclic, MIM# 162800
Phagocyte Defects v0.86 ELANE Zornitza Stark Publications for gene: ELANE were set to
Phagocyte Defects v0.85 ELANE Zornitza Stark Mode of inheritance for gene: ELANE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phagocyte Defects v0.84 ELANE Zornitza Stark reviewed gene: ELANE: Rating: GREEN; Mode of pathogenicity: None; Publications: 10581030, 11001877; Phenotypes: Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700, Neutropaenia, cyclic, MIM# 162800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8506 CYBB Zornitza Stark Marked gene: CYBB as ready
Mendeliome v0.8506 CYBB Zornitza Stark Gene: cybb has been classified as Green List (High Evidence).
Mendeliome v0.8506 CYBB Zornitza Stark Phenotypes for gene: CYBB were changed from to Chronic granulomatous disease, X-linked, MIM# 306400
Mendeliome v0.8505 CYBB Zornitza Stark Publications for gene: CYBB were set to
Mendeliome v0.8504 CYBB Zornitza Stark Mode of inheritance for gene: CYBB was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8503 CYBB Zornitza Stark reviewed gene: CYBB: Rating: GREEN; Mode of pathogenicity: None; Publications: 2556453, 1710153, 9585602; Phenotypes: Chronic granulomatous disease, X-linked, MIM# 306400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phagocyte Defects v0.84 CYBB Zornitza Stark Marked gene: CYBB as ready
Phagocyte Defects v0.84 CYBB Zornitza Stark Gene: cybb has been classified as Green List (High Evidence).
Phagocyte Defects v0.84 CYBB Zornitza Stark Phenotypes for gene: CYBB were changed from to Chronic granulomatous disease, X-linked, MIM# 306400
Phagocyte Defects v0.83 CYBB Zornitza Stark Publications for gene: CYBB were set to
Phagocyte Defects v0.82 CYBB Zornitza Stark Mode of inheritance for gene: CYBB was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phagocyte Defects v0.81 CTSC Zornitza Stark Marked gene: CTSC as ready
Phagocyte Defects v0.81 CTSC Zornitza Stark Gene: ctsc has been classified as Green List (High Evidence).
Phagocyte Defects v0.81 CTSC Zornitza Stark Phenotypes for gene: CTSC were changed from to Papillon-Lefevre syndrome, MIM# 245000
Phagocyte Defects v0.80 CTSC Zornitza Stark Publications for gene: CTSC were set to
Phagocyte Defects v0.79 CTSC Zornitza Stark Mode of inheritance for gene: CTSC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.78 CTSC Zornitza Stark reviewed gene: CTSC: Rating: GREEN; Mode of pathogenicity: None; Publications: 25244098; Phenotypes: Papillon-Lefevre syndrome, MIM# 245000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.4 CSF3R Zornitza Stark Phenotypes for gene: CSF3R were changed from Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014 to Neutropaenia, severe congenital, 7, autosomal recessive, MIM# 617014
Mendeliome v0.8503 CSF3R Zornitza Stark Marked gene: CSF3R as ready
Mendeliome v0.8503 CSF3R Zornitza Stark Gene: csf3r has been classified as Green List (High Evidence).
Mendeliome v0.8503 CSF3R Zornitza Stark Phenotypes for gene: CSF3R were changed from Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014 to Neutropaenia, severe congenital, 7, autosomal recessive, MIM# 617014
Bone Marrow Failure v1.3 CSF3R Zornitza Stark Publications for gene: CSF3R were set to 24753537; 26324699
Mendeliome v0.8502 CSF3R Zornitza Stark Phenotypes for gene: CSF3R were changed from to Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014
Bone Marrow Failure v1.2 CSF3R Zornitza Stark edited their review of gene: CSF3R: Changed publications: 24753537, 26324699, 33511998, 32966608; Changed phenotypes: Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014
Mendeliome v0.8501 CSF3R Zornitza Stark Publications for gene: CSF3R were set to
Mendeliome v0.8500 CSF3R Zornitza Stark Mode of inheritance for gene: CSF3R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8499 CSF3R Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: More than 5 unrelated families reported. Some reports of progression to myelodysplasia.
Mendeliome v0.8499 CSF3R Zornitza Stark reviewed gene: CSF3R: Rating: GREEN; Mode of pathogenicity: None; Publications: 24753537, 26324699, 33511998, 32966608; Phenotypes: Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.2 CSF3R Zornitza Stark changed review comment from: Three unrelated families reported.
Sources: Expert list; to: At least 5 unrelated families reported. Some reports of progression to myelodysplasia.
Sources: Expert list
Phagocyte Defects v0.78 CSF3R Zornitza Stark Marked gene: CSF3R as ready
Phagocyte Defects v0.78 CSF3R Zornitza Stark Gene: csf3r has been classified as Green List (High Evidence).
Phagocyte Defects v0.78 CSF3R Zornitza Stark Phenotypes for gene: CSF3R were changed from to Neutropaenia, severe congenital, 7, autosomal recessive, MIM# 617014
Phagocyte Defects v0.77 CSF3R Zornitza Stark Publications for gene: CSF3R were set to
Phagocyte Defects v0.76 CSF3R Zornitza Stark Mode of inheritance for gene: CSF3R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.75 CSF3R Zornitza Stark reviewed gene: CSF3R: Rating: GREEN; Mode of pathogenicity: None; Publications: 24753537, 26324699, 33511998, 32966608; Phenotypes: Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8499 NUAK2 Zornitza Stark Phenotypes for gene: NUAK2 were changed from Anencephaly to Anencephaly 2, MIM# 619452
Mendeliome v0.8498 NUAK2 Zornitza Stark Deleted their comment
Mendeliome v0.8498 NUAK2 Zornitza Stark edited their review of gene: NUAK2: Changed phenotypes: Anencephaly 2, MIM# 619452
Susceptibility to Viral Infections v0.77 DBR1 Zornitza Stark Phenotypes for gene: DBR1 were changed from Viral infections of the brainstem to {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441; Viral infections of the brainstem
Susceptibility to Viral Infections v0.76 DBR1 Zornitza Stark edited their review of gene: DBR1: Changed phenotypes: {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441, Viral infections of the brainstem
Mendeliome v0.8498 DBR1 Zornitza Stark Phenotypes for gene: DBR1 were changed from Viral infections of the brainstem to {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441; Viral infections of the brainstem
Mendeliome v0.8497 DBR1 Zornitza Stark edited their review of gene: DBR1: Changed phenotypes: {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441, Viral infections of the brainstem
Intellectual disability syndromic and non-syndromic v0.4001 DPYSL5 Zornitza Stark Phenotypes for gene: DPYSL5 were changed from Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities to Ritscher-Schinzel syndrome 4, MIM# 619435; Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Intellectual disability syndromic and non-syndromic v0.4000 DPYSL5 Zornitza Stark edited their review of gene: DPYSL5: Changed phenotypes: Ritscher-Schinzel syndrome 4, MIM# 619435, Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Callosome v0.307 DPYSL5 Zornitza Stark Phenotypes for gene: DPYSL5 were changed from Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities to Ritscher-Schinzel syndrome 4, MIM# 619435; Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Callosome v0.306 DPYSL5 Zornitza Stark edited their review of gene: DPYSL5: Changed phenotypes: Ritscher-Schinzel syndrome 4, MIM# 619435, Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Mendeliome v0.8497 DPYSL5 Zornitza Stark Phenotypes for gene: DPYSL5 were changed from Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities to Ritscher-Schinzel syndrome 4, MIM# 619435; Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Mendeliome v0.8496 DPYSL5 Zornitza Stark reviewed gene: DPYSL5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ritscher-Schinzel syndrome 4, MIM# 619435; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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
Mendeliome v0.8496 RRP7A Zornitza Stark Phenotypes for gene: RRP7A were changed from Microcephaly to Microcephaly 28, primary, autosomal recessive MIM#619453
Mendeliome v0.8495 RRP7A Zornitza Stark edited their review of gene: RRP7A: Changed phenotypes: Microcephaly 28, primary, autosomal recessive MIM#619453
Phagocyte Defects v0.75 CYBA Zornitza Stark Marked gene: CYBA as ready
Phagocyte Defects v0.75 CYBA Zornitza Stark Gene: cyba has been classified as Green List (High Evidence).
Phagocyte Defects v0.75 CYBA Zornitza Stark Phenotypes for gene: CYBA were changed from to Chronic granulomatous disease 4, autosomal recessive, MIM# 233690; MONDO:0009308
Phagocyte Defects v0.74 CYBA Zornitza Stark Publications for gene: CYBA were set to
Phagocyte Defects v0.73 CYBA Zornitza Stark Mode of inheritance for gene: CYBA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8495 CEBPE Zornitza Stark Marked gene: CEBPE as ready
Mendeliome v0.8495 CEBPE Zornitza Stark Gene: cebpe has been classified as Green List (High Evidence).
Phagocyte Defects v0.72 CEBPE Zornitza Stark Marked gene: CEBPE as ready
Phagocyte Defects v0.72 CEBPE Zornitza Stark Gene: cebpe has been classified as Green List (High Evidence).
Phagocyte Defects v0.72 CEBPE Zornitza Stark Phenotypes for gene: CEBPE were changed from Specific granule deficiency, MIM# 245480 to Specific granule deficiency, MIM# 245480
Phagocyte Defects v0.71 CEBPE Zornitza Stark Phenotypes for gene: CEBPE were changed from Specific granule deficiency, MIM# 245480 to Specific granule deficiency, MIM# 245480
Mendeliome v0.8495 CEBPE Zornitza Stark Phenotypes for gene: CEBPE were changed from to Specific granule deficiency, MIM# 245480
Phagocyte Defects v0.71 CEBPE Zornitza Stark Phenotypes for gene: CEBPE were changed from to Specific granule deficiency, MIM# 245480
Mendeliome v0.8494 CEBPE Zornitza Stark Publications for gene: CEBPE were set to
Mendeliome v0.8493 CEBPE Zornitza Stark Mode of inheritance for gene: CEBPE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.70 CEBPE Zornitza Stark Publications for gene: CEBPE were set to
Mendeliome v0.8492 CEBPE Zornitza Stark reviewed gene: CEBPE: Rating: GREEN; Mode of pathogenicity: None; Publications: 10359588, 11313242, 31256937, 29651288; Phenotypes: Specific granule deficiency, MIM# 245480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.69 CEBPE Zornitza Stark Mode of inheritance for gene: CEBPE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v0.68 CEBPE Zornitza Stark reviewed gene: CEBPE: Rating: GREEN; Mode of pathogenicity: None; Publications: 10359588, 11313242, 31256937, 29651288; Phenotypes: Specific granule deficiency, MIM# 245480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Chronic granulomatous disease v1.0 Zornitza Stark promoted panel to version 1.0
Chronic granulomatous disease v0.18 G6PD Zornitza Stark Marked gene: G6PD as ready
Chronic granulomatous disease v0.18 G6PD Zornitza Stark Gene: g6pd has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.18 G6PD Zornitza Stark Publications for gene: G6PD were set to
Chronic granulomatous disease v0.17 G6PD Zornitza Stark reviewed gene: G6PD: Rating: GREEN; Mode of pathogenicity: None; Publications: 34175765, 27458052; Phenotypes: Haemolytic anemia, G6PD deficient (favism), MIM# 300908; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Chronic granulomatous disease v0.17 C17orf62 Zornitza Stark Marked gene: C17orf62 as ready
Chronic granulomatous disease v0.17 C17orf62 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name: CYBC1
Chronic granulomatous disease v0.17 C17orf62 Zornitza Stark Gene: c17orf62 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.17 C17orf62 Zornitza Stark Tag new gene name tag was added to gene: C17orf62.
Chronic granulomatous disease v0.17 NCF2 Zornitza Stark Marked gene: NCF2 as ready
Chronic granulomatous disease v0.17 NCF2 Zornitza Stark Gene: ncf2 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.17 NCF2 Zornitza Stark Publications for gene: NCF2 were set to
Chronic granulomatous disease v0.16 NCF2 Zornitza Stark reviewed gene: NCF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7795241, 10498624; Phenotypes: Chronic granulomatous disease 2, autosomal recessive, MIM# 233710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Chronic granulomatous disease v0.16 CYBB Zornitza Stark Marked gene: CYBB as ready
Chronic granulomatous disease v0.16 CYBB Zornitza Stark Gene: cybb has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.16 CYBB Zornitza Stark Publications for gene: CYBB were set to
Chronic granulomatous disease v0.15 CYBB Zornitza Stark reviewed gene: CYBB: Rating: GREEN; Mode of pathogenicity: None; Publications: 2556453, 1710153, 9585602; Phenotypes: Chronic granulomatous disease, X-linked, MIM# 306400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mackenzie's Mission_Reproductive Carrier Screening v0.102 GK Sarah Righetti reviewed gene: GK: Rating: RED; Mode of pathogenicity: None; Publications: 8651297, 9719371; Phenotypes: Glycerol kinase deficiency, MIM# 307030; Mode of inheritance: None
Mackenzie's Mission_Reproductive Carrier Screening v0.102 SAMD9 Sarah Righetti reviewed gene: SAMD9: Rating: AMBER; Mode of pathogenicity: None; Publications: 16960814, 18094730; Phenotypes: Tumoral calcinosis, familial, normophosphatemic, MIM# 610455; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.102 FTCD Sarah Righetti reviewed gene: FTCD: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 5956503, 5897668, 4413489, 29178637; Phenotypes: Glutamate formiminotransferase deficiency MIM#229100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8492 NCF1 Zornitza Stark Marked gene: NCF1 as ready
Mendeliome v0.8492 NCF1 Zornitza Stark Gene: ncf1 has been classified as Green List (High Evidence).
Mendeliome v0.8492 NCF1 Zornitza Stark Phenotypes for gene: NCF1 were changed from to Chronic granulomatous disease 1, autosomal recessive, MIM# 233700
Mendeliome v0.8491 NCF1 Zornitza Stark Publications for gene: NCF1 were set to
Mendeliome v0.8490 NCF1 Zornitza Stark Mode of inheritance for gene: NCF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8489 NCF1 Zornitza Stark reviewed gene: NCF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 2011585, 11133775, 10706888, 16972229, 16972229; Phenotypes: Chronic granulomatous disease 1, autosomal recessive, MIM# 233700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Chronic granulomatous disease v0.15 NCF1 Zornitza Stark Marked gene: NCF1 as ready
Chronic granulomatous disease v0.15 NCF1 Zornitza Stark Gene: ncf1 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.15 NCF1 Zornitza Stark Phenotypes for gene: NCF1 were changed from Chronic granulomatous disease due to deficiency of NCF-1 MIM#233700 to Chronic granulomatous disease 1, autosomal recessive, MIM# 233700
Chronic granulomatous disease v0.14 NCF1 Zornitza Stark Publications for gene: NCF1 were set to
Chronic granulomatous disease v0.13 NCF1 Zornitza Stark reviewed gene: NCF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 2011585, 11133775, 10706888, 16972229, 16972229; Phenotypes: Chronic granulomatous disease 1, autosomal recessive, MIM# 233700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8489 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to 25500261; 26486031
Mendeliome v0.8488 COL25A1 Zornitza Stark Classified gene: COL25A1 as Green List (high evidence)
Mendeliome v0.8488 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Green List (High Evidence).
Mendeliome v0.8487 COL25A1 Zornitza Stark edited their review of gene: COL25A1: Added comment: PMID: 2643702 - Patient: 273182 reported in DECIPHER, chet COL25A1 missense variants (listed as Likely Pathogenic). Phenotype includes Duane anomaly of the eye.

PMID: 31875546 - Mouse models, including Col25a1 KO and muscle-specific KO mice showed a significant reduction in the number of motor neurons in the cranial nerve nuclei, including the oculomotor, trochlear, trigeminal, and facial motor nuclei. Abnormalities in motor innervation of muscles of the head, such as the extraocular and masseter muscles, were also observed

PMID: 31875546 - Functional studies in human cell lines showed that the reported COL25A1 variants (G382R and G497X) impaired the interaction of COL25A1 with receptor protein tyrosine phosphatases, thereby reducing the ability to attract motor axons.; Changed rating: GREEN; Changed publications: 25500261, 26486031, 31875546, 26437029
Congenital ophthalmoplegia v1.4 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to 25500261; 26486031
Congenital ophthalmoplegia v1.3 COL25A1 Zornitza Stark Classified gene: COL25A1 as Green List (high evidence)
Congenital ophthalmoplegia v1.3 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v1.2 COL25A1 Melanie Marty reviewed gene: COL25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25500261, 26486031, 31875546, 26437029; Phenotypes: Fibrosis of extraocular muscles, congenital, 5, 610004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4000 LTBP1 Zornitza Stark Marked gene: LTBP1 as ready
Intellectual disability syndromic and non-syndromic v0.4000 LTBP1 Zornitza Stark Gene: ltbp1 has been classified as Green List (High Evidence).
Cutis Laxa v0.8 LTBP1 Zornitza Stark Phenotypes for gene: LTBP1 were changed from cutis laxa syndrome to Cutis laxa, autosomal recessive, type IIE MIM#619451
Intellectual disability syndromic and non-syndromic v0.4000 LTBP1 Zornitza Stark Phenotypes for gene: LTBP1 were changed from cutis laxa syndrome to Cutis laxa, autosomal recessive, type IIE MIM#619451
Mendeliome v0.8487 LTBP1 Zornitza Stark Phenotypes for gene: LTBP1 were changed from cutis laxa syndrome to Cutis laxa, autosomal recessive, type IIE MIM#619451
Craniosynostosis v1.24 LTBP1 Zornitza Stark Phenotypes for gene: LTBP1 were changed from cutis laxa syndrome to Cutis laxa, autosomal recessive, type IIE MIM#619451
Aortopathy_Connective Tissue Disorders v1.41 LTBP1 Zornitza Stark Phenotypes for gene: LTBP1 were changed from cutis laxa syndrome to Cutis laxa, autosomal recessive, type IIE MIM#619451
Aortopathy_Connective Tissue Disorders v1.40 LTBP1 Zornitza Stark edited their review of gene: LTBP1: Changed phenotypes: cutis laxa, autosomal recessive, type IIE MIM#619451
Syndromic Retinopathy v0.178 STX3 Zornitza Stark Marked gene: STX3 as ready
Syndromic Retinopathy v0.178 STX3 Zornitza Stark Gene: stx3 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.178 STX3 Zornitza Stark Phenotypes for gene: STX3 were changed from Microvillus inclusion disease, MIM#619445; Retinal dystrophy and microvillus inclusion disease, MIM#619446 to Retinal dystrophy and microvillus inclusion disease, MIM#619446
Syndromic Retinopathy v0.177 STX3 Zornitza Stark Classified gene: STX3 as Green List (high evidence)
Syndromic Retinopathy v0.177 STX3 Zornitza Stark Gene: stx3 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.176 STX3 Zornitza Stark edited their review of gene: STX3: Changed phenotypes: Retinal dystrophy and microvillus inclusion disease, MIM#619446
Syndromic Retinopathy v0.176 STX3 Zornitza Stark gene: STX3 was added
gene: STX3 was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: STX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STX3 were set to 24726755; 29266534; 25358429; 29282386; 30909251; 29282386
Phenotypes for gene: STX3 were set to Microvillus inclusion disease, MIM#619445; Retinal dystrophy and microvillus inclusion disease, MIM#619446
Review for gene: STX3 was set to GREEN
Added comment: At least 5 unrelated families reported. STX3 isoform B (STX3B) predominates in the retina, so mutations in the STX3 gene that affect both isoform A (STX3A) and STX3B cause both retinal and gastrointestinal disease (RDMVID), whereas mutations in STX3 affecting only the STX3A transcript cause only diarrhoea.
Sources: Expert Review
Mendeliome v0.8486 STX3 Zornitza Stark Phenotypes for gene: STX3 were changed from Microvillus inclusion disease, MIM#619445 to Microvillus inclusion disease, MIM#619445; Retinal dystrophy and microvillus inclusion disease, MIM#619446
Mendeliome v0.8485 STX3 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 5 unrelated families reported.

STX3 isoform B (STX3B) predominates in the retina, so mutations in the STX3 gene that affect both isoform A (STX3A) and STX3B cause both retinal and gastrointestinal disease (RDMVID), whereas mutations in STX3 affecting only the STX3A transcript cause only diarrhoea.
Congenital Diarrhoea v1.5 STX3 Zornitza Stark Phenotypes for gene: STX3 were changed from Microvillus inclusion disease, MIM#619445 to Microvillus inclusion disease, MIM#619445; Retinal dystrophy and microvillus inclusion disease, MIM#619446
Mendeliome v0.8485 STX3 Zornitza Stark edited their review of gene: STX3: Changed phenotypes: Microvillus inclusion disease, MIM#619445, Retinal dystrophy and microvillus inclusion disease, MIM#619446
Congenital Diarrhoea v1.4 STX3 Zornitza Stark edited their review of gene: STX3: Changed phenotypes: Microvillus inclusion disease, MIM#619445, Retinal dystrophy and microvillus inclusion disease, MIM#619446
Congenital Diarrhoea v1.4 STX3 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 5 unrelated families reported.

STX3 isoform B (STX3B) predominates in the retina, so mutations in the STX3 gene that affect both isoform A (STX3A) and STX3B cause both retinal and gastrointestinal disease (RDMVID), whereas mutations in STX3 affecting only the STX3A transcript cause only diarrhoea.
Mendeliome v0.8485 STX3 Zornitza Stark Phenotypes for gene: STX3 were changed from Microvillus inclusion disease to Microvillus inclusion disease, MIM#619445
Mendeliome v0.8484 STX3 Zornitza Stark edited their review of gene: STX3: Changed phenotypes: Microvillus inclusion disease, MIM#619445
Congenital Diarrhoea v1.4 STX3 Zornitza Stark Phenotypes for gene: STX3 were changed from Microvillus inclusion disease to Microvillus inclusion disease, MIM#619445
Congenital Diarrhoea v1.3 STX3 Zornitza Stark edited their review of gene: STX3: Changed phenotypes: Microvillus inclusion disease, MIM#619445
Complement Deficiencies v0.43 C1QB Zornitza Stark Marked gene: C1QB as ready
Complement Deficiencies v0.43 C1QB Zornitza Stark Gene: c1qb has been classified as Green List (High Evidence).
Complement Deficiencies v0.43 C1QB Zornitza Stark Phenotypes for gene: C1QB were changed from to C1q deficiency, MIM# 613652
Complement Deficiencies v0.42 C1QB Zornitza Stark Publications for gene: C1QB were set to 2894352; 17513176
Complement Deficiencies v0.42 C1QB Zornitza Stark Publications for gene: C1QB were set to
Complement Deficiencies v0.41 C1QB Zornitza Stark Mode of inheritance for gene: C1QB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v0.40 C1QB Zornitza Stark reviewed gene: C1QB: Rating: GREEN; Mode of pathogenicity: None; Publications: 2894352, 17513176; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8484 C1QA Zornitza Stark Marked gene: C1QA as ready
Mendeliome v0.8484 C1QA Zornitza Stark Gene: c1qa has been classified as Green List (High Evidence).
Mendeliome v0.8484 C1QA Zornitza Stark Phenotypes for gene: C1QA were changed from to C1q deficiency, MIM# 613652
Mendeliome v0.8483 C1QA Zornitza Stark Publications for gene: C1QA were set to
Mendeliome v0.8482 C1QA Zornitza Stark Mode of inheritance for gene: C1QA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8481 C1QA Zornitza Stark reviewed gene: C1QA: Rating: GREEN; Mode of pathogenicity: None; Publications: 9225968, 21654842, 9590289; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v0.40 C1QA Zornitza Stark Marked gene: C1QA as ready
Complement Deficiencies v0.40 C1QA Zornitza Stark Gene: c1qa has been classified as Green List (High Evidence).
Complement Deficiencies v0.40 C1QA Zornitza Stark Phenotypes for gene: C1QA were changed from to C1q deficiency, MIM# 613652
Complement Deficiencies v0.39 C1QA Zornitza Stark Publications for gene: C1QA were set to
Complement Deficiencies v0.38 C1QA Zornitza Stark Mode of inheritance for gene: C1QA was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v0.37 C1QA Zornitza Stark Mode of inheritance for gene: C1QA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v0.36 C1QA Zornitza Stark reviewed gene: C1QA: Rating: GREEN; Mode of pathogenicity: None; Publications: 9225968, 21654842, 9590289; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.232 DKC1 Zornitza Stark Marked gene: DKC1 as ready
Combined Immunodeficiency v0.232 DKC1 Zornitza Stark Gene: dkc1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.232 DKC1 Zornitza Stark Phenotypes for gene: DKC1 were changed from to Dyskeratosis congenita, X-linked MIM# 305000; Bone marrow failure, pulmonary & hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, immunodeficiency; aplastic anaemia; thrombocytopaenia; neurodevelopmental delay; cerebellar hypoplasia; opportunistic infections
Mendeliome v0.8481 CIITA Zornitza Stark Marked gene: CIITA as ready
Mendeliome v0.8481 CIITA Zornitza Stark Gene: ciita has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.231 DKC1 Zornitza Stark Publications for gene: DKC1 were set to
Mendeliome v0.8481 CIITA Zornitza Stark Phenotypes for gene: CIITA were changed from to Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920; varied ID; bronchiolitis; pneumonia; severe autoimmune cytopaenia; CD4 T-cell lymphopaenia; hypogammaglobulinemia; absence of antigen-induced immune response; chronic diarrhoea; recurrent respiratory infections; recurrent gastroenteritis; failure to thrive; liver/biliary tract disease
Combined Immunodeficiency v0.230 DKC1 Zornitza Stark Mode of inheritance for gene: DKC1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8480 CIITA Zornitza Stark Publications for gene: CIITA were set to
Combined Immunodeficiency v0.229 CIITA Zornitza Stark Marked gene: CIITA as ready
Combined Immunodeficiency v0.229 CIITA Zornitza Stark Gene: ciita has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.229 DKC1 Danielle Ariti changed review comment from: More than 20 affected unrelated individuals have been reported; multiple mouse models.

Heterozygous non-frameshift deletion variants and missense variants have been identified in DKC1 in these individuals, including the most common p.Ala353Val.

Typically presents with abnormal skin pigmentation, nail dystrophy, oral leukoplakia, bone marrow failure and immunodeficiencies.

PMID: 9663235 (1998) partial expression in heterozygous females displayed early pigmentary skin changes; to: More than 20 affected unrelated individuals have been reported; multiple mouse models.

Heterozygous deletion variants and missense variants have been identified in DKC1 in these individuals, including the most common p.Ala353Val.

Typically presents with abnormal skin pigmentation, nail dystrophy, oral leukoplakia, bone marrow failure and immunodeficiencies.

