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Clefting v4.111 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from Meier-Gorlin syndrome 6, 616835 to Meier-Gorlin syndrome 6, OMIM:616835
Clefting v4.110 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from SECKEL SYNDROME 1; SCKL1 to Seckel syndrome 1, OMIM:210600
Clefting v4.110 ATR Arina Puzriakova Mode of inheritance for gene: ATR was changed from to BIALLELIC, autosomal or pseudoautosomal
Clefting v4.109 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Pallister-Hall syndrome, 146510 to Pallister-Hall syndrome, OMIM:146510
Clefting v4.108 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from MICROCEPHALY-CAPILLARY MALFORMATION SYNDROME; MICCAP to Microcephaly-capillary malformation syndrome, OMIM:614261
Clefting v4.107 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1; MPPH1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Clefting v4.106 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from CRANIOFRONTONASAL SYNDROME; CFNS to Craniofrontonasal dysplasia, OMIM:304110
Clefting v4.105 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from SHORT-RIB THORACIC DYSPLASIA 3 WITH OR WITHOUT POLYDACTYLY; SRTD3 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Clefting v4.104 LRRC32 Achchuthan Shanmugasundram Classified gene: LRRC32 as Amber List (moderate evidence)
Clefting v4.104 LRRC32 Achchuthan Shanmugasundram Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Clefting v4.103 LRRC32 Achchuthan Shanmugasundram gene: LRRC32 was added
gene: LRRC32 was added to Clefting. Sources: Literature
founder-effect tags were added to gene: LRRC32.
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112; 35656379
Phenotypes for gene: LRRC32 were set to Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074
Review for gene: LRRC32 was set to AMBER
Added comment: PMID:30976112 reported two unrelated families with global developmental delay, cleft palate, and proliferative retinopathy and they were identified with the same homozygous LRRC32 variant c.1630C>T/ p.Arg544Ter. This variant was suggested to be founder variant, as indicated by haplotype analysis.

PMID:35656379 reported a different homozygous LRRC32 variant (c.1354 G > A/ p.Glu452Lys) in a 15-year-old male with cleft palate, prenatal and postnatal severe growth retardation, global developmental delay, dysmorphic facial features and progressive vitreoretinopathy.

This gene has already been associated with relevant phenotypes in OMIM (MIM #619074), but not yet in Gene2Phenotype.
Sources: Literature
Clefting v4.100 TBX1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: TBX1.
Clefting v4.100 RAD21 Sarah Leigh Tag Q4_22_promote_green was removed from gene: RAD21.
Clefting v4.100 TBX1 Sarah Leigh reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v4.100 RAD21 Sarah Leigh reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v4.99 TBX1 Sarah Leigh Source Expert Review Green was added to TBX1.
Source NHS GMS was added to TBX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v4.99 RAD21 Sarah Leigh Source Expert Review Green was added to RAD21.
Source NHS GMS was added to RAD21.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v4.98 ALX1 Sarah Leigh Phenotypes for gene: ALX1 were changed from ?Frontonasal dysplasia 3, 613456 to Frontonasal dysplasia 3, OMIM:613456; frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome, MONDO:0013271
Clefting v4.97 ALX1 Sarah Leigh Publications for gene: ALX1 were set to 20451171; 27324866; 26610632
Clefting v4.96 ALX1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: ALX1.
Clefting v4.96 ALX1 Sarah Leigh Classified gene: ALX1 as Amber List (moderate evidence)
Clefting v4.96 ALX1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Clefting v4.96 ALX1 Sarah Leigh Gene: alx1 has been classified as Amber List (Moderate Evidence).
Clefting v4.95 ALX1 Sarah Leigh reviewed gene: ALX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Clefting v4.95 TP63 Arina Puzriakova Phenotypes for gene: TP63 were changed from Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3, 604292; Orofacial cleft 8, EEC SYNDROME 3, Rapp Hodgkins syndrome, 129400; EEC syndrome (Ectrodactyly, Ectodermal dysplasia and Clefting); AEC (Ankyloblepharon filiforme adnatum, Ectodermal defects and Clefting), Hay Wells syndrome 106260; Limb-mammary syndrome, 603543; ECTRODACTYLY, ECTODERMAL DYSPLASIA, AND CLEFT LIP/PALATE SYNDROME 3; EEC3; Cleft lip to Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM:604292; Hay-Wells syndrome, OMIM:106260; Limb-mammary syndrome, OMIM:603543; Orofacial cleft 8, OMIM:618149; Rapp-Hodgkin syndrome, OMIM:129400; Split-hand/foot malformation 4, OMIM:605289
Clefting v4.94 PTCH1 Arina Puzriakova Phenotypes for gene: PTCH1 were changed from BASAL CELL NEVUS SYNDROME; BCNS, HOLOPROSENCEPHALY 7; HPE7 to Holoprosencephaly 7, OMIM:610828; Basal cell nevus syndrome 1, OMIM:109400
Clefting v4.93 TBL1XR1 Achchuthan Shanmugasundram Classified gene: TBL1XR1 as Amber List (moderate evidence)
Clefting v4.93 TBL1XR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although three patients are reported with clefting in total, this represents a small fraction of total cases with monoallelic TBL1XR1 variants. Hence, this gene should be rated amber.
Clefting v4.93 TBL1XR1 Achchuthan Shanmugasundram Gene: tbl1xr1 has been classified as Amber List (Moderate Evidence).
Clefting v4.92 TBL1XR1 Achchuthan Shanmugasundram gene: TBL1XR1 was added
gene: TBL1XR1 was added to Clefting. Sources: Literature
Mode of inheritance for gene: TBL1XR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBL1XR1 were set to 28687524; 37010288
Phenotypes for gene: TBL1XR1 were set to Pierpont syndrome, OMIM:602342
Review for gene: TBL1XR1 was set to AMBER
Added comment: PMID:28687524 - A seven year-old boy reported with severe developmental delays, hypotonia and dysmorphic features and identified with a de novo heterozygous variant (p.Tyr446Cys) in TBL1XR1 gene had submucous cleft palate.

DECIPHER database - One of 34 patients with heterozygous sequence variants in TBL1XR1 gene in DECIPHER database had orofacial cleft and another patient had unilateral cleft lip and palate.
Sources: Literature
Clefting v4.91 CDK13 Achchuthan Shanmugasundram changed review comment from: PMID:29222009 - One of three patients reported with de novo heterozygous CDK13 variants had submucosal cleft palate.

DECIPHER database - Only one of 42 patients reported with heterozygous sequence variants in CDK13 gene had orofacial cleft as one of the phenotypes.
Sources: Literature; to: Clefting was reported only in a minor proportion of patients with monoallelic CDK13 variants.

PMID:29222009 - One of three patients reported with de novo heterozygous CDK13 variants had submucosal cleft palate.

DECIPHER database - Only one of 42 patients reported with heterozygous sequence variants in CDK13 gene had orofacial cleft as one of the phenotypes.
Sources: Literature
Clefting v4.91 CDK13 Achchuthan Shanmugasundram changed review comment from: PMID:29222009 - One of three patients reported with de novo heterozygous CDK13 variants had submucosal cleft palate.

DECIPHER database - Only one of 42 patients reported with heterozygous sequence variants in CDK13 gene had orofacial cleft as one of the phenotypes.
Sources: Literature; to: PMID:29222009 - One of three patients reported with de novo heterozygous CDK13 variants had submucosal cleft palate.

DECIPHER database - Only one of 42 patients reported with heterozygous sequence variants in CDK13 gene had orofacial cleft as one of the phenotypes.
Sources: Literature
Clefting v4.91 CDK13 Achchuthan Shanmugasundram gene: CDK13 was added
gene: CDK13 was added to Clefting. Sources: Literature
Mode of inheritance for gene: CDK13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK13 were set to 29222009; 37010288
Review for gene: CDK13 was set to RED
Added comment: PMID:29222009 - One of three patients reported with de novo heterozygous CDK13 variants had submucosal cleft palate.

DECIPHER database - Only one of 42 patients reported with heterozygous sequence variants in CDK13 gene had orofacial cleft as one of the phenotypes.
Sources: Literature
Clefting v4.90 NEB Achchuthan Shanmugasundram changed review comment from: PMID:12207937 - A 9 month-old boy from one of five families affected by nemaline myopathy and reported with NEB variants had cleft palate. This patient was homozygous for 1-bp deletion in exon 184, which was also found in the mother, whereas no DNA was available from father.

PMID:21798101 - Two siblings were reported with severe arthrogryposis multiplex congenital and were identified with compound heterozygous variants in NEB gene (c.1152 + 1G > T & c.11318_11319del), of which one patient had cleft palate.

PMID:33376055 - A male foetus of consanguineous parents with a severe congenital syndrome characterized by arthrogryposis detected at 13 weeks of gestation had cleft palate and was identified with homozygous splice-site NEB variant (c.19,102-1G>T).

DECIPHER databse - Of 10 patients with biallelic (compound heterozygous or homozygous) sequence variants in NEB gene reported in DECIPHER database, one patient with compound heterozygous NEB variants had bifid uvula.
Sources: Literature; to: PMID:12207937 - A 9 month-old boy from one of five families affected by nemaline myopathy and reported with NEB variants had cleft palate. This patient was homozygous for 1-bp deletion in exon 184, which was also found in the mother, whereas no DNA was available from father.

PMID:21798101 - Two siblings were reported with severe arthrogryposis multiplex congenital and were identified with compound heterozygous variants in NEB gene (c.1152 + 1G > T & c.11318_11319del), of which one patient had cleft palate.

PMID:33376055 - A male foetus of consanguineous parents with a severe congenital syndrome characterized by arthrogryposis detected at 13 weeks of gestation had cleft palate and was identified with homozygous splice-site NEB variant (c.19,102-1G>T).

DECIPHER databse - Of 10 patients with biallelic (compound heterozygous or homozygous) sequence variants in NEB gene reported in DECIPHER database, one patient with compound heterozygous NEB variants had bifid uvula.

Cleft palate has been associated as one of the clinical presentations of Arthrogryposis multiplex congenita 6 (MIM #619334) in OMIM.
Sources: Literature
Clefting v4.90 NEB Achchuthan Shanmugasundram Publications for gene: NEB were set to 12207937; 21798101; 33376055
Clefting v4.89 NEB Achchuthan Shanmugasundram edited their review of gene: NEB: Changed publications to: 12207937, 21798101, 33376055, 37010288
Clefting v4.89 ECEL1 Achchuthan Shanmugasundram Classified gene: ECEL1 as Amber List (moderate evidence)
Clefting v4.89 ECEL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three cases reported with clefting, it is only present in a small subsection (<10%) of patients with ECEL1 biallelic variants. Hence, this gene should be rated amber.
Clefting v4.89 ECEL1 Achchuthan Shanmugasundram Gene: ecel1 has been classified as Amber List (Moderate Evidence).
Clefting v4.88 NEB Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although there are three unrelated cases reported with cleft palate in literature and a case reported with bifid uvula in the DECIPHER project, clefting has not been consistently reported as a phenotype in patients with biallelic NEB variants and is not fully penetrant in some families .; to: Comment on list classification: Although there are three unrelated cases reported with cleft palate in literature and a case reported with bifid uvula in the DECIPHER project, clefting has not been consistently reported as a phenotype in patients with biallelic NEB variants and is not fully penetrant in at least one family with clefting.
Clefting v4.88 NEB Achchuthan Shanmugasundram Classified gene: NEB as Amber List (moderate evidence)
Clefting v4.88 NEB Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are three unrelated cases reported with cleft palate in literature and a case reported with bifid uvula in the DECIPHER project, clefting has not been consistently reported as a phenotype in patients with biallelic NEB variants and is not fully penetrant in some families .
Clefting v4.88 NEB Achchuthan Shanmugasundram Gene: neb has been classified as Amber List (Moderate Evidence).
Clefting v4.87 NEB Achchuthan Shanmugasundram gene: NEB was added
gene: NEB was added to Clefting. Sources: Literature
Mode of inheritance for gene: NEB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEB were set to 12207937; 21798101; 33376055
Phenotypes for gene: NEB were set to Arthrogryposis multiplex congenita 6, OMIM:619334
Review for gene: NEB was set to AMBER
Added comment: PMID:12207937 - A 9 month-old boy from one of five families affected by nemaline myopathy and reported with NEB variants had cleft palate. This patient was homozygous for 1-bp deletion in exon 184, which was also found in the mother, whereas no DNA was available from father.

PMID:21798101 - Two siblings were reported with severe arthrogryposis multiplex congenital and were identified with compound heterozygous variants in NEB gene (c.1152 + 1G > T & c.11318_11319del), of which one patient had cleft palate.

PMID:33376055 - A male foetus of consanguineous parents with a severe congenital syndrome characterized by arthrogryposis detected at 13 weeks of gestation had cleft palate and was identified with homozygous splice-site NEB variant (c.19,102-1G>T).

DECIPHER databse - Of 10 patients with biallelic (compound heterozygous or homozygous) sequence variants in NEB gene reported in DECIPHER database, one patient with compound heterozygous NEB variants had bifid uvula.
Sources: Literature
Clefting v4.86 ECEL1 Achchuthan Shanmugasundram changed review comment from: PMID:3013119 - Seven individuals from four unrelated families were reported with a wide phenotypic spectrum including severe congenital contractural syndromes and distal arthrogryposis type 5D and were identified with biallelic variants in ECEL1 gene. Of these two individuals from two different families presented with cleft palate. However, literature review in this publication showed only three patients from a total of 34 had cleft palate (9%).

DECIPHER database - The only patient reported in DECIPHER with compound heterozygous sequence variants in ECEL1 gene had cleft soft palate.

This gene was associated with distal arthrogryposis in both OMIM (MIM #615065) and Gene2Phenotype ('definitive' rating in the DD panel). OMIM recorded cleft palate as one of the clinical manifestations affecting some patients with this disorder.
Sources: Literature; to: PMID:3013119 - Seven individuals from four unrelated families were reported with a wide phenotypic spectrum including severe congenital contractural syndromes and distal arthrogryposis type 5D and were identified with biallelic variants in ECEL1 gene. Of these two individuals from two different families presented with cleft palate. However, literature review in this publication showed that only three patients from a total of 34 patients with biallelic ECEL1 variants had cleft palate (9%).

DECIPHER database - The only patient reported in DECIPHER with compound heterozygous sequence variants in ECEL1 gene had cleft soft palate.

This gene was associated with distal arthrogryposis in both OMIM (MIM #615065) and Gene2Phenotype ('definitive' rating in the DD panel). OMIM recorded cleft palate as one of the clinical manifestations affecting some patients with this disorder.
Sources: Literature
Clefting v4.86 ECEL1 Achchuthan Shanmugasundram gene: ECEL1 was added
gene: ECEL1 was added to Clefting. Sources: Literature
Mode of inheritance for gene: ECEL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECEL1 were set to 30131190; 37010288
Phenotypes for gene: ECEL1 were set to Arthrogryposis, distal, type 5D, OMIM:615065
Review for gene: ECEL1 was set to AMBER
Added comment: PMID:3013119 - Seven individuals from four unrelated families were reported with a wide phenotypic spectrum including severe congenital contractural syndromes and distal arthrogryposis type 5D and were identified with biallelic variants in ECEL1 gene. Of these two individuals from two different families presented with cleft palate. However, literature review in this publication showed only three patients from a total of 34 had cleft palate (9%).

DECIPHER database - The only patient reported in DECIPHER with compound heterozygous sequence variants in ECEL1 gene had cleft soft palate.

This gene was associated with distal arthrogryposis in both OMIM (MIM #615065) and Gene2Phenotype ('definitive' rating in the DD panel). OMIM recorded cleft palate as one of the clinical manifestations affecting some patients with this disorder.
Sources: Literature
Clefting v4.85 CDKL5 Achchuthan Shanmugasundram changed review comment from: Sources: Literature; to: Of 16 patients with sequence variants in CDKL5 in the DECIPHER database (https://www.deciphergenomics.org/), one of them had median cleft palate and another one had orofacial cleft.
Sources: Literature
Clefting v4.85 CDKL5 Achchuthan Shanmugasundram gene: CDKL5 was added
gene: CDKL5 was added to Clefting. Sources: Literature
Mode of inheritance for gene: CDKL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDKL5 were set to 37010288
Review for gene: CDKL5 was set to RED
Added comment: Sources: Literature
Clefting v4.83 CSNK2A1 Achchuthan Shanmugasundram gene: CSNK2A1 was added
gene: CSNK2A1 was added to Clefting. Sources: Literature
Mode of inheritance for gene: CSNK2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK2A1 were set to 37010288
Review for gene: CSNK2A1 was set to RED
Added comment: Of 21 patients with sequence variants in CSNK2A1 gene in the DECIPHER database (https://www.deciphergenomics.org/), two of them had cleft palate.
Sources: Literature
Clefting v4.82 SOX5 Achchuthan Shanmugasundram gene: SOX5 was added
gene: SOX5 was added to Clefting. Sources: Literature
Mode of inheritance for gene: SOX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX5 were set to 37010288
Review for gene: SOX5 was set to RED
Added comment: Of 19 patients with sequence variants in SOX5 gene in the DECIPHER database (https://www.deciphergenomics.org/), one had cleft palate and another one had bifid uvula/ submucous cleft hard palate.
Sources: Literature
Clefting v4.81 WDR26 Achchuthan Shanmugasundram gene: WDR26 was added
gene: WDR26 was added to Clefting. Sources: Literature
Mode of inheritance for gene: WDR26 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR26 were set to 37010288
Review for gene: WDR26 was set to RED
Added comment: Of 15 patients with sequence variants in WDR26 in the DECIPHER database (https://www.deciphergenomics.org/), two of them had (median) cleft palate.
Sources: Literature
Clefting v4.80 AMOTL1 Arina Puzriakova Tag Q3_23_promote_green tag was added to gene: AMOTL1.
Clefting v4.80 AMOTL1 Arina Puzriakova Publications for gene: AMOTL1 were set to 33026150; 30375152
Clefting v4.79 AMOTL1 Arina Puzriakova Classified gene: AMOTL1 as Amber List (moderate evidence)
Clefting v4.79 AMOTL1 Arina Puzriakova Added comment: Comment on list classification: There is now sufficient evidence to rate this gene as Green at the next GMS panel update.