PMID: 9663235 (1998) partial expression in heterozygous females displayed early pigmentary skin changes
Mendeliome v0.8479 CIITA Zornitza Stark Mode of inheritance for gene: CIITA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.229 CIITA Zornitza Stark Phenotypes for gene: CIITA were changed from to Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920; varied ID; bronchiolitis; pneumonia; severe autoimmune cytopaenia; CD4 T-cell lymphopaenia; hypogammaglobulinemia; absence of antigen-induced immune response; chronic diarrhoea; recurrent respiratory infections; recurrent gastroenteritis; failure to thrive; liver/biliary tract disease
Mendeliome v0.8478 CIITA Zornitza Stark reviewed gene: CIITA: Rating: GREEN; Mode of pathogenicity: None; Publications: 8402893, 9099848, 11862382, 28676232, 24789686, 20197681, 11466404, 15821736, 12910265; Phenotypes: Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920, varied ID, bronchiolitis, pneumonia, severe autoimmune cytopaenia, CD4 T-cell lymphopaenia, hypogammaglobulinemia, absence of antigen-induced immune response, chronic diarrhoea, recurrent respiratory infections, recurrent gastroenteritis, failure to thrive, liver/biliary tract disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.228 CIITA Zornitza Stark Publications for gene: CIITA were set to
Combined Immunodeficiency v0.227 CIITA Zornitza Stark Mode of inheritance for gene: CIITA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8478 CD40LG Zornitza Stark Marked gene: CD40LG as ready
Mendeliome v0.8478 CD40LG Zornitza Stark Gene: cd40lg has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.226 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Combined Immunodeficiency v0.226 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.226 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from to CHARGE syndrome MIM# 214800; Hypogonadotropic hypogonadism 5 with or without anosmia MIM# 612370; Kallmann syndrome; hypogonadotropic hypogonadism with or without anosmia (HH); Coloboma of the eye; heart anomaly; choanal atresia; intellectual disability; genital and ear anomalies, Deafness; Delayed pubertal development; CNS malformation; Cleft lip; SCID-like features; lymphopaenia; sever T-cell deficiency; hypogammaglobulinaemia
Combined Immunodeficiency v0.225 CHD7 Zornitza Stark Publications for gene: CHD7 were set to
Combined Immunodeficiency v0.224 CHD7 Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8478 CD40LG Zornitza Stark Phenotypes for gene: CD40LG were changed from to Immunodeficiency, X-linked, with hyper-IgM MIM# 308230; Severe opportunistic infections (recurrent), idiopathic neutropaenia; dysgammaglobulinaemia hepatitis; cholangitis; cholangiocarcinoma; autoimmune blood cytopenias; haemolytic anaemia; thrombocytopaenia; diarrhoea; peripheral neuroectodermal tumours
Combined Immunodeficiency v0.223 CD40LG Zornitza Stark Marked gene: CD40LG as ready
Combined Immunodeficiency v0.223 CD40LG Zornitza Stark Gene: cd40lg has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.223 CD40LG Zornitza Stark Phenotypes for gene: CD40LG were changed from Immunodeficiency, X-linked, with hyper-IgM MIM# 308230; Severe opportunistic infections (recurrent), idiopathic neutropaenia; dysgammaglobulinaemia hepatitis; cholangitis; cholangiocarcinoma; autoimmune blood cytopenias; haemolytic anaemia; thrombocytopaenia; diarrhoea; peripheral neuroectodermal tumours to Immunodeficiency, X-linked, with hyper-IgM MIM# 308230; Severe opportunistic infections (recurrent), idiopathic neutropaenia; dysgammaglobulinaemia hepatitis; cholangitis; cholangiocarcinoma; autoimmune blood cytopenias; haemolytic anaemia; thrombocytopaenia; diarrhoea; peripheral neuroectodermal tumours
Combined Immunodeficiency v0.223 CD40LG Zornitza Stark Phenotypes for gene: CD40LG were changed from to Immunodeficiency, X-linked, with hyper-IgM MIM# 308230; Severe opportunistic infections (recurrent), idiopathic neutropaenia; dysgammaglobulinaemia hepatitis; cholangitis; cholangiocarcinoma; autoimmune blood cytopenias; haemolytic anaemia; thrombocytopaenia; diarrhoea; peripheral neuroectodermal tumours
Mendeliome v0.8477 CD40LG Zornitza Stark Publications for gene: CD40LG were set to
Mendeliome v0.8476 CD40LG Zornitza Stark Mode of inheritance for gene: CD40LG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Combined Immunodeficiency v0.222 CD40LG Zornitza Stark Publications for gene: CD40LG were set to
Combined Immunodeficiency v0.221 CD40LG Zornitza Stark Mode of inheritance for gene: CD40LG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8475 CD3G Zornitza Stark Marked gene: CD3G as ready
Mendeliome v0.8475 CD3G Zornitza Stark Gene: cd3g has been classified as Green List (High Evidence).
Mendeliome v0.8475 CD3G Zornitza Stark Phenotypes for gene: CD3G were changed from to Immunodeficiency 17, CD3 gamma deficient MIM# 615607; immune deficiency; autoimmunity; failure to thrive; recurrent gastrointestinal infections; recurrent respiratory infections; autoimmune haemolytic anaemia; bronchiolitis obliterans; low CD3 complex; partial T lymphocytopenia; intractable diarrhoea.
Combined Immunodeficiency v0.220 CD3G Zornitza Stark Marked gene: CD3G as ready
Combined Immunodeficiency v0.220 CD3G Zornitza Stark Gene: cd3g has been classified as Green List (High Evidence).
Mendeliome v0.8474 CD3G Zornitza Stark Publications for gene: CD3G were set to
Mendeliome v0.8473 CD3G Zornitza Stark Mode of inheritance for gene: CD3G was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.220 CD3G Zornitza Stark Phenotypes for gene: CD3G were changed from Immunodeficiency 17; CD3 gamma deficient MIM# 615607; immune deficiency; autoimmunity; failure to thrive; recurrent gastrointestinal infections; recurrent respiratory infections; autoimmune haemolytic anaemia; Bronchiolitis obliterans; low CD3 complex; partial T lymphocytopenia; intractable diarrhoea. to Immunodeficiency 17, CD3 gamma deficient MIM# 615607; immune deficiency; autoimmunity; failure to thrive; recurrent gastrointestinal infections; recurrent respiratory infections; autoimmune haemolytic anaemia; Bronchiolitis obliterans; low CD3 complex; partial T lymphocytopenia; intractable diarrhoea.
Combined Immunodeficiency v0.219 CD3G Zornitza Stark Phenotypes for gene: CD3G were changed from to Immunodeficiency 17; CD3 gamma deficient MIM# 615607; immune deficiency; autoimmunity; failure to thrive; recurrent gastrointestinal infections; recurrent respiratory infections; autoimmune haemolytic anaemia; Bronchiolitis obliterans; low CD3 complex; partial T lymphocytopenia; intractable diarrhoea.
Combined Immunodeficiency v0.218 CD3G Zornitza Stark Publications for gene: CD3G were set to
Combined Immunodeficiency v0.217 CD3G Zornitza Stark Mode of inheritance for gene: CD3G was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.216 DKC1 Danielle Ariti reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9590285, 24914498, 22664374, 10700698, 21931702, 15842668, 12400016, 15240872, 9663235; Phenotypes: Dyskeratosis congenita, X-linked MIM# 305000, Bone marrow failure, pulmonary & hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation, microcephaly, immunodeficiency, aplastic anaemia, thrombocytopaenia, neurodevelopmental delay, cerebellar hypoplasia, opportunistic infections; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Combined Immunodeficiency v0.216 CIITA Danielle Ariti reviewed gene: CIITA: Rating: GREEN; Mode of pathogenicity: None; Publications: 8402893, 9099848, 11862382, 28676232, 24789686, 20197681, 11466404, 15821736, 12910265; Phenotypes: Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920, varied ID, bronchiolitis, pneumonia, severe autoimmune cytopaenia, CD4 T-cell lymphopaenia, hypogammaglobulinemia, absence of antigen-induced immune response, chronic diarrhoea, recurrent respiratory infections, recurrent gastroenteritis, failure to thrive, liver/biliary tract disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8472 WDR26 Zornitza Stark Marked gene: WDR26 as ready
Mendeliome v0.8472 WDR26 Zornitza Stark Gene: wdr26 has been classified as Green List (High Evidence).
Mendeliome v0.8472 WDR26 Zornitza Stark Mode of inheritance for gene: WDR26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8471 WDR26 Zornitza Stark Publications for gene: WDR26 were set to
Mendeliome v0.8470 WDR26 Zornitza Stark Phenotypes for gene: WDR26 were changed from to Skraban-Deardorff syndrome, MIM#617616
Intellectual disability syndromic and non-syndromic v0.3999 WDR26 Zornitza Stark Marked gene: WDR26 as ready
Intellectual disability syndromic and non-syndromic v0.3999 WDR26 Zornitza Stark Gene: wdr26 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3999 WDR26 Zornitza Stark Phenotypes for gene: WDR26 were changed from to Skraban-Deardorff syndrome, MIM#617616
Intellectual disability syndromic and non-syndromic v0.3998 WDR26 Zornitza Stark Publications for gene: WDR26 were set to
Intellectual disability syndromic and non-syndromic v0.3997 WDR26 Zornitza Stark Mode of inheritance for gene: WDR26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3996 DDB1 Zornitza Stark Phenotypes for gene: DDB1 were changed from Syndromic intellectual disability to White-Kernohan syndrome, MIM# 619426; Syndromic intellectual disability
Intellectual disability syndromic and non-syndromic v0.3995 DDB1 Zornitza Stark edited their review of gene: DDB1: Changed phenotypes: White-Kernohan syndrome, MIM# 619426, Syndromic intellectual disability
Mendeliome v0.8469 DDB1 Zornitza Stark Phenotypes for gene: DDB1 were changed from Syndromic intellectual disability to White-Kernohan syndrome, MIM# 619426; Syndromic intellectual disability
Mendeliome v0.8468 DDB1 Zornitza Stark edited their review of gene: DDB1: Changed phenotypes: White-Kernohan syndrome, MIM# 619426, Syndromic intellectual disability
Vascular Malformations_Germline v1.3 GPAA1 Bryony Thompson Marked gene: GPAA1 as ready
Vascular Malformations_Germline v1.3 GPAA1 Bryony Thompson Gene: gpaa1 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v1.3 GPAA1 Bryony Thompson Classified gene: GPAA1 as Amber List (moderate evidence)
Vascular Malformations_Germline v1.3 GPAA1 Bryony Thompson Gene: gpaa1 has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v1.2 GPAA1 Bryony Thompson gene: GPAA1 was added
gene: GPAA1 was added to Vascular Malformations_Germline. Sources: Literature
Mode of inheritance for gene: GPAA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPAA1 were set to 32533362
Phenotypes for gene: GPAA1 were set to Vascular anomalies
Review for gene: GPAA1 was set to AMBER
Added comment: A single family identified with a GPAA1 missense (c.968A > G; p.Asn323Ser) segregating in 4 affected individuals and not among 6 unaffected individuals. Also, supporting in vitro functional assays for the variant impacting function and a gpaa1-deficient zebrafish model displaying several types of developmental defects as well as vascular dysplasia.
Sources: Literature
Combined Immunodeficiency v0.216 CHD7 Danielle Ariti reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 15300250, 26551301, 26538304, 20186815, 17334657; Phenotypes: CHARGE syndrome MIM# 214800, Hypogonadotropic hypogonadism 5 with or without anosmia MIM# 612370, Kallmann syndrome, hypogonadotropic hypogonadism with or without anosmia (HH), Coloboma of the eye, heart anomaly, choanal atresia, intellectual disability, genital and ear anomalies, Deafness, Delayed pubertal development, CNS malformation, Cleft lip, SCID-like features, lymphopaenia, sever T-cell deficiency, hypogammaglobulinaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8468 CD40LG Danielle Ariti reviewed gene: CD40LG: Rating: GREEN; Mode of pathogenicity: None; Publications: 7679801, 7679206, 8094231, 9933119, 15358621, 15997875, 7678782, 7915248, 15367912, 7518839, 16311023, 9933119, 12402041, 7882172, 33475257; Phenotypes: mmunodeficiency, X-linked, with hyper-IgM MIM# 308230, Severe opportunistic infections (recurrent), idiopathic neutropaenia, dysgammaglobulinaemia hepatitis, cholangitis, cholangiocarcinoma, autoimmune blood cytopenias, haemolytic anaemia, thrombocytopaenia, diarrhoea, peripheral neuroectodermal tumours; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Combined Immunodeficiency v0.216 CD40LG Danielle Ariti reviewed gene: CD40LG: Rating: GREEN; Mode of pathogenicity: None; Publications: 7679801, 7679206, 8094231, 9933119, 15358621, 15997875, 7678782, 7915248, 15367912, 7518839, 16311023, 9933119, 12402041, 7882172, 33475257; Phenotypes: Immunodeficiency, X-linked, with hyper-IgM MIM# 308230, Severe opportunistic infections (recurrent), idiopathic neutropaenia, dysgammaglobulinaemia hepatitis, cholangitis, cholangiocarcinoma, autoimmune blood cytopenias, haemolytic anaemia, thrombocytopaenia, diarrhoea, peripheral neuroectodermal tumours; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8468 CD3G Danielle Ariti reviewed gene: CD3G: Rating: GREEN; Mode of pathogenicity: None; Publications: 2872416, 1635567, 17277165, 23590417, 24910257, 18482219, 31921117, 11160319; Phenotypes: Immunodeficiency 17, CD3 gamma deficient MIM# 615607, immune deficiency, autoimmunity, failure to thrive, recurrent gastrointestinal infections, recurrent respiratory infections, autoimmune haemolytic anaemia, bronchiolitis obliterans, low CD3 complex, partial T lymphocytopenia, intractable diarrhoea.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.216 CD3G Danielle Ariti reviewed gene: CD3G: Rating: GREEN; Mode of pathogenicity: None; Publications: 2872416, 1635567, 17277165, 23590417, 24910257, 18482219, 31921117, 11160319; Phenotypes: Immunodeficiency 17, CD3 gamma deficient MIM# 615607, immune deficiency, autoimmunity, failure to thrive, recurrent gastrointestinal infections, recurrent respiratory infections, autoimmune haemolytic anaemia, Bronchiolitis obliterans, low CD3 complex, partial T lymphocytopenia, intractable diarrhoea.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8468 WDR26 Paul De Fazio reviewed gene: WDR26: Rating: GREEN; Mode of pathogenicity: None; Publications: 28686853, 33506510, 33675273; Phenotypes: Skraban-Deardorff syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.3995 WDR26 Paul De Fazio reviewed gene: WDR26: Rating: GREEN; Mode of pathogenicity: None; Publications: 28686853, 33506510, 33675273; Phenotypes: Skraban-Deardorff syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.3995 ABCD4 Zornitza Stark Marked gene: ABCD4 as ready
Intellectual disability syndromic and non-syndromic v0.3995 ABCD4 Zornitza Stark Gene: abcd4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3995 ABCD4 Zornitza Stark Phenotypes for gene: ABCD4 were changed from to Methylmalonic aciduria and homocystinuria, cblJ type, MIM# 614857
Intellectual disability syndromic and non-syndromic v0.3994 ABCD4 Zornitza Stark Publications for gene: ABCD4 were set to
Intellectual disability syndromic and non-syndromic v0.3993 ABCD4 Zornitza Stark Mode of inheritance for gene: ABCD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3992 ABCD4 Zornitza Stark reviewed gene: ABCD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22922874, 31113616, 30651581, 28572511, 33729671; Phenotypes: Methylmalonic aciduria and homocystinuria, cblJ type, MIM# 614857; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8468 ABCD4 Zornitza Stark Publications for gene: ABCD4 were set to 22922874; 31113616; 30651581; 28572511
Mendeliome v0.8467 ABCD4 Zornitza Stark reviewed gene: ABCD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33729671; Phenotypes: Methylmalonic aciduria and homocystinuria, cblJ type, MIM# 614857; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8467 ABCD4 Zornitza Stark Marked gene: ABCD4 as ready
Mendeliome v0.8467 ABCD4 Zornitza Stark Gene: abcd4 has been classified as Green List (High Evidence).
Mendeliome v0.8467 ABCD4 Zornitza Stark Phenotypes for gene: ABCD4 were changed from to Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857
Mendeliome v0.8466 ABCD4 Zornitza Stark Publications for gene: ABCD4 were set to
Mendeliome v0.8465 ABCD4 Zornitza Stark Mode of inheritance for gene: ABCD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8464 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
Mendeliome v0.8464 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Green List (High Evidence).
Mendeliome v0.8464 ABCD1 Zornitza Stark Phenotypes for gene: ABCD1 were changed from to Adrenoleukodystrophy MIM#300100
Mendeliome v0.8463 ABCD1 Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8462 ABCD1 Zornitza Stark changed review comment from: Ataxia is a feature of this progressive disorder.
Sources: Expert list; to: Well established gene-disease association.
Sources: Expert list
Mendeliome v0.8462 RAD21 Zornitza Stark Phenotypes for gene: RAD21 were changed from ?Mungan syndrome, 611376; Cornelia de Lange syndrome 4, 614701; Holoprocencephaly to Mungan syndrome, 611376; Cornelia de Lange syndrome 4, 614701; Holoprocencephaly
Mendeliome v0.8461 RAD21 Zornitza Stark Publications for gene: RAD21 were set to 31334757; 25575569; 32193685; 31704779
Mendeliome v0.8460 RAD21 Zornitza Stark reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: None; Publications: 14638363, 32193685, 25575569; Phenotypes: Mungan syndrome, MIM# 611376: Barrett esophagus, megaduodenum, cardiac abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.49 RAD21 Zornitza Stark Marked gene: RAD21 as ready
Gastrointestinal neuromuscular disease v0.49 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.49 RAD21 Zornitza Stark Phenotypes for gene: RAD21 were changed from Mungan syndrome: Barrett esophagus, megaduodenum, cardiac abnormalities to Mungan syndrome, MIM# 611376: Barrett esophagus, megaduodenum, cardiac abnormalities
Gastrointestinal neuromuscular disease v0.48 RAD21 Zornitza Stark Publications for gene: RAD21 were set to
Gastrointestinal neuromuscular disease v0.47 RAD21 Zornitza Stark reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: None; Publications: 14638363, 32193685, 25575569; Phenotypes: Mungan syndrome, MIM# 611376; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3992 CCBE1 Zornitza Stark Marked gene: CCBE1 as ready
Intellectual disability syndromic and non-syndromic v0.3992 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3992 CCBE1 Zornitza Stark Phenotypes for gene: CCBE1 were changed from to Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510; lymphangiectasia and lymphoedema; facial abnormalities; dysmorphic features; hypoalbuminaemia; intellectual disability; hypoglobulinaemia
Intellectual disability syndromic and non-syndromic v0.3991 CCBE1 Zornitza Stark Publications for gene: CCBE1 were set to
Intellectual disability syndromic and non-syndromic v0.3990 CCBE1 Zornitza Stark Mode of inheritance for gene: CCBE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3989 CCBE1 Zornitza Stark reviewed gene: CCBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19935664, 19911200, 19287381, 25925991, 27345729, 21778431; Phenotypes: Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510, lymphangiectasia and lymphoedema, facial abnormalities, dysmorphic features, hypoalbuminaemia, intellectual disability, hypoglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8460 CCBE1 Zornitza Stark Marked gene: CCBE1 as ready
Mendeliome v0.8460 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Mendeliome v0.8460 CCBE1 Zornitza Stark Phenotypes for gene: CCBE1 were changed from to Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510; lymphangiectasia and lymphoedema; facial abnormalities; dysmorphic features; hypoalbuminaemia; intellectual disability; hypoglobulinaemia
Mendeliome v0.8459 CCBE1 Zornitza Stark Publications for gene: CCBE1 were set to
Mendeliome v0.8458 CCBE1 Zornitza Stark Mode of inheritance for gene: CCBE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8457 CCBE1 Zornitza Stark reviewed gene: CCBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19935664, 19911200, 19287381, 25925991, 27345729, 21778431; Phenotypes: Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510, lymphangiectasia and lymphoedema, facial abnormalities, dysmorphic features, hypoalbuminaemia, intellectual disability, hypoglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8457 CD27 Zornitza Stark Marked gene: CD27 as ready
Mendeliome v0.8457 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
Mendeliome v0.8457 CD27 Zornitza Stark Phenotypes for gene: CD27 were changed from to Lymphoproliferative syndrome 2; CD27-deficiency MIM# 615122; hepatosplenomegaly; reduced CD8+ T-cell function; lymphadenopathy; hepatosplenomegaly; fever; increased susceptibility to EBV infection; aplastic anaemia
Mendeliome v0.8456 CD27 Zornitza Stark Publications for gene: CD27 were set to
Mendeliome v0.8455 CD27 Zornitza Stark Mode of inheritance for gene: CD27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8454 CD27 Zornitza Stark reviewed gene: CD27: Rating: GREEN; Mode of pathogenicity: None; Publications: 22197273, 22801960, 22365582, 25843314, 11062504; Phenotypes: Lymphoproliferative syndrome 2, CD27-deficiency MIM# 615122, hepatosplenomegaly, reduced CD8+ T-cell function, lymphadenopathy, hepatosplenomegaly, fever, increased susceptibility to EBV infection, aplastic anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.306 ZNF148 Zornitza Stark Marked gene: ZNF148 as ready
Callosome v0.306 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Callosome v0.306 ZNF148 Zornitza Stark Classified gene: ZNF148 as Green List (high evidence)
Callosome v0.306 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Callosome v0.305 ZNF148 Zornitza Stark gene: ZNF148 was added
gene: ZNF148 was added to Callosome. Sources: Literature
Mode of inheritance for gene: ZNF148 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF148 were set to 27964749
Phenotypes for gene: ZNF148 were set to Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies; MIM#617260
Review for gene: ZNF148 was set to GREEN
Added comment: Four unrelated individuals with de novo heterozygous nonsense or frameshift mutations (all resulting in premature termination codons in the last exon of ZNF148, predicted to escape nonsense-mediated mRNA decay and result in expression of a truncated protein). Phenotype characterised by underdevelopment of the corpus callosum, mild to moderate developmental delay and ID, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations. No functional studies to date.
Sources: Literature
Mendeliome v0.8454 ZNF148 Zornitza Stark Marked gene: ZNF148 as ready
Mendeliome v0.8454 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Mendeliome v0.8454 ZNF148 Zornitza Stark Classified gene: ZNF148 as Green List (high evidence)
Mendeliome v0.8454 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Mendeliome v0.8453 RAC3 Zornitza Stark Marked gene: RAC3 as ready
Mendeliome v0.8453 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Mendeliome v0.8453 RAC3 Zornitza Stark Classified gene: RAC3 as Green List (high evidence)
Mendeliome v0.8453 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Mendeliome v0.8452 PCLO Zornitza Stark Phenotypes for gene: PCLO were changed from to Pontocerebellar hypoplasia, type 3, MIM#608027
Mendeliome v0.8451 PCLO Zornitza Stark Publications for gene: PCLO were set to
Mendeliome v0.8450 PCLO Zornitza Stark Mode of inheritance for gene: PCLO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v1.16 PCLO Zornitza Stark Phenotypes for gene: PCLO were changed from to Pontocerebellar hypoplasia, type 3, MIM#608027
Cerebellar and Pontocerebellar Hypoplasia v1.15 PCLO Zornitza Stark Publications for gene: PCLO were set to
Cerebellar and Pontocerebellar Hypoplasia v1.14 PCLO Zornitza Stark Mode of inheritance for gene: PCLO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8449 ZNF148 Natalie Tan gene: ZNF148 was added
gene: ZNF148 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF148 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF148 were set to PMID: 27964749
Phenotypes for gene: ZNF148 were set to Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies; MIM#617260
Review for gene: ZNF148 was set to GREEN
Added comment: Four unrelated individuals with de novo heterozygous nonsense or frameshift mutations (all resulting in premature termination codons in the last exon of ZNF148, predicted to escape nonsense-mediated mRNA decay and result in expression of a truncated protein). Phenotype characterised by underdevelopment of the corpus callosum, mild to moderate developmental delay and ID, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations. No functional studies to date.
Sources: Literature
Mendeliome v0.8449 RAC3 Natalie Tan gene: RAC3 was added
gene: RAC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to PMID: 30293988; 29276006
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Multiple unrelated individuals with heterozygous missense variants and a concordant phenotype (severe intellectual disability with brain malformations). No functional studies to date.
Sources: Literature
Gastrointestinal neuromuscular disease v0.47 EDN3 Zornitza Stark edited their review of gene: EDN3: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.47 EDN3 Zornitza Stark Marked gene: EDN3 as ready
Gastrointestinal neuromuscular disease v0.47 EDN3 Zornitza Stark Gene: edn3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.47 EDN3 Zornitza Stark Phenotypes for gene: EDN3 were changed from Waardenburg syndrome w/pigmentary abnormalities to Waardenburg syndrome, type 4B, MIM# 613265
Gastrointestinal neuromuscular disease v0.46 EDN3 Zornitza Stark reviewed gene: EDN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Waardenburg syndrome, type 4B, MIM# 613265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8449 CHRNA4 Zornitza Stark Marked gene: CHRNA4 as ready
Mendeliome v0.8449 CHRNA4 Zornitza Stark Gene: chrna4 has been classified as Green List (High Evidence).
Mendeliome v0.8449 CHRNA4 Zornitza Stark Phenotypes for gene: CHRNA4 were changed from to Epilepsy, nocturnal frontal lobe, 1, MIM# 600513
Mendeliome v0.8448 CHRNA4 Zornitza Stark Publications for gene: CHRNA4 were set to
Mendeliome v0.8447 CHRNA4 Zornitza Stark Mode of pathogenicity for gene: CHRNA4 was changed from to Other
Mendeliome v0.8446 CHRNA4 Zornitza Stark Mode of inheritance for gene: CHRNA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8445 CHRNA4 Zornitza Stark reviewed gene: CHRNA4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 14623738, 23114665; Phenotypes: Epilepsy, nocturnal frontal lobe, 1, MIM# 600513; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1148 CHRNA4 Zornitza Stark Marked gene: CHRNA4 as ready
Genetic Epilepsy v0.1148 CHRNA4 Zornitza Stark Gene: chrna4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1148 CHRNA4 Zornitza Stark Phenotypes for gene: CHRNA4 were changed from to Epilepsy, nocturnal frontal lobe, 1, MIM# 600513
Genetic Epilepsy v0.1147 CHRNA4 Zornitza Stark Publications for gene: CHRNA4 were set to
Genetic Epilepsy v0.1146 CHRNA4 Zornitza Stark Mode of pathogenicity for gene: CHRNA4 was changed from to Other
Genetic Epilepsy v0.1145 CHRNA4 Zornitza Stark Mode of inheritance for gene: CHRNA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.216 CD27 Zornitza Stark Marked gene: CD27 as ready
Combined Immunodeficiency v0.216 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.216 CD27 Zornitza Stark Phenotypes for gene: CD27 were changed from to Lymphoproliferative syndrome 2; CD27-deficiency MIM# 615122; hepatosplenomegaly; reduced CD8+ T-cell function; lymphadenopathy; hepatosplenomegaly; fever; increased susceptibility to EBV infection; aplastic anaemia
Combined Immunodeficiency v0.215 CD27 Zornitza Stark Publications for gene: CD27 were set to
Combined Immunodeficiency v0.214 CD27 Zornitza Stark Mode of inheritance for gene: CD27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.213 CCBE1 Zornitza Stark Marked gene: CCBE1 as ready
Combined Immunodeficiency v0.213 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.213 CCBE1 Zornitza Stark Phenotypes for gene: CCBE1 were changed from to Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510; lymphangiectasia and lymphoedema; facial abnormalities; dysmorphic features; hypoalbuminaemia; intellectual disability; hypoglobulinaemia
Combined Immunodeficiency v0.212 CCBE1 Zornitza Stark Publications for gene: CCBE1 were set to
Combined Immunodeficiency v0.212 CCBE1 Zornitza Stark Mode of inheritance for gene: CCBE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.211 BLM Zornitza Stark Marked gene: BLM as ready
Combined Immunodeficiency v0.211 BLM Zornitza Stark Gene: blm has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.211 BLM Zornitza Stark Phenotypes for gene: BLM were changed from to Bloom Syndrome MIM# 210900; Short stature, dysmorphic facies; sun-sensitive; immunoglobulin deficiency (IgA, IgG, IgM); erythema; marrow failure; leukaemia; lymphoma; chromosomal instability; predisposition to malignancies
Combined Immunodeficiency v0.210 BLM Zornitza Stark Publications for gene: BLM were set to
Combined Immunodeficiency v0.209 BLM Zornitza Stark Mode of inheritance for gene: BLM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1144 CHRNA4 Melanie Marty reviewed gene: CHRNA4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 14623738, 23114665; Phenotypes: Epilepsy, nocturnal frontal lobe, 1, MIM# 600513; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v0.208 CD27 Danielle Ariti reviewed gene: CD27: Rating: GREEN; Mode of pathogenicity: None; Publications: 22197273, 22801960, 22365582, 25843314, 11062504; Phenotypes: Lymphoproliferative syndrome 2, CD27-deficiency MIM# 615122, hepatosplenomegaly, reduced CD8+ T-cell function, lymphadenopathy, hepatosplenomegaly, fever, increased susceptibility to EBV infection, aplastic anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.208 CCBE1 Danielle Ariti reviewed gene: CCBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19935664, 19911200, 19287381, 25925991, 27345729, 21778431; Phenotypes: Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510, lymphangiectasia and lymphoedema, facial abnormalities, dysmorphic features, hypoalbuminaemia, intellectual disability, hypoglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.208 BLM Danielle Ariti reviewed gene: BLM: Rating: GREEN; Mode of pathogenicity: None; Publications: 17407155, 9285778, 7585968, 8079989, 12242442, 11101838; Phenotypes: Bloom Syndrome MIM# 210900, Short stature, dysmorphic facies, sun-sensitive, immunoglobulin deficiency (IgA, IgG, IgM), erythema, marrow failure, leukaemia, lymphoma, chromosomal instability, predisposition to malignancies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v0.0 ZPR1 Zornitza Stark gene: ZPR1 was added
gene: ZPR1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ZPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZPR1 were set to 29851065
Phenotypes for gene: ZPR1 were set to ?Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies, OMIM:619321
Growth failure v0.0 XRCC4 Zornitza Stark gene: XRCC4 was added
gene: XRCC4 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: XRCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XRCC4 were set to 25728776
Phenotypes for gene: XRCC4 were set to short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism
Growth failure v0.0 WRN Zornitza Stark gene: WRN was added
gene: WRN was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: WRN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WRN were set to Werner syndrome
Growth failure v0.0 THRB Zornitza Stark gene: THRB was added
gene: THRB was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: THRB was set to Unknown
Growth failure v0.0 TBCE Zornitza Stark gene: TBCE was added
gene: TBCE was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Growth failure v0.0 STAT5B Zornitza Stark gene: STAT5B was added
gene: STAT5B was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: STAT5B was set to BIALLELIC, autosomal or pseudoautosomal
Growth failure v0.0 SPRED1 Zornitza Stark gene: SPRED1 was added
gene: SPRED1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SPRED1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPRED1 were set to 21548021; 17704776; 19443465; 19366998; 21649642
Phenotypes for gene: SPRED1 were set to Legius Syndrome; Neurofibromatosis-like syndrome
Growth failure v0.0 SOX3 Zornitza Stark gene: SOX3 was added
gene: SOX3 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SOX3 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: SOX3 were set to 15800844
Phenotypes for gene: SOX3 were set to Panhypopituitarism, X-linked, OMIM:312000; Mental retardation, X-linked, with isolated growth hormone deficiency, OMIM:300123; Panhypopituitarism, X-linked, MONDO:0010712; Intellectual disability, X-linked, with panhypopituitarism, MONDO:0010252
Mode of pathogenicity for gene: SOX3 was set to Other - please provide details in the comments
Growth failure v0.0 SOX2 Zornitza Stark gene: SOX2 was added
gene: SOX2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Growth failure v0.0 SMC3 Zornitza Stark gene: SMC3 was added
gene: SMC3 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
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
Growth failure v0.0 SMC1A Zornitza Stark gene: SMC1A was added
gene: SMC1A was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SMC1A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: SMC1A were set to Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771; Cornelia de Lange syndrome 2, MONDO:0010370; Cornelia de Lange syndrome 2, OMIM:300590; Developmental and epileptic encephalopathy 85, with or without midline brain defects, OMIM:301044
Growth failure v0.0 SMARCAL1 Zornitza Stark gene: SMARCAL1 was added
gene: SMARCAL1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SMARCAL1 was set to Unknown
Growth failure v0.0 SHOX2 Zornitza Stark gene: SHOX2 was added
gene: SHOX2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SHOX2 was set to Unknown
Growth failure v0.0 SHOX Zornitza Stark gene: SHOX was added
gene: SHOX was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SHOX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Growth failure v0.0 SAMD9 Zornitza Stark gene: SAMD9 was added
gene: SAMD9 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: SAMD9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SAMD9 were set to 27182967
Phenotypes for gene: SAMD9 were set to MIRAGE syndrome, 617053
Mode of pathogenicity for gene: SAMD9 was set to Other - please provide details in the comments
Growth failure v0.0 RPS6KA3 Zornitza Stark gene: RPS6KA3 was added
gene: RPS6KA3 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: RPS6KA3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: RPS6KA3 were set to Coffin Lowry
Growth failure v0.0 RPL10 Zornitza Stark gene: RPL10 was added
gene: RPL10 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
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
Phenotypes for gene: RPL10 were set to Mental retardation, X-linked, syndromic, 35
Growth failure v0.0 ROR2 Zornitza Stark gene: ROR2 was added
gene: ROR2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ROR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ROR2 were set to Robinow
Growth failure v0.0 RNU4ATAC Zornitza Stark gene: RNU4ATAC was added
gene: RNU4ATAC was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: RNU4ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU4ATAC were set to 21474760
Phenotypes for gene: RNU4ATAC were set to MOPD I
Growth failure v0.0 RBBP8 Zornitza Stark gene: RBBP8 was added
gene: RBBP8 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: RBBP8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBBP8 were set to 24389050, 21998596
Phenotypes for gene: RBBP8 were set to seckel syndrome but with proportionate head/height impairment, cafe au lair macules
Growth failure v0.0 RAPSN Zornitza Stark gene: RAPSN was added
gene: RAPSN was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: RAPSN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAPSN were set to Fetal Akinesia Deformation Sequence; Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency, 608931Myasthenic syndrome, congenital, associated with facial dysmorphism and acetylcholine receptordeficiency, 608931Fetal akinesia deformation sequence, 208150
Growth failure v0.0 RAD21 Zornitza Stark gene: RAD21 was added
gene: RAD21 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: RAD21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAD21 were set to Cornelia De Lange
Growth failure v0.0 PROP1 Zornitza Stark gene: PROP1 was added
gene: PROP1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PROP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PROP1 were set to Pituitary hormone deficiency, combined
Growth failure v0.0 PROKR2 Zornitza Stark gene: PROKR2 was added
gene: PROKR2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PROKR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PROKR2 were set to 22319038
Phenotypes for gene: PROKR2 were set to hypopituitarism, Hypoplastic corpus callosum, normal or small anterior pituitary, Club foot, syrinx spinal cord, microcephaly, epilepsy
Growth failure v0.0 POU1F1 Zornitza Stark gene: POU1F1 was added
gene: POU1F1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: POU1F1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: POU1F1 were set to GH, PRL deficiencies; variable degree of TSH deficiency
Growth failure v0.0 PNPLA6 Zornitza Stark gene: PNPLA6 was added
gene: PNPLA6 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 25480986
Phenotypes for gene: PNPLA6 were set to Oliver-Mcfarlane syndrome, Trichomegaly, GH deficiency, retinal dystrophy, hypogonadotrophic hypogonadism
Growth failure v0.0 PITX2 Zornitza Stark gene: PITX2 was added
gene: PITX2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PITX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PITX2 were set to AXENFELD-RIEGER SYNDROME
Growth failure v0.0 PCNT Zornitza Stark gene: PCNT was added
gene: PCNT was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PCNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCNT were set to 18157127; 18174396
Phenotypes for gene: PCNT were set to Seckel syndrome, MOPD type II - growth restrction, microcephaly, prominent nose, micrognathia, squeaky voice, insulin resistance, 210720; MOPDII
Growth failure v0.0 PAPPA2 Zornitza Stark gene: PAPPA2 was added
gene: PAPPA2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: PAPPA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAPPA2 were set to 26902202
Phenotypes for gene: PAPPA2 were set to Proportionate Short Stature, High Circulating IGF-I, IGFBP-3, and ALS, Mild Microcephaly, thin Long Bones and Decreased Bone Mineral Density
Growth failure v0.0 OTX2 Zornitza Stark gene: OTX2 was added
gene: OTX2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: OTX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OTX2 were set to 18728160
Phenotypes for gene: OTX2 were set to Microcephaly, bilateral anopthalmia, developmental delay, cleft palate
Growth failure v0.0 ORC6 Zornitza Stark gene: ORC6 was added
gene: ORC6 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ORC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ORC6 were set to 21358632
Phenotypes for gene: ORC6 were set to Meier-Gorlin; micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia; Meier-Gorlin syndrome 3, 613803
Growth failure v0.0 ORC4 Zornitza Stark gene: ORC4 was added
gene: ORC4 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ORC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ORC4 were set to 21358632
Phenotypes for gene: ORC4 were set to Meier-Gorlin syndrome 2, 613800; micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia; Meier-Gorlin
Growth failure v0.0 ORC1 Zornitza Stark gene: ORC1 was added
gene: ORC1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ORC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ORC1 were set to 21358632
Phenotypes for gene: ORC1 were set to Meier-Gorlin syndrome 1, 224690; microtia, beaked nose, patellar aplasia/hypoplasia, mammary hypoplasia, micrognathia; Meier-Gorlin
Growth failure v0.0 NIPBL Zornitza Stark gene: NIPBL was added
gene: NIPBL was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
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
Growth failure v0.0 MCM5 Zornitza Stark gene: MCM5 was added
gene: MCM5 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: MCM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM5 were set to 28198391
Phenotypes for gene: MCM5 were set to ?Meier-Gorlin syndrome 8
Growth failure v0.0 LIG4 Zornitza Stark gene: LIG4 was added
gene: LIG4 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: LIG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG4 were set to 11779494, 16088910,
Phenotypes for gene: LIG4 were set to microcephaly, growth retardation, immunodeficiency, developmental delay
Growth failure v0.0 LIG1 Zornitza Stark gene: LIG1 was added
gene: LIG1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG1 were set to 1581963, 1351188
Phenotypes for gene: LIG1 were set to immunodeficiency, sun sensitivity, growth reatrdation
Growth failure v0.0 LHX4 Zornitza Stark gene: LHX4 was added
gene: LHX4 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: LHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LHX4 were set to 11567216, 18073311
Phenotypes for gene: LHX4 were set to hypopituitarism
Growth failure v0.0 LHX3 Zornitza Stark gene: LHX3 was added
gene: LHX3 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: LHX3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LHX3 were set to GH, TSH, LH, FSH, PRL deficiencies
Growth failure v0.0 KMT2D Zornitza Stark gene: KMT2D was added
gene: KMT2D was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: KMT2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KMT2D were set to Kabuki
Growth failure v0.0 KHDC3L Zornitza Stark gene: KHDC3L was added
gene: KHDC3L was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: KHDC3L was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: KHDC3L were set to 29574422
Phenotypes for gene: KHDC3L were set to pregnancy loss; Hydatidiform mole, recurrent, 2 OMIM:614293; hydatidiform mole, recurrent, 2 MONDO:0013671; Failure to thrive; IUGR
Growth failure v0.0 KDM6A Zornitza Stark gene: KDM6A was added
gene: KDM6A was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: KDM6A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: KDM6A were set to Kabuki
Growth failure v0.0 INTS8 Zornitza Stark gene: INTS8 was added
gene: INTS8 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: INTS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS8 were set to 28542170
Phenotypes for gene: INTS8 were set to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, OMIM:618572
Growth failure v0.0 INSR Zornitza Stark gene: INSR was added
gene: INSR was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: INSR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: INSR were set to Leprechaunism
Growth failure v0.0 IGFBP3 Zornitza Stark gene: IGFBP3 was added
gene: IGFBP3 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: IGFBP3 was set to Unknown
Publications for gene: IGFBP3 were set to 10364674
Phenotypes for gene: IGFBP3 were set to Silver Russell Syndrome
Growth failure v0.0 IGFBP1 Zornitza Stark gene: IGFBP1 was added
gene: IGFBP1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: IGFBP1 was set to Unknown
Publications for gene: IGFBP1 were set to 10364674
Phenotypes for gene: IGFBP1 were set to Silver-Russell Syndrome
Growth failure v0.0 IGFALS Zornitza Stark gene: IGFALS was added
gene: IGFALS was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: IGFALS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGFALS were set to 14762184
Phenotypes for gene: IGFALS were set to very low IGF-I levels; Short stature; delayed puberty
Growth failure v0.0 IFT172 Zornitza Stark gene: IFT172 was added
gene: IFT172 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: IFT172 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT172 were set to 25664603
Phenotypes for gene: IFT172 were set to GH deficiency, retinopathy, metaphyseal dysplasia
Growth failure v0.0 HESX1 Zornitza Stark gene: HESX1 was added
gene: HESX1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: HESX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: HESX1 were set to Septo-optic dysplasia; variable involvement of pituitary hormones
Growth failure v0.0 HDAC8 Zornitza Stark gene: HDAC8 was added
gene: HDAC8 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
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)
Phenotypes for gene: HDAC8 were set to Cornelia De Lange
Growth failure v0.0 H19 Zornitza Stark gene: H19 was added
gene: H19 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: H19 was set to Unknown
Phenotypes for gene: H19 were set to Russell-Silver syndrome
Growth failure v0.0 GPR161 Zornitza Stark gene: GPR161 was added
gene: GPR161 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GPR161 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPR161 were set to 25322266
Phenotypes for gene: GPR161 were set to Short stature with hypopituitarism, intellectual disability, sparse or absent hair in the frontal area, hypotelorism, broad nasal root, thick alae nasi, nail hypoplasia, short fifth finger, 2-3 toe syndactyl. MRI showed hypoplastic pituitary gland, empty sella, ectopic neurohypophysis, and interrupted pituitary stalk
Growth failure v0.0 GLI3 Zornitza Stark gene: GLI3 was added
gene: GLI3 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLI3 were set to 9054938
Phenotypes for gene: GLI3 were set to Pallister-Hall syndrome
Growth failure v0.0 GLI2 Zornitza Stark gene: GLI2 was added
gene: GLI2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GLI2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GLI2 were set to Holoprosencephaly, hypopituitarism
Growth failure v0.0 GHSR Zornitza Stark gene: GHSR was added
gene: GHSR was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GHSR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GHSR were set to 16511605
Phenotypes for gene: GHSR were set to Idiopathic short stature, GH deficiency
Growth failure v0.0 GHRHR Zornitza Stark gene: GHRHR was added
gene: GHRHR was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GHRHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GHRHR were set to Growth hormone deficiency
Growth failure v0.0 GHR Zornitza Stark gene: GHR was added
gene: GHR was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GHR were set to Laron syndrome
Growth failure v0.0 GH1 Zornitza Stark gene: GH1 was added
gene: GH1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GH1 were set to Growth hormone deficiency
Growth failure v0.0 FGFR1 Zornitza Stark gene: FGFR1 was added
gene: FGFR1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: FGFR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR1 were set to 22319038
Growth failure v0.0 FGF8 Zornitza Stark gene: FGF8 was added
gene: FGF8 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: FGF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGF8 were set to 22319038
Phenotypes for gene: FGF8 were set to hypopituitarism, absent corpus callosum, Holoprosencephaly, Moebius syndrome, craniofacial defects, high arched palate, maxillary hypoplasia, microcepahly, spastic diplegia
Growth failure v0.0 FGD1 Zornitza Stark gene: FGD1 was added
gene: FGD1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: FGD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: FGD1 were set to Aarskog
Growth failure v0.0 FANCM Zornitza Stark gene: FANCM was added
gene: FANCM was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: FANCM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCM were set to 16116422; 25078778; 19423727
Phenotypes for gene: FANCM were set to Fanconi anemia, complementation group M, 614087; Fanconi anemia; Fanconi Anemia
Growth failure v0.0 ERCC8 Zornitza Stark gene: ERCC8 was added
gene: ERCC8 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ERCC8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC8 were set to cockayne
Growth failure v0.0 ERCC6 Zornitza Stark gene: ERCC6 was added
gene: ERCC6 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ERCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC6 were set to Cockayne syndrome, type B, 133540
Growth failure v0.0 EPHX1 Zornitza Stark gene: EPHX1 was added
gene: EPHX1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: EPHX1 was set to Unknown
Phenotypes for gene: EPHX1 were set to ?Fetal hydantoin syndromeDiphenylhydantoin toxicityHypercholanemia, familial, 607748{Preeclampsia, susceptibility to}, 189800
Growth failure v0.0 EP300 Zornitza Stark gene: EP300 was added
gene: EP300 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: EP300 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EP300 were set to Rubenstein Taybi
Growth failure v0.0 DOK7 Zornitza Stark gene: DOK7 was added
gene: DOK7 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: DOK7 was set to Unknown
Phenotypes for gene: DOK7 were set to Myasthenia, limb-girdle, familial, 254300Fetal akinesia deformation sequence, 208150
Growth failure v0.0 DNA2 Zornitza Stark gene: DNA2 was added
gene: DNA2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNA2 were set to 24389050; 31045292
Phenotypes for gene: DNA2 were set to Seckel syndrome 8, OMIM:615807
Growth failure v0.0 DHCR7 Zornitza Stark gene: DHCR7 was added
gene: DHCR7 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DHCR7 were set to Smith Lemli Opitz
Growth failure v0.0 CRIPT Zornitza Stark gene: CRIPT was added
gene: CRIPT was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: CRIPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRIPT were set to PMC3912419
Phenotypes for gene: CRIPT were set to frontal bossing, high forehead, sparse hair and eyebrows, telecanthus, mild proptosis (staring look), upturned nostrils, and hypoplastic terminal phalanges with brachydactyly
Growth failure v0.0 CREBBP Zornitza Stark gene: CREBBP was added
gene: CREBBP was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CREBBP were set to Rubenstein Taybi
Growth failure v0.0 COL1A1 Zornitza Stark gene: COL1A1 was added
gene: COL1A1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: COL1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: COL1A1 were set to Osteogenesis imperfecta, type I, 166200; Osteogenesis imperfecta, type II, 166210; Osteogenesis imperfecta, type III, 259420; OI; Osteogenesis imperfecta, type IV, 166220
Growth failure v0.0 CHD7 Zornitza Stark gene: CHD7 was added
gene: CHD7 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD7 were set to 16400610
Phenotypes for gene: CHD7 were set to CHARGE syndrome, 214800; CHARGE syndrome - ocular coloboma, choanal atresia, cranial nerve defects, distinctive external and inner ear abnormalities, hearing loss, cardiovascular malformations, urogenital anomalies, and growth retardation
Growth failure v0.0 CENPJ Zornitza Stark gene: CENPJ was added
gene: CENPJ was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: CENPJ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPJ were set to 20522431
Phenotypes for gene: CENPJ were set to seckel syndrome
Growth failure v0.0 CDT1 Zornitza Stark gene: CDT1 was added
gene: CDT1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: CDT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDT1 were set to 21358632
Phenotypes for gene: CDT1 were set to Meier-Gorlin syndrome 4, 613804; micrognathia, microtia, patellar hypoplasia/aplasia, mammary hypoplasia; Meier-Gorlin
Growth failure v0.0 CDC6 Zornitza Stark gene: CDC6 was added
gene: CDC6 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
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 patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia; ?Meier-Gorlin syndrome 5, 613805
Growth failure v0.0 BTK Zornitza Stark gene: BTK was added
gene: BTK was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: BTK was set to Unknown
Growth failure v0.0 ATRX Zornitza Stark gene: ATRX was added
gene: ATRX was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: ATRX was set to Unknown
Phenotypes for gene: ATRX were set to SGA, which is sometimes called intrauterine growth restriction (IUGR),
Growth failure v0.0 ATRIP Zornitza Stark gene: ATRIP was added
gene: ATRIP was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Red
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 microcephaly, micrognathia, small ear lobes, dental crowding
Growth failure v0.0 ZFP57 Zornitza Stark gene: ZFP57 was added
gene: ZFP57 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: ZFP57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFP57 were set to 18622393
Phenotypes for gene: ZFP57 were set to diabetes mellitus, transient neonatal, 1MONDO:0011073; Diabetes mellitus, transient neonatal 1 OMIM:601410; IUGR; Multi Locus Imprinting Disturbance
Growth failure v0.0 RNPC3 Zornitza Stark gene: RNPC3 was added
gene: RNPC3 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: RNPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNPC3 were set to 32462814; 29866761; 24480542
Phenotypes for gene: RNPC3 were set to ?Growth hormone deficiency, isolated, type V, 618160; isolated growth hormone deficiency
Growth failure v0.0 RAP1B Zornitza Stark gene: RAP1B was added
gene: RAP1B was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: RAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAP1B were set to 26280580; 32627184
Phenotypes for gene: RAP1B were set to short stature; Syndromic intellectual disability
Growth failure v0.0 PLK4 Zornitza Stark gene: PLK4 was added
gene: PLK4 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: PLK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLK4 were set to 27650967; 25320347; 25344692
Phenotypes for gene: PLK4 were set to microcephaly and chorioretinopathy 2, MONDO:0014516; Microcephaly and chorioretinopathy, autosomal recessive, 2, OMIM:616171
Growth failure v0.0 PADI6 Zornitza Stark gene: PADI6 was added
gene: PADI6 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: PADI6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PADI6 were set to 33221824; 32928291; 29574422
Phenotypes for gene: PADI6 were set to miscarriages in the family; Preimplantation embryonic lethality 2 OMIM:617234; Short stature; preimplantation embryonic lethality 2 MONDO:0014978; Multi Locus Imprinting Disturbance; IUGR; Beckwith-Wiedemann syndrome
Growth failure v0.0 NLRP7 Zornitza Stark gene: NLRP7 was added
gene: NLRP7 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: NLRP7 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP7 were set to 28561018
Phenotypes for gene: NLRP7 were set to hydatidiform mole, recurrent, 1 MONDO:0009273; Short stature; fetal wastage; Hydatidiform mole, recurrent, 1 OMIM:231090; IUGR; Multi Locus Imprinting Disturbance
Growth failure v0.0 NLRP5 Zornitza Stark gene: NLRP5 was added
gene: NLRP5 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: NLRP5 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP5 were set to 26323243; 29574422
Phenotypes for gene: NLRP5 were set to body asymmetry; Short stature; Failure to thrive; multilocus imprinting disturbances; IUGR
Growth failure v0.0 NLRP2 Zornitza Stark gene: NLRP2 was added
gene: NLRP2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: NLRP2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP2 were set to 30877238; 33090377; 29574422; 26323243; 19300480
Phenotypes for gene: NLRP2 were set to Maternal effect gene- causing phenotypes that include IUGR
Growth failure v0.0 NHLRC2 Zornitza Stark gene: NHLRC2 was added
gene: NHLRC2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: NHLRC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC2 were set to 29423877; 32435055
Phenotypes for gene: NHLRC2 were set to FINCA syndrome OMIM:618278
Growth failure v0.0 NBAS Zornitza Stark gene: NBAS was added
gene: NBAS was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: NBAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBAS were set to 31761904
Phenotypes for gene: NBAS were set to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, 614800
Growth failure v0.0 MTX2 Zornitza Stark gene: MTX2 was added
gene: MTX2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; growth retardation; arterial calcification; lipodystrophy
Growth failure v0.0 MSTO1 Zornitza Stark gene: MSTO1 was added
gene: MSTO1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: MSTO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MSTO1 were set to 29339779; 28554942; 31604776; 28544275; 31130378
Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia, OMIM:617675
Growth failure v0.0 KDM3B Zornitza Stark gene: KDM3B was added
gene: KDM3B was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KDM3B were set to 30929739
Phenotypes for gene: KDM3B were set to Behavioral abnormality; Seizures; Global developmental delay; Short stature; Intellectual disability
Growth failure v0.0 INTS1 Zornitza Stark gene: INTS1 was added
gene: INTS1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: INTS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS1 were set to 28542170; 31428919; 30622326
Phenotypes for gene: INTS1 were set to Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, OMIM:618571, MONDO:0032817
Growth failure v0.0 FOXP4 Zornitza Stark gene: FOXP4 was added
gene: FOXP4 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Growth failure v0.0 COG4 Zornitza Stark gene: COG4 was added
gene: COG4 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: COG4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COG4 were set to 30290151; 31949312
Phenotypes for gene: COG4 were set to microcephalic osteodysplastic dysplasia, Saul-Wilson type, MONDO:0019407; Saul-Wilson syndrome, OMIM:618150
Mode of pathogenicity for gene: COG4 was set to Other
Growth failure v0.0 CEP57 Zornitza Stark gene: CEP57 was added
gene: CEP57 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: CEP57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP57 were set to 24259107; 21552266
Phenotypes for gene: CEP57 were set to Mosaic variegated aneuploidy syndrome 2, 614114
Growth failure v0.0 CCDC186 Zornitza Stark gene: CCDC186 was added
gene: CCDC186 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: CCDC186 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC186 were set to 33259146; 28600779
Phenotypes for gene: CCDC186 were set to failure to thrive and developmental delay
Growth failure v0.0 ANAPC1 Zornitza Stark gene: ANAPC1 was added
gene: ANAPC1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Amber
Mode of inheritance for gene: ANAPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANAPC1 were set to 31303264
Phenotypes for gene: ANAPC1 were set to Rothmund Thomson syndrome type 1, OMIM:618625, MONDO:0016368
Growth failure v0.0 UBE2T Zornitza Stark gene: UBE2T was added
gene: UBE2T was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: UBE2T was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE2T were set to 26046368
Phenotypes for gene: UBE2T were set to Falcon anemia; 616435 Fanconi anemia, complementation group T; Fanconi anemia, complementation group T, 616435
Growth failure v0.0 TRIM37 Zornitza Stark gene: TRIM37 was added
gene: TRIM37 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: TRIM37 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIM37 were set to Mulibrey nanism; Mulibery Nanism, 253250
Growth failure v0.0 TOP3A Zornitza Stark gene: TOP3A was added
gene: TOP3A was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: TOP3A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TOP3A were set to Microcephaly, growth restriction, and increased sister chromatid exchange 2; MGRISCE2 (Bloom-like syndrome) 618097; 618097 MGRISCE2 (Bloom-like syndrome)
Growth failure v0.0 SRCAP Zornitza Stark gene: SRCAP was added
gene: SRCAP was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SRCAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SRCAP were set to Floating-Harbor syndrome, 136140; Floating Harbor
Growth failure v0.0 SOS2 Zornitza Stark gene: SOS2 was added
gene: SOS2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SOS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOS2 were set to 25795793; 26173643
Phenotypes for gene: SOS2 were set to Noonan syndrome 9
Mode of pathogenicity for gene: SOS2 was set to Other - please provide details in the comments
Growth failure v0.0 SOS1 Zornitza Stark gene: SOS1 was added
gene: SOS1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SOS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOS1 were set to 17143285; 17586837; 17143282; 19438935
Phenotypes for gene: SOS1 were set to Noonan syndrome; Rasopathy; Noonan syndrome 4
Mode of pathogenicity for gene: SOS1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 SLX4 Zornitza Stark gene: SLX4 was added
gene: SLX4 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SLX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLX4 were set to 21240275; 21240277
Phenotypes for gene: SLX4 were set to 613951 Fanconi Anemia Fanconi anemia, complementation group P; Fanconi anemia, complementation group P, 613951; Fanconi Anemia
Growth failure v0.0 SHOC2 Zornitza Stark gene: SHOC2 was added
gene: SHOC2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: SHOC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHOC2 were set to 23918763; 19684605; 22528146
Phenotypes for gene: SHOC2 were set to Noonan with loss of anagen hair; Noonan-like syndrome with loose anagen hair
Mode of pathogenicity for gene: SHOC2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 RIT1 Zornitza Stark gene: RIT1 was added
gene: RIT1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: RIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RIT1 were set to 24939608; 25124994; 23791108
Phenotypes for gene: RIT1 were set to Rasopathy; Noonan syndrome type 8; Noonan syndrome 8
Mode of pathogenicity for gene: RIT1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 RAF1 Zornitza Stark gene: RAF1 was added
gene: RAF1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: RAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAF1 were set to 17603483; 17603482
Phenotypes for gene: RAF1 were set to Noonan syndrome 5; Noonan syndrome; LEOPARD syndrome 2; Rasopathy; LEOPARD syndrome
Mode of pathogenicity for gene: RAF1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 PTPN11 Zornitza Stark gene: PTPN11 was added
gene: PTPN11 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN11 were set to 16263833; 17603483; 17497712; 12634870; 11704759; 18678287; 15384080; 15240615; 12529711
Phenotypes for gene: PTPN11 were set to Noonan syndrome; LEOPARD syndrome 1; Noonan syndrome 1; LEOPARD syndrome
Mode of pathogenicity for gene: PTPN11 was set to Other - please provide details in the comments
Growth failure v0.0 PPP1CB Zornitza Stark gene: PPP1CB was added
gene: PPP1CB was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PPP1CB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP1CB were set to 27264673; 27681385; 28211982
Phenotypes for gene: PPP1CB were set to Noonan syndrome-like disorder with loose anagen hair 2, 617506; Rasopathy with developmental delay, short stature and sparse slow-growing hair
Growth failure v0.0 PLAG1 Zornitza Stark gene: PLAG1 was added
gene: PLAG1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PLAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLAG1 were set to 28796236
Phenotypes for gene: PLAG1 were set to SRS; Silver-Russell syndrome
Growth failure v0.0 PIK3R1 Zornitza Stark gene: PIK3R1 was added
gene: PIK3R1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PIK3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIK3R1 were set to SHORT syndrome, 269880; SHORT
Growth failure v0.0 PALB2 Zornitza Stark gene: PALB2 was added
gene: PALB2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: PALB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PALB2 were set to 17200672; 17200671
Phenotypes for gene: PALB2 were set to Fanconi anemia, complementation group N, 610832; 610832 Fanconi anemia, complementation group N
Growth failure v0.0 OBSL1 Zornitza Stark gene: OBSL1 was added
gene: OBSL1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: OBSL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OBSL1 were set to 21737058
Phenotypes for gene: OBSL1 were set to 3M; 3-M syndrome 2, 612921
Growth failure v0.0 NRAS Zornitza Stark gene: NRAS was added
gene: NRAS was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: NRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRAS were set to 19966803; 19775298
Phenotypes for gene: NRAS were set to Cardio-Facio-cutanenous syndrome; A restricted spectrum of NRAS mutations causes Noonan syndrome. (Nat Genet. 42: 27-29, 2010.); Noonan syndrome; CFC Syndrome; Noonan syndrome 6
Mode of pathogenicity for gene: NRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 NBN Zornitza Stark gene: NBN was added
gene: NBN was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: NBN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NBN were set to Nijmegen; Nijmegen breakage syndrome, 251260
Growth failure v0.0 MAP2K2 Zornitza Stark gene: MAP2K2 was added
gene: MAP2K2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: MAP2K2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP2K2 were set to 16439621; 21396583; 23379592
Phenotypes for gene: MAP2K2 were set to CFC syndrome; Cardiofaciocutaneous Syndrome; Cardiofaciocutaneous syndrome; Cardiofaciocutaneous syndrome 4; Cardio-Facio-Cutaneous syndrome; Cardio-Facio-Cutaneous syndrome type 4
Mode of pathogenicity for gene: MAP2K2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 MAP2K1 Zornitza Stark gene: MAP2K1 was added
gene: MAP2K1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP2K1 were set to 23321623; 16439621; 21396583; 16825433
Phenotypes for gene: MAP2K1 were set to Cardiofaciocutaneous syndrome 3; CFC syndrome; ?Noonan syndrome; Cardiofaciocutaneous Syndrome; Cardiofaciocutaneous syndrome; Cardio-Facio-Cutaneous syndrome; LEOPARD syndrome
Mode of pathogenicity for gene: MAP2K1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 LZTR1 Zornitza Stark gene: LZTR1 was added
gene: LZTR1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: LZTR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LZTR1 were set to 29469822; 25795793
Phenotypes for gene: LZTR1 were set to increased nuchal translucency; Prenatal hydrops; cardiac findings; Noonan syndrome 10
Growth failure v0.0 KRAS Zornitza Stark gene: KRAS was added
gene: KRAS was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRAS were set to 21396583
Phenotypes for gene: KRAS were set to Noonan syndrome 3; CFC syndrome; Cardiofaciocutaneous syndrome 2; Cardiofaciocutaneous Syndrome; Noonan syndrome; Rasopathy; Cardio-Facio-Cutaneous syndrome
Mode of pathogenicity for gene: KRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 IGF2 Zornitza Stark gene: IGF2 was added
gene: IGF2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: IGF2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: IGF2 were set to 26154720
Phenotypes for gene: IGF2 were set to Pre- and post-natal growth failure; SRS; ?Growth restriction, severe, with distinctive facies, 616489; Silver-Russell phenptype; IUGR
Growth failure v0.0 IGF1R Zornitza Stark gene: IGF1R was added
gene: IGF1R was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: IGF1R was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: IGF1R were set to 15q-Del; Insulin likegrowthfactorI,resistanceto,270450; Insulin-Like Growth Factor I Resistance
Growth failure v0.0 IGF1 Zornitza Stark gene: IGF1 was added
gene: IGF1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: IGF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IGF1 were set to Insulin-Like Growth Factor I Deficiency; Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; IGF1
Growth failure v0.0 HRAS Zornitza Stark gene: HRAS was added
gene: HRAS was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: HRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HRAS were set to 16969868; 16443854; 21396583; 16170316
Phenotypes for gene: HRAS were set to Costello syndrome, 218040; Costello; Costello syndrome
Mode of pathogenicity for gene: HRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 HMGA2 Zornitza Stark gene: HMGA2 was added
gene: HMGA2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: HMGA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HMGA2 were set to 29655892
Phenotypes for gene: HMGA2 were set to Silver-Russell syndrome 5, MONDO:0020795; Silver-Russell syndrome 5, OMIM:618908
Growth failure v0.0 FGFR3 Zornitza Stark gene: FGFR3 was added
gene: FGFR3 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FGFR3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FGFR3 were set to Hypochondroplasia, 146000
Growth failure v0.0 FANCL Zornitza Stark gene: FANCL was added
gene: FANCL was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FANCL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCL were set to 25754594; 12724401; 19405097; 12973351; 16474160
Phenotypes for gene: FANCL were set to Fanconi anemia; 614083Fanconi anemia, complementation group L; Fanconi anemia, complementation group L, 614083; Fanconi Anemia
Growth failure v0.0 FANCI Zornitza Stark gene: FANCI was added
gene: FANCI was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FANCI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCI were set to 17452773; 11239453
Phenotypes for gene: FANCI were set to 609053 Fanconi anemia, complementation group I; Fanconi anemia; Fanconi anemia, complementation group I, 609053; Fanconi Anemia
Growth failure v0.0 FANCG Zornitza Stark gene: FANCG was added
gene: FANCG was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FANCG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCG were set to 16493006; 9806548
Phenotypes for gene: FANCG were set to 614082 Fanconi anemia, complementation group G; hypogonadism and reduced fertility; Fanconi Anemia; bone marrow failure; a typical facial appearance with small head, eyes, and mouth; cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots); hearing loss; Fanconi anemia; and susceptibility to cancer, predominantly acute myeloid leukemia.; Fanconi anemia, complementation group G, 614082; Fanconi anemia complementation group G; malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii); pre- and postnatal growth retardation
Growth failure v0.0 FANCF Zornitza Stark gene: FANCF was added
gene: FANCF was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FANCF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCF were set to 10615118
Phenotypes for gene: FANCF were set to Fanconi anemia, complementation group F, 603467; Fanconi anemia; 603467 Fanconi anemia, complementation group F; Fanconi Anemia
Growth failure v0.0 FANCE Zornitza Stark gene: FANCE was added
gene: FANCE was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FANCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCE were set to 7662964; 10205272; 9147877; 9382107
Phenotypes for gene: FANCE were set to Fanconi anemia; Fanconi anemia, complementation group E, 600901; 600901 Fanconi anemia, complementation group E; Fanconi Anemia
Growth failure v0.0 FANCD2 Zornitza Stark gene: FANCD2 was added
gene: FANCD2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FANCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCD2 were set to 11239454
Phenotypes for gene: FANCD2 were set to Fanconi anemia; 227646 Fanconi anemia, complementation group D2; Fanconi anemia, complementation group D2, 227646; Fanconi Anemia
Growth failure v0.0 FANCC Zornitza Stark gene: FANCC was added
gene: FANCC was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FANCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCC were set to 16493006; 1574115
Phenotypes for gene: FANCC were set to hypogonadism and reduced fertility; Fanconi Anemia; bone marrow failure; a typical facial appearance with small head, eyes, and mouth; Fanconi anemia, complementation group C, 227645; cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots); hearing loss; Fanconi anemia; and susceptibility to cancer, predominantly acute myeloid leukemia.; 227645 Fanconi anemia, complementation group C; malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii); pre- and postnatal growth retardation
Growth failure v0.0 FANCB Zornitza Stark gene: FANCB was added
gene: FANCB was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FANCB was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: FANCB were set to Fanconi anemia, complementation group B, 300514; Falcon anemia; VACTERL Association with Hydrocephalus; Fanconi Anaemia; Fanconi Anemia Type B; 300514 Fanconi anemia, complementation group B; Fanconi anemia; Fanconi Anemia, X-Linked
Growth failure v0.0 FANCA Zornitza Stark gene: FANCA was added
gene: FANCA was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: FANCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCA were set to 16493006; 8896563
Phenotypes for gene: FANCA were set to hypogonadism and reduced fertility; Fanconi Anemia; bone marrow failure; a typical facial appearance with small head, eyes, and mouth; 227650 Fanconi anemia complementation group A; cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots); hearing loss; Fanconi anemia; and susceptibility to cancer, predominantly acute myeloid leukemia.; Fanconi anemia, complementation group A, 227650; malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii); pre- and postnatal growth retardation
Growth failure v0.0 ERCC4 Zornitza Stark gene: ERCC4 was added
gene: ERCC4 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: ERCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC4 were set to 23623386; 23623389; 24027083
Phenotypes for gene: ERCC4 were set to 615272 Fanconi anemia, complementation group Q; Fanconi anemia, complementation group Q, 615272
Growth failure v0.0 CUL7 Zornitza Stark gene: CUL7 was added
gene: CUL7 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: CUL7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CUL7 were set to 3M; 3-M syndrome 1, 273750
Growth failure v0.0 CDKN1C Zornitza Stark gene: CDKN1C was added
gene: CDKN1C was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: CDKN1C was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Phenotypes for gene: CDKN1C were set to Beckwith-Wiedemann syndrome, 130650; Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies; SRS/BWS
Growth failure v0.0 CCDC8 Zornitza Stark gene: CCDC8 was added
gene: CCDC8 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: CCDC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC8 were set to 21737058
Phenotypes for gene: CCDC8 were set to 3M; 3-M syndrome 3, 614205
Growth failure v0.0 CBL Zornitza Stark gene: CBL was added
gene: CBL was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: CBL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CBL were set to 20619386; 20543203; 19571318
Phenotypes for gene: CBL were set to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia; NOONAN SYNDROME-LIKE DISORDER WITH OR WITHOUT JUVENILE MEYLOMONOCYTIC LEUKEMIA
Mode of pathogenicity for gene: CBL was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 BRIP1 Zornitza Stark gene: BRIP1 was added
gene: BRIP1 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: BRIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRIP1 were set to 14630800; 16153896; 16116424; 16116423
Phenotypes for gene: BRIP1 were set to Fanconi anemia, complementation group J, 609054; 609054 Fanconi anemia, complementation group J
Growth failure v0.0 BRCA2 Zornitza Stark gene: BRCA2 was added
gene: BRCA2 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: BRCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRCA2 were set to 24395671; 11239453; 14670928; 12065746; 28185119
Phenotypes for gene: BRCA2 were set to Fanconi anemia, complementation group D1, 605724; 605724 Fanconi anemia, complementation group D1
Growth failure v0.0 BRAF Zornitza Stark gene: BRAF was added
gene: BRAF was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to 16474404; 21396583; 16825433; 19206169
Phenotypes for gene: BRAF were set to Noonan Syndrome; LEOPARD Syndrome; Cardiofaciocutaneous Syndrome; Cardiofaciocutaneous syndrome; Cardio-facio-cutaneous syndrome; LEOPARD syndrome 3
Mode of pathogenicity for gene: BRAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Growth failure v0.0 BLM Zornitza Stark gene: BLM was added
gene: BLM was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: BLM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BLM were set to Bloom syndrome, 210900; 210900 Bloom syndrome; Bloom
Growth failure v0.0 ANKRD11 Zornitza Stark gene: ANKRD11 was added
gene: ANKRD11 was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: ANKRD11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANKRD11 were set to 21782149
Phenotypes for gene: ANKRD11 were set to KBG syndrome, 148050; KBG
Growth failure v0.0 ACAN Zornitza Stark gene: ACAN was added
gene: ACAN was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green
Mode of inheritance for gene: ACAN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ACAN were set to 24762113; 27870580
Phenotypes for gene: ACAN were set to Spondyloepimetaphyseal dysplasia, aggrecan type (AR), 612813; ?Spondyloepiphyseal dysplasia, Kimberley type (AD), 608361; short stature, accelerated bone maturation, Spondyloepiphyseal dysplasia, early onset osteoarthritis; Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (AD), 165800
Growth failure v0.0 Zornitza Stark Added panel Growth failure in early childhood
Mendeliome v0.8445 SYP Elena Savva reviewed gene: SYP: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 23966691, 19377476; Phenotypes: Mental retardation, X-linked 96 MIM#300802; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8445 ZIC3 Zornitza Stark Marked gene: ZIC3 as ready
Mendeliome v0.8445 ZIC3 Zornitza Stark Gene: zic3 has been classified as Green List (High Evidence).
Mendeliome v0.8445 ZIC3 Zornitza Stark Phenotypes for gene: ZIC3 were changed from to Congenital heart defects, nonsyndromic, 1, X-linked (MIM#306955); Heterotaxy, visceral, 1, X-linked (MIM#306955); VACTERL association, X-linked, MIM# 314390
Mendeliome v0.8444 ZIC3 Zornitza Stark Publications for gene: ZIC3 were set to
Mendeliome v0.8443 ZIC3 Zornitza Stark Mode of inheritance for gene: ZIC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8442 ZIC3 Zornitza Stark edited their review of gene: ZIC3: Changed phenotypes: Congenital heart defects, nonsyndromic, 1, X-linked (MIM#306955), Heterotaxy, visceral, 1, X-linked (MIM#306955), VACTERL association, X-linked, MIM# 314390
Mendeliome v0.8442 ZIC3 Zornitza Stark changed review comment from: This gene belongs on the Heterotaxy panel.; to: Well established gene-disease associations.
Mendeliome v0.8442 ZIC3 Zornitza Stark edited their review of gene: ZIC3: Changed rating: GREEN
Mendeliome v0.8442 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Mendeliome v0.8442 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Mendeliome v0.8442 VPS13B Zornitza Stark Phenotypes for gene: VPS13B were changed from to Cohen syndrome, MIM# 216550
Mendeliome v0.8441 VPS13B Zornitza Stark Mode of inheritance for gene: VPS13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8440 VPS13B Zornitza Stark reviewed gene: VPS13B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cohen syndrome, MIM# 216550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8440 VPS13B Zornitza Stark Deleted their review
Mendeliome v0.8440 TULP1 Zornitza Stark Marked gene: TULP1 as ready
Mendeliome v0.8440 TULP1 Zornitza Stark Gene: tulp1 has been classified as Green List (High Evidence).
Mendeliome v0.8440 TULP1 Zornitza Stark Phenotypes for gene: TULP1 were changed from to Retinitis pigmentosa 14 M(MIM#600132); Leber congenital amaurosis 15, MIM# 613843
Mendeliome v0.8439 TULP1 Zornitza Stark Publications for gene: TULP1 were set to
Mendeliome v0.8438 TULP1 Zornitza Stark Mode of inheritance for gene: TULP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8437 TULP1 Zornitza Stark commented on gene: TULP1: Several families also reported with LCA.
Mendeliome v0.8437 TULP1 Zornitza Stark edited their review of gene: TULP1: Changed publications: 15024725
Mendeliome v0.8437 TULP1 Zornitza Stark reviewed gene: TULP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis 15, MIM# 613843; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8437 TOPORS Zornitza Stark Marked gene: TOPORS as ready
Mendeliome v0.8437 TOPORS Zornitza Stark Gene: topors has been classified as Green List (High Evidence).
Mendeliome v0.8437 TOPORS Zornitza Stark Phenotypes for gene: TOPORS were changed from to Retinitis pigmentosa 31 (MIM#609923)
Mendeliome v0.8436 TOPORS Zornitza Stark Publications for gene: TOPORS were set to
Mendeliome v0.8435 TOPORS Zornitza Stark Mode of inheritance for gene: TOPORS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3989 SUFU Zornitza Stark Phenotypes for gene: SUFU were changed from Joubert syndrome 32, MIM#617757 to Joubert syndrome 32, MIM#617757; SUFU-related neurodevelopmental syndrome
Intellectual disability syndromic and non-syndromic v0.3988 SUFU Zornitza Stark Publications for gene: SUFU were set to 28965847
Intellectual disability syndromic and non-syndromic v0.3987 SUFU Zornitza Stark Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3986 SUFU Zornitza Stark Classified gene: SUFU as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3986 SUFU Zornitza Stark Gene: sufu has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3985 SUFU Zornitza Stark edited their review of gene: SUFU: Added comment: Heterozygous truncating variants in SUFU in 15 subjects from 6 unrelated families of various ethnic backgrounds (familial and de novo cases). Clinical features of early-onset (congenital) ocular ataxia and developmental delay, with some phenotypic variability. Neuroimaging revealed subtle cerebellar changes, but no full-blown molar tooth sign of Joubert syndrome. Paper reports that condition reported here and SUFU-associated Basal cell nevus syndrome (Gorlin) are likely allelic disorders, as there is currently no convincing evidence for a clinical overlap.