At least 16 individuals from 12 families have been identified with heterozygous variants in a AMOTL1 hotspot (PMIDs: 30375152; 33026150; 36751037). The most common clinical features were orofacial clefting (15/16; 94%), large and dysplastic ears (10/16; 62.5%), congenital heart disease (8/16; 50%), tall stature (7/16; 44%), hearing loss (5/16; 31%), liver disease (5/16; 31%), and neurodevelopmental disease (5/16; 31%).
Clefting v4.79 AMOTL1 Arina Puzriakova Gene: amotl1 has been classified as Amber List (Moderate Evidence).
Clefting v4.78 AMOTL1 Irina Ziravecka reviewed gene: AMOTL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 36751037; Phenotypes: orofacial clefting, cardiac anomalies, tall stature; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v4.78 UBE3B Achchuthan Shanmugasundram Classified gene: UBE3B as Amber List (moderate evidence)
Clefting v4.78 UBE3B Achchuthan Shanmugasundram Gene: ube3b has been classified as Amber List (Moderate Evidence).
Clefting v4.77 UBE3B Achchuthan Shanmugasundram gene: UBE3B was added
gene: UBE3B was added to Clefting. Sources: Literature
Mode of inheritance for gene: UBE3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE3B were set to 23200864; 23687348; 37010288
Phenotypes for gene: UBE3B were set to Kaufman oculocerebrofacial syndrome, OMIM:244450
Review for gene: UBE3B was set to AMBER
Added comment: PMID:23687348 - One of two patients reported with biallelic variants in UBE3B in this study and one of four patients reported in PMID:23200864 and reviewed here had submucous cleft palate.

DECIPHER database - One of three patients with homozygous sequence variants in UBE3B had median cleft palate.
Sources: Literature
Clefting v4.76 TCF12 Achchuthan Shanmugasundram gene: TCF12 was added
gene: TCF12 was added to Clefting. Sources: Literature
Mode of inheritance for gene: TCF12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCF12 were set to 23354436; 31353793; 37010288
Phenotypes for gene: TCF12 were set to Craniosynostosis 3, OMIM:615314
Review for gene: TCF12 was set to RED
Added comment: Clefting has only been rarely reported in patients with TCF12 variants and hence this gene should be rated red.

PMID:23354436 - One of 73 individuals (from 38 families) reported with craniosynostosis and identified with heterozygous variants in TCF12 gene had cleft lip and cleft palate.

PMID:31353793 - Of two cases reported with heterozygous TCF12 variants, one had hidden cleft palate.

DECIPHER database - One of 11 patients with heterozygous sequence variants in TCF12 had bifid uvula.
Sources: Literature
Clefting v4.75 SOX11 Achchuthan Shanmugasundram gene: SOX11 was added
gene: SOX11 was added to Clefting. Sources: Literature
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 29437512; 37010288
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, OMIM:615866
Review for gene: SOX11 was set to RED
Added comment: Cleft palate is a minor clinical indication that is only observed in <10% of patients with SOX11 variants. Hence, this gene should be rated red.

PMID:29437512 - A 14-year-old boy with a phenotype resembling mild Coffin-Siris syndrome and identified with heterozygous SOX11 variant had cleft palate. However, cleft palate was not present in any of the previously reported patients (12 cases) reviewed in this publication.

DECIPHER database - Of 12 patients with heterozygous sequence variants in SOX11 gene, only one patient had cleft soft palate.
Sources: Literature
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Classified gene: SMARCB1 as Amber List (moderate evidence)
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are 3 unrelated cases in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants. Hence, this gene should be rated amber.
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Classified gene: SMARCB1 as Amber List (moderate evidence)
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are 3 unrelated cases in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants. Hence, this gene should be rated amber.
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Classified gene: SMARCB1 as Amber List (moderate evidence)
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are 3 unrelated cases in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants. Hence, this gene should be rated amber.
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Classified gene: SMARCB1 as Amber List (moderate evidence)
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are 3 unrelated cases in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants. Hence, this gene should be rated amber.
Clefting v4.74 SMARCB1 Achchuthan Shanmugasundram Gene: smarcb1 has been classified as Amber List (Moderate Evidence).
Clefting v4.73 SMARCB1 Achchuthan Shanmugasundram Classified gene: SMARCB1 as Red List (low evidence)
Clefting v4.73 SMARCB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are 3 unrelated cases in total, these represent only a minor fraction of patients (from total of 23) reported with SMARCB1 variants. Hence, this gene should be rated amber.
Clefting v4.73 SMARCB1 Achchuthan Shanmugasundram Gene: smarcb1 has been classified as Red List (Low Evidence).
Clefting v4.72 SMARCB1 Achchuthan Shanmugasundram gene: SMARCB1 was added
gene: SMARCB1 was added to Clefting. Sources: Literature
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCB1 were set to 25168959; 37010288
Phenotypes for gene: SMARCB1 were set to Coffin-Siris syndrome 3, OMIM:614608
Review for gene: SMARCB1 was set to AMBER
Added comment: PMID:25168959 - Two of ten patients reported with Coffin-Siris syndrome and heterozygous variants in SMARCB1 had cleft palate.

DECIPHER database - One of 13 patients identified with heterozygous sequence variants in SMARCB1 had cleft palate.
Sources: Literature
Clefting v4.71 SIN3A Achchuthan Shanmugasundram gene: SIN3A was added
gene: SIN3A was added to Clefting. Sources: Literature
Mode of inheritance for gene: SIN3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIN3A were set to 33437032; 37010288
Phenotypes for gene: SIN3A were set to Witteveen-Kolk syndrome, OMIM:613406
Review for gene: SIN3A was set to RED
Added comment: Clefting was reported only in a minor fraction of patients (<10%) and hence should be rated red.

PMID:33437032 - Of 28 patients with heterozugous variants in SIN3A gene, one patient had submucous cleft hard palate and another with deletion variant had orofacial cleft (both these are reported in DECIPHER database).

DECIPHER database - In addition to the above mentioned patients, one with heterozygous sequence variant had submucous cleft soft panel (from 31 in total), while an additional patient with deletion had cleft hard palate (from 54 patients with CNV variants).
Sources: Literature
Clefting v4.70 PUF60 Achchuthan Shanmugasundram changed review comment from: PMID:24140112 - One patient identified with heterozygous variant in PUF60 gene (p.His169Tyr) had cleft palate.

PMID:27804958 - Five patients were reported with sequence variants in PUF60 gene and none of them had cleft lip/ palate as one of the clinical presentations.

DECIPHER database - Of 27 patients with heterozygous sequence variants in PUF60, only one had submucous cleft hard palate.
Sources: Literature; to: Clefting has only been identified in a minor fraction of patients with monoallelic variants in PUF60 gene and hence this gene should be rated red in this panel.

PMID:24140112 - One patient identified with heterozygous variant in PUF60 gene (p.His169Tyr) had cleft palate.

PMID:27804958 - Five patients were reported with sequence variants in PUF60 gene and none of them had cleft lip/ palate as one of the clinical presentations.

DECIPHER database - Of 27 patients with heterozygous sequence variants in PUF60, only one had submucous cleft hard palate.
Sources: Literature
Clefting v4.70 PUF60 Achchuthan Shanmugasundram gene: PUF60 was added
gene: PUF60 was added to Clefting. Sources: Literature
Mode of inheritance for gene: PUF60 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PUF60 were set to 24140112; 27804958; 37010288
Phenotypes for gene: PUF60 were set to Verheij syndrome, OMIM:615583
Review for gene: PUF60 was set to RED
Added comment: PMID:24140112 - One patient identified with heterozygous variant in PUF60 gene (p.His169Tyr) had cleft palate.