Functional studies showed no differences in cilia occurrence, morphology, or localization of ciliary proteins, such as smoothened. However, analysis of expression of HH signaling target genes detected a significant increase in the general signaling activity in COMA patient–derived fibroblasts compared with control cells. We observed higher basal HH signaling activity resulting in increased basal expression levels of GLI1, GLI2, GLI3, and Patched1. Neuroimaging revealed subtle cerebellar changes, but no full-blown molar tooth sign. Knockout mice with SuFu deficiency demonstrated that SuFu is required for proper midhindbrain patterning and controls cerebellar patterning.; Changed rating: GREEN; Changed publications: 28965847, 33024317; Changed phenotypes: Joubert syndrome 32, MIM#617757, SUFU-related neurodevelopmental syndrome; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8434 SUFU Zornitza Stark Marked gene: SUFU as ready
Mendeliome v0.8434 SUFU Zornitza Stark Gene: sufu has been classified as Green List (High Evidence).
Mendeliome v0.8434 SUFU Zornitza Stark Phenotypes for gene: SUFU were changed from to Joubert syndrome 32, MIM#617757; SUFU-related neurodevelopmental syndrome; Basal cell nevus syndrome, MIM# 109400
Mendeliome v0.8433 SUFU Zornitza Stark Publications for gene: SUFU were set to
Mendeliome v0.8432 SUFU Zornitza Stark Mode of inheritance for gene: SUFU was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8431 SUFU Zornitza Stark edited their review of gene: SUFU: Changed phenotypes: Joubert syndrome 32, MIM#617757, SUFU-related neurodevelopmental syndrome, Basal cell nevus syndrome, MIM# 109400
Mendeliome v0.8431 SUFU Zornitza Stark changed review comment from: Two unrelated families described with what are postulated to be hypomorphic bi-allelic variants in this gene and Joubert syndrome. Note gene also causes dominant Basal Cell Nevus Syndrome.; to: Two unrelated families described with what are postulated to be hypomorphic bi-allelic variants in this gene and Joubert syndrome.
Mendeliome v0.8431 SUFU Zornitza Stark edited their review of gene: SUFU: Added comment: Mono-allelic variants are also associated with Basal cell nevus syndrome/predisposition to medulloblastoma.; Changed rating: GREEN; Changed publications: 28965847, 19533801, 31485359; Changed phenotypes: Joubert syndrome 32, MIM#617757, Basal cell nevus syndrome, MIM# 109400; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8431 SCNN1G Zornitza Stark Marked gene: SCNN1G as ready
Mendeliome v0.8431 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
Mendeliome v0.8431 SCNN1G Zornitza Stark Phenotypes for gene: SCNN1G were changed from to Liddle syndrome 2, MIM# 618114; Pseudohypoaldosteronism, type I, MIM# 264350
Mendeliome v0.8430 SCNN1G Zornitza Stark Publications for gene: SCNN1G were set to
Mendeliome v0.8429 SCNN1G Zornitza Stark Mode of inheritance for gene: SCNN1G was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8428 SCNN1G Zornitza Stark Deleted their comment
Mendeliome v0.8428 SCNN1G Zornitza Stark edited their review of gene: SCNN1G: Added comment: Variants resulting in constitutive activation of epithelial sodium channel activity have been demonstrated in the beta and gamma subunits as the cause of the autosomal dominant form of hypertension, Liddle syndrome, which is characterized by volume expansion, hypokalemia, and alkalosis.

Variants causing loss of epithelial sodium channel activity cause the converse phenotype of volume depletion, hyperkalaemia and acidosis characteristic of patients with pseudohypoaldosteronism type I.

Well established gene-disease associations.; Changed rating: GREEN; Changed phenotypes: Liddle syndrome 2, MIM# 618114, Pseudohypoaldosteronism, type I, MIM# 264350; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8428 SCLT1 Zornitza Stark Marked gene: SCLT1 as ready
Mendeliome v0.8428 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Green List (High Evidence).
Mendeliome v0.8428 SCLT1 Zornitza Stark Phenotypes for gene: SCLT1 were changed from to Orofaciodigital syndrome type IX; Senior-Loken syndrome; Bardet-Biedl syndrome
Mendeliome v0.8427 SCLT1 Zornitza Stark Publications for gene: SCLT1 were set to
Mendeliome v0.8426 SCLT1 Zornitza Stark Mode of inheritance for gene: SCLT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8425 RPGR Zornitza Stark Marked gene: RPGR as ready
Mendeliome v0.8425 RPGR Zornitza Stark Gene: rpgr has been classified as Green List (High Evidence).
Mendeliome v0.8425 RPGR Zornitza Stark Phenotypes for gene: RPGR were changed from to Retinitis pigmentosa 3 (MIM#300029)
Mendeliome v0.8424 RPGR Zornitza Stark Publications for gene: RPGR were set to
Mendeliome v0.8423 RPGR Zornitza Stark Mode of inheritance for gene: RPGR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8422 PRKCSH Zornitza Stark Marked gene: PRKCSH as ready
Mendeliome v0.8422 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Green List (High Evidence).
Mendeliome v0.8422 PRKCSH Zornitza Stark Phenotypes for gene: PRKCSH were changed from to Polycystic liver disease 1 (MIM#174050)
Mendeliome v0.8421 PRKCSH Zornitza Stark Publications for gene: PRKCSH were set to
Mendeliome v0.8420 PRKCSH Zornitza Stark Mode of pathogenicity for gene: PRKCSH was changed from to None
Mendeliome v0.8419 PRKCSH Zornitza Stark Mode of inheritance for gene: PRKCSH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8418 PRKCSH Zornitza Stark reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 11047756, 29038287, 12529853, 12577059; Phenotypes: Polycystic liver disease 1 (MIM#174050); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polycystic liver disease v0.27 PRKCSH Zornitza Stark commented on gene: PRKCSH: Well established gene-disease association.
Mendeliome v0.8418 PRKCSH Zornitza Stark Deleted their review
Mendeliome v0.8418 POC1B Zornitza Stark Marked gene: POC1B as ready
Mendeliome v0.8418 POC1B Zornitza Stark Gene: poc1b has been classified as Green List (High Evidence).
Mendeliome v0.8418 POC1B Zornitza Stark Phenotypes for gene: POC1B were changed from to Cone-rod dystrophy 20 (MIM#615973)
Mendeliome v0.8417 POC1B Zornitza Stark Publications for gene: POC1B were set to
Mendeliome v0.8416 POC1B Zornitza Stark Mode of inheritance for gene: POC1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8415 POC1B Zornitza Stark Deleted their review
Mendeliome v0.8415 POC1B Zornitza Stark Deleted their comment
Mendeliome v0.8415 PMM2 Zornitza Stark Marked gene: PMM2 as ready
Mendeliome v0.8415 PMM2 Zornitza Stark Gene: pmm2 has been classified as Green List (High Evidence).
Mendeliome v0.8415 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia (MIM#212065)
Mendeliome v0.8414 PMM2 Zornitza Stark Publications for gene: PMM2 were set to
Mendeliome v0.8413 PMM2 Zornitza Stark Mode of inheritance for gene: PMM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8412 PMM2 Zornitza Stark edited their review of gene: PMM2: Added comment: Well established gene-disease association.; Changed rating: GREEN; Changed publications: 28108845
Mendeliome v0.8412 PMM2 Zornitza Stark Deleted their comment
Mendeliome v0.8412 PKHD1 Zornitza Stark Marked gene: PKHD1 as ready
Mendeliome v0.8412 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Mendeliome v0.8412 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200
Mendeliome v0.8411 PKHD1 Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8410 PKHD1 Zornitza Stark changed review comment from: Included due to phenotypic overlap with nephronophthisis.; to: Well established gene-disease association.
Mendeliome v0.8410 MUC1 Zornitza Stark edited their review of gene: MUC1: Changed publications: 29186029, 29156055, 29520014
Mendeliome v0.8410 MUC1 Zornitza Stark Marked gene: MUC1 as ready
Mendeliome v0.8410 MUC1 Zornitza Stark Gene: muc1 has been classified as Green List (High Evidence).
Mendeliome v0.8410 MUC1 Zornitza Stark Phenotypes for gene: MUC1 were changed from to Medullary cystic kidney disease 1 (MIM#174000)
Mendeliome v0.8409 MUC1 Zornitza Stark Publications for gene: MUC1 were set to
Mendeliome v0.8408 MUC1 Zornitza Stark Mode of inheritance for gene: MUC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8407 MUC1 Zornitza Stark Deleted their comment
Mendeliome v0.8407 MUC1 Zornitza Stark edited their review of gene: MUC1: Added comment: Well established gene-disease association, but note main variant type not readily tractable by NGS.; Changed rating: GREEN; Changed mode of pathogenicity: Other; Changed publications: Medullary cystic kidney disease 1 (MIM#174000); Changed phenotypes: Medullary cystic kidney disease 1 (MIM#174000); Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8407 KIF7 Zornitza Stark Marked gene: KIF7 as ready
Mendeliome v0.8407 KIF7 Zornitza Stark Gene: kif7 has been classified as Green List (High Evidence).
Mendeliome v0.8407 KIF7 Zornitza Stark Phenotypes for gene: KIF7 were changed from to Joubert syndrome 12, MIM# 200990; Acrocallosal syndrome, MIM# 200990; MONDO:0008708; Hydrolethalus syndrome 2, MIM# 614120
Mendeliome v0.8406 KIF7 Zornitza Stark Publications for gene: KIF7 were set to
Mendeliome v0.8405 KIF7 Zornitza Stark Mode of inheritance for gene: KIF7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8404 KIAA0753 Zornitza Stark Marked gene: KIAA0753 as ready
Mendeliome v0.8404 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Mendeliome v0.8404 KIAA0753 Zornitza Stark Phenotypes for gene: KIAA0753 were changed from to Orofaciodigital syndrome XV, MIM# 617127; Joubert syndrome
Mendeliome v0.8403 KIAA0753 Zornitza Stark Publications for gene: KIAA0753 were set to
Mendeliome v0.8402 KIAA0753 Zornitza Stark Mode of inheritance for gene: KIAA0753 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8401 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed phenotypes: Orofaciodigital syndrome XV 617127, Joubert syndrome; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8401 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed rating: GREEN
Mendeliome v0.8401 KIAA0586 Zornitza Stark Marked gene: KIAA0586 as ready
Mendeliome v0.8401 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Green List (High Evidence).
Mendeliome v0.8401 KIAA0586 Zornitza Stark Phenotypes for gene: KIAA0586 were changed from to Joubert syndrome 23, MIM# 616490; Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546
Mendeliome v0.8400 KIAA0586 Zornitza Stark Publications for gene: KIAA0586 were set to
Mendeliome v0.8399 KIAA0586 Zornitza Stark Mode of inheritance for gene: KIAA0586 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8398 KIAA0586 Zornitza Stark edited their review of gene: KIAA0586: Changed phenotypes: Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546, Joubert syndrome
Mendeliome v0.8398 IFT52 Zornitza Stark Marked gene: IFT52 as ready
Mendeliome v0.8398 IFT52 Zornitza Stark Gene: ift52 has been classified as Green List (High Evidence).
Mendeliome v0.8398 IFT52 Zornitza Stark Phenotypes for gene: IFT52 were changed from to Short-rib thoracic dysplasia 16 with or without polydactyly, MIM# 617102
Mendeliome v0.8397 IFT52 Zornitza Stark Publications for gene: IFT52 were set to
Mendeliome v0.8396 IFT52 Zornitza Stark Mode of inheritance for gene: IFT52 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8395 IFT27 Zornitza Stark Marked gene: IFT27 as ready
Mendeliome v0.8395 IFT27 Zornitza Stark Gene: ift27 has been classified as Green List (High Evidence).
Mendeliome v0.8395 IFT27 Zornitza Stark Phenotypes for gene: IFT27 were changed from to Bardet-Biedl syndrome 19, MIM#615996
Mendeliome v0.8394 IFT27 Zornitza Stark Publications for gene: IFT27 were set to
Mendeliome v0.8393 IFT27 Zornitza Stark Mode of inheritance for gene: IFT27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.643 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Mitochondrial disease v0.643 POLG2 Zornitza Stark Gene: polg2 has been classified as Green List (High Evidence).
Mendeliome v0.8392 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Mendeliome v0.8392 POLG2 Zornitza Stark Gene: polg2 has been classified as Green List (High Evidence).
Mendeliome v0.8392 POLG2 Zornitza Stark Phenotypes for gene: POLG2 were changed from to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131; Mitochondrial DNA depletion syndrome 16 , MIM# 618528
Mendeliome v0.8391 POLG2 Zornitza Stark Publications for gene: POLG2 were set to
Mendeliome v0.8390 POLG2 Zornitza Stark Mode of inheritance for gene: POLG2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.643 POLG2 Zornitza Stark Phenotypes for gene: POLG2 were changed from to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131; Mitochondrial DNA depletion syndrome 16 , MIM# 618528
Mendeliome v0.8389 POLG2 Zornitza Stark reviewed gene: POLG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16685652, 21555342, 27592148, 31778857; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131, Mitochondrial DNA depletion syndrome 16 , MIM# 618528; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.642 POLG2 Zornitza Stark Publications for gene: POLG2 were set to
Mitochondrial disease v0.641 POLG2 Zornitza Stark Mode of inheritance for gene: POLG2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.640 POLG2 Zornitza Stark reviewed gene: POLG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16685652, 21555342, 27592148, 31778857; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131, Mitochondrial DNA depletion syndrome 16 , MIM# 618528; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Marked gene: PCDHGC4 as ready
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Classified gene: PCDHGC4 as Green List (high evidence)
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Mendeliome v0.8388 PCDHGC4 Zornitza Stark gene: PCDHGC4 was added
gene: PCDHGC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PCDHGC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDHGC4 were set to 34244665
Phenotypes for gene: PCDHGC4 were set to Intellectual disability; Seizures
Review for gene: PCDHGC4 was set to GREEN
Added comment: Eight variants reported in 19 members of nine unreleted families with a neurodevelopmental syndrome. Severe or moderate intellectual disabilty in eight families and seizures in four families. Four of the variants were LoF, in silico analysis of the remaining missense (n=3) and splice variants were predicted to be pathogenic.
Sources: Literature
Genetic Epilepsy v0.1144 PCDHGC4 Zornitza Stark Classified gene: PCDHGC4 as Green List (high evidence)
Genetic Epilepsy v0.1144 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1143 PCDHGC4 Zornitza Stark Classified gene: PCDHGC4 as Green List (high evidence)
Genetic Epilepsy v0.1143 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1142 PCDHGC4 Zornitza Stark Marked gene: PCDHGC4 as ready
Genetic Epilepsy v0.1142 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1142 PCDHGC4 Zornitza Stark gene: PCDHGC4 was added
gene: PCDHGC4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PCDHGC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDHGC4 were set to 34244665
Phenotypes for gene: PCDHGC4 were set to Intellectual disability; Seizures
Review for gene: PCDHGC4 was set to GREEN
Added comment: Eight variants reported in 19 members of nine unreleted families with a neurodevelopmental syndrome. Severe or moderate intellectual disabilty in eight families and seizures in four families. Four of the variants were LoF, in silico analysis of the remaining missense (n=3) and splice variants were predicted to be pathogenic.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3985 PCDHGC4 Zornitza Stark Marked gene: PCDHGC4 as ready
Intellectual disability syndromic and non-syndromic v0.3985 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3985 PCDHGC4 Zornitza Stark Classified gene: PCDHGC4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3985 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3984 PCDHGC4 Zornitza Stark gene: PCDHGC4 was added
gene: PCDHGC4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PCDHGC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDHGC4 were set to 34244665
Phenotypes for gene: PCDHGC4 were set to Intellectual disability; Seizures
Review for gene: PCDHGC4 was set to GREEN
Added comment: Eight variants reported in 19 members of nine unreleted families with a neurodevelopmental syndrome. Severe or moderate intellectual disabilty in eight families and seizures in four families. Four of the variants were LoF, in silico analysis of the remaining missense (n=3) and splice variants were predicted to be pathogenic.
Sources: Literature
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Marked gene: ATP6V0A4 as ready
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Gene: atp6v0a4 has been classified as Green List (High Evidence).
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Phenotypes for gene: ATP6V0A4 were changed from to Renal tubular acidosis, distal, autosomal recessive, MIM#602722
Mendeliome v0.8386 ATP6V0A4 Zornitza Stark Publications for gene: ATP6V0A4 were set to
Mendeliome v0.8385 ATP6V0A4 Zornitza Stark Mode of inheritance for gene: ATP6V0A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8384 ATP6V0A4 Zornitza Stark reviewed gene: ATP6V0A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12414817, 10973252; Phenotypes: Renal tubular acidosis, distal, autosomal recessive, MIM#602722; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3983 CEP85L Zornitza Stark Marked gene: CEP85L as ready
Intellectual disability syndromic and non-syndromic v0.3983 CEP85L Zornitza Stark Gene: cep85l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3983 CEP85L Zornitza Stark Classified gene: CEP85L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3983 CEP85L Zornitza Stark Gene: cep85l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3982 CEP85L Zornitza Stark gene: CEP85L was added
gene: CEP85L was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: CEP85L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CEP85L were set to 32097630
Phenotypes for gene: CEP85L were set to Lissencephaly, posterior predominant
Review for gene: CEP85L was set to GREEN
Added comment: Thirteen individuals reported with mono allelic variants in this gene, inherited in two of the families. Mouse model had neuronal migration defects.
Sources: Expert Review
Mendeliome v0.8384 ICK Zornitza Stark Marked gene: ICK as ready
Mendeliome v0.8384 ICK Zornitza Stark Gene: ick has been classified as Green List (High Evidence).
Mendeliome v0.8384 ICK Zornitza Stark Phenotypes for gene: ICK were changed from to Endocrine-cerebroosteodysplasia (MIM#612651)
Mendeliome v0.8383 ICK Zornitza Stark Publications for gene: ICK were set to
Mendeliome v0.8382 ICK Zornitza Stark Mode of inheritance for gene: ICK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8381 HNF1B Zornitza Stark Marked gene: HNF1B as ready
Mendeliome v0.8381 HNF1B Zornitza Stark Gene: hnf1b has been classified as Green List (High Evidence).
Mendeliome v0.8381 HNF1B Zornitza Stark Tag SV/CNV tag was added to gene: HNF1B.
Mendeliome v0.8381 HNF1B Zornitza Stark Phenotypes for gene: HNF1B were changed from to Renal cysts and diabetes syndrome, MIM# 137920
Mendeliome v0.8380 HNF1B Zornitza Stark Mode of inheritance for gene: HNF1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8379 HNF1B Zornitza Stark changed review comment from: Included due to phenotypic overlap with nephronophthisis.; to: Well established gene-disease association, CNVs common.
Mendeliome v0.8379 GDF1 Zornitza Stark Marked gene: GDF1 as ready
Mendeliome v0.8379 GDF1 Zornitza Stark Gene: gdf1 has been classified as Green List (High Evidence).
Mendeliome v0.8379 GDF1 Zornitza Stark Phenotypes for gene: GDF1 were changed from to Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530
Mendeliome v0.8378 GDF1 Zornitza Stark Publications for gene: GDF1 were set to
Mendeliome v0.8377 GDF1 Zornitza Stark Mode of inheritance for gene: GDF1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.8376 GDF1 Zornitza Stark edited their review of gene: GDF1: Added comment: PMID: 32144877 - founder PTC in Arab population causing congenital heart detects AND right isomerism in 3 (unrelated?) families. Reviews other publications and reports additional chet (two PTC) or homozygous (missense) families with situs inversus and/or heart defects. No apparent genotype-phenotype correlation btw dominant and recessive disease.; Changed rating: GREEN; Changed publications: 32144877; Changed phenotypes: Congenital heart defects, multiple types, 6 613854, Right atrial isomerism (Ivemark) 208530; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8376 EVC2 Zornitza Stark Marked gene: EVC2 as ready
Mendeliome v0.8376 EVC2 Zornitza Stark Gene: evc2 has been classified as Green List (High Evidence).
Mendeliome v0.8376 EVC2 Zornitza Stark Phenotypes for gene: EVC2 were changed from to Ellis-van Creveld syndrome (MIM#225500)
Mendeliome v0.8375 EVC2 Zornitza Stark Publications for gene: EVC2 were set to
Mendeliome v0.8374 EVC2 Zornitza Stark Mode of inheritance for gene: EVC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8373 EVC Zornitza Stark Marked gene: EVC as ready
Mendeliome v0.8373 EVC Zornitza Stark Gene: evc has been classified as Green List (High Evidence).
Mendeliome v0.8373 EVC Zornitza Stark Phenotypes for gene: EVC were changed from to Ellis-van Creveld syndrome, MIM# 225500
Mendeliome v0.8372 EVC Zornitza Stark Publications for gene: EVC were set to
Mendeliome v0.8371 EVC Zornitza Stark Mode of inheritance for gene: EVC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8370 DCDC2 Zornitza Stark Marked gene: DCDC2 as ready
Mendeliome v0.8370 DCDC2 Zornitza Stark Gene: dcdc2 has been classified as Green List (High Evidence).
Mendeliome v0.8370 DCDC2 Zornitza Stark Phenotypes for gene: DCDC2 were changed from to Nephronophthisis 19, MIM# 616217; Sclerosing cholangitis, neonatal, MIM# 617394
Mendeliome v0.8369 DCDC2 Zornitza Stark Publications for gene: DCDC2 were set to
Mendeliome v0.8368 DCDC2 Zornitza Stark Mode of inheritance for gene: DCDC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8367 DCDC2 Zornitza Stark changed review comment from: Only a single case with nephronophthisis, most reports are for cholangitis, though zebrafish model has renal cysts.; to: At least 5 families reported with cholangitis, and two with nephronophthisis, though zebrafish model has renal cysts.
Mendeliome v0.8367 DCDC2 Zornitza Stark edited their review of gene: DCDC2: Changed rating: GREEN; Changed publications: 25557784, 27319779, 27469900; Changed phenotypes: Nephronophthisis 19, MIM# 616217, Sclerosing cholangitis, neonatal, MIM# 617394; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8367 CRELD1 Zornitza Stark Marked gene: CRELD1 as ready
Mendeliome v0.8367 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Mendeliome v0.8367 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from to Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217
Mendeliome v0.8366 CRELD1 Zornitza Stark Publications for gene: CRELD1 were set to
Mendeliome v0.8365 CRELD1 Zornitza Stark Mode of inheritance for gene: CRELD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8364 CRELD1 Zornitza Stark reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740159; Phenotypes: Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8364 CRB2 Zornitza Stark Marked gene: CRB2 as ready
Mendeliome v0.8364 CRB2 Zornitza Stark Gene: crb2 has been classified as Green List (High Evidence).
Mendeliome v0.8364 CRB2 Zornitza Stark Phenotypes for gene: CRB2 were changed from to Ventriculomegaly with cystic kidney disease, MIM# 219730; Focal segmental glomerulosclerosis 9, MIM# 616220
Mendeliome v0.8363 CRB2 Zornitza Stark Publications for gene: CRB2 were set to
Mendeliome v0.8362 CRB2 Zornitza Stark Mode of inheritance for gene: CRB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8361 CRB2 Zornitza Stark changed review comment from: More than 7 unrelated families reported, mouse model. Some have presented predominantly with proteinuria, and some more with a multi-system ciliopathy phenotype, and yet others with RP.; to: VM with renal disease: More than 7 unrelated families reported, mouse model. Some have presented predominantly with proteinuria, and some more with a multi-system ciliopathy phenotype, and yet others with RP.

FSGS: at least 4 families and animal model.
Mendeliome v0.8361 CRB2 Zornitza Stark edited their review of gene: CRB2: Changed publications: 25557780, 33687977, 32051522, 30212996, 33575434, 31438467, 30593785, 25557779; Changed phenotypes: Ventriculomegaly with cystic kidney disease, MIM# 219730, Focal segmental glomerulosclerosis 9, MIM# 616220
Mendeliome v0.8361 CEP55 Zornitza Stark Marked gene: CEP55 as ready
Mendeliome v0.8361 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Mendeliome v0.8361 CEP55 Zornitza Stark Phenotypes for gene: CEP55 were changed from to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500
Mendeliome v0.8360 CEP55 Zornitza Stark Publications for gene: CEP55 were set to
Mendeliome v0.8359 CEP55 Zornitza Stark Mode of inheritance for gene: CEP55 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8358 CEP55 Zornitza Stark reviewed gene: CEP55: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8358 CENPF Zornitza Stark Marked gene: CENPF as ready
Mendeliome v0.8358 CENPF Zornitza Stark Gene: cenpf has been classified as Green List (High Evidence).
Mendeliome v0.8358 CENPF Zornitza Stark Phenotypes for gene: CENPF were changed from to Stromme syndrome (MIM#243605)
Mendeliome v0.8357 CENPF Zornitza Stark Publications for gene: CENPF were set to
Mendeliome v0.8356 CENPF Zornitza Stark Mode of inheritance for gene: CENPF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8355 C8orf37 Zornitza Stark Marked gene: C8orf37 as ready
Mendeliome v0.8355 C8orf37 Zornitza Stark Gene: c8orf37 has been classified as Green List (High Evidence).
Mendeliome v0.8355 C8orf37 Zornitza Stark Phenotypes for gene: C8orf37 were changed from to Bardet-Biedl syndrome 21, MIM#617406; Retinitis pigmentosa 64, MIM#614500
Mendeliome v0.8354 C8orf37 Zornitza Stark Publications for gene: C8orf37 were set to
Mendeliome v0.8353 C8orf37 Zornitza Stark Mode of inheritance for gene: C8orf37 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8352 C2CD3 Zornitza Stark Marked gene: C2CD3 as ready
Mendeliome v0.8352 C2CD3 Zornitza Stark Gene: c2cd3 has been classified as Green List (High Evidence).
Mendeliome v0.8352 C2CD3 Zornitza Stark Phenotypes for gene: C2CD3 were changed from to Orofaciodigital syndrome XIV, MIM# 615948; MONDO:0014413
Mendeliome v0.8351 C2CD3 Zornitza Stark Publications for gene: C2CD3 were set to
Mendeliome v0.8350 C2CD3 Zornitza Stark Mode of inheritance for gene: C2CD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8348 CHRM3 Zornitza Stark Marked gene: CHRM3 as ready
Mendeliome v0.8348 CHRM3 Zornitza Stark Gene: chrm3 has been classified as Green List (High Evidence).
Mendeliome v0.8348 CHRM3 Zornitza Stark Phenotypes for gene: CHRM3 were changed from to Prune belly syndrome, MIM# 100100
Mendeliome v0.8347 CHRM3 Zornitza Stark Publications for gene: CHRM3 were set to
Mendeliome v0.8346 CHRM3 Zornitza Stark Mode of inheritance for gene: CHRM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8345 CHRM3 Zornitza Stark reviewed gene: CHRM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22077972, 31441039; Phenotypes: Prune belly syndrome, MIM# 100100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.46 CHRM3 Zornitza Stark Marked gene: CHRM3 as ready
Gastrointestinal neuromuscular disease v0.46 CHRM3 Zornitza Stark Gene: chrm3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.46 CHRM3 Zornitza Stark Phenotypes for gene: CHRM3 were changed from Posterior urethral valves & prune belly syndrome to Prune belly syndrome, MIM# 100100; Posterior urethral valves & prune belly syndrome
Gastrointestinal neuromuscular disease v0.45 CHRM3 Zornitza Stark Publications for gene: CHRM3 were set to
Gastrointestinal neuromuscular disease v0.44 CHRM3 Zornitza Stark edited their review of gene: CHRM3: Changed rating: GREEN
Gastrointestinal neuromuscular disease v0.44 CHRM3 Zornitza Stark reviewed gene: CHRM3: Rating: ; Mode of pathogenicity: None; Publications: 22077972, 31441039; Phenotypes: Prune belly syndrome, MIM# 100100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.44 ACTA2 Zornitza Stark Marked gene: ACTA2 as ready
Gastrointestinal neuromuscular disease v0.44 ACTA2 Zornitza Stark Gene: acta2 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.44 ACTA2 Zornitza Stark Phenotypes for gene: ACTA2 were changed from Vascular aneurysms & dissections, patent ductus arteriosus, mydriasis to Multisystemic smooth muscle dysfunction syndrome, MIM# 613834; Vascular aneurysms & dissections, patent ductus arteriosus, mydriasis
Gastrointestinal neuromuscular disease v0.43 ACTA2 Zornitza Stark Publications for gene: ACTA2 were set to
Gastrointestinal neuromuscular disease v0.42 ACTA2 Zornitza Stark Mode of inheritance for gene: ACTA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gastrointestinal neuromuscular disease v0.41 ACTA2 Zornitza Stark reviewed gene: ACTA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20734336, 29300374; Phenotypes: Multisystemic smooth muscle dysfunction syndrome, MIM# 613834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Ciliopathies and Nephronophthisis v1.0 Zornitza Stark promoted panel to version 1.0
Renal Ciliopathies and Nephronophthisis v0.322 IFT74 Zornitza Stark Marked gene: IFT74 as ready
Renal Ciliopathies and Nephronophthisis v0.322 IFT74 Zornitza Stark Added comment: Comment when marking as ready: No renal involvement in the individuals reported with the Joubert phenotype.
Renal Ciliopathies and Nephronophthisis v0.322 IFT74 Zornitza Stark Gene: ift74 has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v0.322 C2CD3 Zornitza Stark edited their review of gene: C2CD3: Changed rating: AMBER
Renal Ciliopathies and Nephronophthisis v0.322 EVC Zornitza Stark changed review comment from: Primarily a skeletal ciliopathy, short ribs and narrow chest are a feature.; to: Primarily a skeletal ciliopathy, short ribs and narrow chest are a feature. Renal abnormalities not prominent.
Renal Ciliopathies and Nephronophthisis v0.322 EVC Zornitza Stark edited their review of gene: EVC: Changed rating: RED
Mendeliome v0.8345 ARHGAP42 Zornitza Stark Marked gene: ARHGAP42 as ready
Mendeliome v0.8345 ARHGAP42 Zornitza Stark Gene: arhgap42 has been classified as Red List (Low Evidence).
Mendeliome v0.8345 ARHGAP42 Zornitza Stark gene: ARHGAP42 was added
gene: ARHGAP42 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGAP42 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGAP42 were set to 34232960
Phenotypes for gene: ARHGAP42 were set to Interstitial lung disease; systemic hypertension; immunological abnormalities
Review for gene: ARHGAP42 was set to RED
Added comment: Single individual reported with homozygous LoF variant, chILD disorder, systemic hypertension, and immunological findings.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.29 ARHGAP42 Zornitza Stark Marked gene: ARHGAP42 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.29 ARHGAP42 Zornitza Stark Gene: arhgap42 has been classified as Red List (Low Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.29 ARHGAP42 Zornitza Stark Phenotypes for gene: ARHGAP42 were changed from to Interstitial lung disease; systemic hypertension; immunological abnormalities
Pulmonary Fibrosis_Interstitial Lung Disease v0.28 ARHGAP42 Zornitza Stark gene: ARHGAP42 was added
gene: ARHGAP42 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: ARHGAP42 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGAP42 were set to 34232960
Review for gene: ARHGAP42 was set to RED
Added comment: Single individual reported with homozygous LoF variant, chILD disorder, systemic hypertension, and immunological findings.
Sources: Literature
Renal Ciliopathies and Nephronophthisis v0.322 SCLT1 Zornitza Stark Phenotypes for gene: SCLT1 were changed from Orofaciodigital syndrome type IX; Senior-Loken syndrome to Senior-Loken syndrome; Bardet-Biedl syndrome
Renal Ciliopathies and Nephronophthisis v0.321 SCLT1 Zornitza Stark Classified gene: SCLT1 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v0.321 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.320 SCLT1 Zornitza Stark changed review comment from: Reports of individual patients with overlapping features suggestive of ciliopathy, mouse model recapitulates phenotype.
Sources: Expert list; to: Reports of individual patients with overlapping features suggestive of ciliopathy, mouse model recapitulates phenotype. Two individuals with BBS and one with Senior-Loken, with renal involvement.
Sources: Expert list
Renal Ciliopathies and Nephronophthisis v0.320 SCLT1 Zornitza Stark edited their review of gene: SCLT1: Changed phenotypes: Orofaciodigital syndrome type IX, Senior-Loken syndrome, Bardet-Biedl syndrome
Renal Ciliopathies and Nephronophthisis v0.320 WDR34 Zornitza Stark changed review comment from: At least 5 families reported with a skeletal ciliopathy, supportive mouse model and other functional data.; to: At least 5 families reported with a skeletal ciliopathy, supportive mouse model and other functional data; however, no renal involvement.
Renal Ciliopathies and Nephronophthisis v0.320 WDR34 Zornitza Stark edited their review of gene: WDR34: Changed rating: RED
Renal Ciliopathies and Nephronophthisis v0.320 WDR60 Zornitza Stark Marked gene: WDR60 as ready
Renal Ciliopathies and Nephronophthisis v0.320 WDR60 Zornitza Stark Gene: wdr60 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.320 WDR60 Zornitza Stark Phenotypes for gene: WDR60 were changed from to Short-rib thoracic dysplasia 8 with or without polydactyly, MIM# 615503
Renal Ciliopathies and Nephronophthisis v0.319 WDR60 Zornitza Stark Publications for gene: WDR60 were set to
Renal Ciliopathies and Nephronophthisis v0.318 WDR60 Zornitza Stark Mode of inheritance for gene: WDR60 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.317 WDR60 Zornitza Stark changed review comment from: Four unrelated families reported, three with skeletal ciliopathy and one with RP and polydactyly only.; to: Four unrelated families reported, including renal involvement, although features are predominantly skeletal.
Renal Ciliopathies and Nephronophthisis v0.317 WDR60 Zornitza Stark edited their review of gene: WDR60: Changed phenotypes: Short-rib thoracic dysplasia 8 with or without polydactyly, MIM# 615503
Renal Ciliopathies and Nephronophthisis v0.317 WDR35 Zornitza Stark Marked gene: WDR35 as ready
Renal Ciliopathies and Nephronophthisis v0.317 WDR35 Zornitza Stark Gene: wdr35 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.317 WDR35 Zornitza Stark Phenotypes for gene: WDR35 were changed from to Short-rib thoracic dysplasia 7 with or without polydactyly, MIM#614091; MONDO:0013569; Cranioectodermal dysplasia 2, MIM# 613610
Renal Ciliopathies and Nephronophthisis v0.316 WDR35 Zornitza Stark Publications for gene: WDR35 were set to
Renal Ciliopathies and Nephronophthisis v0.315 WDR35 Zornitza Stark Mode of inheritance for gene: WDR35 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.314 WDR35 Zornitza Stark changed review comment from: Well established gene-disease association. Bi-allelic variants in this gene also cause cranioectodermal dysplasia.; to: Well established gene-disease associations, renal involvement reported in both.
Renal Ciliopathies and Nephronophthisis v0.314 WDR35 Zornitza Stark edited their review of gene: WDR35: Changed phenotypes: Short-rib thoracic dysplasia 7 with or without polydactyly, MIM#614091, MONDO:0013569, Cranioectodermal dysplasia 2, MIM# 613610
Renal Ciliopathies and Nephronophthisis v0.314 WDR19 Zornitza Stark Phenotypes for gene: WDR19 were changed from Nephronophthisis 13, MIM# 614377; Senior-Loken syndrome 8, MIM# 616307; Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376; Cranioectodermal dysplasia 4, MIM# 614378 to Nephronophthisis 13, MIM# 614377; Senior-Loken syndrome 8, MIM# 616307
Renal Ciliopathies and Nephronophthisis v0.313 WDR19 Zornitza Stark Marked gene: WDR19 as ready
Renal Ciliopathies and Nephronophthisis v0.313 WDR19 Zornitza Stark Gene: wdr19 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.313 WDR19 Zornitza Stark Phenotypes for gene: WDR19 were changed from to Nephronophthisis 13, MIM# 614377; Senior-Loken syndrome 8, MIM# 616307; Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376; Cranioectodermal dysplasia 4, MIM# 614378
Renal Ciliopathies and Nephronophthisis v0.312 WDR19 Zornitza Stark Publications for gene: WDR19 were set to
Renal Ciliopathies and Nephronophthisis v0.311 WDR19 Zornitza Stark Mode of inheritance for gene: WDR19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.310 WDR19 Zornitza Stark changed review comment from: Variants in this gene are associated with a range of ciliopathies. Two families reported with a predominantly skeletal phenotype.; to: Variants in this gene are associated with a range of ciliopathies, including nephronophthisis and Senior-Loken syndrome.
Renal Ciliopathies and Nephronophthisis v0.310 WDR19 Zornitza Stark edited their review of gene: WDR19: Changed rating: GREEN
Renal Ciliopathies and Nephronophthisis v0.310 WDR19 Zornitza Stark edited their review of gene: WDR19: Changed publications: 22019273, 23559409, 23683095; Changed phenotypes: Nephronophthisis 13, MIM# 614377, Senior-Loken syndrome 8, MIM# 616307
Renal Ciliopathies and Nephronophthisis v0.310 TTC8 Zornitza Stark Marked gene: TTC8 as ready
Renal Ciliopathies and Nephronophthisis v0.310 TTC8 Zornitza Stark Gene: ttc8 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.310 TTC8 Zornitza Stark Phenotypes for gene: TTC8 were changed from to Bardet-Biedl syndrome 8, MIM# 615985
Renal Ciliopathies and Nephronophthisis v0.309 TTC8 Zornitza Stark Publications for gene: TTC8 were set to
Renal Ciliopathies and Nephronophthisis v0.308 TTC8 Zornitza Stark Mode of inheritance for gene: TTC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.307 TTC21B Zornitza Stark Marked gene: TTC21B as ready
Renal Ciliopathies and Nephronophthisis v0.307 TTC21B Zornitza Stark Gene: ttc21b has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.307 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819
Renal Ciliopathies and Nephronophthisis v0.306 TTC21B Zornitza Stark Publications for gene: TTC21B were set to
Renal Ciliopathies and Nephronophthisis v0.305 TTC21B Zornitza Stark Mode of inheritance for gene: TTC21B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.304 TTC21B Zornitza Stark reviewed gene: TTC21B: Rating: GREEN; Mode of pathogenicity: None; Publications: 21258341; Phenotypes: Nephronophthisis 12, MIM# 613820, Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.304 TMEM67 Zornitza Stark Marked gene: TMEM67 as ready
Renal Ciliopathies and Nephronophthisis v0.304 TMEM67 Zornitza Stark Gene: tmem67 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.304 TMEM67 Zornitza Stark Phenotypes for gene: TMEM67 were changed from to Nephronophthisis 11, MIM# 613550; Joubert syndrome 6, MIM# 610688; Meckel syndrome 3, MIM# 607361
Renal Ciliopathies and Nephronophthisis v0.303 TMEM67 Zornitza Stark Publications for gene: TMEM67 were set to
Renal Ciliopathies and Nephronophthisis v0.302 TMEM67 Zornitza Stark Mode of inheritance for gene: TMEM67 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.301 TMEM67 Zornitza Stark changed review comment from: Bi-allelic variants in this gene are associated with a range of ciliopathies, including JBTS and Meckel syndrome. Multiple families with each.; to: Bi-allelic variants in this gene are associated with a range of ciliopathies, including Nerphronophtisis, JBTS and Meckel syndrome. Multiple families with each.
Renal Ciliopathies and Nephronophthisis v0.301 TMEM67 Zornitza Stark edited their review of gene: TMEM67: Changed phenotypes: Nephronophthisis 11, MIM# 613550, Joubert syndrome 6, MIM# 610688, Meckel syndrome 3, MIM# 607361
Renal Ciliopathies and Nephronophthisis v0.301 TMEM231 Zornitza Stark Marked gene: TMEM231 as ready
Renal Ciliopathies and Nephronophthisis v0.301 TMEM231 Zornitza Stark Gene: tmem231 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.301 TMEM231 Zornitza Stark Phenotypes for gene: TMEM231 were changed from to Joubert syndrome 20, MIM# 614970; MONDO:0013994; Meckel syndrome 11, MIM# 615397; MONDO:0014164
Renal Ciliopathies and Nephronophthisis v0.300 TMEM231 Zornitza Stark Publications for gene: TMEM231 were set to
Renal Ciliopathies and Nephronophthisis v0.299 TMEM231 Zornitza Stark Mode of inheritance for gene: TMEM231 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.298 TMEM231 Zornitza Stark changed review comment from: More than 3 unrelated families reported with each phenotype, functional data.; to: More than 3 unrelated families reported with each phenotype, functional data. Renal involvement common in Meckel.
Renal Ciliopathies and Nephronophthisis v0.298 TMEM216 Zornitza Stark Marked gene: TMEM216 as ready
Renal Ciliopathies and Nephronophthisis v0.298 TMEM216 Zornitza Stark Gene: tmem216 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.298 TMEM216 Zornitza Stark Phenotypes for gene: TMEM216 were changed from to Joubert syndrome 2, MIM# 608091; Meckel syndrome 2, MIM# 603194
Renal Ciliopathies and Nephronophthisis v0.297 TMEM216 Zornitza Stark Publications for gene: TMEM216 were set to
Renal Ciliopathies and Nephronophthisis v0.296 TMEM216 Zornitza Stark Mode of inheritance for gene: TMEM216 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.295 TMEM216 Zornitza Stark changed review comment from: p.Arg73Leu is a founder Jewish variant.

Multiple families reported with JBTS and with Meckel syndrome.; to: p.Arg73Leu is a founder Jewish variant.