PMID:27804958 - Five patients were reported with sequence variants in PUF60 gene and none of them had cleft lip/ palate as one of the clinical presentations.

DECIPHER database - Of 27 patients with heterozygous sequence variants in PUF60, only one had submucous cleft hard palate.
Sources: Literature
Clefting v4.69 POLR2A Achchuthan Shanmugasundram gene: POLR2A was added
gene: POLR2A was added to Clefting. Sources: Literature
Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2A were set to 31353023; 37010288
Phenotypes for gene: POLR2A were set to Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, OMIM:618603
Review for gene: POLR2A was set to RED
Added comment: This gene should be rated red as clefting has only been reported in a minor fraction of patients with monoallelic variants in POLR2A.

PMID:31353023 - 16 individuals were identified with heterozygous variants in POLR2A, of which only one patient had cleft lip.

DECIPHER database - Of 14 patients with heterozygous sequence variants, one had cleft palate and another had bifid uvula.
Sources: Literature
Clefting v4.68 POLA1 Achchuthan Shanmugasundram changed review comment from: PMID:3100651 - Nine patients from five unrelated families were identified with POLA1 variants, of which one patient from family C (has two reported patients) was reported with bifid uvula.

DECIPHER database - One of two patients with hemizygous sequence variants had bifid uvula.
Sources: Literature; to: Bifid uvula is a minor clinical indication that is only found in two patients with POLA1 variants and it is not fully penetrant in the family. Hence, this gene should be rated red.

PMID:3100651 - Nine patients from five unrelated families were identified with POLA1 variants, of which one patient from family C (has two reported patients) was reported with bifid uvula.

DECIPHER database - One of two patients with hemizygous sequence variants had bifid uvula.
Sources: Literature
Clefting v4.68 POLA1 Achchuthan Shanmugasundram gene: POLA1 was added
gene: POLA1 was added to Clefting. Sources: Literature
Mode of inheritance for gene: POLA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: POLA1 were set to 31006512; 37010288
Review for gene: POLA1 was set to RED
Added comment: PMID:3100651 - Nine patients from five unrelated families were identified with POLA1 variants, of which one patient from family C (has two reported patients) was reported with bifid uvula.

DECIPHER database - One of two patients with hemizygous sequence variants had bifid uvula.
Sources: Literature
Clefting v4.67 NOTCH2 Achchuthan Shanmugasundram Publications for gene: NOTCH2 were set to 9188663; 30329210; 37010288
Clefting v4.67 NOTCH2 Achchuthan Shanmugasundram Publications for gene: NOTCH2 were set to 9188663; 30329210
Clefting v4.66 NOTCH2 Achchuthan Shanmugasundram edited their review of gene: NOTCH2: Changed publications to: 9188663, 30329210, 37010288
Clefting v4.66 NOTCH2 Achchuthan Shanmugasundram Classified gene: NOTCH2 as Amber List (moderate evidence)
Clefting v4.66 NOTCH2 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are three cases reported with cleft lip/ palate or cleft of uvula, these are reported only in a minor proportion of patients and hence this gene can only be rated amber.
Clefting v4.66 NOTCH2 Achchuthan Shanmugasundram Gene: notch2 has been classified as Amber List (Moderate Evidence).
Clefting v4.65 NOTCH2 Achchuthan Shanmugasundram gene: NOTCH2 was added
gene: NOTCH2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: NOTCH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH2 were set to 9188663; 30329210
Phenotypes for gene: NOTCH2 were set to Hajdu-Cheney syndrome, OMIM:102500
Review for gene: NOTCH2 was set to AMBER
Added comment: PMID:9188663 - An 8.5-year-old boy with NOTCH2 variant and Hajdu-Cheney syndrome was reported with cleft lip and palate.

PMID:30329210 - A 32-year-old male patient with a de novo truncating variant in NOTCH2 and presenting with Hajdu-Cheney syndrome had high arched palate and cleft of uvula.

DECIPHER database - One of seven patients with heterozygous sequence variants in NOTCH2 was identified with submucous cleft hard palate.
Sources: Literature
Clefting v4.64 MAGEL2 Achchuthan Shanmugasundram gene: MAGEL2 was added
gene: MAGEL2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAGEL2 were set to 31397880; 37010288
Phenotypes for gene: MAGEL2 were set to Schaaf-Yang syndrome, OMIM:615547
Review for gene: MAGEL2 was set to RED
Added comment: Cleft palate is a minor feature of Schaaf-Yang syndrome and is present only in less than 10% of cases. Hence, this gene should be rated red.

PMID:31397880 - One of five patients presented in this study with heterozygous variants in MAGEL2 gene had cleft palate.

DECIPHER database - One of 20 patients with heterozygous sequence variants in MAGEL2 had cleft palate.
Sources: Literature
Clefting v4.63 EP300 Achchuthan Shanmugasundram changed review comment from: This gene should be rated red as clefting has only been reported in a very small fraction of patients (<5%) identified with monoallleic variants in EP300.

PMID:27648933 - One of 52 patients with Rubinstein-Taybi syndrome caused by monoallelic variants in EP300 gene had cleft lip and palate.

DECIPHER database - Of 58 patients with heterozygous sequence variants in EP300, cleft palate, orofacial cleft and bifid uvula were found in one patient each.
Sources: Literature; to: This gene should be rated red as clefting has only been reported in a very small fraction of patients (<5%) identified with monoallelic variants in EP300.

PMID:27648933 - One of 52 patients with Rubinstein-Taybi syndrome caused by monoallelic variants in EP300 gene had cleft lip and palate.

DECIPHER database - Of 58 patients with heterozygous sequence variants in EP300, cleft palate, orofacial cleft and bifid uvula were found in one patient each.
Sources: Literature
Clefting v4.63 EP300 Achchuthan Shanmugasundram gene: EP300 was added
gene: EP300 was added to Clefting. Sources: Literature
Mode of inheritance for gene: EP300 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EP300 were set to 27648933; 37010288
Phenotypes for gene: EP300 were set to Rubinstein-Taybi syndrome 2, OMIM:613684
Review for gene: EP300 was set to RED
Added comment: This gene should be rated red as clefting has only been reported in a very small fraction of patients (<5%) identified with monoallleic variants in EP300.

PMID:27648933 - One of 52 patients with Rubinstein-Taybi syndrome caused by monoallelic variants in EP300 gene had cleft lip and palate.

DECIPHER database - Of 58 patients with heterozygous sequence variants in EP300, cleft palate, orofacial cleft and bifid uvula were found in one patient each.
Sources: Literature
Clefting v4.62 CHD3 Achchuthan Shanmugasundram changed review comment from: Of 28 patients with heterozygous sequence variants in CHD3 gene from DECIPHER database, one patient had cleft palate and another had submucous cleft hard palate.
Sources: Literature; to: Of 28 patients with heterozygous sequence variants in CHD3 gene from DECIPHER database, one patient had cleft palate and another had submucous cleft hard palate.
Sources: Literature
Clefting v4.62 CHD3 Achchuthan Shanmugasundram gene: CHD3 was added
gene: CHD3 was added to Clefting. Sources: Literature
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to 37010288
Phenotypes for gene: CHD3 were set to Snijders Blok-Campeau syndrome, OMIM:618205
Review for gene: CHD3 was set to RED
Added comment: Of 28 patients with heterozygous sequence variants in CHD3 gene from DECIPHER database, one patient had cleft palate and another had submucous cleft hard palate.
Sources: Literature
Clefting v4.61 AUTS2 Achchuthan Shanmugasundram Classified gene: AUTS2 as Amber List (moderate evidence)
Clefting v4.61 AUTS2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five cases reported with cleft lip/ palate. However, clefting has only been reported in less than 10% of patients with monoalellic variants in AUTS2 from the DECIPHER database. Hence, this gene should be rated amber.
Clefting v4.61 AUTS2 Achchuthan Shanmugasundram Gene: auts2 has been classified as Amber List (Moderate Evidence).
Clefting v4.60 AUTS2 Achchuthan Shanmugasundram gene: AUTS2 was added
gene: AUTS2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: AUTS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AUTS2 were set to 31788251; 37010288
Phenotypes for gene: AUTS2 were set to Intellectual developmental disorder, autosomal dominant 26, OMIM:615834
Review for gene: AUTS2 was set to AMBER
Added comment: PMID:31788251 - A patient identified with a de novo heterozygous AUTS2 variant (c.1464_1467del ACTC/ p.Tyr488Ter) was reported with autism and cleft lip and palate.