Multiple families reported with JBTS and with Meckel syndrome. Renal involvement common in Meckel.
Renal Ciliopathies and Nephronophthisis v0.295 TMEM138 Zornitza Stark Marked gene: TMEM138 as ready
Renal Ciliopathies and Nephronophthisis v0.295 TMEM138 Zornitza Stark Gene: tmem138 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.295 TMEM138 Zornitza Stark Phenotypes for gene: TMEM138 were changed from to Joubert syndrome 16, MIM# 614465; MONDO:0013764
Renal Ciliopathies and Nephronophthisis v0.294 TMEM138 Zornitza Stark Publications for gene: TMEM138 were set to
Renal Ciliopathies and Nephronophthisis v0.293 TMEM138 Zornitza Stark Mode of inheritance for gene: TMEM138 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.292 TMEM138 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 5 unrelated families reported. Renal cysts/nephrnophthisis reported.
Renal Ciliopathies and Nephronophthisis v0.292 TMEM107 Zornitza Stark Marked gene: TMEM107 as ready
Renal Ciliopathies and Nephronophthisis v0.292 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v0.292 TMEM107 Zornitza Stark Phenotypes for gene: TMEM107 were changed from to Meckel syndrome 13 (MIM#617562); Orofaciodigital syndrome XVI (MIM#617563)
Renal Ciliopathies and Nephronophthisis v0.291 TMEM107 Zornitza Stark Publications for gene: TMEM107 were set to
Renal Ciliopathies and Nephronophthisis v0.290 TMEM107 Zornitza Stark Mode of inheritance for gene: TMEM107 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.289 TMEM107 Zornitza Stark Classified gene: TMEM107 as Amber List (moderate evidence)
Renal Ciliopathies and Nephronophthisis v0.289 TMEM107 Zornitza Stark Gene: tmem107 has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v0.288 TMEM107 Zornitza Stark commented on gene: TMEM107: Renal phenotype observed in MKS.
Renal Ciliopathies and Nephronophthisis v0.288 TMEM107 Zornitza Stark reviewed gene: TMEM107: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Renal Ciliopathies and Nephronophthisis v0.288 TCTN3 Zornitza Stark Marked gene: TCTN3 as ready
Renal Ciliopathies and Nephronophthisis v0.288 TCTN3 Zornitza Stark Gene: tctn3 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.288 TCTN3 Zornitza Stark Phenotypes for gene: TCTN3 were changed from to Joubert syndrome 18, MIM# 614815; MONDO:0013896; Mohr-Majewski syndrome; Meckel-Gruber syndrome
Renal Ciliopathies and Nephronophthisis v0.287 TCTN3 Zornitza Stark Publications for gene: TCTN3 were set to
Renal Ciliopathies and Nephronophthisis v0.286 TCTN3 Zornitza Stark Mode of inheritance for gene: TCTN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.285 TCTN3 Zornitza Stark changed review comment from: Three unrelated families reported with JBTS phenotype. Variants in this gene are associated with other ciliopathies as well (OFD and Mohr-Majewski).; to: Variants in this gene are associated with a range of ciliopathies, but renal involvement reported in Mohr-Majewski and Meckel-Gruber presentations.
Renal Ciliopathies and Nephronophthisis v0.285 TCTN3 Zornitza Stark edited their review of gene: TCTN3: Changed publications: 22883145, 32139166, 25118024, 22883145, 34096792; Changed phenotypes: Joubert syndrome 18, MIM# 614815, MONDO:0013896, Mohr-Majewski syndrome, Meckel-Gruber syndrome
Renal Ciliopathies and Nephronophthisis v0.285 TCTN2 Zornitza Stark Marked gene: TCTN2 as ready
Renal Ciliopathies and Nephronophthisis v0.285 TCTN2 Zornitza Stark Gene: tctn2 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.285 TCTN2 Zornitza Stark Phenotypes for gene: TCTN2 were changed from to Joubert syndrome 24, MIM# 616654; MONDO:0014724; Meckel syndrome 8, MIM# 613885; MONDO:0013482
Renal Ciliopathies and Nephronophthisis v0.284 TCTN2 Zornitza Stark Publications for gene: TCTN2 were set to
Renal Ciliopathies and Nephronophthisis v0.283 TCTN2 Zornitza Stark Mode of inheritance for gene: TCTN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.282 TCTN2 Zornitza Stark changed review comment from: At least 5 families reported with JBTS phenotype, and 3 with Meckel phenotype; mouse model.; to: At least 5 families reported with JBTS phenotype, and 3 with Meckel phenotype; mouse model. Renal abnormalities are part of the Meckel phenotype.
Renal Ciliopathies and Nephronophthisis v0.282 TCTN1 Zornitza Stark Marked gene: TCTN1 as ready
Renal Ciliopathies and Nephronophthisis v0.282 TCTN1 Zornitza Stark Gene: tctn1 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.282 TCTN1 Zornitza Stark Phenotypes for gene: TCTN1 were changed from to Joubert syndrome 13, MIM# 614173
Renal Ciliopathies and Nephronophthisis v0.281 TCTN1 Zornitza Stark Publications for gene: TCTN1 were set to
Renal Ciliopathies and Nephronophthisis v0.280 TCTN1 Zornitza Stark Mode of inheritance for gene: TCTN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.279 TCTN1 Zornitza Stark Classified gene: TCTN1 as Red List (low evidence)
Renal Ciliopathies and Nephronophthisis v0.279 TCTN1 Zornitza Stark Gene: tctn1 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.278 TCTN1 Zornitza Stark changed review comment from: At least 4 unrelated families reported, mouse model.; to: At least 4 unrelated families reported with JBTS, mouse model. Renal involvement not reported.
Renal Ciliopathies and Nephronophthisis v0.278 TCTN1 Zornitza Stark edited their review of gene: TCTN1: Changed rating: RED
Renal Ciliopathies and Nephronophthisis v0.278 RPGRIP1L Zornitza Stark Marked gene: RPGRIP1L as ready
Renal Ciliopathies and Nephronophthisis v0.278 RPGRIP1L Zornitza Stark Gene: rpgrip1l has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.278 RPGRIP1L Zornitza Stark Phenotypes for gene: RPGRIP1L were changed from to Joubert syndrome 7, MIM# 611560; Meckel syndrome 5, MIM# 611561; COACH syndrome 3, MIM# 619113; Nephronophthisis
Renal Ciliopathies and Nephronophthisis v0.277 RPGRIP1L Zornitza Stark Publications for gene: RPGRIP1L were set to
Renal Ciliopathies and Nephronophthisis v0.276 RPGRIP1L Zornitza Stark Mode of inheritance for gene: RPGRIP1L was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.276 RPGRIP1L Zornitza Stark Mode of inheritance for gene: RPGRIP1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.274 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Renal Ciliopathies and Nephronophthisis v0.274 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.274 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to Orofaciodigital syndrome I, MIM# 311200; Joubert syndrome 10, MIM# 300804
Renal Ciliopathies and Nephronophthisis v0.273 OFD1 Zornitza Stark Publications for gene: OFD1 were set to
Renal Ciliopathies and Nephronophthisis v0.272 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Renal Ciliopathies and Nephronophthisis v0.271 OFD1 Zornitza Stark changed review comment from: XLD. Polydactyly is a rare feature. Primarily facial/neurological features.; to: Gene is associated with multiple ciliopathy phenotypes but renal involvement reported with JBTS/OFD.
Renal Ciliopathies and Nephronophthisis v0.271 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed publications: 19800048, 22353940
Renal Ciliopathies and Nephronophthisis v0.271 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed rating: GREEN; Changed phenotypes: Orofaciodigital syndrome I, MIM# 311200, Joubert syndrome 10, MIM# 300804; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Renal Ciliopathies and Nephronophthisis v0.271 NPHP4 Zornitza Stark Marked gene: NPHP4 as ready
Renal Ciliopathies and Nephronophthisis v0.271 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.271 NPHP4 Zornitza Stark Phenotypes for gene: NPHP4 were changed from to Nephronophthisis 4, MIM# 606966; Senior-Loken syndrome 4, MIM# 606996
Renal Ciliopathies and Nephronophthisis v0.270 NPHP4 Zornitza Stark Publications for gene: NPHP4 were set to
Renal Ciliopathies and Nephronophthisis v0.269 NPHP4 Zornitza Stark Mode of inheritance for gene: NPHP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.268 NPHP4 Zornitza Stark reviewed gene: NPHP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12244321, 12205563, 34013113; Phenotypes: Nephronophthisis 4, MIM# 606966, Senior-Loken syndrome 4, MIM# 606996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.268 MKS1 Zornitza Stark Marked gene: MKS1 as ready
Renal Ciliopathies and Nephronophthisis v0.268 MKS1 Zornitza Stark Gene: mks1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.268 MKS1 Zornitza Stark Phenotypes for gene: MKS1 were changed from to Bardet-Biedl syndrome 13, MIM# 615990; MONDO:0014441; Meckel syndrome 1, MIM# 249000
Renal Ciliopathies and Nephronophthisis v0.267 MKS1 Zornitza Stark Publications for gene: MKS1 were set to
Renal Ciliopathies and Nephronophthisis v0.266 MKS1 Zornitza Stark Mode of inheritance for gene: MKS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.265 MKS1 Zornitza Stark changed review comment from: Well established ciliopathy gene, two families reported with BBS phenotype.; to: Well established ciliopathy gene, two families reported with BBS phenotype and renal cysts are a prominent feature of Meckel syndrome.
Renal Ciliopathies and Nephronophthisis v0.265 MKS1 Zornitza Stark edited their review of gene: MKS1: Changed publications: 18327255, 24608809, 17377820; Changed phenotypes: Bardet-Biedl syndrome 13, MIM# 615990, MONDO:0014441, Meckel syndrome 1, MIM# 249000
Renal Ciliopathies and Nephronophthisis v0.265 MKKS Zornitza Stark Marked gene: MKKS as ready
Renal Ciliopathies and Nephronophthisis v0.265 MKKS Zornitza Stark Gene: mkks has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.265 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from to Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome, MIM# 236700
Renal Ciliopathies and Nephronophthisis v0.264 MKKS Zornitza Stark Publications for gene: MKKS were set to
Renal Ciliopathies and Nephronophthisis v0.263 MKKS Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.262 MKKS Zornitza Stark reviewed gene: MKKS: Rating: GREEN; Mode of pathogenicity: None; Publications: 10802661; Phenotypes: McKusick-Kaufman syndrome, MIM# 236700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.262 KIF7 Zornitza Stark Marked gene: KIF7 as ready
Renal Ciliopathies and Nephronophthisis v0.262 KIF7 Zornitza Stark Gene: kif7 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.262 KIF7 Zornitza Stark Phenotypes for gene: KIF7 were changed from to Acrocallosal syndrome, MIM# 200990; Joubert syndrome 12, MIM# 200990
Renal Ciliopathies and Nephronophthisis v0.261 KIF7 Zornitza Stark Mode of inheritance for gene: KIF7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.260 KIF7 Zornitza Stark Classified gene: KIF7 as Red List (low evidence)
Renal Ciliopathies and Nephronophthisis v0.260 KIF7 Zornitza Stark Gene: kif7 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.259 KIF7 Zornitza Stark changed review comment from: Polydactyly is a feature of acrocallosal syndrome, but overall predominantly neurological presentation.; to: Overall predominantly neurological presentation.
Renal Ciliopathies and Nephronophthisis v0.259 KIF7 Zornitza Stark edited their review of gene: KIF7: Changed rating: RED
Renal Ciliopathies and Nephronophthisis v0.259 KIAA0753 Zornitza Stark Marked gene: KIAA0753 as ready
Renal Ciliopathies and Nephronophthisis v0.259 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.259 KIAA0753 Zornitza Stark Phenotypes for gene: KIAA0753 were changed from to Short-rib skeletal dysplasia; Orofaciodigital syndrome XV, MIM# 617127; Jeune ATD
Renal Ciliopathies and Nephronophthisis v0.258 KIAA0753 Zornitza Stark Publications for gene: KIAA0753 were set to
Renal Ciliopathies and Nephronophthisis v0.257 KIAA0753 Zornitza Stark Mode of inheritance for gene: KIAA0753 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.256 KIAA0753 Zornitza Stark Classified gene: KIAA0753 as Red List (low evidence)
Renal Ciliopathies and Nephronophthisis v0.256 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.255 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed rating: RED
Renal Ciliopathies and Nephronophthisis v0.255 KIAA0753 Zornitza Stark changed review comment from: Four individuals from three unrelated families reported with a predominantly skeletal ciliopathy phenotype.
Sources: Expert list; to: Four individuals from three unrelated families reported with a predominantly skeletal ciliopathy phenotype, one with OFD, and one with Jeune. Only the individual with OFD is reported to have had renal involvement (hydronephrosis) which may or may not be considered part of a ciliopathy phenotype.
Sources: Expert list
Renal Ciliopathies and Nephronophthisis v0.255 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed phenotypes: Short-rib skeletal dysplasia, Orofaciodigital syndrome XV, MIM# 617127, Jeune ATD
Renal Ciliopathies and Nephronophthisis v0.255 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed publications: 29138412, 26643951, 31816441
Renal Ciliopathies and Nephronophthisis v0.255 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed publications: 29138412, 26643951; Changed phenotypes: Short-rib skeletal dysplasia, Orofaciodigital syndrome XV, MIM# 617127
Renal Ciliopathies and Nephronophthisis v0.255 KIAA0586 Zornitza Stark Marked gene: KIAA0586 as ready
Renal Ciliopathies and Nephronophthisis v0.255 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.255 KIAA0586 Zornitza Stark Phenotypes for gene: KIAA0586 were changed from to Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546; Joubert syndrome 23, MIM# 616490
Renal Ciliopathies and Nephronophthisis v0.254 KIAA0586 Zornitza Stark Publications for gene: KIAA0586 were set to
Renal Ciliopathies and Nephronophthisis v0.253 KIAA0586 Zornitza Stark Mode of inheritance for gene: KIAA0586 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.252 KIAA0586 Zornitza Stark Classified gene: KIAA0586 as Red List (low evidence)
Renal Ciliopathies and Nephronophthisis v0.252 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.251 KIAA0586 Zornitza Stark changed review comment from: Four unrelated families reported with a severe neurological/skeletal phenotype. However, note same variant identified in three of the families, indicative of founder effect. Gene is also associated with Joubert syndrome.; to: Multiple families reported with JBTS/ATD phenotype. Renal involvement not reported.
Renal Ciliopathies and Nephronophthisis v0.251 KIAA0586 Zornitza Stark edited their review of gene: KIAA0586: Changed rating: RED
Renal Ciliopathies and Nephronophthisis v0.251 KIAA0586 Zornitza Stark edited their review of gene: KIAA0586: Changed publications: 26166481, 26096313, 29146704
Renal Ciliopathies and Nephronophthisis v0.251 KIAA0586 Zornitza Stark edited their review of gene: KIAA0586: Changed rating: GREEN; Changed publications: 26166481, 26096313; Changed phenotypes: Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546, Joubert syndrome 23, MIM# 616490
Joubert syndrome and other neurological ciliopathies v1.10 KIAA0556 Zornitza Stark Marked gene: KIAA0556 as ready
Joubert syndrome and other neurological ciliopathies v1.10 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v1.10 KIAA0556 Zornitza Stark Classified gene: KIAA0556 as Green List (high evidence)
Joubert syndrome and other neurological ciliopathies v1.10 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v1.9 KIAA0556 Zornitza Stark gene: KIAA0556 was added
gene: KIAA0556 was added to Joubert syndrome and other neurological ciliopathies. Sources: Expert Review
new gene name tags were added to gene: KIAA0556.
Mode of inheritance for gene: KIAA0556 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0556 were set to 26714646; 27245168
Phenotypes for gene: KIAA0556 were set to Joubert syndrome 26, MIM# 616784
Review for gene: KIAA0556 was set to GREEN
Added comment: 5 individuals from two families reported, supportive mouse model.

New HGNC approved name is KATNIP.
Sources: Expert Review
Amelogenesis imperfecta v0.1 KCNJ1 Meaghan Wall changed review comment from: Hercílio Martelli-Júnior et al, screened 8 patients with confirmed Bartter syndrome for dental abnormalities. Typical features of AI were found in 2 girls. One affected girl had BS due to a homozygous mutation of exon 5 of the KCNJ1.; to: Hercílio Martelli-Júnior et al, screened 8 patients with confirmed Bartter syndrome for dental abnormalities. Typical features of AI were found in 2 girls. One affected girl had BS due to a homozygous variant in exon 5 of KCNJ1.
Renal Ciliopathies and Nephronophthisis v0.251 KIAA0556 Zornitza Stark Marked gene: KIAA0556 as ready
Renal Ciliopathies and Nephronophthisis v0.251 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Red List (Low Evidence).
Mendeliome v0.8344 KIAA0556 Zornitza Stark changed review comment from: 5 individuals from two families reported, supportive mouse model.; to: 5 individuals from two families reported, supportive mouse model.

New HGNC approved name is KATNIP.
Mendeliome v0.8344 KIAA0556 Zornitza Stark Tag new gene name tag was added to gene: KIAA0556.
Renal Ciliopathies and Nephronophthisis v0.251 KIAA0556 Zornitza Stark Phenotypes for gene: KIAA0556 were changed from to Joubert syndrome 26, MIM# 616784
Amelogenesis imperfecta v0.1 KCNJ1 Meaghan Wall reviewed gene: KCNJ1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 23341834; Phenotypes: Amelogenesis imperfecta, Bartter syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8344 KIAA0556 Zornitza Stark Marked gene: KIAA0556 as ready
Mendeliome v0.8344 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Green List (High Evidence).
Mendeliome v0.8344 KIAA0556 Zornitza Stark Phenotypes for gene: KIAA0556 were changed from to Joubert syndrome 26, MIM# 616784
Mendeliome v0.8343 KIAA0556 Zornitza Stark Publications for gene: KIAA0556 were set to
Mendeliome v0.8342 KIAA0556 Zornitza Stark Mode of inheritance for gene: KIAA0556 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8341 KIAA0556 Zornitza Stark reviewed gene: KIAA0556: Rating: GREEN; Mode of pathogenicity: None; Publications: 26714646, 27245168; Phenotypes: Joubert syndrome 26, MIM# 616784; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.250 KIAA0556 Zornitza Stark Publications for gene: KIAA0556 were set to
Renal Ciliopathies and Nephronophthisis v0.249 KIAA0556 Zornitza Stark Mode of inheritance for gene: KIAA0556 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.248 KIAA0556 Zornitza Stark Classified gene: KIAA0556 as Red List (low evidence)
Renal Ciliopathies and Nephronophthisis v0.248 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.247 KIAA0556 Zornitza Stark reviewed gene: KIAA0556: Rating: RED; Mode of pathogenicity: None; Publications: 26714646, 27245168; Phenotypes: Joubert syndrome 26, MIM# 616784; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.247 IFT43 Zornitza Stark Marked gene: IFT43 as ready
Renal Ciliopathies and Nephronophthisis v0.247 IFT43 Zornitza Stark Gene: ift43 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.247 IFT43 Zornitza Stark Phenotypes for gene: IFT43 were changed from to Short-rib thoracic dysplasia 18 with polydactyly, MIM# 617866; Cranioectodermal dysplasia 3, MIM# 614099
Renal Ciliopathies and Nephronophthisis v0.246 IFT43 Zornitza Stark Publications for gene: IFT43 were set to
Renal Ciliopathies and Nephronophthisis v0.245 IFT43 Zornitza Stark Mode of inheritance for gene: IFT43 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.244 IFT43 Zornitza Stark changed review comment from: Two families reported with short-rib thoracic dysplasia and two with cranioectodermal dysplasia.; to: Two families reported with short-rib thoracic dysplasia and two with cranioectodermal dysplasia. Renal involvement including nephronophthisis/cysts in both.
Renal Ciliopathies and Nephronophthisis v0.244 IFT27 Zornitza Stark Marked gene: IFT27 as ready
Renal Ciliopathies and Nephronophthisis v0.244 IFT27 Zornitza Stark Gene: ift27 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.244 IFT27 Zornitza Stark Phenotypes for gene: IFT27 were changed from to Bardet-Biedl syndrome 19, MIM#615996
Renal Ciliopathies and Nephronophthisis v0.243 IFT27 Zornitza Stark Publications for gene: IFT27 were set to
Renal Ciliopathies and Nephronophthisis v0.242 IFT27 Zornitza Stark Mode of inheritance for gene: IFT27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.3 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920 to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964
Mendeliome v0.8341 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781 to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781
Ciliopathies v1.6 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781 to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781
Amelogenesis imperfecta v0.1 AMTN Meaghan Wall changed review comment from: In a Costa Rican family segregating autosomal dominant hypomineralized amelogenesis imperfecta, Smith et al. (2016) identified a heterozygous deletion/insertion mutation in the amelotin gene that segregated with the phenotype in the family. The mutation was predicted to result in an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 amino acids.

Mode of pathogenicity not established. Toxic gain of function proposed as Atmn KO and +/- in mice did not recapitulate the human phenotype.; to: In a Costa Rican family segregating autosomal dominant hypomineralized amelogenesis imperfecta, Smith et al. (2016) identified a heterozygous deletion/insertion mutation in the amelotin gene that segregated with the phenotype in the family. The mutation was predicted to result in an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 amino acids.

Mode of pathogenicity not established. Toxic gain of function proposed as Atmn KO and +/- mice did not recapitulate the human phenotype.
Renal Ciliopathies and Nephronophthisis v0.240 IFT140 Zornitza Stark Marked gene: IFT140 as ready
Renal Ciliopathies and Nephronophthisis v0.240 IFT140 Zornitza Stark Gene: ift140 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.240 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964
Renal Ciliopathies and Nephronophthisis v0.239 IFT140 Zornitza Stark Publications for gene: IFT140 were set to
Amelogenesis imperfecta v0.1 AMTN Meaghan Wall reviewed gene: AMTN: Rating: ; Mode of pathogenicity: Other; Publications: PMID: 27412008, 25715379, 26620968; Phenotypes: hypomineralised amelogenesis imperfecta, ?Amelogenesis imperfecta, type IIIB; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Ciliopathies and Nephronophthisis v0.238 IFT140 Zornitza Stark Mode of inheritance for gene: IFT140 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.237 IFT140 Zornitza Stark edited their review of gene: IFT140: Changed phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, MONDO:0009964
Renal Ciliopathies and Nephronophthisis v0.237 IFT140 Zornitza Stark reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 22503633, 23418020; Phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.237 LZTFL1 Zornitza Stark Marked gene: LZTFL1 as ready
Renal Ciliopathies and Nephronophthisis v0.237 LZTFL1 Zornitza Stark Gene: lztfl1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.237 LZTFL1 Zornitza Stark Phenotypes for gene: LZTFL1 were changed from to Bardet-Biedl syndrome 17 (MIM#615994)
Renal Ciliopathies and Nephronophthisis v0.236 LZTFL1 Zornitza Stark Publications for gene: LZTFL1 were set to
Renal Ciliopathies and Nephronophthisis v0.235 LZTFL1 Zornitza Stark Mode of inheritance for gene: LZTFL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.234 LZTFL1 Zornitza Stark reviewed gene: LZTFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal Dysplasia_Fetal v0.54 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from Cranioectodermal dysplasia 1, MIM# 218330; Beemer-Langer syndrome to Cranioectodermal dysplasia 1, MIM# 218330; MONDO:0021093; Beemer-Langer syndrome
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.2 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from Cranioectodermal dysplasia 1, MIM# 218330; Beemer-Langer syndrome to Cranioectodermal dysplasia 1, MIM# 218330; MONDO:0021093; Beemer-Langer syndrome
Mendeliome v0.8340 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from Cranioectodermal dysplasia 1, MIM# MIM#218330 to Cranioectodermal dysplasia 1, MIM# MIM#218330; MONDO:0021093
Craniosynostosis v1.23 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from Cranioectodermal dysplasia 1 MIM#218330 to Cranioectodermal dysplasia 1 MIM#218330; MONDO:0021093
Ciliopathies v1.5 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from Cranioectodermal dysplasia 1, MIM# 218330; Beemer-Langer syndrome to Cranioectodermal dysplasia 1, MIM# 218330; MONDO:0021093; Beemer-Langer syndrome
Renal Ciliopathies and Nephronophthisis v0.234 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from Cranioectodermal dysplasia 1, MIM# 218330 to Cranioectodermal dysplasia 1, MIM# 218330; MONDO:0021093
Renal Ciliopathies and Nephronophthisis v0.233 IFT122 Zornitza Stark Marked gene: IFT122 as ready
Renal Ciliopathies and Nephronophthisis v0.233 IFT122 Zornitza Stark Gene: ift122 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.233 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from to Cranioectodermal dysplasia 1, MIM# 218330
Renal Ciliopathies and Nephronophthisis v0.232 IFT122 Zornitza Stark Publications for gene: IFT122 were set to
Renal Ciliopathies and Nephronophthisis v0.231 IFT122 Zornitza Stark Mode of inheritance for gene: IFT122 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.230 IFT122 Zornitza Stark reviewed gene: IFT122: Rating: GREEN; Mode of pathogenicity: None; Publications: 20493458, 23826986, 28370949, 33717254, 26792575; Phenotypes: Cranioectodermal dysplasia 1, MIM# 218330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8339 LINGO4 Zornitza Stark Marked gene: LINGO4 as ready
Mendeliome v0.8339 LINGO4 Zornitza Stark Gene: lingo4 has been classified as Green List (High Evidence).
Mendeliome v0.8339 LINGO4 Zornitza Stark Classified gene: LINGO4 as Green List (high evidence)
Mendeliome v0.8339 LINGO4 Zornitza Stark Gene: lingo4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3981 LINGO4 Zornitza Stark Marked gene: LINGO4 as ready
Intellectual disability syndromic and non-syndromic v0.3981 LINGO4 Zornitza Stark Gene: lingo4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3981 LINGO4 Zornitza Stark Classified gene: LINGO4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3981 LINGO4 Zornitza Stark Gene: lingo4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3980 LINGO1 Zornitza Stark edited their review of gene: LINGO1: Changed rating: AMBER
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Marked gene: ARFGEF3 as ready
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Gene: arfgef3 has been classified as Green List (High Evidence).
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Classified gene: ARFGEF3 as Green List (high evidence)
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Gene: arfgef3 has been classified as Green List (High Evidence).
Dystonia - isolated/combined v1.4 ARFGEF3 Zornitza Stark Marked gene: ARFGEF3 as ready
Dystonia - isolated/combined v1.4 ARFGEF3 Zornitza Stark Gene: arfgef3 has been classified as Green List (High Evidence).
Dystonia - isolated/combined v1.4 ARFGEF3 Zornitza Stark Classified gene: ARFGEF3 as Green List (high evidence)
Dystonia - isolated/combined v1.4 ARFGEF3 Zornitza Stark Gene: arfgef3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3980 IMPDH2 Zornitza Stark reviewed gene: IMPDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with dystonia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3980 IMPDH2 Zornitza Stark Marked gene: IMPDH2 as ready
Intellectual disability syndromic and non-syndromic v0.3980 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3980 IMPDH2 Zornitza Stark Phenotypes for gene: IMPDH2 were changed from to Neurodevelopmental disorder with dystonia
Intellectual disability syndromic and non-syndromic v0.3979 IMPDH2 Zornitza Stark Classified gene: IMPDH2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3979 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Mendeliome v0.8337 IMPDH2 Zornitza Stark Marked gene: IMPDH2 as ready
Mendeliome v0.8337 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Mendeliome v0.8337 IMPDH2 Zornitza Stark Phenotypes for gene: IMPDH2 were changed from Dystonia to Neurodevelopmental disorder with dystonia
Mendeliome v0.8336 IMPDH2 Zornitza Stark Classified gene: IMPDH2 as Green List (high evidence)
Mendeliome v0.8336 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Dystonia - complex v0.185 IMPDH2 Zornitza Stark Marked gene: IMPDH2 as ready
Dystonia - complex v0.185 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Dystonia - complex v0.185 IMPDH2 Zornitza Stark Phenotypes for gene: IMPDH2 were changed from Dystonia to Neurodevelopmental disorder with dystonia
Dystonia - complex v0.184 IMPDH2 Zornitza Stark Classified gene: IMPDH2 as Green List (high evidence)
Dystonia - complex v0.184 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Mendeliome v0.8335 LINGO4 Laura Raiti gene: LINGO4 was added
gene: LINGO4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LINGO4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LINGO4 were set to PMID: 33098801
Phenotypes for gene: LINGO4 were set to Developmental Delay, Intellectual disability, speech disorder
Review for gene: LINGO4 was set to GREEN
Added comment: 3 unrelated individuals
1 x individual compound heterozygous for 2x missense variants:
c.679C>A; c.1262G>A p.Leu227Met; p.Arg421Gln comp het. Phenotype: infancy-onset
generalized dystonia; DD/hypo, ID, speech disorder (isolated plus non-MD symptoms) NDD

1 x individual homozygous for missense variant: c.679C>A p.Leu227Met Phenotype: DD/hypo, ID, speech disorder

1 x individual homozygous for missense variant: c.1673G>A p.Ser558Asn Phenotype: DD/hypo, ID, speech disorder
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3978 LINGO4 Laura Raiti gene: LINGO4 was added
gene: LINGO4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LINGO4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LINGO4 were set to PMID: 33098801
Phenotypes for gene: LINGO4 were set to Developmental Delay, Intellectual disability, speech disorder
Review for gene: LINGO4 was set to GREEN
Added comment: 3 unrelated individuals
1 x individual compound heterozygous for 2x missense variants:
c.679C>A; c.1262G>A p.Leu227Met; p.Arg421Gln comp het. Phenotype: infancy-onset
generalized dystonia; DD/hypo, ID, speech disorder (isolated plus non-MD symptoms) NDD

1 x individual homozygous for missense variant: c.679C>A p.Leu227Met Phenotype: DD/hypo, ID, speech disorder

1 x individual homozygous for missense variant: c.1673G>A p.Ser558Asn Phenotype: DD/hypo, ID, speech disorder
Sources: Literature
Mendeliome v0.8335 ARFGEF3 Laura Raiti gene: ARFGEF3 was added
gene: ARFGEF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARFGEF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARFGEF3 were set to PMID: 33098801
Phenotypes for gene: ARFGEF3 were set to Dystonia
Review for gene: ARFGEF3 was set to GREEN
Added comment: 3 x unrelated individuals
1 x de novo missense variant: c.6212T>C p.Met2071Thr, phenotype: infancy-onset generalized dystonia (isolated)
1x stop-gain variant c.1773T>G p.Tyr591* (inherited from mosaic mother), phenotype: infancy-onset generalized dystonia (isolated)
1 x de novo missense variant (Gene Matcher) c.250A>C p.Met84Leu childhood-onset generalized dystonia (isolated)
Sources: Literature
Dystonia - isolated/combined v1.3 ARFGEF3 Laura Raiti gene: ARFGEF3 was added
gene: ARFGEF3 was added to Dystonia - isolated/combined. Sources: Literature
Mode of inheritance for gene: ARFGEF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARFGEF3 were set to PMID: 33098801
Phenotypes for gene: ARFGEF3 were set to Dystonia
Review for gene: ARFGEF3 was set to GREEN
Added comment: 3 x unrelated individuals
1 x de novo missense variant: c.6212T>C p.Met2071Thr, phenotype: infancy-onset generalized dystonia (isolated)
1x stop-gain variant c.1773T>G p.Tyr591* inherited from mosaic mother), phenotype: infancy-onset generalized dystonia (isolated)
1 x de novo missense variant (Gene Matcher) c.250A>C p.Met84Leu childhood-onset generalized dystonia (isolated)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3978 IMPDH2 Laura Raiti gene: IMPDH2 was added
gene: IMPDH2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: IMPDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IMPDH2 were set to PMID: 33098801
Added comment: 6 unrelated individuals
1x individual in a dystonia cohort index case with infancy-onset dystonia and other neurological manifestations with a de-novo missense variant, c.338G>A (p.Gly113Glu) in IMPDH2, predicted to disrupt an invariant residue within the cystathionine-β-synthase (CBS) domain pair of the encoded protein.
IMPDH2 encodes IMPDH2, a key enzyme in the purine biosynthetic pathway, expressed throughout the brain and not linked previously to any human Mendelian condition.
1x individual with a de-novo substitution, c.337G>A (p.Gly113Arg), was found in in-house whole-exome sequencing data from 500 individuals with neurodevelopmental disorders. Through GeneMatcher, de novo variants identified:
3 x missense: c.729G>C (p.Gln243His), c.619G>C (p.Gly207Arg), and c.619G>A (p.Gly207Arg)
1 x deletion: c.478_480delTCC (p.Ser160del)
The six variants were predicted to be deleterious and none of them seen in control databases. All affected conserved amino acids and resided in and around the cystathionine-β-synthase domain pair.
The described variants are situated in and around the CBS domain pair, a regulatory element in which clustering of pathogenic missense variants has already been shown for the homologue of IMPDH2, IMPDH1.

The variant carriers shared similar neurodevelopmental phenotypes. Apart from the dystonia cohort index case, one participant had evidence of dystonic posturing. Modelling of the variants on 3D protein structures revealed spatial clustering near specific functional sites, predicted to result in deregulation of IMPDH2 activity. Additionally, thermal-shift assays showed that the c.619G>A (p.Gly207Arg) variant, identified as within the CBS domain pair, and c.729G>C (p.Gln243His), which is in close vicinity, affected the stability or folding behaviour of IMPDH2.
Sources: Literature
Mendeliome v0.8335 IMPDH2 Laura Raiti gene: IMPDH2 was added
gene: IMPDH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IMPDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IMPDH2 were set to PMID: 33098801
Phenotypes for gene: IMPDH2 were set to Dystonia
Review for gene: IMPDH2 was set to GREEN
Added comment: 6 unrelated individuals
1x individual in a dystonia cohort index case with infancy-onset dystonia and other neurological manifestations with a de-novo missense variant, c.338G>A (p.Gly113Glu) in IMPDH2, predicted to disrupt an invariant residue within the cystathionine-β-synthase (CBS) domain pair of the encoded protein.
IMPDH2 encodes IMPDH2, a key enzyme in the purine biosynthetic pathway, expressed throughout the brain and not linked previously to any human Mendelian condition.
1x individual with a de-novo substitution, c.337G>A (p.Gly113Arg), was found in in-house whole-exome sequencing data from 500 individuals with neurodevelopmental disorders. Through GeneMatcher, de novo variants identified:
3 x missense: c.729G>C (p.Gln243His), c.619G>C (p.Gly207Arg), and c.619G>A (p.Gly207Arg)
1 x deletion: c.478_480delTCC (p.Ser160del)
The six variants were predicted to be deleterious and none of them seen in control databases. All affected conserved amino acids and resided in and around the cystathionine-β-synthase domain pair.
The described variants are situated in and around the CBS domain pair, a regulatory element in which clustering of pathogenic missense variants has already been shown for the homologue of IMPDH2, IMPDH1.

The variant carriers shared similar neurodevelopmental phenotypes. Apart from the dystonia cohort index case, one participant had evidence of dystonic posturing. Modelling of the variants on 3D protein structures revealed spatial clustering near specific functional sites, predicted to result in deregulation of IMPDH2 activity. Additionally, thermal-shift assays showed that the c.619G>A (p.Gly207Arg) variant, identified as within the CBS domain pair, and c.729G>C (p.Gln243His), which is in close vicinity, affected the stability or folding behaviour of IMPDH2.
Sources: Literature
Dystonia - complex v0.183 IMPDH2 Laura Raiti gene: IMPDH2 was added
gene: IMPDH2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: IMPDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IMPDH2 were set to PMID: 33098801
Phenotypes for gene: IMPDH2 were set to Dystonia
Review for gene: IMPDH2 was set to GREEN
Added comment: 6 unrelated individuals
1x individual in a dystonia cohort index case with infancy-onset dystonia and other neurological manifestations with a de-novo missense variant, c.338G>A (p.Gly113Glu) in IMPDH2, predicted to disrupt an invariant residue within the cystathionine-β-synthase (CBS) domain pair of the encoded protein.
IMPDH2 encodes IMPDH2, a key enzyme in the purine biosynthetic pathway, expressed throughout the brain and not linked previously to any human Mendelian condition.
1x individual with a de-novo substitution, c.337G>A (p.Gly113Arg), was found in in-house whole-exome sequencing data from 500 individuals with neurodevelopmental disorders. Through GeneMatcher, de novo variants identified:
3 x missense: c.729G>C (p.Gln243His), c.619G>C (p.Gly207Arg), and c.619G>A (p.Gly207Arg)
1 x deletion: c.478_480delTCC (p.Ser160del)
The six variants were predicted to be deleterious and none of them seen in control databases. All affected conserved amino acids and resided in and around the cystathionine-β-synthase domain pair.
The described variants are situated in and around the CBS domain pair, a regulatory element in which clustering of pathogenic missense variants has already been shown for the homologue of IMPDH2, IMPDH1.

The variant carriers shared similar neurodevelopmental phenotypes. Apart from the dystonia cohort index case, one participant had evidence of dystonic posturing. Modelling of the variants on 3D protein structures revealed spatial clustering near specific functional sites, predicted to result in deregulation of IMPDH2 activity. Additionally, thermal-shift assays showed that the c.619G>A (p.Gly207Arg) variant, identified as within the CBS domain pair, and c.729G>C (p.Gln243His), which is in close vicinity, affected the stability or folding behaviour of IMPDH2.
Sources: Literature
Renal Ciliopathies and Nephronophthisis v0.230 IFT172 Zornitza Stark Marked gene: IFT172 as ready
Renal Ciliopathies and Nephronophthisis v0.230 IFT172 Zornitza Stark Gene: ift172 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.230 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from to Bardet-Biedl syndrome; Short-rib thoracic dysplasia 10 with or without polydactyly, MIM# 615630
Renal Ciliopathies and Nephronophthisis v0.229 IFT172 Zornitza Stark Publications for gene: IFT172 were set to
Renal Ciliopathies and Nephronophthisis v0.228 IFT172 Zornitza Stark Mode of inheritance for gene: IFT172 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.227 IFT172 Zornitza Stark changed review comment from: Three families reported with a BBS phenotype, although this association is not listed in OMIM or MONDO. Gene is associated with other ciliopathies as well.; to: Three families reported with a BBS phenotype, although this association is not listed in OMIM or MONDO. Gene is also associated with skeletal ciliopathy, with nephronophthisis reported.
Renal Ciliopathies and Nephronophthisis v0.227 IFT172 Zornitza Stark edited their review of gene: IFT172: Changed publications: 30761183, 26763875, 25168386, 24140113; Changed phenotypes: Bardet-Biedl syndrome, Short-rib thoracic dysplasia 10 with or without polydactyly, MIM# 615630
Renal Ciliopathies and Nephronophthisis v0.227 DYNC2H1 Zornitza Stark Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091 to Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091; MONDO:0013127MONDO:0013127
Renal Ciliopathies and Nephronophthisis v0.226 DYNC2H1 Zornitza Stark edited their review of gene: DYNC2H1: Changed phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091, MONDO:0013127
Mendeliome v0.8335 DYNC2H1 Zornitza Stark Publications for gene: DYNC2H1 were set to 19442771; 19361615; 22499340; 23456818; 27925158
Mendeliome v0.8334 DYNC2H1 Zornitza Stark changed review comment from: More than 50 unrelated families reported.; to: More than 50 unrelated families reported with predominantly skeletal dysplasia.

Association with RP: - Five affected probands with homozygous and compound heterozygous missense and PTC variants - Associated with the NM_001080463.1 transcript (predominant isoform in retina from retinal organoid studies). PMID 32753734
Mendeliome v0.8334 DYNC2H1 Zornitza Stark edited their review of gene: DYNC2H1: Changed publications: 19442771, 19361615, 22499340, 23456818, 27925158, 32753734; Changed phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091, MONDO:0013127, Non-syndromic retinitis pigmentosa
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.97 DYNC2H1 Zornitza Stark Marked gene: DYNC2H1 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.97 DYNC2H1 Zornitza Stark Gene: dync2h1 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.97 DYNC2H1 Zornitza Stark Classified gene: DYNC2H1 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.97 DYNC2H1 Zornitza Stark Gene: dync2h1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.226 DYNC2H1 Zornitza Stark Marked gene: DYNC2H1 as ready
Renal Ciliopathies and Nephronophthisis v0.226 DYNC2H1 Zornitza Stark Gene: dync2h1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.226 DYNC2H1 Zornitza Stark Phenotypes for gene: DYNC2H1 were changed from to Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091
Renal Ciliopathies and Nephronophthisis v0.225 DYNC2H1 Zornitza Stark Publications for gene: DYNC2H1 were set to
Renal Ciliopathies and Nephronophthisis v0.224 DYNC2H1 Zornitza Stark Mode of inheritance for gene: DYNC2H1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.223 DYNC2H1 Zornitza Stark reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31730820; Phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8334 STK36 Zornitza Stark Phenotypes for gene: STK36 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 46, MIM# 619436
Mendeliome v0.8333 STK36 Zornitza Stark edited their review of gene: STK36: Changed phenotypes: Ciliary dyskinesia, primary, 46, MIM# 619436
Heterotaxy v1.8 STK36 Zornitza Stark Phenotypes for gene: STK36 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 46, MIM# 619436
Heterotaxy v1.7 STK36 Zornitza Stark edited their review of gene: STK36: Changed phenotypes: Ciliary dyskinesia, primary, 46, MIM# 619436
Ciliary Dyskinesia v1.10 STK36 Zornitza Stark Phenotypes for gene: STK36 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 46, MIM# 619436
Ciliary Dyskinesia v1.9 STK36 Zornitza Stark edited their review of gene: STK36: Changed phenotypes: Ciliary dyskinesia, primary, 46, MIM# 619436
Mendeliome v0.8333 KIF20A Zornitza Stark Marked gene: KIF20A as ready
Mendeliome v0.8333 KIF20A Zornitza Stark Gene: kif20a has been classified as Red List (Low Evidence).
Mendeliome v0.8333 KIF20A Zornitza Stark edited their review of gene: KIF20A: Changed rating: RED
Mendeliome v0.8333 KIF20A Zornitza Stark gene: KIF20A was added
gene: KIF20A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF20A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF20A were set to 29357359
Phenotypes for gene: KIF20A were set to Cardiomyopathy, familial restrictive, 6, MIM# 619433
Review for gene: KIF20A was set to GREEN
Added comment: Single family reported, two affected sibs, perinatal lethal cardiomyopathy, compound het variants in this gene.
Sources: Literature
Cardiomyopathy_Paediatric v0.97 KIF20A Zornitza Stark Marked gene: KIF20A as ready
Cardiomyopathy_Paediatric v0.97 KIF20A Zornitza Stark Gene: kif20a has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.97 KIF20A Zornitza Stark gene: KIF20A was added
gene: KIF20A was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: KIF20A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF20A were set to 29357359
Phenotypes for gene: KIF20A were set to Cardiomyopathy, familial restrictive, 6, MIM# 619433
Review for gene: KIF20A was set to RED
Added comment: Single family reported, two affected sibs, perinatal lethal cardiomyopathy, compound het variants in this gene.
Sources: Literature
Gastrointestinal neuromuscular disease v0.41 ACTG2 Zornitza Stark Publications for gene: ACTG2 were set to
Gastrointestinal neuromuscular disease v0.40 ACTG2 Zornitza Stark edited their review of gene: ACTG2: Added comment: More than 20 unrelated families reported.; Changed publications: 24676022, 26647307
Gastrointestinal neuromuscular disease v0.40 ACTG2 Zornitza Stark Marked gene: ACTG2 as ready
Gastrointestinal neuromuscular disease v0.40 ACTG2 Zornitza Stark Gene: actg2 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v0.40 ACTG2 Zornitza Stark Phenotypes for gene: ACTG2 were changed from Visceral myopathy, 155310 to Visceral myopathy, 155310; Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, MIM# 619431
Gastrointestinal neuromuscular disease v0.39 ACTG2 Zornitza Stark Mode of inheritance for gene: ACTG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gastrointestinal neuromuscular disease v0.38 ACTG2 Zornitza Stark reviewed gene: ACTG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, MIM# 619431; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8332 ACTG2 Zornitza Stark Phenotypes for gene: ACTG2 were changed from Visceral myopathy, MIM#155310 to Visceral myopathy, MIM#155310; Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, MIM# 619431
Mendeliome v0.8331 ACTG2 Zornitza Stark edited their review of gene: ACTG2: Changed phenotypes: Visceral myopathy, MIM#155310, Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, MIM# 619431
Combined Immunodeficiency v0.208 ADA Zornitza Stark Marked gene: ADA as ready
Combined Immunodeficiency v0.208 ADA Zornitza Stark Gene: ada has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.208 ADA Zornitza Stark Phenotypes for gene: ADA were changed from to Severe combined immunodeficiency due to ADA deficiency, MIM# 102700; MONDO:0007064
Combined Immunodeficiency v0.207 ADA Zornitza Stark Publications for gene: ADA were set to
Combined Immunodeficiency v0.206 ADA Zornitza Stark Mode of inheritance for gene: ADA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.205 ADA Zornitza Stark reviewed gene: ADA: Rating: GREEN; Mode of pathogenicity: None; Publications: 3007108, 3475710, 8178821, 8227344, 2783588; Phenotypes: Severe combined immunodeficiency due to ADA deficiency, MIM# 102700, MONDO:0007064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.223 CEP41 Zornitza Stark Marked gene: CEP41 as ready
Renal Ciliopathies and Nephronophthisis v0.223 CEP41 Zornitza Stark Gene: cep41 has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v0.223 CEP41 Zornitza Stark Phenotypes for gene: CEP41 were changed from to Joubert syndrome 15, MIM# 614464
Renal Ciliopathies and Nephronophthisis v0.222 CEP41 Zornitza Stark Publications for gene: CEP41 were set to
Renal Ciliopathies and Nephronophthisis v0.221 CEP41 Zornitza Stark Mode of inheritance for gene: CEP41 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.220 CEP41 Zornitza Stark Classified gene: CEP41 as Amber List (moderate evidence)
Renal Ciliopathies and Nephronophthisis v0.220 CEP41 Zornitza Stark Gene: cep41 has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v0.219 CEP41 Zornitza Stark reviewed gene: CEP41: Rating: AMBER; Mode of pathogenicity: None; Publications: 22246503; Phenotypes: Joubert syndrome 15, MIM# 614464; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.205 B2M Zornitza Stark Phenotypes for gene: B2M were changed from Immunodeficiency 43 MIM# 241600; Sinopulmonary infections; Purple-red skin lesions; - Decreased serum IgG; Decreased B cells; Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c; MONDO:0009434 to Immunodeficiency 43 MIM# 241600; Sinopulmonary infections; Purple-red skin lesions; Decreased serum IgG; Decreased B cells; Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c; MONDO:0009434
Mendeliome v0.8331 B2M Zornitza Stark Marked gene: B2M as ready
Mendeliome v0.8331 B2M Zornitza Stark Gene: b2m has been classified as Green List (High Evidence).
Mendeliome v0.8331 B2M Zornitza Stark Phenotypes for gene: B2M were changed from to Immunodeficiency 43 MIM# 241600; Sinopulmonary infections; Purple-red skin lesions; Decreased serum IgG; Decreased B cells; Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c; MONDO:0009434; Amyloidosis, familial visceral, MIM# 105200
Mendeliome v0.8330 B2M Zornitza Stark Publications for gene: B2M were set to
Mendeliome v0.8329 B2M Zornitza Stark Mode of inheritance for gene: B2M was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8328 B2M Zornitza Stark reviewed gene: B2M: Rating: GREEN; Mode of pathogenicity: None; Publications: 4186801, 16549777, 25702838, 11118151, 6165007, 22693999; Phenotypes: Immunodeficiency 43 MIM# 241600, Sinopulmonary infections, Purple-red skin lesions, Decreased serum IgG, Decreased B cells, Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c, MONDO:0009434, Amyloidosis, familial visceral, MIM# 105200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.204 B2M Zornitza Stark Marked gene: B2M as ready
Combined Immunodeficiency v0.204 B2M Zornitza Stark Gene: b2m has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.204 B2M Zornitza Stark Phenotypes for gene: B2M were changed from to Immunodeficiency 43 MIM# 241600; Sinopulmonary infections; Purple-red skin lesions; - Decreased serum IgG; Decreased B cells; Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c; MONDO:0009434
Combined Immunodeficiency v0.203 B2M Zornitza Stark Publications for gene: B2M were set to
Combined Immunodeficiency v0.202 B2M Zornitza Stark Mode of inheritance for gene: B2M was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.201 B2M Danielle Ariti reviewed gene: B2M: Rating: GREEN; Mode of pathogenicity: None; Publications: 4186801, 16549777, 25702838, 11118151, 6165007; Phenotypes: Immunodeficiency 43 MIM# 241600, Sinopulmonary infections, Purple-red skin lesions, - Decreased serum IgG, Decreased B cells, Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.219 CEP290 Zornitza Stark Marked gene: CEP290 as ready
Renal Ciliopathies and Nephronophthisis v0.219 CEP290 Zornitza Stark Gene: cep290 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.219 CEP290 Zornitza Stark Phenotypes for gene: CEP290 were changed from to Senior-Loken syndrome 6, MIM# 610189
Renal Ciliopathies and Nephronophthisis v0.218 CEP290 Zornitza Stark Publications for gene: CEP290 were set to
Renal Ciliopathies and Nephronophthisis v0.217 CEP290 Zornitza Stark Mode of inheritance for gene: CEP290 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.216 CEP290 Zornitza Stark changed review comment from: Variants in this gene cause a range of ciliopathies. The association with BBS is rare.; to: Variants in this gene cause a range of ciliopathies, including Senior-Loken syndrome/nephronophthisis.
Renal Ciliopathies and Nephronophthisis v0.216 CEP290 Zornitza Stark edited their review of gene: CEP290: Changed publications: 18327255, 20690115, 16682973, 32208788; Changed phenotypes: Senior-Loken syndrome 6, MIM# 610189
Deafness_IsolatedAndComplex v1.85 AK2 Zornitza Stark Marked gene: AK2 as ready
Deafness_IsolatedAndComplex v1.85 AK2 Zornitza Stark Gene: ak2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.85 AK2 Zornitza Stark Classified gene: AK2 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.85 AK2 Zornitza Stark Gene: ak2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.84 AK2 Zornitza Stark gene: AK2 was added
gene: AK2 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: AK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AK2 were set to 19043417; 19043416
Phenotypes for gene: AK2 were set to Reticular dysgenesis MIM# 267500; Combined immunodeficiency; neutropaenia; leukopaenia; lymphopaenia; agranulocytosis; deafness; MONDO:0009973
Review for gene: AK2 was set to GREEN
Added comment: PMID: 19043417 (2009). 6 affected individuals from 5 unrelated families (3 of the families showed evidence of consanguinity). Homozygous (5 individuals) and compound heterozygous (1 individual) variants in the AK2 gene. Variants included missense, deletion and inframe indel, resulting in protein LoF. Available parents were sequenced and found heterozygous for the variants, supporting bi-allelic inheritance.

PMID: 19043416 (2009). 7 affected individuals from 6 unrelated families (2 separate consanguineous & 4 non-consanguineous families). Homozygous and compound heterozygous variants detected (missense, deletion, inframe indel), resulting in protein LoF. Reticular dysgenesis phenotype including Leukopenia, lymphopenia and agranulocytosis in all affected individuals and sensorineural deafness in 7 individuals.
Sources: Literature
Mendeliome v0.8328 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis, MIM# 267500 to Reticular dysgenesis, MIM# 267500; MONDO:0009973
Mendeliome v0.8327 AK2 Zornitza Stark Publications for gene: AK2 were set to 19043416
Mendeliome v0.8326 AK2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association.

PMID: 19043417 (2009). 6 affected individuals from 5 unrelated families (3 of the families showed evidence of consanguinity). Homozygous (5 individuals) and compound heterozygous (1 individual) variants in the AK2 gene. Variants included missense, deletion and inframe indel, resulting in protein LoF. Available parents were sequenced and found heterozygous for the variants, supporting bi-allelic inheritance.

PMID: 19043416 (2009). 7 affected individuals from 6 unrelated families (2 separate consanguineous & 4 non-consanguineous families). Homozygous and compound heterozygous variants detected (missense, deletion, inframe indel), resulting in protein LoF. Reticular dysgenesis phenotype including Leukopenia, lymphopenia and agranulocytosis in all affected individuals and sensorineural deafness in 7 individuals.
Mendeliome v0.8326 AK2 Zornitza Stark edited their review of gene: AK2: Changed phenotypes: Reticular dysgenesis, MIM# 267500, MONDO:0009973
Mendeliome v0.8326 AK2 Zornitza Stark edited their review of gene: AK2: Changed publications: 19043416, 19043417
Bone Marrow Failure v1.2 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis, MIM# 267500 to Reticular dysgenesis, MIM# 267500; MONDO:0009973
Bone Marrow Failure v1.1 AK2 Zornitza Stark Publications for gene: AK2 were set to 19043416; 19043417
Bone Marrow Failure v1.1 AK2 Zornitza Stark Publications for gene: AK2 were set to 19043416; 19043417
Bone Marrow Failure v1.1 AK2 Zornitza Stark Publications for gene: AK2 were set to 19043416
Bone Marrow Failure v1.0 AK2 Zornitza Stark edited their review of gene: AK2: Changed publications: 19043416, 19043417
Bone Marrow Failure v1.0 AK2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association.

PMID: 19043417 (2009). 6 affected individuals from 5 unrelated families (3 of the families showed evidence of consanguinity). Homozygous (5 individuals) and compound heterozygous (1 individual) variants in the AK2 gene. Variants included missense, deletion and inframe indel, resulting in protein LoF. Available parents were sequenced and found heterozygous for the variants, supporting bi-allelic inheritance.

PMID: 19043416 (2009). 7 affected individuals from 6 unrelated families (2 separate consanguineous & 4 non-consanguineous families). Homozygous and compound heterozygous variants detected (missense, deletion, inframe indel), resulting in protein LoF. Reticular dysgenesis phenotype including Leukopenia, lymphopenia and agranulocytosis in all affected individuals and sensorineural deafness in 7 individuals.
Bone Marrow Failure v1.0 AK2 Zornitza Stark edited their review of gene: AK2: Changed phenotypes: Reticular dysgenesis, MIM# 267500, MONDO:0009973
Combined Immunodeficiency v0.201 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis MIM# 267500; Combined immunodeficiency; neutropaenia; leukopaenia; lymphopaenia; agranulocytosis; deafness to Reticular dysgenesis MIM# 267500; Combined immunodeficiency; neutropaenia; leukopaenia; lymphopaenia; agranulocytosis; deafness; MONDO:0009973
Severe Combined Immunodeficiency (absent T absent B cells) v0.27 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis MIM# 267500; Combined immunodeficiency; neutropaenia; leukopaenia; lymphopaenia; agranulocytosis; deafness to Reticular dysgenesis MIM# 267500; MONDO:0009973; Combined immunodeficiency; neutropaenia; leukopaenia; lymphopaenia; agranulocytosis; deafness
Severe Combined Immunodeficiency (absent T absent B cells) v0.26 AK2 Zornitza Stark edited their review of gene: AK2: Changed publications: 19043417, 19043416, 33628209
Severe Combined Immunodeficiency (absent T absent B cells) v0.26 AK2 Zornitza Stark Marked gene: AK2 as ready
Severe Combined Immunodeficiency (absent T absent B cells) v0.26 AK2 Zornitza Stark Added comment: Comment when marking as ready: Variants in this gene identified in SCID cohorts, e.g. PMID 33628209
Severe Combined Immunodeficiency (absent T absent B cells) v0.26 AK2 Zornitza Stark Gene: ak2 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T absent B cells) v0.26 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from to Reticular dysgenesis MIM# 267500; Combined immunodeficiency; neutropaenia; leukopaenia; lymphopaenia; agranulocytosis; deafness
Severe Combined Immunodeficiency (absent T absent B cells) v0.25 AK2 Zornitza Stark Publications for gene: AK2 were set to 19043417; 19043416
Severe Combined Immunodeficiency (absent T absent B cells) v0.24 AK2 Zornitza Stark Publications for gene: AK2 were set to
Severe Combined Immunodeficiency (absent T absent B cells) v0.23 AK2 Zornitza Stark Mode of inheritance for gene: AK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency (absent T absent B cells) v0.22 AK2 Zornitza Stark reviewed gene: AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19043417, 19043416; Phenotypes: Reticular dysgenesis MIM# 267500, Combined immunodeficiency, neutropaenia, leukopaenia, lymphopaenia, agranulocytosis, deafness; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.200 AK2 Zornitza Stark Marked gene: AK2 as ready
Combined Immunodeficiency v0.200 AK2 Zornitza Stark Gene: ak2 has been classified as Green List (High Evidence).
Combined Immunodeficiency v0.200 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from to Reticular dysgenesis MIM# 267500; Combined immunodeficiency; neutropaenia; leukopaenia; lymphopaenia; agranulocytosis; deafness
Combined Immunodeficiency v0.199 AK2 Zornitza Stark Publications for gene: AK2 were set to
Combined Immunodeficiency v0.198 AK2 Zornitza Stark Mode of inheritance for gene: AK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v0.197 AK2 Danielle Ariti changed review comment from: PMID: 19043417. 6 affected individuals from 5 unrelated families (3 of the families showed evidence of consanguinity). Homozygous (5 individuals) and compound heterozygous (1 individual) variants in the AK2 gene. Variants included missense, deletion and inframe indel, resulting in protein LoF. Available parents were sequenced and found heterozygous for the variants, supporting bi-allelic inheritance.

PMID: 19043416. 7 affected individuals from 6 unrelated families (2 separate consanguineous & 4 non-consanguineous families). Homozygous and compound heterozygous variants detected (missense, deletion, inframe indel), resulting in protein LoF.

Reticular dysgenesis phenotype including Leukopenia, lymphopenia and agranulocytosis in all affected individuals and sensorineural deafness in 7 individuals.; to: PMID: 19043417 (2009). 6 affected individuals from 5 unrelated families (3 of the families showed evidence of consanguinity). Homozygous (5 individuals) and compound heterozygous (1 individual) variants in the AK2 gene. Variants included missense, deletion and inframe indel, resulting in protein LoF. Available parents were sequenced and found heterozygous for the variants, supporting bi-allelic inheritance.

PMID: 19043416 (2009). 7 affected individuals from 6 unrelated families (2 separate consanguineous & 4 non-consanguineous families). Homozygous and compound heterozygous variants detected (missense, deletion, inframe indel), resulting in protein LoF.

Reticular dysgenesis phenotype including Leukopenia, lymphopenia and agranulocytosis in all affected individuals and sensorineural deafness in 7 individuals.
Sources: Literature
Combined Immunodeficiency v0.197 AK2 Danielle Ariti reviewed gene: AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19043417, 19043416; Phenotypes: Reticular dysgenesis MIM# 267500, Combined immunodeficiency, neutropenia, leukopenia, lymphopenia, agranulocytosis, deafness; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary angioedema v1.1 Zornitza Stark Panel types changed to Melbourne Genomics; Victorian Clinical Genetics Services; Rare Disease
Hereditary angioedema v1.0 Zornitza Stark promoted panel to version 1.0
Hereditary angioedema v0.17 SERPING1 Zornitza Stark Marked gene: SERPING1 as ready
Hereditary angioedema v0.17 SERPING1 Zornitza Stark Gene: serping1 has been classified as Green List (High Evidence).
Hereditary angioedema v0.17 SERPING1 Zornitza Stark Phenotypes for gene: SERPING1 were changed from to Angioedema, hereditary, 1 and 2, MIM# 106100
Hereditary angioedema v0.16 SERPING1 Zornitza Stark Mode of inheritance for gene: SERPING1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary angioedema v0.15 SERPING1 Zornitza Stark reviewed gene: SERPING1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angioedema, hereditary, 1 and 2, MIM# 106100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary angioedema v0.15 F12 Zornitza Stark Marked gene: F12 as ready
Hereditary angioedema v0.15 F12 Zornitza Stark Gene: f12 has been classified as Amber List (Moderate Evidence).
Hereditary angioedema v0.15 F12 Zornitza Stark Phenotypes for gene: F12 were changed from to Angioedema, hereditary, 3, MIM# 610618
Hereditary angioedema v0.14 F12 Zornitza Stark Publications for gene: F12 were set to
Hereditary angioedema v0.13 F12 Zornitza Stark Tag founder tag was added to gene: F12.
Hereditary angioedema v0.13 F12 Zornitza Stark Classified gene: F12 as Amber List (moderate evidence)
Hereditary angioedema v0.13 F12 Zornitza Stark Gene: f12 has been classified as Amber List (Moderate Evidence).
Hereditary angioedema v0.12 F12 Zornitza Stark reviewed gene: F12: Rating: AMBER; Mode of pathogenicity: None; Publications: 16638441, 17186468, 19178938; Phenotypes: Angioedema, hereditary, 3, MIM# 610618; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Ciliopathies and Nephronophthisis v0.216 CEP104 Zornitza Stark Marked gene: CEP104 as ready
Renal Ciliopathies and Nephronophthisis v0.216 CEP104 Zornitza Stark Gene: cep104 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.216 CEP104 Zornitza Stark Phenotypes for gene: CEP104 were changed from to Joubert syndrome 25, MIM# 616781; MONDO:0014770
Renal Ciliopathies and Nephronophthisis v0.215 CEP104 Zornitza Stark Mode of inheritance for gene: CEP104 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.214 CEP104 Zornitza Stark Classified gene: CEP104 as Red List (low evidence)
Renal Ciliopathies and Nephronophthisis v0.214 CEP104 Zornitza Stark Gene: cep104 has been classified as Red List (Low Evidence).
Renal Ciliopathies and Nephronophthisis v0.213 CEP104 Zornitza Stark reviewed gene: CEP104: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 25, MIM# 616781; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.213 CC2D2A Zornitza Stark Marked gene: CC2D2A as ready
Renal Ciliopathies and Nephronophthisis v0.213 CC2D2A Zornitza Stark Gene: cc2d2a has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.213 CC2D2A Zornitza Stark Phenotypes for gene: CC2D2A were changed from to Meckel syndrome 6, MIM# 612284
Renal Ciliopathies and Nephronophthisis v0.212 CC2D2A Zornitza Stark Mode of inheritance for gene: CC2D2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.211 CC2D2A Zornitza Stark reviewed gene: CC2D2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Meckel syndrome 6, MIM# 612284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.211 BBS2 Zornitza Stark Marked gene: BBS2 as ready
Renal Ciliopathies and Nephronophthisis v0.211 BBS2 Zornitza Stark Gene: bbs2 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.211 BBS2 Zornitza Stark Phenotypes for gene: BBS2 were changed from to Bardet-Biedl syndrome 2, MIM# 615981
Renal Ciliopathies and Nephronophthisis v0.210 BBS2 Zornitza Stark Publications for gene: BBS2 were set to
Renal Ciliopathies and Nephronophthisis v0.209 BBS2 Zornitza Stark Mode of inheritance for gene: BBS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.208 BBS2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Renal anomalies reported.
Renal Ciliopathies and Nephronophthisis v0.208 BBS12 Zornitza Stark Marked gene: BBS12 as ready
Renal Ciliopathies and Nephronophthisis v0.208 BBS12 Zornitza Stark Gene: bbs12 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.208 BBS12 Zornitza Stark Phenotypes for gene: BBS12 were changed from to Bardet-Biedl syndrome 12, MIM# 615989
Renal Ciliopathies and Nephronophthisis v0.207 BBS12 Zornitza Stark Publications for gene: BBS12 were set to
Renal Ciliopathies and Nephronophthisis v0.206 BBS12 Zornitza Stark Mode of inheritance for gene: BBS12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.205 BBS12 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Renal anomalies reported.
Renal Ciliopathies and Nephronophthisis v0.205 BBS10 Zornitza Stark Marked gene: BBS10 as ready
Renal Ciliopathies and Nephronophthisis v0.205 BBS10 Zornitza Stark Gene: bbs10 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.205 BBS10 Zornitza Stark Phenotypes for gene: BBS10 were changed from to Bardet-Biedl syndrome 10, MIM# 615987
Renal Ciliopathies and Nephronophthisis v0.204 BBS10 Zornitza Stark Publications for gene: BBS10 were set to
Renal Ciliopathies and Nephronophthisis v0.203 BBS10 Zornitza Stark Mode of inheritance for gene: BBS10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.202 BBS10 Zornitza Stark changed review comment from: BBS10 represents a major locus for BBS, with mutations in the BBS10 gene accounting for approximately 20% of BBS patients; to: BBS10 represents a major locus for BBS, with mutations in the BBS10 gene accounting for approximately 20% of BBS patients. Renal anomalies, including cysts reported.
Optic Atrophy v1.0 Zornitza Stark promoted panel to version 1.0
Optic Atrophy v0.140 OPA1 Zornitza Stark Marked gene: OPA1 as ready
Optic Atrophy v0.140 OPA1 Zornitza Stark Gene: opa1 has been classified as Green List (High Evidence).
Optic Atrophy v0.140 OPA1 Zornitza Stark Phenotypes for gene: OPA1 were changed from to Optic atrophy 1 165500; Optic atrophy plus syndrome, MIM# 125250; Behr syndrome, MIM# 210000
Optic Atrophy v0.139 OPA1 Zornitza Stark Mode of inheritance for gene: OPA1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic Atrophy v0.138 OPA1 Zornitza Stark reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Optic atrophy 1 165500, Optic atrophy plus syndrome, MIM# 125250, Behr syndrome, MIM# 210000; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8326 TMEM126A Zornitza Stark Marked gene: TMEM126A as ready
Mendeliome v0.8326 TMEM126A Zornitza Stark Gene: tmem126a has been classified as Green List (High Evidence).
Mendeliome v0.8326 TMEM126A Zornitza Stark Phenotypes for gene: TMEM126A were changed from to Optic atrophy 7, MIM# 612989; MONDO:0013069; Syndromic auditory neuropathy spectrum disorder
Mendeliome v0.8325 TMEM126A Zornitza Stark Publications for gene: TMEM126A were set to
Mendeliome v0.8324 TMEM126A Zornitza Stark Mode of inheritance for gene: TMEM126A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8323 TMEM126A Zornitza Stark reviewed gene: TMEM126A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19327736, 20405026, 22815638, 33879611, 31119195, 30961538; Phenotypes: Optic atrophy 7, MIM# 612989, MONDO:0013069, Syndromic auditory neuropathy spectrum disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v0.138 TMEM126A Zornitza Stark Marked gene: TMEM126A as ready
Optic Atrophy v0.138 TMEM126A Zornitza Stark Gene: tmem126a has been classified as Green List (High Evidence).
Optic Atrophy v0.138 TMEM126A Zornitza Stark Phenotypes for gene: TMEM126A were changed from to Optic atrophy 7, MIM# 612989; MONDO:0013069
Optic Atrophy v0.137 TMEM126A Zornitza Stark Publications for gene: TMEM126A were set to
Optic Atrophy v0.136 TMEM126A Zornitza Stark Mode of inheritance for gene: TMEM126A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v0.135 TMEM126A Zornitza Stark reviewed gene: TMEM126A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19327736, 20405026, 22815638, 33879611, 31119195, 30961538; Phenotypes: Optic atrophy 7, MIM# 612989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
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).
Mendeliome v0.8323 MYC Zornitza Stark Marked gene: MYC as ready
Mendeliome v0.8323 MYC Zornitza Stark Gene: myc has been classified as Red List (Low Evidence).
Mendeliome v0.8323 MYC Zornitza Stark Phenotypes for gene: MYC were changed from to Burkitt lymphoma, somatic, MIM# 113970
Mendeliome v0.8322 MYC Zornitza Stark Mode of inheritance for gene: MYC was changed from Unknown to Other
Mendeliome v0.8321 MYC Zornitza Stark Classified gene: MYC as Red List (low evidence)
Mendeliome v0.8321 MYC Zornitza Stark Gene: myc has been classified as Red List (Low Evidence).
Mendeliome v0.8320 MYC Zornitza Stark reviewed gene: MYC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Burkitt lymphoma, somatic, MIM# 113970; Mode of inheritance: Other
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
Metal Metabolism Disorders v0.23 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Monogenic Diabetes v0.21 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Intellectual disability syndromic and non-syndromic v0.3978 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The more severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The more severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Mendeliome v0.8318 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The more severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3978 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The more severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Optic Atrophy v0.135 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The more severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Optic Atrophy v0.135 ATG7 Zornitza Stark Marked gene: ATG7 as ready
Optic Atrophy v0.135 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Optic Atrophy v0.135 ATG7 Zornitza Stark Classified gene: ATG7 as Green List (high evidence)
Optic Atrophy v0.135 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Optic Atrophy v0.134 ATG7 Zornitza Stark gene: ATG7 was added
gene: ATG7 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG7 were set to 34161705
Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, SCAR31, MIM#619422
Review for gene: ATG7 was set to GREEN
Added comment: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3978 ATG7 Zornitza Stark Marked gene: ATG7 as ready
Intellectual disability syndromic and non-syndromic v0.3978 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3978 ATG7 Zornitza Stark Classified gene: ATG7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3978 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3977 ATG7 Zornitza Stark gene: ATG7 was added
gene: ATG7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG7 were set to 34161705
Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, SCAR31, MIM#619422
Review for gene: ATG7 was set to GREEN
Added comment: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Ataxia - paediatric v0.287 ATG7 Zornitza Stark Marked gene: ATG7 as ready
Ataxia - paediatric v0.287 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.287 ATG7 Zornitza Stark Classified gene: ATG7 as Green List (high evidence)
Ataxia - paediatric v0.287 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.286 ATG7 Zornitza Stark gene: ATG7 was added
gene: ATG7 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG7 were set to 34161705
Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, SCAR31, MIM#619422
Review for gene: ATG7 was set to GREEN
Added comment: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Mendeliome v0.8318 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Mendeliome v0.8318 ATG7 Zornitza Stark Marked gene: ATG7 as ready
Mendeliome v0.8318 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Mendeliome v0.8318 ATG7 Zornitza Stark Classified gene: ATG7 as Green List (high evidence)
Mendeliome v0.8318 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Mendeliome v0.8317 ATG7 Zornitza Stark gene: ATG7 was added
gene: ATG7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG7 were set to 34161705
Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, SCAR31, MIM#619422
Review for gene: ATG7 was set to GREEN
Added comment: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.
Sources: Literature
Mendeliome v0.8316 ADA Zornitza Stark Marked gene: ADA as ready
Mendeliome v0.8316 ADA Zornitza Stark Gene: ada has been classified as Green List (High Evidence).
Mendeliome v0.8316 ADA Zornitza Stark Phenotypes for gene: ADA were changed from to Severe combined immunodeficiency due to ADA deficiency, MIM# 102700; MONDO:0007064
Mendeliome v0.8315 ADA Zornitza Stark Publications for gene: ADA were set to
Mendeliome v0.8314 ADA Zornitza Stark Mode of inheritance for gene: ADA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8313 ADA Zornitza Stark reviewed gene: ADA: Rating: GREEN; Mode of pathogenicity: None; Publications: 3007108, 3475710, 8178821, 8227344, 2783588; Phenotypes: Severe combined immunodeficiency due to ADA deficiency, MIM# 102700, MONDO:0007064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency (absent T absent B cells) v0.22 ADA Zornitza Stark Marked gene: ADA as ready
Severe Combined Immunodeficiency (absent T absent B cells) v0.22 ADA Zornitza Stark Gene: ada has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T absent B cells) v0.22 ADA Zornitza Stark Phenotypes for gene: ADA were changed from to Severe combined immunodeficiency due to ADA deficiency, MIM# 102700; MONDO:0007064
Severe Combined Immunodeficiency (absent T absent B cells) v0.21 ADA Zornitza Stark Publications for gene: ADA were set to
Severe Combined Immunodeficiency (absent T absent B cells) v0.20 ADA Zornitza Stark Mode of inheritance for gene: ADA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency (absent T absent B cells) v0.19 ADA Zornitza Stark changed review comment from: Well established gene-disease association, multiple families, variable severity.; to: Well established gene-disease association, multiple families, variable severity.
Severe Combined Immunodeficiency (absent T absent B cells) v0.19 ADA Zornitza Stark edited their review of gene: ADA: Changed publications: 3007108, 3475710, 8178821, 8227344, 2783588
Severe Combined Immunodeficiency (absent T absent B cells) v0.19 ADA Zornitza Stark reviewed gene: ADA: Rating: GREEN; Mode of pathogenicity: None; Publications: 46025, 3007108, 3475710, 8178821, 8227344, 2783588; Phenotypes: Severe combined immunodeficiency due to ADA deficiency, MIM# 102700, MONDO:0007064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.226 C2orf69 Zornitza Stark Marked gene: C2orf69 as ready
Leukodystrophy - paediatric v0.226 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.226 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Leukodystrophy - paediatric v0.226 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.115 C2orf69 Zornitza Stark Marked gene: C2orf69 as ready
Autoinflammatory Disorders v0.115 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.115 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Autoinflammatory Disorders v0.115 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.225 C2orf69 Zornitza Stark gene: C2orf69 was added
gene: C2orf69 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Review for gene: C2orf69 was set to GREEN
Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature
Autoinflammatory Disorders v0.114 C2orf69 Zornitza Stark gene: C2orf69 was added
gene: C2orf69 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Review for gene: C2orf69 was set to GREEN
Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature
Genetic Epilepsy v0.1141 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Genetic Epilepsy v0.1141 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3976 C2orf69 Zornitza Stark Marked gene: C2orf69 as ready
Intellectual disability syndromic and non-syndromic v0.3976 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3976 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3976 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1140 C2orf69 Zornitza Stark gene: C2orf69 was added
gene: C2orf69 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Review for gene: C2orf69 was set to GREEN
Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature
Mendeliome v0.8313 C2orf69 Zornitza Stark Marked gene: C2orf69 as ready
Mendeliome v0.8313 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mendeliome v0.8313 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Mendeliome v0.8313 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3975 C2orf69 Zornitza Stark gene: C2orf69 was added
gene: C2orf69 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Review for gene: C2orf69 was set to GREEN
Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature
Mendeliome v0.8312 C2orf69 Zornitza Stark gene: C2orf69 was added
gene: C2orf69 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Review for gene: C2orf69 was set to GREEN
Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature
Mitochondrial disease v0.640 C2orf69 Zornitza Stark Marked gene: C2orf69 as ready
Mitochondrial disease v0.640 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mitochondrial disease v0.640 C2orf69 Zornitza Stark edited their review of gene: C2orf69: Changed publications: 34038740, 33945503
Mitochondrial disease v0.640 C2orf69 Zornitza Stark Publications for gene: C2orf69 were set to 34038740
Mitochondrial disease v0.639 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Mitochondrial disease v0.639 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mitochondrial disease v0.638 C2orf69 Zornitza Stark gene: C2orf69 was added
gene: C2orf69 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Review for gene: C2orf69 was set to GREEN
Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3974 KDM3B Zornitza Stark Phenotypes for gene: KDM3B were changed from Intellectual disability; dysmorphic features; short stature; no OMIM number yet to Diets-Jongmans syndrome, MIM# 618846; Intellectual disability; dysmorphic features; short stature
Intellectual disability syndromic and non-syndromic v0.3973 KDM3B Zornitza Stark reviewed gene: KDM3B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diets-Jongmans syndrome, MIM# 618846, Intellectual disability, dysmorphic features, short stature, Intellectual disability, short stature, deafness; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.83 KDM3B Zornitza Stark Phenotypes for gene: KDM3B were changed from Intellectual disability; short stature; deafness to Diets-Jongmans syndrome, MIM# 618846; Intellectual disability; short stature; deafness
Deafness_IsolatedAndComplex v1.82 KDM3B Zornitza Stark edited their review of gene: KDM3B: Changed phenotypes: Diets-Jongmans syndrome, MIM# 618846, Intellectual disability, short stature, deafness
Mendeliome v0.8311 KDM3B Zornitza Stark Phenotypes for gene: KDM3B were changed from Intellectual disability; dysmorphic features; short stature to Diets-Jongmans syndrome, MIM# 618846; Intellectual disability; dysmorphic features; short stature
Mendeliome v0.8310 KDM3B Zornitza Stark edited their review of gene: KDM3B: Changed phenotypes: Diets-Jongmans syndrome, MIM# 618846, Intellectual disability, dysmorphic features, short stature
Cancer Predisposition_Paediatric v0.105 KDM3B Zornitza Stark Marked gene: KDM3B as ready
Cancer Predisposition_Paediatric v0.105 KDM3B Zornitza Stark Gene: kdm3b has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.105 KDM3B Zornitza Stark Phenotypes for gene: KDM3B were changed from to Diets-Jongmans syndrome, MIM# 618846; Cancer predisposition
Cancer Predisposition_Paediatric v0.104 KDM3B Zornitza Stark Classified gene: KDM3B as Green List (high evidence)
Cancer Predisposition_Paediatric v0.104 KDM3B Zornitza Stark Gene: kdm3b has been classified as Green List (High Evidence).
Mendeliome v0.8310 NYNRIN Zornitza Stark Marked gene: NYNRIN as ready
Mendeliome v0.8310 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8310 NYNRIN Zornitza Stark Phenotypes for gene: NYNRIN were changed from to Wilms tumour predisposition
Mendeliome v0.8309 NYNRIN Zornitza Stark Classified gene: NYNRIN as Amber List (moderate evidence)
Mendeliome v0.8309 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Cancer Predisposition_Paediatric v0.103 NYNRIN Zornitza Stark Marked gene: NYNRIN as ready
Cancer Predisposition_Paediatric v0.103 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Cancer Predisposition_Paediatric v0.103 NYNRIN Zornitza Stark Phenotypes for gene: NYNRIN were changed from to Wilms tumour predisposition
Cancer Predisposition_Paediatric v0.102 NYNRIN Zornitza Stark Classified gene: NYNRIN as Amber List (moderate evidence)
Cancer Predisposition_Paediatric v0.102 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8308 FBXW7 Zornitza Stark Phenotypes for gene: FBXW7 were changed from FBXW7-related neurodevelopmental syndrome to FBXW7-related neurodevelopmental syndrome; Wilms tumour predisposition
Mendeliome v0.8307 FBXW7 Zornitza Stark Publications for gene: FBXW7 were set to 33057194
Mendeliome v0.8306 FBXW7 Zornitza Stark reviewed gene: FBXW7: Rating: GREEN; Mode of pathogenicity: None; Publications: 30885698, 26482194; Phenotypes: Wilms tumour predisposition; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cancer Predisposition_Paediatric v0.101 KDM3B Laura Raiti gene: KDM3B was added
gene: KDM3B was added to Cancer Predisposition_Paediatric. Sources: Literature
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM3B were set to PMID: 30885698; 29351919
Review for gene: KDM3B was set to GREEN
Added comment: PMID: 30885698
2 two de-novo KDM3B mutations identified.
- 1 child (missense mutation) with Wilms tumour and a hyperpigmented lesion on her
buttock
- 1 child (truncating variant) with hepatoblastoma, hyperpigmentation and hypopigmentation, autism, and intellectual disability