DECIPHER database - Of 44 patients reported with heterozygous sequence variants, 4 patients had cleft lip or cleft palate (2 - cleft palate; 1 - cleft soft palate; 1 - unilateral cleft lip).
Sources: Literature
Clefting v4.59 ARID1A Achchuthan Shanmugasundram Phenotypes for gene: ARID1A were changed from to Coffin-Siris syndrome 2, OMIM:614607
Clefting v4.58 ARID1A Achchuthan Shanmugasundram edited their review of gene: ARID1A: Changed phenotypes to: Coffin-Siris syndrome 2, OMIM:614607
Clefting v4.58 ARID1A Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Clefting is a minor feature on patients with monoallelic variants in ARID1A gene and it can be rated amber although there are three cases with clefting form a total of 34 cases.; to: Comment on list classification: Clefting is a minor feature on patients with monoallelic variants in ARID1A gene and it should be rated amber although there are three cases with clefting (from a total of 34 cases).
Clefting v4.58 ARID1A Achchuthan Shanmugasundram Classified gene: ARID1A as Amber List (moderate evidence)
Clefting v4.58 ARID1A Achchuthan Shanmugasundram Added comment: Comment on list classification: Clefting is a minor feature on patients with monoallelic variants in ARID1A gene and it can be rated amber although there are three cases with clefting form a total of 34 cases.
Clefting v4.58 ARID1A Achchuthan Shanmugasundram Gene: arid1a has been classified as Amber List (Moderate Evidence).
Clefting v4.57 ARID1A Achchuthan Shanmugasundram gene: ARID1A was added
gene: ARID1A was added to Clefting. Sources: Literature
Mode of inheritance for gene: ARID1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1A were set to 25168959; 37010288
Review for gene: ARID1A was set to AMBER
Added comment: PMID:25168959 - Two of eight patients with heterozygous variants in ARID1A gene had cleft palate.

DECIPHER database - One of 26 patients with heterozygous sequence variants in ARID1A gene had cleft palate.
Sources: Literature
Clefting v4.56 ADNP Achchuthan Shanmugasundram changed review comment from: PMID:29724491 - One child from a worldwide cohort of 78 individuals with variants in ADNP gene had submucous cleft palate.

DECIPHER database - Of 66 patients identified with heterozygous sequence variants in ADNP gene, one each (three in total) was reported with cleft soft palate, submucous cleft hard palate and submucous cleft lip.
Sources: Literature; to: Cleft lip/ palate has only been reported rarely in patients identified with monoallelic variants in ADNP gene.

PMID:29724491 - One child from a worldwide cohort of 78 individuals with variants in ADNP gene had submucous cleft palate.

DECIPHER database - Of 66 patients identified with heterozygous sequence variants in ADNP gene, one each (three in total) was reported with cleft soft palate, submucous cleft hard palate and submucous cleft lip.
Sources: Literature
Clefting v4.56 ADNP Achchuthan Shanmugasundram gene: ADNP was added
gene: ADNP was added to Clefting. Sources: Literature
Mode of inheritance for gene: ADNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADNP were set to 29724491; 37010288
Phenotypes for gene: ADNP were set to Helsmoortel-van der Aa syndrome, OMIM:615873
Review for gene: ADNP was set to RED
Added comment: PMID:29724491 - One child from a worldwide cohort of 78 individuals with variants in ADNP gene had submucous cleft palate.

DECIPHER database - Of 66 patients identified with heterozygous sequence variants in ADNP gene, one each (three in total) was reported with cleft soft palate, submucous cleft hard palate and submucous cleft lip.
Sources: Literature
Clefting v4.55 ZC4H2 Achchuthan Shanmugasundram changed review comment from: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Literature; to: PMID:31206972 - Of 42 families identified with de novo and inherited variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Literature
Clefting v4.55 ZC4H2 Achchuthan Shanmugasundram Mode of inheritance for gene: ZC4H2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram edited their review of gene: ZC4H2: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are ten patients reported with cleft palate. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: There are ten unrelated patients reported with cleft palate. Hence, this gene can be promoted to green rating in the next GMS update.
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram changed review comment from: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients were had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Literature; to: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Literature
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram changed review comment from: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients were had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.
Sources: Literature; to: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients were had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.

Cleft palate has been recorded as one of the clinical presentations of female-restricted Wieacker-Wolff syndrome (MIM #301041) in OMIM.
Sources: Literature
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram Classified gene: ZC4H2 as Amber List (moderate evidence)
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are ten patients reported with cleft palate. Hence, this gene can be promoted to green rating in the next GMS update.
Clefting v4.54 ZC4H2 Achchuthan Shanmugasundram Gene: zc4h2 has been classified as Amber List (Moderate Evidence).
Clefting v4.53 ZC4H2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: ZC4H2.
Clefting v4.53 ZC4H2 Achchuthan Shanmugasundram gene: ZC4H2 was added
gene: ZC4H2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: ZC4H2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZC4H2 were set to 31206972; 37010288
Phenotypes for gene: ZC4H2 were set to Wieacker-Wolff syndrome, female-restricted, OMIM:301041
Review for gene: ZC4H2 was set to GREEN
Added comment: PMID:31206972 - Of 42 families identified with variants in de novo and inherited heterozygous variants in ZC4H2 gene, eight patients were had cleft palate in addition to several other clinical presentations. These included one patient with cleft palate from the DDD study (DECIPHER database)

DECIPHER database - Of 13 patients with monoallelic sequence variants, three patients had cleft palate.
Sources: Literature
Clefting v4.52 TRRAP Achchuthan Shanmugasundram changed review comment from: PMID:30827496 - Out of 13 unrelated individuals with a complex syndromic neurodevelopmental disorder comprising global developmental delay and intellectual disability and identified with monoallelic variants in TRRAP gene, five had cleft lip and palate.

DECIPHER database - Out of 18 patients with heterozygous sequence variants in TRRAP gene, two were reported with cleft lip and palate.
Sources: Literature; to: PMID:30827496 - Out of 13 unrelated individuals with a complex syndromic neurodevelopmental disorder comprising global developmental delay and intellectual disability and identified with monoallelic variants in TRRAP gene, five had cleft lip and palate.

DECIPHER database - Out of 18 patients with heterozygous sequence variants in TRRAP gene, two were reported with cleft lip and palate.

OMIM has also recorded cleft lip and palate as clinical presentations of the syndrome associated with dominant variants in TRRAP (MIM #618454).
Sources: Literature
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Deleted their comment
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Classified gene: TRRAP as Amber List (moderate evidence)
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be promoted to green rating at the next major update.
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Gene: trrap has been classified as Amber List (Moderate Evidence).
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Classified gene: TRRAP as Amber List (moderate evidence)
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be promoted green rating at the next major update.
Clefting v4.52 TRRAP Achchuthan Shanmugasundram Gene: trrap has been classified as Amber List (Moderate Evidence).
Clefting v4.51 TRRAP Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: TRRAP.
Clefting v4.51 TRRAP Achchuthan Shanmugasundram gene: TRRAP was added
gene: TRRAP was added to Clefting. Sources: Literature
Mode of inheritance for gene: TRRAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRRAP were set to 30827496; 37010288
Phenotypes for gene: TRRAP were set to Developmental delay with or without dysmorphic facies and autism, OMIM:618454
Review for gene: TRRAP was set to GREEN
Added comment: PMID:30827496 - Out of 13 unrelated individuals with a complex syndromic neurodevelopmental disorder comprising global developmental delay and intellectual disability and identified with monoallelic variants in TRRAP gene, five had cleft lip and palate.

DECIPHER database - Out of 18 patients with heterozygous sequence variants in TRRAP gene, two were reported with cleft lip and palate.
Sources: Literature
Clefting v4.50 TRAF7 Achchuthan Shanmugasundram Classified gene: TRAF7 as Amber List (moderate evidence)
Clefting v4.50 TRAF7 Achchuthan Shanmugasundram Gene: traf7 has been classified as Amber List (Moderate Evidence).
Clefting v4.49 TRAF7 Achchuthan Shanmugasundram Publications for gene: TRAF7 were set to 32376980; 37010288
Clefting v4.49 TRAF7 Achchuthan Shanmugasundram Publications for gene: TRAF7 were set to 32376980
Clefting v4.48 TRAF7 Achchuthan Shanmugasundram edited their review of gene: TRAF7: Changed publications to: 32376980, 37010288
Clefting v4.48 TRAF7 Achchuthan Shanmugasundram gene: TRAF7 was added
gene: TRAF7 was added to Clefting. Sources: Literature
Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRAF7 were set to 32376980
Phenotypes for gene: TRAF7 were set to Cardiac, facial, and digital anomalies with developmental delay, OMIM:618164
Review for gene: TRAF7 was set to AMBER
Added comment: PMID:32376980 - 45 patients were identified with heterozygous variants in TRAF7 gene, of which one patient had cleft palate and three patients had submucous cleft palate.