PMID: 29351919
2 individuals with KDM3B variants
- 1 individual had a KDM3B truncating variant with acute myeloid leukaemia, mild intellectual disability, and hip dysplasia
- 1 individual had a de novo missense KDM3B with Hodgkins lymphoma and
moderate intellectual disability.
KDM3B is highly intolerant to both protein-truncating variants (pLI=1·00)
and non-synonymous variation (Z=4·99; the Z score is the
deviation of observation from expectation for non-synonymous variants).

KDM3B is involved in H3K9 demethylation, which is part of chromatin remodeling. Mutations in several components of chromatin remodeling pathways have been found to cause both syndromes characterized by ID and syndromes with cancer predisposition
Sources: Literature
Mendeliome v0.8306 NYNRIN Laura Raiti gene: NYNRIN was added
gene: NYNRIN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NYNRIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NYNRIN were set to PMID: 30885698
Review for gene: NYNRIN was set to AMBER
Added comment: 3 individuals with Wilms Tumour reported (2 children from 1 family, the 3rd child from a second family).
Biallelic truncating mutations in NYNRIN in three children with Wilms Tumour from two families, each parent was heterozygous for one of the mutations.
One of the affected children had an inguinal hernia and another had epilepsy, hypothyroidism, and intellectual disability.
Sources: Literature
Cancer Predisposition_Paediatric v0.101 NYNRIN Laura Raiti gene: NYNRIN was added
gene: NYNRIN was added to Cancer Predisposition_Paediatric. Sources: Literature
Mode of inheritance for gene: NYNRIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NYNRIN were set to PMID: 30885698
Review for gene: NYNRIN was set to AMBER
Added comment: 3 individuals with Wilms Tumour reported (2 children from 1 family, the 3rd child from a second family).
Biallelic truncating mutations in NYNRIN in three children with Wilms Tumour from two families, each parent was heterozygous for one of the mutations.
One of the affected children had an inguinal hernia and another had epilepsy, hypothyroidism, and intellectual disability.
Sources: Literature
Cancer Predisposition_Paediatric v0.101 FBXW7 Laura Raiti gene: FBXW7 was added
gene: FBXW7 was added to Cancer Predisposition_Paediatric. Sources: Literature
Mode of inheritance for gene: FBXW7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXW7 were set to PMID: 30885698; PMID: 26482194
Review for gene: FBXW7 was set to GREEN
Added comment: PMID: 30885698
4 individuals with germline truncating variants in FBXW7. Highly intolerant to protein-truncating variants with pLI score= 1.
- 1 individual developed a second malignancy (osteosarcoma) as an adult in addition to childhood Wilms tumour.
- 1 individual had a de novo missense variant (a child with an extra-renal rhabdoid tumour)

PMID: 26482194
1 patient with Hodgkin lymphoma, adult Wilms tumour, early-onset breast cancer, and a constitutional FBXW7 deletion was reported
Sources: Literature
Deafness_IsolatedAndComplex v1.82 YARS Zornitza Stark Marked gene: YARS as ready
Deafness_IsolatedAndComplex v1.82 YARS Zornitza Stark Gene: yars has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.82 YARS Zornitza Stark Classified gene: YARS as Green List (high evidence)
Deafness_IsolatedAndComplex v1.82 YARS Zornitza Stark Gene: yars has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.81 YARS Zornitza Stark gene: YARS was added
gene: YARS was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: YARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YARS were set to 30304524; 29232904; 27633801
Phenotypes for gene: YARS were set to Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418
Review for gene: YARS was set to GREEN
Added comment: Mono-allelic variants are associated with CMT. However, 10 individuals from three unrelated families reported with bi-allelic variants and a severe phenotype, comprising ID, nystagmus, deafness, liver dysfunction and a range of other features.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3973 YARS Zornitza Stark Phenotypes for gene: YARS were changed from Intellectual disability; deafness; nystagmus; liver dysfunction to Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418
Intellectual disability syndromic and non-syndromic v0.3972 YARS Zornitza Stark edited their review of gene: YARS: Changed phenotypes: Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418
Mendeliome v0.8306 YARS Zornitza Stark Phenotypes for gene: YARS were changed from Charcot-Marie-Tooth disease, dominant intermediate C 608323; Bi-allelic variants: ID, deafness, nystagmus to Charcot-Marie-Tooth disease, dominant intermediate C, MIM# 608323; MONDO:0012012; Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418
Mendeliome v0.8305 YARS Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: Mono-allelic disease: More than 5 unrelated families reported.
Mendeliome v0.8305 YARS Zornitza Stark edited their review of gene: YARS: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8305 YARS Zornitza Stark edited their review of gene: YARS: Changed phenotypes: Charcot-Marie-Tooth disease, dominant intermediate C, MIM# 608323, MONDO:0012012, Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418
Renal Ciliopathies and Nephronophthisis v0.202 BBS1 Zornitza Stark Marked gene: BBS1 as ready
Renal Ciliopathies and Nephronophthisis v0.202 BBS1 Zornitza Stark Gene: bbs1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.202 BBS1 Zornitza Stark Phenotypes for gene: BBS1 were changed from to Bardet-Biedl syndrome 1, MIM# 209900
Renal Ciliopathies and Nephronophthisis v0.201 BBS1 Zornitza Stark Publications for gene: BBS1 were set to
Renal Ciliopathies and Nephronophthisis v0.200 BBS1 Zornitza Stark Mode of inheritance for gene: BBS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.199 BBS1 Zornitza Stark changed review comment from: Well established gene-disease association.

Some suggestion that heterozygotes may have an increased frequency of obesity, hypertension, diabetes mellitus, and renal disease.; to: Well established gene-disease association. Renal abnormalities reported.

Some suggestion that heterozygotes may have an increased frequency of obesity, hypertension, diabetes mellitus, and renal disease.
Intellectual disability syndromic and non-syndromic v0.3972 ERGIC3 Zornitza Stark Phenotypes for gene: ERGIC3 were changed from 33710394; 31585110 to Intellectual disability
Intellectual disability syndromic and non-syndromic v0.3971 ERGIC3 Zornitza Stark Publications for gene: ERGIC3 were set to ERGIC3
Intellectual disability syndromic and non-syndromic v0.3970 ERGIC3 Zornitza Stark reviewed gene: ERGIC3: Rating: AMBER; Mode of pathogenicity: None; Publications: 33710394, 31585110; Phenotypes: Intellectual disability; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.3970 ZC3H14 Zornitza Stark Publications for gene: ZC3H14 were set to 21734151; 33710394
Intellectual disability syndromic and non-syndromic v0.3969 ZC3H14 Zornitza Stark reviewed gene: ZC3H14: Rating: AMBER; Mode of pathogenicity: None; Publications: 28666327; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8305 ZC3H14 Zornitza Stark Publications for gene: ZC3H14 were set to 21734151; 28666327
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Added comment: PMID: 33710394
1 Finnish family with a hom splice variant, severe ID. Classed a VUS. No functional evidence; Changed publications: 21734151, 28666327, 33710394
Mendeliome v0.8304 ZC3H14 Zornitza Stark Deleted their comment
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Added comment: Two families and a mouse model.; Changed phenotypes: Mental retardation, autosomal recessive 56, OMIM# 617125
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Changed publications: 21734151, 28666327
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Changed rating: AMBER; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8304 ZC3H14 Zornitza Stark Publications for gene: ZC3H14 were set to 21734151
Mendeliome v0.8303 ZC3H14 Zornitza Stark Mode of inheritance for gene: ZC3H14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8302 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Mendeliome v0.8302 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.107 DLX5 Zornitza Stark Mode of inheritance for gene: DLX5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v0.106 DLX5 Zornitza Stark reviewed gene: DLX5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1139 RNF2 Zornitza Stark Marked gene: RNF2 as ready
Genetic Epilepsy v0.1139 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1139 RNF2 Zornitza Stark Classified gene: RNF2 as Amber List (moderate evidence)
Genetic Epilepsy v0.1139 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1138 RNF2 Zornitza Stark gene: RNF2 was added
gene: RNF2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RNF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNF2 were set to 33864376
Phenotypes for gene: RNF2 were set to epilepsy; intellectual disability; intrauterine growth retardation
Review for gene: RNF2 was set to AMBER
Added comment: Not associated with any phenotype in OMIM. PMID:33864376 (Luo et al 2021) report 2 cases of children with de novo missense variants (p.R70H and p.S82R) in RNF2 and a phenotype of intrauterine growth retardation, severe intellectual disabilities, behavioral problems, seizures, feeding difficulties and dysmorphic features. Seizures started in infancy. Both variants are absent from gnomad. Functional studies in Drosophila showed that the disease-linked variants (p.R70H and p.S82R) behave as LoF alleles.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3969 RNF2 Zornitza Stark Marked gene: RNF2 as ready
Intellectual disability syndromic and non-syndromic v0.3969 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3969 RNF2 Zornitza Stark Classified gene: RNF2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3969 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3968 RNF2 Zornitza Stark gene: RNF2 was added
gene: RNF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RNF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNF2 were set to 33864376
Phenotypes for gene: RNF2 were set to epilepsy; intellectual disability; intrauterine growth retardation
Review for gene: RNF2 was set to AMBER
Added comment: Not associated with any phenotype in OMIM. PMID:33864376 (Luo et al 2021) report 2 cases of children with de novo missense variants (p.R70H and p.S82R) in RNF2 and a phenotype of intrauterine growth retardation, severe intellectual disabilities, behavioral problems, seizures, feeding difficulties and dysmorphic features. Seizures started in infancy. Both variants are absent from gnomad. Functional studies in Drosophila showed that the disease-linked variants (p.R70H and p.S82R) behave as LoF alleles.
Sources: Literature
Mendeliome v0.8302 RNF2 Zornitza Stark Marked gene: RNF2 as ready
Mendeliome v0.8302 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8302 RNF2 Zornitza Stark Classified gene: RNF2 as Amber List (moderate evidence)
Mendeliome v0.8302 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3967 RING1 Zornitza Stark Marked gene: RING1 as ready
Intellectual disability syndromic and non-syndromic v0.3967 RING1 Zornitza Stark Gene: ring1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3967 RING1 Zornitza Stark gene: RING1 was added
gene: RING1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RING1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RING1 were set to 29386386
Phenotypes for gene: RING1 were set to microcephaly; intellectual disability
Review for gene: RING1 was set to RED
Added comment: Not associated with any phenotype in OMIM. PMID: 29386386 - Pierce et al 2018 - report a 13 yo female with a de novo RING1 p.R95Q variant and syndromic neurodevelopmental disabilities. Early motor and language development were normal but were delayed after the first year of life. Cognitive testing showed a verbal IQ of 55 and a visual performance IQ of 63. Head circumference at birth was -4.9 SD, and -4.2 SD at age 13 which falls into the severe microcephaly category. C. elegans with either the missense mutation or complete knockout of spat-3 (the suggested RING1 ortholog) were defective in monoubiquitylation of histone H2A and had defects in neuronal migration and axon guidance.
Sources: Literature
Mendeliome v0.8301 RING1 Zornitza Stark Marked gene: RING1 as ready
Mendeliome v0.8301 RING1 Zornitza Stark Gene: ring1 has been classified as Red List (Low Evidence).
Mendeliome v0.8301 RING1 Zornitza Stark Classified gene: RING1 as Red List (low evidence)
Mendeliome v0.8301 RING1 Zornitza Stark Gene: ring1 has been classified as Red List (Low Evidence).
Cone-rod Dystrophy v0.29 IRX5 Zornitza Stark Marked gene: IRX5 as ready
Cone-rod Dystrophy v0.29 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Cone-rod Dystrophy v0.29 IRX5 Zornitza Stark Classified gene: IRX5 as Amber List (moderate evidence)
Cone-rod Dystrophy v0.29 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Cone-rod Dystrophy v0.28 IRX5 Zornitza Stark gene: IRX5 was added
gene: IRX5 was added to Cone-rod Dystrophy. Sources: Literature
SV/CNV tags were added to gene: IRX5.
Mode of inheritance for gene: IRX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRX5 were set to 33891002; 28041643; 32045705; 22581230; 17230486
Phenotypes for gene: IRX5 were set to cone dystrophy, MONDO:0000455
Mode of pathogenicity for gene: IRX5 was set to Other
Review for gene: IRX5 was set to AMBER
Added comment: Evidence from CNVs only

Duplication of gene
-------------------
PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.

Loss of function/gene
---------
PMID: 28041643 - Carss et al 2017 - screened a cohort of 722 individuals with inherited retinal disease using WES/WGS. 1 case reported with a biallelic deletion in IRX5 reported which leads to a frameshift ENST00000394636.4; c.1362_1366delTAAAG, p.Lys455ProfsTer19 in a patient with retinitis pigmentosa.

PMID: 32045705 - Apuzzo et al 2020 - report 2 cases of loss of a region in 16q12.1q21 which encompasses IRX5 and IRX6 and many other genes, which together with 3 other previous reports of deletions in this region help define a syndrome with features that include dysmorphic features, short stature, microcephaly, global developmental delay/intellectual disability, autism spectrum disorder (ASD) and ocular abnormalities (nystagmus and strabismus).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3966 IRX5 Zornitza Stark Marked gene: IRX5 as ready
Intellectual disability syndromic and non-syndromic v0.3966 IRX5 Zornitza Stark Gene: irx5 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3966 IRX5 Zornitza Stark Phenotypes for gene: IRX5 were changed from to Hamamy syndrome, MIM# 611174
Intellectual disability syndromic and non-syndromic v0.3965 IRX5 Zornitza Stark Publications for gene: IRX5 were set to
Intellectual disability syndromic and non-syndromic v0.3964 IRX5 Zornitza Stark Mode of inheritance for gene: IRX5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3963 IRX5 Zornitza Stark Classified gene: IRX5 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3963 IRX5 Zornitza Stark Gene: irx5 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3962 IRX5 Zornitza Stark reviewed gene: IRX5: Rating: RED; Mode of pathogenicity: None; Publications: 22581230, 27453922; Phenotypes: Hamamy syndrome, MIM# 611174; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8300 IRX5 Zornitza Stark Marked gene: IRX5 as ready
Mendeliome v0.8300 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8300 IRX5 Zornitza Stark Tag SV/CNV tag was added to gene: IRX5.
Mendeliome v0.8300 IRX5 Zornitza Stark Phenotypes for gene: IRX5 were changed from to Hamamy syndrome, MIM# 611174; cone dystrophy, MONDO:0000455
Mendeliome v0.8299 IRX5 Zornitza Stark Publications for gene: IRX5 were set to
Mendeliome v0.8298 IRX5 Zornitza Stark Mode of inheritance for gene: IRX5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8297 IRX5 Zornitza Stark Classified gene: IRX5 as Amber List (moderate evidence)
Mendeliome v0.8297 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8296 IRX5 Zornitza Stark edited their review of gene: IRX5: Changed rating: AMBER
Mendeliome v0.8296 IRX5 Zornitza Stark reviewed gene: IRX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581230, 27453922; Phenotypes: Hamamy syndrome, MIM# 611174; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cone-rod Dystrophy v0.27 IRX6 Zornitza Stark Mode of pathogenicity for gene: IRX6 was changed from None to Other
Cone-rod Dystrophy v0.26 IRX6 Zornitza Stark Marked gene: IRX6 as ready
Cone-rod Dystrophy v0.26 IRX6 Zornitza Stark Gene: irx6 has been classified as Amber List (Moderate Evidence).
Cone-rod Dystrophy v0.26 IRX6 Zornitza Stark Classified gene: IRX6 as Amber List (moderate evidence)
Cone-rod Dystrophy v0.26 IRX6 Zornitza Stark Gene: irx6 has been classified as Amber List (Moderate Evidence).
Cone-rod Dystrophy v0.25 IRX6 Zornitza Stark Tag SV/CNV tag was added to gene: IRX6.
Cone-rod Dystrophy v0.25 IRX6 Zornitza Stark gene: IRX6 was added
gene: IRX6 was added to Cone-rod Dystrophy. Sources: Literature
Mode of inheritance for gene: IRX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRX6 were set to 33891002
Phenotypes for gene: IRX6 were set to cone dystrophy, MONDO:0000455
Review for gene: IRX6 was set to AMBER
Added comment: PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.

Evidence from CNVs only, two genes included.
Sources: Literature
Mendeliome v0.8296 IRX6 Zornitza Stark reviewed gene: IRX6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8296 IRX6 Zornitza Stark Marked gene: IRX6 as ready
Mendeliome v0.8296 IRX6 Zornitza Stark Gene: irx6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8296 IRX6 Zornitza Stark Classified gene: IRX6 as Amber List (moderate evidence)
Mendeliome v0.8296 IRX6 Zornitza Stark Gene: irx6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3962 RAB3GAP1 Zornitza Stark Marked gene: RAB3GAP1 as ready
Intellectual disability syndromic and non-syndromic v0.3962 RAB3GAP1 Zornitza Stark Gene: rab3gap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3962 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from to Warburg micro syndrome 1, MIM# 600118; Martsolf syndrome 2, MIM# 619420
Intellectual disability syndromic and non-syndromic v0.3961 RAB3GAP1 Zornitza Stark Publications for gene: RAB3GAP1 were set to
Intellectual disability syndromic and non-syndromic v0.3960 RAB3GAP1 Zornitza Stark Mode of inheritance for gene: RAB3GAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3959 RAB3GAP1 Zornitza Stark reviewed gene: RAB3GAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15696165, 20512159, 23420520, 23420520, 30730599; Phenotypes: Warburg micro syndrome 1, MIM# 600118, Martsolf syndrome 2, MIM# 619420; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8295 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from Warburg micro syndrome 1, MIM# 600118 to Warburg micro syndrome 1, MIM# 600118; Martsolf syndrome 2, MIM# 619420
Mendeliome v0.8294 RAB3GAP1 Zornitza Stark Publications for gene: RAB3GAP1 were set to 15696165; 20512159; 23420520
Mendeliome v0.8293 RAB3GAP1 Zornitza Stark changed review comment from: Rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. Multiple families reported.; to: Warburg micro: Rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe ID, spastic diplegia, and hypogonadism. Multiple families reported.

Martsolf syndrome is characterised by cataracts, mild to severe ID, dysmorphic features. Two families reported.
Mendeliome v0.8293 RAB3GAP1 Zornitza Stark edited their review of gene: RAB3GAP1: Changed publications: 15696165, 20512159, 23420520, 23420520, 30730599; Changed phenotypes: Warburg micro syndrome 1, MIM# 600118, Martsolf syndrome 2, MIM# 619420
Cataract v0.284 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from Warburg micro syndrome 1, MIM# 600118 to Warburg micro syndrome 1, MIM# 600118; Martsolf syndrome 2, MIM# 619420
Cataract v0.283 RAB3GAP1 Zornitza Stark Publications for gene: RAB3GAP1 were set to 15696165; 20512159; 23420520
Cataract v0.282 RAB3GAP1 Zornitza Stark changed review comment from: Rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe ID, spastic diplegia, and hypogonadism. Multiple families reported.; to: Warburg micro: Rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe ID, spastic diplegia, and hypogonadism. Multiple families reported.

Martsolf syndrome is characterised by cataracts, mild to severe ID, dysmorphic features. Two families reported.
Cataract v0.282 RAB3GAP1 Zornitza Stark edited their review of gene: RAB3GAP1: Changed publications: 15696165, 20512159, 23420520, 23420520, 30730599; Changed phenotypes: Warburg micro syndrome 1, MIM# 600118, Martsolf syndrome 2, MIM# 619420
Mendeliome v0.8293 CXCR2 Zornitza Stark Marked gene: CXCR2 as ready
Mendeliome v0.8293 CXCR2 Zornitza Stark Gene: cxcr2 has been classified as Red List (Low Evidence).
Mendeliome v0.8293 CXCR2 Zornitza Stark gene: CXCR2 was added
gene: CXCR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CXCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CXCR2 were set to 24777453
Phenotypes for gene: CXCR2 were set to WHIM syndrome 2, 619407
Review for gene: CXCR2 was set to RED
Added comment: 2 sisters with neutropaenia, myelokathexis, and recurrent bacterial infections and homozygous frameshift variant in this gene.
Sources: Expert list
Phagocyte Defects v0.67 CXCR2 Zornitza Stark Marked gene: CXCR2 as ready
Phagocyte Defects v0.67 CXCR2 Zornitza Stark Gene: cxcr2 has been classified as Red List (Low Evidence).
Phagocyte Defects v0.67 CXCR2 Zornitza Stark gene: CXCR2 was added
gene: CXCR2 was added to Phagocyte Defects. Sources: Expert list
Mode of inheritance for gene: CXCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CXCR2 were set to 24777453
Phenotypes for gene: CXCR2 were set to WHIM syndrome 2 619407
Review for gene: CXCR2 was set to RED
Added comment: 2 sisters with neutropaenia, myelokathexis, and recurrent bacterial infections and homozygous frameshift variant in this gene.
Sources: Expert list
Complement Deficiencies v0.36 C4A Bryony Thompson Tag for review tag was added to gene: C4A.
Complement Deficiencies v0.36 C4B Bryony Thompson Tag for review tag was added to gene: C4B.
Mendeliome v0.8292 RING1 Eleanor Williams gene: RING1 was added
gene: RING1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RING1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RING1 were set to 29386386
Phenotypes for gene: RING1 were set to microcephaly; intellectual disability
Review for gene: RING1 was set to RED
Added comment: Not associated with any phenotype in OMIM.

PMID: 29386386 - Pierce et al 2018 - report a 13 yo female with a de novo RING1 p.R95Q variant and syndromic neurodevelopmental disabilities. Early motor and language development were normal but were delayed after the first year of life. Cognitive testing showed a verbal IQ of 55 and a visual performance IQ of 63. Head circumference at birth was -4.9 SD, and -4.2 SD at age 13 which falls into the severe microcephaly category. C. elegans with either the missense mutation or complete knockout of spat-3 (the suggested RING1 ortholog) were defective in monoubiquitylation of histone H2A and had defects in neuronal migration and axon guidance.
Sources: Literature
Mendeliome v0.8292 RNF2 Eleanor Williams gene: RNF2 was added
gene: RNF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RNF2 were set to 33864376
Phenotypes for gene: RNF2 were set to epilepsy; intellectual disability; intrauterine growth retardation
Review for gene: RNF2 was set to AMBER
Added comment: Not associated with any phenotype in OMIM.

PMID:33864376 (Luo et al 2021) report 2 cases of children with de novo missense variants (p.R70H and p.S82R) in RNF2 and a phenotype of intrauterine growth retardation, severe intellectual disabilities, behavioral problems, seizures, feeding difficulties and dysmorphic features. Seizures started in infancy. Both variants are absent from gnomad. Functional studies in Drosophila showed that the disease-linked variants (p.R70H and p.S82R) behave as LoF alleles.
Sources: Literature
Mendeliome v0.8292 IRX5 Eleanor Williams edited their review of gene: IRX5: Changed publications: 33891002, 28041643, 32045705, 22581230, 17230486; Changed phenotypes: cone dystrophy, MONDO:0000455, retinitis pigmentosa, MONDO:0019200
Mendeliome v0.8292 IRX5 Eleanor Williams changed review comment from: Associated with Hamamy syndrome #611174 (AR) in OMIM. Hamamy syndrome is characterised by craniofacial dysmorphism, hearing loss, skeletal anomalies, microcytic hypochromic anemia and congenital heart defects. Severe myopia has also been reported. Homozygous missense variants in IRX5 were reported in 2 families with this condition.

Cone dystrophy
-------------------
PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.; to: Associated with Hamamy syndrome #611174 (AR) in OMIM. Hamamy syndrome is characterised by craniofacial dysmorphism, hearing loss, skeletal anomalies, microcytic hypochromic anemia and congenital heart defects. Severe myopia has also been reported. Homozygous missense variants in IRX5 were reported in 2 families with this condition (PMID: 22581230;17230486)

Duplication of gene
-------------------
PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.

Loss of function/gene
---------
PMID: 28041643 - Carss et al 2017 - screened a cohort of 722 individuals with inherited retinal disease using WES/WGS. 1 case reported with a biallelic deletion in IRX5 reported which leads to a frameshift ENST00000394636.4; c.1362_1366delTAAAG, p.Lys455ProfsTer19 in a patient with retinitis pigmentosa.

PMID: 32045705 - Apuzzo et al 2020 - report 2 cases of loss of a region in 16q12.1q21 which encompasses IRX5 and IRX6 and many other genes, which together with 3 other previous reports of deletions in this region help define a syndrome with features that include dysmorphic features, short stature, microcephaly, global developmental delay/intellectual disability, autism spectrum disorder (ASD) and ocular abnormalities (nystagmus and strabismus).
Mendeliome v0.8292 IRX6 Eleanor Williams changed review comment from: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature; to: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature
Mendeliome v0.8292 SLCO2A1 Zornitza Stark Marked gene: SLCO2A1 as ready
Mendeliome v0.8292 SLCO2A1 Zornitza Stark Gene: slco2a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3959 GNB2 Zornitza Stark Marked gene: GNB2 as ready
Intellectual disability syndromic and non-syndromic v0.3959 GNB2 Zornitza Stark Gene: gnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3959 GNB2 Zornitza Stark Publications for gene: GNB2 were set to 31698099
Intellectual disability syndromic and non-syndromic v0.3958 GNB2 Zornitza Stark Classified gene: GNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3958 GNB2 Zornitza Stark Gene: gnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3957 GNB2 Zornitza Stark reviewed gene: GNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31698099, 33971351, 34183358, 33057194; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8292 GNB2 Zornitza Stark Publications for gene: GNB2 were set to 31698099
Mendeliome v0.8291 GNB2 Zornitza Stark Classified gene: GNB2 as Green List (high evidence)
Mendeliome v0.8291 GNB2 Zornitza Stark Gene: gnb2 has been classified as Green List (High Evidence).
Mendeliome v0.8290 GNB2 Zornitza Stark reviewed gene: GNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31698099, 33971351, 34183358; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia - adult onset v0.135 FAT2 Seb Lunke Marked gene: FAT2 as ready
Ataxia - adult onset v0.135 FAT2 Seb Lunke Gene: fat2 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.135 FAT2 Seb Lunke Phenotypes for gene: FAT2 were changed from Spinocerebellar ataxia 45 to Spinocerebellar ataxia 45, MIM#617769
Ataxia - adult onset v0.134 FAT2 Seb Lunke Classified gene: FAT2 as Green List (high evidence)
Ataxia - adult onset v0.134 FAT2 Seb Lunke Gene: fat2 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.133 FAT2 Seb Lunke Publications for gene: FAT2 were set to 29053796
Ataxia - adult onset v0.132 FAT2 Seb Lunke reviewed gene: FAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33884300; Phenotypes: Spinocerebellar ataxia 45, MIM#617769; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Callosome v0.304 HID1 Zornitza Stark Classified gene: HID1 as Green List (high evidence)
Callosome v0.304 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.13 HID1 Zornitza Stark Marked gene: HID1 as ready
Pituitary hormone deficiency v0.13 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.13 HID1 Zornitza Stark Classified gene: HID1 as Green List (high evidence)
Pituitary hormone deficiency v0.13 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Callosome v0.303 HID1 Zornitza Stark gene: HID1 was added
gene: HID1 was added to Callosome. Sources: Literature
Mode of inheritance for gene: HID1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HID1 were set to 33999436
Phenotypes for gene: HID1 were set to Syndromic infantile encephalopathy; Hypopituitarism
Review for gene: HID1 was set to GREEN
Added comment: 7 individuals from 6 unrelated families reported. Clinical features included: hypopituitarism in combination with brain atrophy, thin corpus callosum, severe developmental delay, visual impairment, and epilepsy
Sources: Literature
Pituitary hormone deficiency v0.12 HID1 Zornitza Stark gene: HID1 was added
gene: HID1 was added to Pituitary hormone deficiency. Sources: Literature
Mode of inheritance for gene: HID1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HID1 were set to 33999436
Phenotypes for gene: HID1 were set to Syndromic infantile encephalopathy; Hypopituitarism
Review for gene: HID1 was set to GREEN
Added comment: 7 individuals from 6 unrelated families reported. Clinical features included: hypopituitarism in combination with brain atrophy, thin corpus callosum, severe developmental delay, visual impairment, and epilepsy.
Sources: Literature
Leukodystrophy - adult onset v0.87 TACO1 Seb Lunke Marked gene: TACO1 as ready
Leukodystrophy - adult onset v0.87 TACO1 Seb Lunke Gene: taco1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3957 HID1 Zornitza Stark Marked gene: HID1 as ready
Intellectual disability syndromic and non-syndromic v0.3957 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.87 TACO1 Seb Lunke gene: TACO1 was added
gene: TACO1 was added to Leukodystrophy - adult onset. Sources: Literature
Mode of inheritance for gene: TACO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TACO1 were set to 33709035
Phenotypes for gene: TACO1 were set to Leukoencephalopathy, adult onset
Review for gene: TACO1 was set to RED
Added comment: 50yo female with hom c.676G>T (p.Glu226Ter) variant. Onset of slowly progressive spastic gait and mild cognitive impairment in her 30s. 24yo carrier daughter healthy.

Live imaging microscopy in primary fibroblasts showed a mild reduction of optic atrophy gene 1 long forms, which are the active mediators of mitochondrial fusion (figure 1C), however mitochondrial network morphology was comparable to controls, with the highest percentage of cells showing fused and interconnected organelles.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3957 HID1 Zornitza Stark Classified gene: HID1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3957 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3956 HID1 Zornitza Stark Classified gene: HID1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3956 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Mendeliome v0.8290 HID1 Zornitza Stark Marked gene: HID1 as ready
Mendeliome v0.8290 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3955 HID1 Zornitza Stark gene: HID1 was added
gene: HID1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HID1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HID1 were set to 33999436
Phenotypes for gene: HID1 were set to Syndromic infantile encephalopathy; Hypopituitarism
Review for gene: HID1 was set to GREEN
Added comment: 7 individuals from 6 unrelated families reported. Clinical features included: hypopituitarism in combination with brain atrophy, thin corpus callosum, severe developmental delay, visual impairment, and epilepsy
Sources: Literature
Mendeliome v0.8290 HID1 Zornitza Stark Classified gene: HID1 as Green List (high evidence)
Mendeliome v0.8290 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Mendeliome v0.8289 HID1 Zornitza Stark gene: HID1 was added
gene: HID1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HID1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HID1 were set to 33999436
Phenotypes for gene: HID1 were set to Syndromic infantile encephalopathy; Hypopituitarism
Review for gene: HID1 was set to GREEN
Added comment: 7 individuals from 6 unrelated families reported. Clinical features included: hypopituitarism in combination with brain atrophy, thin corpus callosum, severe developmental delay, visual impairment, and epilepsy
Sources: Literature
Genetic Epilepsy v0.1137 HID1 Zornitza Stark Marked gene: HID1 as ready
Genetic Epilepsy v0.1137 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1137 HID1 Zornitza Stark Classified gene: HID1 as Green List (high evidence)
Genetic Epilepsy v0.1137 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1136 HID1 Zornitza Stark gene: HID1 was added
gene: HID1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: HID1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HID1 were set to 33999436
Phenotypes for gene: HID1 were set to Syndromic infantile encephalopathy; Hypopituitarism
Review for gene: HID1 was set to GREEN
Added comment: 7 individuals from 6 unrelated families reported. Clinical features included: hypopituitarism in combination with brain atrophy, thin corpus callosum, severe developmental delay, visual impairment, and epilepsy
Sources: Literature
Mendeliome v0.8288 KIF1B Zornitza Stark Marked gene: KIF1B as ready
Mendeliome v0.8288 KIF1B Zornitza Stark Gene: kif1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8288 KIF1B Zornitza Stark Phenotypes for gene: KIF1B were changed from to Charcot-Marie-Tooth disease, type 2A1 MIM#118210; Hypotonia, coloboma, hypoplasia of the corpus callosum, severe neurodevelopmental delay
Mendeliome v0.8287 KIF1B Zornitza Stark Publications for gene: KIF1B were set to
Mendeliome v0.8286 KIF1B Zornitza Stark Mode of inheritance for gene: KIF1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8285 KIF1B Zornitza Stark reviewed gene: KIF1B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3954 KIF1B Zornitza Stark Marked gene: KIF1B as ready
Intellectual disability syndromic and non-syndromic v0.3954 KIF1B Zornitza Stark Gene: kif1b has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3954 KIF1B Zornitza Stark Classified gene: KIF1B as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3954 KIF1B Zornitza Stark Gene: kif1b has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3953 ERGIC3 Seb Lunke Marked gene: ERGIC3 as ready
Intellectual disability syndromic and non-syndromic v0.3953 ERGIC3 Seb Lunke Gene: ergic3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3953 ERGIC3 Seb Lunke Classified gene: ERGIC3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3953 ERGIC3 Seb Lunke Gene: ergic3 has been classified as Amber List (Moderate Evidence).
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).
Intellectual disability syndromic and non-syndromic v0.3952 ERGIC3 Seb Lunke gene: ERGIC3 was added
gene: ERGIC3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ERGIC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERGIC3 were set to ERGIC3
Phenotypes for gene: ERGIC3 were set to 33710394; 31585110
Review for gene: ERGIC3 was set to AMBER
Added comment: PMID: 33710394 - two homozygous sibs with mild ID, a novel canonical splice (c.717+1G>A). Absent in gnomAD, no splice studies. Classed as a VUS.

PMID: 31585110 - 1 hom (p.Gln233Argfs*10) in a male 8yo with Growth retardation, Microcephaly, Learning disability, Facial dysmorphism, Abnormal pigmentation.
Sources: Literature
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
Mendeliome v0.8285 NUF2 Zornitza Stark Marked gene: NUF2 as ready
Mendeliome v0.8285 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Mendeliome v0.8285 NUF2 Zornitza Stark Classified gene: NUF2 as Red List (low evidence)
Mendeliome v0.8285 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Mendeliome v0.8284 ERGIC3 Seb Lunke Marked gene: ERGIC3 as ready
Mendeliome v0.8284 ERGIC3 Seb Lunke Gene: ergic3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8284 ERGIC3 Seb Lunke Classified gene: ERGIC3 as Amber List (moderate evidence)
Mendeliome v0.8284 ERGIC3 Seb Lunke Gene: ergic3 has been classified as Amber List (Moderate Evidence).
Cataract v0.282 FYCO1 Zornitza Stark Marked gene: FYCO1 as ready
Cataract v0.282 FYCO1 Zornitza Stark Gene: fyco1 has been classified as Green List (High Evidence).
Cataract v0.282 FYCO1 Zornitza Stark Phenotypes for gene: FYCO1 were changed from to Cataract 18, MIM#610019
Mendeliome v0.8283 FYCO1 Zornitza Stark Marked gene: FYCO1 as ready
Mendeliome v0.8283 FYCO1 Zornitza Stark Gene: fyco1 has been classified as Green List (High Evidence).
Mendeliome v0.8283 FYCO1 Zornitza Stark Phenotypes for gene: FYCO1 were changed from to Cataract 18, MIM#610019
Mendeliome v0.8282 FYCO1 Zornitza Stark Publications for gene: FYCO1 were set to
Mendeliome v0.8281 FYCO1 Zornitza Stark Mode of inheritance for gene: FYCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3951 JPH3 Seb Lunke Marked gene: JPH3 as ready
Intellectual disability syndromic and non-syndromic v0.3951 JPH3 Seb Lunke Gene: jph3 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3951 JPH3 Seb Lunke gene: JPH3 was added
gene: JPH3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: JPH3 was set to Unknown
Publications for gene: JPH3 were set to 33824468
Phenotypes for gene: JPH3 were set to Intellectual disability; dystonia
Review for gene: JPH3 was set to RED
Added comment: One homozygous truncating variant (NM_020655.4: c.1740dup; p.(Val581Argfs*137)) found in a female individual affected with genetically undetermined neurodevelopmental anomalies (including delayed motor milestones, abnormal social communication, language difficulties and borderline cognitive impairment) and paroxysmal attacks of dystonia since her early infancy. No functional work were performed.

Only STRs disease causing, see separate STR list. No evidence for SNVs etc.
Sources: Literature
Mendeliome v0.8280 FYCO1 Zornitza Stark reviewed gene: FYCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32355443; Phenotypes: Cataract 18, MIM#610019; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.281 FYCO1 Zornitza Stark Publications for gene: FYCO1 were set to
Cataract v0.280 FYCO1 Zornitza Stark Mode of inheritance for gene: FYCO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.280 FYCO1 Zornitza Stark Mode of inheritance for gene: FYCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8280 JPH3 Seb Lunke Publications for gene: JPH3 were set to
Mendeliome v0.8279 MYT1 Zornitza Stark Publications for gene: MYT1 were set to 28612832; 32871052; 27358179
Mendeliome v0.8278 JPH3 Seb Lunke Marked gene: JPH3 as ready
Mendeliome v0.8278 JPH3 Seb Lunke Gene: jph3 has been classified as Red List (Low Evidence).
Mendeliome v0.8278 JPH3 Seb Lunke Phenotypes for gene: JPH3 were changed from to Intellectual disability; dystonia
Mendeliome v0.8277 MYT1 Zornitza Stark changed review comment from: Five unrelated individuals reported with variants in this gene and OAV spectrum.; to: Five unrelated individuals reported with variants in this gene and OAV spectrum.

Single individual reported with missense variant as part of an ID cohort, limited evidence for disease association.
Mendeliome v0.8277 JPH3 Seb Lunke Classified gene: JPH3 as Red List (low evidence)
Mendeliome v0.8277 JPH3 Seb Lunke Added comment: Comment on list classification: Only STRs disease causing, see separate STR list. No evidence for SNVs etc.
Mendeliome v0.8277 JPH3 Seb Lunke Gene: jph3 has been classified as Red List (Low Evidence).
Mendeliome v0.8276 MYT1 Zornitza Stark edited their review of gene: MYT1: Changed publications: 28612832, 32871052, 27358179, 33710394
Mendeliome v0.8276 MYT1 Zornitza Stark Marked gene: MYT1 as ready
Mendeliome v0.8276 MYT1 Zornitza Stark Gene: myt1 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.40 MYT1 Zornitza Stark Marked gene: MYT1 as ready
Mandibulofacial Acrofacial dysostosis v0.40 MYT1 Zornitza Stark Gene: myt1 has been classified as Green List (High Evidence).
Mandibulofacial Acrofacial dysostosis v0.40 MYT1 Zornitza Stark Phenotypes for gene: MYT1 were changed from to Craniofacial microsomia; OAV spectrum
Mandibulofacial Acrofacial dysostosis v0.39 MYT1 Zornitza Stark Publications for gene: MYT1 were set to
Mandibulofacial Acrofacial dysostosis v0.38 MYT1 Zornitza Stark Mode of inheritance for gene: MYT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mandibulofacial Acrofacial dysostosis v0.37 MYT1 Zornitza Stark reviewed gene: MYT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28612832, 32871052, 27358179; Phenotypes: Craniofacial microsomia, OAV spectrum; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8276 MYT1 Zornitza Stark Phenotypes for gene: MYT1 were changed from to Craniofacial microsomia; OAV spectrum
Mendeliome v0.8275 MYT1 Zornitza Stark Publications for gene: MYT1 were set to
Mendeliome v0.8274 MYT1 Zornitza Stark Mode of inheritance for gene: MYT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8273 MYT1 Zornitza Stark reviewed gene: MYT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28612832, 32871052, 27358179; Phenotypes: Craniofacial microsomia, OAV spectrum; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3950 HEATR5B Seb Lunke Marked gene: HEATR5B as ready
Intellectual disability syndromic and non-syndromic v0.3950 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3950 HEATR5B Seb Lunke Classified gene: HEATR5B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3950 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1135 HEATR5B Seb Lunke Marked gene: HEATR5B as ready
Genetic Epilepsy v0.1135 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1135 HEATR5B Seb Lunke Classified gene: HEATR5B as Amber List (moderate evidence)
Genetic Epilepsy v0.1135 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.13 HEATR5B Seb Lunke Marked gene: HEATR5B as ready
Cerebellar and Pontocerebellar Hypoplasia v1.13 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.13 HEATR5B Seb Lunke Classified gene: HEATR5B as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.13 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3949 MYT1 Zornitza Stark Marked gene: MYT1 as ready
Intellectual disability syndromic and non-syndromic v0.3949 MYT1 Zornitza Stark Gene: myt1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3949 MYT1 Zornitza Stark Classified gene: MYT1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3949 MYT1 Zornitza Stark Gene: myt1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3948 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from Alternating hemiplegia of childhood 1, MIM# 104290; Developmental and epileptic encephalopathy, polymicrogyria to Alternating hemiplegia of childhood 1, MIM# 104290; Developmental and epileptic encephalopathy, polymicrogyria
Intellectual disability syndromic and non-syndromic v0.3947 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from Alternating hemiplegia of childhood 1, MIM# 104290; Developmental and epileptic encephalopathy, polymicrogyria to Alternating hemiplegia of childhood 1, MIM# 104290; Developmental and epileptic encephalopathy, polymicrogyria
Intellectual disability syndromic and non-syndromic v0.3947 HEATR5B Seb Lunke gene: HEATR5B was added
gene: HEATR5B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HEATR5B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR5B were set to 33824466
Phenotypes for gene: HEATR5B were set to pontocerebellar hypoplasia; intellectual disability; seizures
Review for gene: HEATR5B was set to AMBER
Added comment: Four affected children from two families presenting with pontocerebellar hypoplasiawith neonatal seizures, severe ID and motor delay. Two homozygous splice variants were reported (c.5051–1G>A and c.5050+4A>G) in intron 31 of HEATR5B gene. Aberrant splicing was found in patient fibroblasts, which correlated with reduced levels of HEATR5B protein. Homozygous knockout mice were not viable. *NOTE: gene (and alias) not found in OMIM
Sources: Literature
Genetic Epilepsy v0.1134 HEATR5B Seb Lunke gene: HEATR5B was added
gene: HEATR5B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: HEATR5B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR5B were set to 33824466
Phenotypes for gene: HEATR5B were set to pontocerebellar hypoplasia; intellectual disability; seizures
Review for gene: HEATR5B was set to AMBER
Added comment: Four affected children from two families presenting with pontocerebellar hypoplasiawith neonatal seizures, severe ID and motor delay. Two homozygous splice variants were reported (c.5051–1G>A and c.5050+4A>G) in intron 31 of HEATR5B gene. Aberrant splicing was found in patient fibroblasts, which correlated with reduced levels of HEATR5B protein. Homozygous knockout mice were not viable. *NOTE: gene (and alias) not found in OMIM
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3947 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from Alternating hemiplegia of childhood 1, MIM# 104290 to Alternating hemiplegia of childhood 1, MIM# 104290; Developmental and epileptic encephalopathy, polymicrogyria
Cerebellar and Pontocerebellar Hypoplasia v1.12 HEATR5B Seb Lunke gene: HEATR5B was added
gene: HEATR5B was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: HEATR5B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR5B were set to 33824466
Phenotypes for gene: HEATR5B were set to pontocerebellar hypoplasia; intellectual disability; seizures
Review for gene: HEATR5B was set to AMBER
Added comment: Four affected children from two families presenting with pontocerebellar hypoplasiawith neonatal seizures, severe ID and motor delay. Two homozygous splice variants were reported (c.5051–1G>A and c.5050+4A>G) in intron 31 of HEATR5B gene. Aberrant splicing was found in patient fibroblasts, which correlated with reduced levels of HEATR5B protein. Homozygous knockout mice were not viable. *NOTE: gene (and alias) not found in OMIM
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3946 ATP1A2 Zornitza Stark Publications for gene: ATP1A2 were set to
Intellectual disability syndromic and non-syndromic v0.3945 ATP1A2 Zornitza Stark changed review comment from: Although some of the symptoms of this condition are episodic, intellectual disability is a recognised feature.; to: Alternating hemiplegia: Although some of the symptoms of this condition are episodic, intellectual disability is a recognised feature.
Intellectual disability syndromic and non-syndromic v0.3945 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Added comment: PMID 33880529: six individuals with de novo missense variants reported and DD/EE/PMG.; Changed publications: 33880529; Changed phenotypes: Alternating hemiplegia of childhood 1, MIM# 104290, Developmental and epileptic encephalopathy, polymicrogyria
Mendeliome v0.8273 HEATR5B Seb Lunke Phenotypes for gene: HEATR5B were changed from pontocerebellar hypoplasia to pontocerebellar hypoplasia; intellectual disability; seizures
Mendeliome v0.8272 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from to Alternating hemiplegia of childhood 1, MIM#104290; Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations; Developmental and epileptic encephalopathy, polymicrogyria
Mendeliome v0.8271 ATP1A2 Zornitza Stark Publications for gene: ATP1A2 were set to
Mendeliome v0.8270 ATP1A2 Zornitza Stark Mode of inheritance for gene: ATP1A2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8269 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Added comment: Association with alternating hemiplegia is well established.

PMID 31608932: Three individuals from two unrelated families reported with balleliic LoF variants in this gene and hydrops/congenital abnormalities. Mouse model is perinatal lethal.

PMID 33880529: six individuals with de novo missense variants reported and DD/EE/PMG.; Changed rating: GREEN; Changed publications: 31608932, 33880529; Changed phenotypes: Alternating hemiplegia of childhood 1, MIM#104290, Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations, Developmental and epileptic encephalopathy, polymicrogyria; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8269 HEATR5B Seb Lunke Marked gene: HEATR5B as ready
Mendeliome v0.8269 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Polymicrogyria and Schizencephaly v0.164 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from hydrops fetalis; microcephaly; arthrogryposis; extensive cortical malformations to Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations; Developmental and epileptic encephalopathy, polymicrogyria
Polymicrogyria and Schizencephaly v0.163 ATP1A2 Zornitza Stark Mode of inheritance for gene: ATP1A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.162 ATP1A2 Zornitza Stark changed review comment from: Three individuals from two unrelated families reported with balleliic LoF variants in this gene and hydrops/congenital abnormalities. Mouse model is perinatal lethal. This is a distinct phenotype from the mono allelic variants associated with alternating hemiplegia.; to: Three individuals from two unrelated families reported with balleliic LoF variants in this gene and hydrops/congenital abnormalities. Mouse model is perinatal lethal. This is a distinct phenotype from the mono allelic variants associated with alternating hemiplegia.

33880529: six individuals with de novo missense variants reported and DD/EE/PMG.
Polymicrogyria and Schizencephaly v0.162 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Changed publications: 31608932, 33880529; Changed phenotypes: Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations, Developmental and epileptic encephalopathy, polymicrogyria; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1133 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Genetic Epilepsy v0.1133 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1133 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from to developmental and epileptic encephalopathy; early or neonatal onset seizures, polymicrogyria
Genetic Epilepsy v0.1132 ATP1A2 Zornitza Stark Publications for gene: ATP1A2 were set to
Genetic Epilepsy v0.1131 ATP1A2 Zornitza Stark Mode of inheritance for gene: ATP1A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8269 HEATR5B Seb Lunke Classified gene: HEATR5B as Amber List (moderate evidence)
Mendeliome v0.8269 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3945 ATP1A3 Zornitza Stark Phenotypes for gene: ATP1A3 were changed from Alternating hemiplegia of childhood 2, MIM#614820 to Alternating hemiplegia of childhood 2, MIM#614820; Developmental and epileptic encephalopathy, polymicrogyria
Intellectual disability syndromic and non-syndromic v0.3944 ATP1A3 Zornitza Stark Publications for gene: ATP1A3 were set to
Intellectual disability syndromic and non-syndromic v0.3943 ATP1A3 Zornitza Stark edited their review of gene: ATP1A3: Added comment: PMID 33880529: 16 individuals reported with DD/EE and PMG.; Changed rating: GREEN; Changed publications: 33880529; Changed phenotypes: Alternating hemiplegia of childhood 2, MIM#614820, Developmental and epileptic encephalopathy, polymicrogyria
Mendeliome v0.8268 ATP1A3 Zornitza Stark edited their review of gene: ATP1A3: Changed phenotypes: Alternating hemiplegia of childhood 2, MIM# 614820, CAPOS syndrome, MIM# 601338, Dystonia-12, MIM# 128235, Polymicrogyria, Developmental and epileptic encephalopathy
Mendeliome v0.8268 ATP1A3 Zornitza Stark edited their review of gene: ATP1A3: Changed publications: 15260953, 22842232, 24468074, 33762331, 33880529
Genetic Epilepsy v0.1130 ATP1A3 Zornitza Stark Marked gene: ATP1A3 as ready
Genetic Epilepsy v0.1130 ATP1A3 Zornitza Stark Gene: atp1a3 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.162 ATP1A3 Zornitza Stark Publications for gene: ATP1A3 were set to PMID: 33762331
Intellectual disability syndromic and non-syndromic v0.3943 ZC3H14 Seb Lunke reviewed gene: ZC3H14: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genetic Epilepsy v0.1130 ATP1A3 Zornitza Stark Phenotypes for gene: ATP1A3 were changed from to developmental and epileptic encephalopathy; early or neonatal onset seizures, polymicrogyria
Polymicrogyria and Schizencephaly v0.161 ATP1A3 Zornitza Stark changed review comment from: Eight individuals with de novo variants reported.; to: Eight individuals with de novo variants reported.

PMID 33880529: further 16 individuals reported.
Genetic Epilepsy v0.1129 ATP1A3 Zornitza Stark Publications for gene: ATP1A3 were set to
Polymicrogyria and Schizencephaly v0.161 ATP1A3 Zornitza Stark edited their review of gene: ATP1A3: Changed publications: 33762331, 33880529; Changed phenotypes: Polymicrogyria, epilepsy, developmental delay, epileptic encephalopathy
Genetic Epilepsy v0.1128 ATP1A3 Zornitza Stark Mode of inheritance for gene: ATP1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3943 ZC3H14 Seb Lunke Publications for gene: ZC3H14 were set to PubMed: 21734151
Genetic Epilepsy v0.1127 ATP1A3 Zornitza Stark reviewed gene: ATP1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8268 SAMD9L Zornitza Stark Phenotypes for gene: SAMD9L were changed from Ataxia-pancytopenia syndrome, MIM# 159550 to Ataxia-pancytopenia syndrome, MIM# 159550; Intellectual disability
Mendeliome v0.8267 SAMD9L Zornitza Stark Publications for gene: SAMD9L were set to 27259050; 30923096; 30322869
Mendeliome v0.8266 SAMD9L Zornitza Stark changed review comment from: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.; to: Ataxia-pancytopaenia: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.

ID: single individual reported, limited evidence of association.
Intellectual disability syndromic and non-syndromic v0.3942 SAMD9L Zornitza Stark Publications for gene: SAMD9L were set to
Mendeliome v0.8266 SAMD9L Zornitza Stark edited their review of gene: SAMD9L: Changed publications: 27259050, 30923096, 30322869, 33710394
Intellectual disability syndromic and non-syndromic v0.3941 SAMD9L Zornitza Stark Marked gene: SAMD9L as ready
Intellectual disability syndromic and non-syndromic v0.3941 SAMD9L Zornitza Stark Gene: samd9l has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3941 SAMD9L Zornitza Stark Classified gene: SAMD9L as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3941 SAMD9L Zornitza Stark Gene: samd9l has been classified as Red List (Low Evidence).
Microcephaly v1.32 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Kidneyome_SuperPanel v4.69 Bryony Thompson Changed child panels to: Renal Tubulointerstitial Disease; Renal Hypertension and Disorders of Aldosterone Metabolism; Haematuria_Alport; Branchio-oto-renal Syndrome; Renal Ciliopathies and Nephronophthisis; Proteinuria; Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic; Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic; Renal Tubulopathies; Nephrolithiasis and Nephrocalcinosis; Renal Macrocystic Disease; Atypical Haemolytic Uraemic Syndrome_MPGN; Renal abnormalities of calcium and phosphate metabolism; Renal Abnormalities of Magnesium Metabolism; Renal Amyloidosis; Bartter Syndrome; Metabolic renal disease; Dent disease; Renal Tubular Dysgenesis; Hyperoxaluria
Panel types changed to Superpanel; Victorian Clinical Genetics Services; KidGen; Royal Melbourne Hospital
Hyperthyroidism v0.19 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.96 DYNC2H1 Ee Ming Wong gene: DYNC2H1 was added
gene: DYNC2H1 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: DYNC2H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DYNC2H1 were set to PMID: 32753734
Phenotypes for gene: DYNC2H1 were set to non-syndromic retinitis pigmentosa
Review for gene: DYNC2H1 was set to GREEN
gene: DYNC2H1 was marked as current diagnostic
Added comment: - Five affected probands with homozygous and compound heterozygous missense and PTC variants
- Associated with the NM_001080463.1 transcript (predominant isoform in retina from retinal organoid studies)
Sources: Literature
Ataxia - paediatric v0.285 PITRM1 Zornitza Stark Phenotypes for gene: PITRM1 were changed from Cerebellar atrophy; mental retardation; spinocerebellar ataxia; cognitive decline; psychosis to Spinocerebellar ataxia-30 (SCAR30), MIM#619405; intellectual disability; cognitive decline; psychosis
Ataxia - paediatric v0.284 PITRM1 Zornitza Stark edited their review of gene: PITRM1: Changed phenotypes: Spinocerebellar ataxia-30 (SCAR30), MIM#619405, intellectual disability, cognitive decline, psychosis
Intellectual disability syndromic and non-syndromic v0.3940 PITRM1 Zornitza Stark Phenotypes for gene: PITRM1 were changed from Ataxia; Intellectual disability to Spinocerebellar ataxia-30 (SCAR30), MIM#619405; intellectual disability; cognitive decline; psychosis
Intellectual disability syndromic and non-syndromic v0.3939 PITRM1 Zornitza Stark edited their review of gene: PITRM1: Changed phenotypes: Spinocerebellar ataxia-30 (SCAR30), MIM#619405, intellectual disability, cognitive decline, psychosis
Mitochondrial disease v0.637 PITRM1 Zornitza Stark Phenotypes for gene: PITRM1 were changed from Cerebellar atrophy; mental retardation; spinocerebellar ataxia; cognitive decline; psychosis to Spinocerebellar ataxia-30 (SCAR30), MIM#619405; intellectual disability; cognitive decline; psychosis
Mitochondrial disease v0.636 PITRM1 Zornitza Stark reviewed gene: PITRM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia-30 (SCAR30), MIM#619405, intellectual disability, cognitive decline, psychosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8266 PITRM1 Zornitza Stark Phenotypes for gene: PITRM1 were changed from Ataxia; Intellectual disability to Spinocerebellar ataxia-30 (SCAR30), MIM#619405; intellectual disability; cognitive decline; psychosis
Mendeliome v0.8265 PITRM1 Zornitza Stark edited their review of gene: PITRM1: Changed phenotypes: Spinocerebellar ataxia-30 (SCAR30), MIM#619405
Dystonia - complex v0.183 VPS41 Zornitza Stark Phenotypes for gene: VPS41 were changed from Dystonia; intellectual disability to Spinocerebellar ataxia-29 (SCAR29), MIM#619389; Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Dystonia - complex v0.182 VPS41 Zornitza Stark edited their review of gene: VPS41: Changed phenotypes: Spinocerebellar ataxia-29 (SCAR29), MIM#619389, Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Ataxia - paediatric v0.284 VPS41 Zornitza Stark Phenotypes for gene: VPS41 were changed from Dystonia; intellectual disability; ataxia; cerebellar atrophy to Spinocerebellar ataxia-29 (SCAR29), MIM#619389; Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Ataxia - paediatric v0.283 VPS41 Zornitza Stark edited their review of gene: VPS41: Changed phenotypes: Spinocerebellar ataxia-29 (SCAR29), MIM#619389, Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Intellectual disability syndromic and non-syndromic v0.3939 VPS41 Zornitza Stark Phenotypes for gene: VPS41 were changed from Dystonia; intellectual disability to Spinocerebellar ataxia-29 (SCAR29), MIM#619389; Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Intellectual disability syndromic and non-syndromic v0.3938 VPS41 Zornitza Stark edited their review of gene: VPS41: Changed phenotypes: Spinocerebellar ataxia-29 (SCAR29), MIM#619389, Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Regression v0.356 VPS41 Zornitza Stark Phenotypes for gene: VPS41 were changed from Dystonia; intellectual disability to Spinocerebellar ataxia-29 (SCAR29), MIM#619389; Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Regression v0.355 VPS41 Zornitza Stark edited their review of gene: VPS41: Changed phenotypes: Spinocerebellar ataxia-29 (SCAR29), MIM#619389, Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Mendeliome v0.8265 VPS41 Zornitza Stark Phenotypes for gene: VPS41 were changed from Dystonia; intellectual disability to Spinocerebellar ataxia-29 (SCAR29), MIM#619389; Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Mendeliome v0.8264 IRX6 Eleanor Williams gene: IRX6 was added
gene: IRX6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IRX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRX6 were set to 33891002
Phenotypes for gene: IRX6 were set to cone dystrophy, MONDO:0000455
Mode of pathogenicity for gene: IRX6 was set to Other
Review for gene: IRX6 was set to GREEN
Added comment: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature
Mendeliome v0.8264 IRX5 Eleanor Williams reviewed gene: IRX5: Rating: GREEN; Mode of pathogenicity: Other; Publications: 33891002; Phenotypes: cone dystrophy, MONDO:0000455; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.3938 GNB2 Arina Puzriakova reviewed gene: GNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31698099, 33971351, 34183358; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8264 EPHA7 Zornitza Stark Tag SV/CNV tag was added to gene: EPHA7.
Mendeliome v0.8264 EPHA7 Zornitza Stark Marked gene: EPHA7 as ready
Mendeliome v0.8264 EPHA7 Zornitza Stark Gene: epha7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8264 EPHA7 Zornitza Stark Classified gene: EPHA7 as Amber List (moderate evidence)
Mendeliome v0.8264 EPHA7 Zornitza Stark Gene: epha7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8263 EPHA7 Zornitza Stark gene: EPHA7 was added
gene: EPHA7 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: EPHA7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPHA7 were set to 34176129
Phenotypes for gene: EPHA7 were set to Intellectual disability
Review for gene: EPHA7 was set to AMBER
Added comment: Lévy et al (2021 - PMID: 34176129) provide evidence that haploinssuficiency of EPHA7 results in a neurodevelopmental disorder.

The authors report on 12 individuals belonging to 9 unrelated families, all harboring with 6q microdeletions spanning EPHA7.

Overlapping features included DD (13/13), ID (10/10 - mild in most cases, individuals with larger CNVs/additional variants had more severe phenotype), speech delay and behavioral disorders. Variable other features incl. hypotonia (70%), non specific facial features, eye abnormalities (40%) and cardiac defects (25%).

The CNVs ranged from 152 kb to few Mb in size but in 4 subjects (P5-8) were only minimal, involving only EPHA7.

9 out of 12 individuals had inherited the deletion (5 subjects paternal, 4 maternal), in 1 subject (P12) this occured de novo, while for 2 others inheritance was not specified. Most deletions were inherited from an unaffected parent (in 6/7 families), with unclear contribution in a further one.

The authors discuss on previous studies suggesting an important role for EphA7 in brain development (modulation of cell-cell adhesion and repulsion, regulation of dendrite morphogenesis in early corticogenesis, role in dendritic spine formation later in development. EphA7 has also been proposed to drive neuronal maturation and synaptic function).

Haploinsufficiency for other ephrins or ephrin receptors has been implicated in other NDDs.

Overall Lévy et al promote incomplete penetrance and variable expressivity with haploinsufficiency of this gene being a risk factor for NDD. [The gene has also an %HI of 2.76% and a pLI of 1].
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.3938 EPHA7 Zornitza Stark Marked gene: EPHA7 as ready
Intellectual disability syndromic and non-syndromic v0.3938 EPHA7 Zornitza Stark Gene: epha7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3938 EPHA7 Zornitza Stark Classified gene: EPHA7 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3938 EPHA7 Zornitza Stark Gene: epha7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3937 EPHA7 Zornitza Stark gene: EPHA7 was added
gene: EPHA7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
SV/CNV tags were added to gene: EPHA7.
Mode of inheritance for gene: EPHA7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPHA7 were set to 34176129
Phenotypes for gene: EPHA7 were set to Intellectual disability
Review for gene: EPHA7 was set to AMBER
Added comment: Lévy et al (2021 - PMID: 34176129) provide evidence that haploinssuficiency of EPHA7 results in a neurodevelopmental disorder.

The authors report on 12 individuals belonging to 9 unrelated families, all harboring with 6q microdeletions spanning EPHA7.

Overlapping features included DD (13/13), ID (10/10 - mild in most cases, individuals with larger CNVs/additional variants had more severe phenotype), speech delay and behavioral disorders. Variable other features incl. hypotonia (70%), non specific facial features, eye abnormalities (40%) and cardiac defects (25%).

The CNVs ranged from 152 kb to few Mb in size but in 4 subjects (P5-8) were only minimal, involving only EPHA7.



9 out of 12 individuals had inherited the deletion (5 subjects paternal, 4 maternal), in 1 subject (P12) this occured de novo, while for 2 others inheritance was not specified. Most deletions were inherited from an unaffected parent (in 6/7 families), with unclear contribution in a further one.

The authors discuss on previous studies suggesting an important role for EphA7 in brain development (modulation of cell-cell adhesion and repulsion, regulation of dendrite morphogenesis in early corticogenesis, role in dendritic spine formation later in development. EphA7 has also been proposed to drive neuronal maturation and synaptic function).

Haploinsufficiency for other ephrins or ephrin receptors has been implicated in other NDDs.

Overall Lévy et al promote incomplete penetrance and variable expressivity with haploinsufficiency of this gene being a risk factor for NDD. [The gene has also an %HI of 2.76% and a pLI of 1].
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3936 DNM1 Zornitza Stark Marked gene: DNM1 as ready
Intellectual disability syndromic and non-syndromic v0.3936 DNM1 Zornitza Stark Gene: dnm1 has been classified as Green List (High Evidence).
Mendeliome v0.8262 DNM1 Zornitza Stark Marked gene: DNM1 as ready
Mendeliome v0.8262 DNM1 Zornitza Stark Gene: dnm1 has been classified as Green List (High Evidence).
Mendeliome v0.8262 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from to Developmental and epileptic encephalopathy 31, OMIM:616346
Mendeliome v0.8261 DNM1 Zornitza Stark Publications for gene: DNM1 were set to
Mendeliome v0.8260 DNM1 Zornitza Stark Mode of inheritance for gene: DNM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8259 DNM1 Zornitza Stark reviewed gene: DNM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25262651, 27066543, 33372033, 34172529; Phenotypes: Developmental and epileptic encephalopathy 31, OMIM:616346; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3936 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from to Developmental and epileptic encephalopathy 31, OMIM:616346
Intellectual disability syndromic and non-syndromic v0.3935 DNM1 Zornitza Stark Publications for gene: DNM1 were set to
Ciliopathies v1.4 PDIA6 Zornitza Stark Marked gene: PDIA6 as ready
Ciliopathies v1.4 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3934 DNM1 Zornitza Stark Mode of inheritance for gene: DNM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1127 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from to Developmental and epileptic encephalopathy 31, OMIM:616346
Intellectual disability syndromic and non-syndromic v0.3933 DNM1 Zornitza Stark reviewed gene: DNM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25262651, 27066543, 33372033, 34172529; Phenotypes: Developmental and epileptic encephalopathy 31, OMIM:616346; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1126 DNM1 Zornitza Stark Publications for gene: DNM1 were set to
Genetic Epilepsy v0.1125 DNM1 Zornitza Stark Mode of inheritance for gene: DNM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.199 B9D2 Zornitza Stark Marked gene: B9D2 as ready
Renal Ciliopathies and Nephronophthisis v0.199 B9D2 Zornitza Stark Gene: b9d2 has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v0.199 B9D2 Zornitza Stark Phenotypes for gene: B9D2 were changed from to Meckel syndrome 10, MIM# 614175
Renal Ciliopathies and Nephronophthisis v0.198 B9D2 Zornitza Stark Publications for gene: B9D2 were set to
Renal Ciliopathies and Nephronophthisis v0.197 B9D2 Zornitza Stark Mode of inheritance for gene: B9D2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.196 B9D2 Zornitza Stark Classified gene: B9D2 as Amber List (moderate evidence)
Renal Ciliopathies and Nephronophthisis v0.196 B9D2 Zornitza Stark Gene: b9d2 has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v0.195 B9D2 Zornitza Stark reviewed gene: B9D2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21763481; Phenotypes: Meckel syndrome 10, MIM# 614175; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v1.4 PDIA6 Zornitza Stark Classified gene: PDIA6 as Amber List (moderate evidence)
Ciliopathies v1.4 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Amber List (Moderate Evidence).
Ciliopathies v1.3 PDIA6 Zornitza Stark gene: PDIA6 was added
gene: PDIA6 was added to Ciliopathies. Sources: Expert Review
Mode of inheritance for gene: PDIA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDIA6 were set to 33495992
Phenotypes for gene: PDIA6 were set to Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes
Review for gene: PDIA6 was set to AMBER
Added comment: 1 case with asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes. Whole exome sequencing revealed a homozygous frameshift variant in the PDIA6 gene. RNA expression was reduced in a gene dosage‐dependent manner, supporting a loss‐of‐function effect of this variant. Phenotypic correlation with the previously reported mouse model recapitulated the growth defect and delay, early lethality, coagulation, diabetes, immunological, and polycystic kidney disease phenotypes. The phenotype of the current patient is consistent with phenotypes associated with the disruption of PDIA6 and the sensors of UPR in mice and humans.
Sources: Expert Review
Ciliopathies v1.2 GRK2 Zornitza Stark Marked gene: GRK2 as ready
Ciliopathies v1.2 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Ciliopathies v1.2 GRK2 Zornitza Stark Classified gene: GRK2 as Amber List (moderate evidence)
Ciliopathies v1.2 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.0 Zornitza Stark promoted panel to version 1.0
Ciliopathies v1.1 GRK2 Zornitza Stark gene: GRK2 was added
gene: GRK2 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: GRK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRK2 were set to 33200460
Phenotypes for gene: GRK2 were set to Jeune asphyxiating thoracic dystrophy (ATD)
Review for gene: GRK2 was set to AMBER
Added comment: Two unrelated families reported and some functional data.
Sources: Literature
Genetic Epilepsy v0.1124 DNM1 Arina Puzriakova reviewed gene: DNM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25262651, 27066543, 33372033, 34172529; Phenotypes: Developmental and epileptic encephalopathy 31, OMIM:616346; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8259 GRK2 Zornitza Stark Marked gene: GRK2 as ready
Mendeliome v0.8259 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8259 GRK2 Zornitza Stark Classified gene: GRK2 as Amber List (moderate evidence)
Mendeliome v0.8259 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).