DECIPHER database - One of 15 patients with heterozygous sequence variants in TRAF7 gene had cleft palate as one of the clinical presentations.
Sources: Literature
Clefting v4.47 STAG2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are ten cases identified with cleft lip/ palate, cleft soft palate or submucous cleft soft palate. Hence, this gene can be promoted to green rating at the next GMS review.; to: Comment on list classification: There are eight unrelated cases identified with cleft lip/ palate and two cases were identified with cleft soft palate or submucous cleft soft palate. Hence, this gene should be promoted to green rating at the next GMS review.
Clefting v4.47 STAG2 Achchuthan Shanmugasundram Classified gene: STAG2 as Amber List (moderate evidence)
Clefting v4.47 STAG2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are ten cases identified with cleft lip/ palate, cleft soft palate or submucous cleft soft palate. Hence, this gene can be promoted to green rating at the next GMS review.
Clefting v4.47 STAG2 Achchuthan Shanmugasundram Gene: stag2 has been classified as Amber List (Moderate Evidence).
Clefting v4.46 STAG2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: STAG2.
Clefting v4.46 STAG2 Achchuthan Shanmugasundram gene: STAG2 was added
gene: STAG2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: STAG2 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: STAG2 were set to 28296084; 29263825; 30158690; 31334757; 33014403; 37010288
Phenotypes for gene: STAG2 were set to Holoprosencephaly 13, X-linked, OMIM:301043; Mullegama-Klein-Martinez syndrome, OMIM:301022
Review for gene: STAG2 was set to GREEN
Added comment: PMID:33014403 - Two female patients identified with de novo variants in STAG2. One had cleft lip/ palate and other had cleft palate. In addition, five additional cases with cleft lip/ palate were also reported from literature review in this publication.

DECIPHER database - Of ten patients with sequence variants in STAG2 gene, one each was identified with cleft palate, cleft soft palate and submucous cleft soft palate (PMID:37010288).
Sources: Literature
Clefting v4.45 SMARCA4 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: SMARCA4.
Clefting v4.45 SMARCA4 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.45 SMARCA4 Achchuthan Shanmugasundram Classified gene: SMARCA4 as Amber List (moderate evidence)
Clefting v4.45 SMARCA4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated cases with cleft plate and one case each with submucous cleft palate and bifid uvula. This gene can be promoted to green rating in the next GMS review.
Clefting v4.45 SMARCA4 Achchuthan Shanmugasundram Gene: smarca4 has been classified as Amber List (Moderate Evidence).
Clefting v4.44 SMARCA4 Achchuthan Shanmugasundram Classified gene: SMARCA4 as Amber List (moderate evidence)
Clefting v4.44 SMARCA4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated cases with cleft plate and one case each with submucous cleft palate and bifid uvula. This gene can be promoted to green rating in the next GMS review.
Clefting v4.44 SMARCA4 Achchuthan Shanmugasundram Gene: smarca4 has been classified as Amber List (Moderate Evidence).
Clefting v4.43 SMARCA4 Achchuthan Shanmugasundram gene: SMARCA4 was added
gene: SMARCA4 was added to Clefting. Sources: Literature
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA4 were set to 25168959; 37010288
Phenotypes for gene: SMARCA4 were set to Coffin-Siris syndrome 4, OMIM:614609
Review for gene: SMARCA4 was set to GREEN
Added comment: PMID:25168959 - 4 of 12 patients with variants in SMARCA4 had cleft palate and another patient had submucous cleft palate.

DECIPHER database - One of 22 patients with heterozygous sequence variants had cleft palate and another patient had bifid uvula (PMID:37010288)
Sources: Literature
Clefting v4.42 POGZ Achchuthan Shanmugasundram Classified gene: POGZ as Amber List (moderate evidence)
Clefting v4.42 POGZ Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three unrelated cases reported with either cleft palate or bifid uvula in total, this phenotype is not consistently present in patients with monoallelic variants in POGZ gene. Hence, this gene should only be rated amber.
Clefting v4.42 POGZ Achchuthan Shanmugasundram Gene: pogz has been classified as Amber List (Moderate Evidence).
Clefting v4.41 POGZ Achchuthan Shanmugasundram Publications for gene: POGZ were set to 26739615; 31782611
Clefting v4.40 POGZ Achchuthan Shanmugasundram changed review comment from: PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula.

The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.
Sources: Literature; to: PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula (PMID:37010288).

The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.
Sources: Literature
Clefting v4.40 POGZ Achchuthan Shanmugasundram edited their review of gene: POGZ: Changed publications to: 26739615, 31782611, 37010288
Clefting v4.40 POGZ Achchuthan Shanmugasundram gene: POGZ was added
gene: POGZ was added to Clefting. Sources: Literature
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to 26739615; 31782611
Phenotypes for gene: POGZ were set to White-Sutton syndrome, OMIM:616364
Review for gene: POGZ was set to AMBER
Added comment: PMID:26739615 - Five unrelated individuals were identified with de novo truncating variants in POGZ gene, of which one individual had cleft palate and another one had bifid uvula.

PMID:31782611 - In this cohort of 22 individuals with 21 different loss of function variants in POGZ, two patients were reported with bifid uvula.

DECIPHER database - Of 42 patients with heterozygous sequence variants, one had cleft palate and another one had bifid uvula.

The OMIM entry for White-Sutton syndrome (MIM #616364) does not currently include cleft lip/ palate as one of the clinical manifestations of this syndrome.
Sources: Literature
Clefting v4.39 PGM1 Achchuthan Shanmugasundram Classified gene: PGM1 as Amber List (moderate evidence)
Clefting v4.39 PGM1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>10 unrelated cases) for this gene to be rated green at the next GMS review.
Clefting v4.39 PGM1 Achchuthan Shanmugasundram Gene: pgm1 has been classified as Amber List (Moderate Evidence).
Clefting v4.38 PGM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PGM1.
Clefting v4.38 PGM1 Achchuthan Shanmugasundram Phenotypes for gene: PGM1 were changed from Cleft palate to Congenital disorder of glycosylation, type It, OMIM:14921
Clefting v4.37 PGM1 Achchuthan Shanmugasundram Publications for gene: PGM1 were set to 24499211; 37010288
Clefting v4.37 PGM1 Achchuthan Shanmugasundram Publications for gene: PGM1 were set to
Clefting v4.36 PGM1 Achchuthan Shanmugasundram Mode of inheritance for gene: PGM1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Clefting v4.35 PGM1 Achchuthan Shanmugasundram changed review comment from: PMID:24499211 - 19 patients from 16 families with biallelic variants in PGM1 and presenting with CGG1T. Of these, 16 patients from 13 different families had cleft palate and/ or bifid uvula.

DECIPHER database - Only one patient reported with compound heterozygous variant in PGM1 gene and this patient had cleft palate (PMID:37010288); to: PMID:24499211 - 19 patients from 16 families with biallelic variants in PGM1 and presenting with CGG1T. Of these, 16 patients from 13 different families had cleft palate and/ or bifid uvula.

DECIPHER database - Only one patient reported with compound heterozygous variant in PGM1 gene and this patient had cleft palate (PMID:37010288)

OMIM associated autosomal recessive PGM1 variants to congenital disorder of glycosylation, type It (MIM #14921) and cleft palate and bifid uvula have been recorded as clinical presentations of this disorder.
Clefting v4.35 PGM1 Achchuthan Shanmugasundram reviewed gene: PGM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24499211, 37010288; Phenotypes: Congenital disorder of glycosylation, type It, OMIM:14921; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v4.35 PGAP3 Achchuthan Shanmugasundram Classified gene: PGAP3 as Amber List (moderate evidence)
Clefting v4.35 PGAP3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>10 unrelated cases) available for promoting this gene to green rating in the next GMS review.
Clefting v4.35 PGAP3 Achchuthan Shanmugasundram Gene: pgap3 has been classified as Amber List (Moderate Evidence).
Clefting v4.34 PGAP3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PGAP3.
Clefting v4.34 PGAP3 Achchuthan Shanmugasundram gene: PGAP3 was added
gene: PGAP3 was added to Clefting. Sources: Literature
Mode of inheritance for gene: PGAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGAP3 were set to 28390064; 37010288
Phenotypes for gene: PGAP3 were set to Hyperphosphatasia with impaired intellectual development syndrome 4, OMIM:615716
Review for gene: PGAP3 was set to GREEN
Added comment: PMID:28390064 - 10 patients from eight families presented with developmental delay, severe intellectual disability, distinct facial dysmorphism and increased alkaline phosphatase. Nine patients from seven families were homozygous for the same variant (c.402dupC/ p.M135Hfs*28), while one patient had a different homozygous variant ( c.817_820delGACT/ p.D273Sfs*37). Of nine patients with p.M135Hfs*28 variant, eight patients from seven families (except one of the two patients from family 7) had cleft palate. But, the only patient with the different variant did not have cleft palate.

DECIPHER database - Of seven patients reported with biallelic sequence variants, three patents with homozygous variants were reported with cleft palate and two patients with compound heterozygous variants were reported with cleft soft palate (PMID:37010288).

OMIM associated patients with autosomal recessive variants in PGAP3 to hyperphosphatasia with impaired intellectual development syndrome 4 (MIM #615716) and cleft palate has been recorded as one of the clinical manifestations occurring in some patients.
Sources: Literature
Clefting v4.33 MED13L Achchuthan Shanmugasundram changed review comment from: PMID:25137640 - Cleft palate was present in the patient reported with intellectual disability and dysmorphic facial features.
PMID:25712080 - Cleft palate was reported in a single case (patient 1) of MED13L haploinsufficiency.
PMID:29159987 - One of the two patients reported with de novo variants had repaired posterior cleft palate and the other had only high palate.
PMID:29511999 - One of 36 patients with monoallelic variants had posterior cleft palate.
DECIPHER database - Of 72 patients reported with heterozygous sequence variants, cleft palate was reported in two patients, cleft soft palate in one and submucous cleft hard palate in one patient (PMID:37010288).; to: Although there are more than three cases reported with clefting, this feature is not consistently found in patients with monoallelic variants in MED13L gene.

PMID:25137640 - Cleft palate was present in the patient reported with intellectual disability and dysmorphic facial features.
PMID:25712080 - Cleft palate was reported in a single case (patient 1) of MED13L haploinsufficiency.
PMID:29159987 - One of the two patients reported with de novo variants had repaired posterior cleft palate and the other had only high palate.
PMID:29511999 - One of 36 patients with monoallelic variants had posterior cleft palate.
DECIPHER database - Of 72 patients reported with heterozygous sequence variants, cleft palate was reported in two patients, cleft soft palate in one and submucous cleft hard palate in one patient (PMID:37010288).
Clefting v4.33 MED13L Achchuthan Shanmugasundram Publications for gene: MED13L were set to 25137640; 25712080; 29159987; 29511999; 37010288
Clefting v4.33 MED13L Achchuthan Shanmugasundram Publications for gene: MED13L were set to 25137640; 25712080; 29159987; 29511999; 37010288
Clefting v4.33 MED13L Achchuthan Shanmugasundram Publications for gene: MED13L were set to 25137640; 25712080
Clefting v4.32 MED13L Achchuthan Shanmugasundram changed review comment from: PMID:25137640 - Cleft palate was present in the patient reported with intellectual disability and dysmorphic facial features.
PMID:25712080 - Cleft palate was reported in a single case (patient 1) of MED13L haploinsufficiency.
PMID:29159987 - One of the two patients reported with de novo variants had repaired posterior cleft palate and the other had only high palate.
PMID:29511999 - One of 36 patients with monoallelic variants had posterior cleft palate.
DECIPHER database - Of 72 patients reported with heterozygous sequence variants, cleft palate was reported in two patients, cleft soft palate in one and submucous cleft hard palate in one patient.; to: PMID:25137640 - Cleft palate was present in the patient reported with intellectual disability and dysmorphic facial features.
PMID:25712080 - Cleft palate was reported in a single case (patient 1) of MED13L haploinsufficiency.
PMID:29159987 - One of the two patients reported with de novo variants had repaired posterior cleft palate and the other had only high palate.
PMID:29511999 - One of 36 patients with monoallelic variants had posterior cleft palate.
DECIPHER database - Of 72 patients reported with heterozygous sequence variants, cleft palate was reported in two patients, cleft soft palate in one and submucous cleft hard palate in one patient (PMID:37010288).
Clefting v4.32 MED13L Achchuthan Shanmugasundram edited their review of gene: MED13L: Changed publications to: 25137640, 25712080, 29159987, 29511999, 37010288
Clefting v4.32 MED13L Achchuthan Shanmugasundram reviewed gene: MED13L: Rating: AMBER; Mode of pathogenicity: None; Publications: 25712080, 29159987, 29511999; Phenotypes: Impaired intellectual development and distinctive facial features with or without cardiac defects, OMIM:616789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v4.32 KMT2A Achchuthan Shanmugasundram Classified gene: KMT2A as Amber List (moderate evidence)
Clefting v4.32 KMT2A Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three cases reported with clefting, it is only present in a very small subsection of patients with KMT2A monoallelic variants. Hence, this gene can only be rated amber with current evidence.
Clefting v4.32 KMT2A Achchuthan Shanmugasundram Gene: kmt2a has been classified as Amber List (Moderate Evidence).
Clefting v4.31 KMT2A Achchuthan Shanmugasundram gene: KMT2A was added
gene: KMT2A was added to Clefting. Sources: Literature
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2A were set to 25929198; 30305169; 31710778; 37010288
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome, OMIM:605130
Review for gene: KMT2A was set to AMBER
Added comment: PMID:25929198 - De novo KMT2A variant (p.Arg1083Ter) in monozygotic twins and they had submucosal cleft palate.

PMID:30305169 - Two of 14 patients with KMT2A variants and presenting with Wiedemann–Steiner syndrome had cleft palate.

PMID:31710778 - Both patients reported with KMT2A variants had only high arched palate and not cleft palate.

DECIPHER database - None of the reported patients had cleft lip/ palate and only one of 115 had bifid uvula (PMID:37010288)
Sources: Literature
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: KAT6B.
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Deleted their comment
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Deleted their comment
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Classified gene: KAT6B as Amber List (moderate evidence)
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Added comment: Comment on list classification: Although clefting is a minor feature in patients reported with monoallelic KAT6B variants, it has been reported in more than 20 cases so far. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.30 KAT6B Achchuthan Shanmugasundram Gene: kat6b has been classified as Amber List (Moderate Evidence).
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Classified gene: KAT6B as Amber List (moderate evidence)
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Added comment: Comment on list classification: Although clefting is a minor feature in patients reported with monoallelic KAT6B variants, it has been reported in more than 20 cases so far. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Gene: kat6b has been classified as Amber List (Moderate Evidence).
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Classified gene: KAT6B as Amber List (moderate evidence)
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Added comment: Comment on list classification: Although clefting is a minor feature in patients reported with monoallelic KAT6B variants, it has been reported in more than 20 cases so far. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.29 KAT6B Achchuthan Shanmugasundram Gene: kat6b has been classified as Amber List (Moderate Evidence).
Clefting v4.28 GLI2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although cleating is a minor feature in patients reported with monoallelic GLI2 variants, it has been reported in more than 15 cases. Hence, this gene should be promoted to green rating in the next GMS review.; to: Comment on list classification: Although clefting is a minor feature in patients reported with monoallelic GLI2 variants, it has been reported in more than 15 cases. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.28 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736 to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting v4.28 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736 to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting v4.28 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736 to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting v4.27 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736 to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting v4.27 KAT6B Achchuthan Shanmugasundram Phenotypes for gene: KAT6B were changed from Genitopatellar syndrome, 606170; GTPTS to Genitopatellar syndrome, OMIM:606170; SBBYSS syndrome, OMIM:603736
Clefting v4.26 KAT6B Achchuthan Shanmugasundram Publications for gene: KAT6B were set to 20182757; 27031267; 32424177; 37010288
Clefting v4.26 KAT6B Achchuthan Shanmugasundram Publications for gene: KAT6B were set to 20182757; 27031267
Clefting v4.25 KAT6B Achchuthan Shanmugasundram reviewed gene: KAT6B: Rating: AMBER; Mode of pathogenicity: None; Publications: 32424177, 37010288; Phenotypes: Genitopatellar syndrome, OMIM:606170, SBBYSS syndrome, OMIM:603736; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v4.25 HNRNPK Achchuthan Shanmugasundram Classified gene: HNRNPK as Amber List (moderate evidence)
Clefting v4.25 HNRNPK Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available to promote this gene to green rating in the next GMS review.
Clefting v4.25 HNRNPK Achchuthan Shanmugasundram Gene: hnrnpk has been classified as Amber List (Moderate Evidence).
Clefting v4.24 HNRNPK Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: HNRNPK.
Clefting v4.24 HNRNPK Achchuthan Shanmugasundram Phenotypes for gene: HNRNPK were changed from Au-Kline syndrome, OMIM:616580 to Au-Kline syndrome, OMIM:616580
Clefting v4.24 HNRNPK Achchuthan Shanmugasundram Phenotypes for gene: HNRNPK were changed from to Au-Kline syndrome, OMIM:616580
Clefting v4.23 HNRNPK Achchuthan Shanmugasundram changed review comment from: PMID:29904177 reported six new cases and reviewed additional cases from literature with Au-Kline syndrome and monoallelic variants in HNRNPK gene. Of 12 patients reported and reviewed in this publication, five had cleft palate and two others had bifid uvula.

Three out of six patients reported with heterozygous sequence variants in HNRNPK gene had cleft palate as one of the phenotypes (PMID:37010288).

OMIM reported that patients with Au-Kline syndrome (MIM #616580) caused by autosomal dominant variants in HNRNPK gene has cleft palate/ bifid uvula as clinical manifestations.
Sources: Literature; to: PMID:29904177 reported six new cases and reviewed additional cases from literature with Au-Kline syndrome and monoallelic variants in HNRNPK gene. Of 12 patients reported and reviewed in this publication, five had cleft palate and two others had bifid uvula.

Three out of six patients reported with heterozygous sequence variants in HNRNPK gene in the DECIPHER database had cleft palate as one of the phenotypes (PMID:37010288).

OMIM reported that patients with Au-Kline syndrome (MIM #616580) caused by autosomal dominant variants in HNRNPK gene has cleft palate/ bifid uvula as clinical manifestations.
Sources: Literature
Clefting v4.23 HNRNPK Achchuthan Shanmugasundram edited their review of gene: HNRNPK: Changed phenotypes to: Au-Kline syndrome, OMIM:616580
Clefting v4.23 HNRNPK Achchuthan Shanmugasundram gene: HNRNPK was added
gene: HNRNPK was added to Clefting. Sources: Literature
Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPK were set to 29904177; 37010288
Review for gene: HNRNPK was set to GREEN
Added comment: PMID:29904177 reported six new cases and reviewed additional cases from literature with Au-Kline syndrome and monoallelic variants in HNRNPK gene. Of 12 patients reported and reviewed in this publication, five had cleft palate and two others had bifid uvula.

Three out of six patients reported with heterozygous sequence variants in HNRNPK gene had cleft palate as one of the phenotypes (PMID:37010288).

OMIM reported that patients with Au-Kline syndrome (MIM #616580) caused by autosomal dominant variants in HNRNPK gene has cleft palate/ bifid uvula as clinical manifestations.
Sources: Literature
Clefting v4.22 GLI2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: GLI2.
Clefting v4.22 GLI2 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.22 GLI2 Achchuthan Shanmugasundram Classified gene: GLI2 as Amber List (moderate evidence)
Clefting v4.22 GLI2 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although cleating is a minor feature in patients reported with monoallelic GLI2 variants, it has been reported in more than 15 cases. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.22 GLI2 Achchuthan Shanmugasundram Gene: gli2 has been classified as Amber List (Moderate Evidence).
Clefting v4.21 GLI2 Achchuthan Shanmugasundram Classified gene: GLI2 as Amber List (moderate evidence)
Clefting v4.21 GLI2 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although cleating is a minor feature in patients reported with monoallelic GLI2 variants, it has been reported in more than 15 cases. Hence, this gene should be promoted to green rating in the next GMS review.
Clefting v4.21 GLI2 Achchuthan Shanmugasundram Gene: gli2 has been classified as Amber List (Moderate Evidence).
Clefting v4.20 GLI2 Achchuthan Shanmugasundram gene: GLI2 was added
gene: GLI2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: GLI2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLI2 were set to 24744436; 37010288
Phenotypes for gene: GLI2 were set to Culler-Jones syndrome, OMIM:615849; Holoprosencephaly 9, OMIM:610829
Review for gene: GLI2 was set to GREEN
Added comment: In ~400 screened individuals with HPE spectrum disorders, 112 individuals were identified with variants in GLI2 gene, of which 16 cases had cleft lip/ palate (PMID:24744436).

Three out of 17 patients reported with heterozygous GLI2 sequence variants in the DECIPHER database presented with cleft lip/ palate as one of the phenotypes (PMID:37010288).

OMIM reported cleft lip/ palate as one of the clinical presentations in a subset of patients with Culler-Jones syndrome (MIM #615849) and holoprosencephaly 9 (MIM #610829). These are diseases associated with autosomal dominant variants in GLI2 gene.
Sources: Literature
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Classified gene: FGFR3 as Amber List (moderate evidence)
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three unrelated cases reported with cleft lip and/or palate, this is not consistently found in patients with monoallelic variants in FGFR3 gene. Hence, this gene should be rated amber.
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Classified gene: FGFR3 as Amber List (moderate evidence)
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three unrelated cases reported with cleft lip and/or palate, this is not consistently found in patients with monoallelic variants in FGFR3 gene. Hence, this gene should be rated amber.
Clefting v4.19 FGFR3 Achchuthan Shanmugasundram Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Classified gene: FGFR3 as Amber List (moderate evidence)
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three unrelated cases reported with cleft lip and/or palate, this is not consistently found in patients with monoallelic variants in FGFR3 gene. Hence, this gene should be rated amber.
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Classified gene: FGFR3 as Amber List (moderate evidence)
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are more than three unrelated cases reported with cleft lip and/or palate, this is not consistently found in patients with monoallelic variants in FGFR3 gene. Hence, this gene should be rated amber.
Clefting v4.18 FGFR3 Achchuthan Shanmugasundram Gene: fgfr3 has been classified as Amber List (Moderate Evidence).
Clefting v4.17 FGFR3 Achchuthan Shanmugasundram gene: FGFR3 was added
gene: FGFR3 was added to Clefting. Sources: Literature
Mode of inheritance for gene: FGFR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR3 were set to 22565872; 29150894; 37010288
Phenotypes for gene: FGFR3 were set to Muenke syndrome, OMIM:602849; Hypochondroplasia, OMIM:146000
Review for gene: FGFR3 was set to AMBER
Added comment: PMID:22565872 included 21 patients with variants in FGFR3 and presenting with Muenke syndrome in this study, of which 16 patients had structural anomaly of the palate. However, only one patient had cleft lip and palate.

PMID:29150894 reported a father and two children with FGFR3 variant and presenting with hypochondroplasia, of which only the daughter had cleft palate.

2 out of 15 patients reported in DECIPHER database with monoallelic sequence variants had cleft palate.
Sources: Literature
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram changed review comment from: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one patient reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature; to: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one patient reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram changed review comment from: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - A patient with compound heterozygous stop gain variants in CNTNAP1 gene (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature; to: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one patient reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram changed review comment from: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - Of seven patients reported with biallelic variants in CNTNAP1 gene, single patient with compound heterozygous stop gain variants (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature; to: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - A patient with compound heterozygous stop gain variants in CNTNAP1 gene (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram edited their review of gene: CNTNAP1: Changed rating: GREEN
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram changed review comment from: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one patient reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature; to: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - Of seven patients reported with biallelic variants in CNTNAP1 gene, single patient with compound heterozygous stop gain variants (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature
Clefting v4.16 CNTNAP1 Achchuthan Shanmugasundram edited their review of gene: CNTNAP1: Changed rating: AMBER
Clefting v4.16 ARID1B Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although there are three unrelated cases reported, clefting is not consistently present in patients with monoallelic variants in this gene. Hence, this gene should be rated amber.; to: Comment on list classification: Although there are more than three unrelated cases reported, clefting is not consistently present in patients with monoallelic variants in this gene. Hence, this gene should be rated amber.
Clefting v4.16 ARID1B Achchuthan Shanmugasundram changed review comment from: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

One patient with ARID1B variant (c.3183_3184​insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients with ARID1B variants (c.4155_4156​insA/ p.Asn1386LysfsTer18 & c.2620+5G​>A) were reported with bifid uvula in DECIPHER database.
Sources: Literature; to: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

Of >100 patients with ARID1B variants in the DECIPHER database, only one patient (c.3183_3184​insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients (c.4155_4156​insA/ p.Asn1386LysfsTer18 & c.2620+5G​>A) were reported with bifid uvula.
Sources: Literature
Clefting v4.16 ARID1B Achchuthan Shanmugasundram Classified gene: ARID1B as Amber List (moderate evidence)
Clefting v4.16 ARID1B Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are three unrelated cases reported, clefting is not consistently present in patients with monoallelic variants in this gene. Hence, this gene should be rated amber.
Clefting v4.16 ARID1B Achchuthan Shanmugasundram Gene: arid1b has been classified as Amber List (Moderate Evidence).
Clefting v4.15 ARID1B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ARID1B.
Clefting v4.15 ARID1B Achchuthan Shanmugasundram Deleted their comment
Clefting v4.15 ARID1B Achchuthan Shanmugasundram edited their review of gene: ARID1B: Changed rating: AMBER
Clefting v4.15 CHD4 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.15 CHD4 Achchuthan Shanmugasundram Classified gene: CHD4 as Amber List (moderate evidence)
Clefting v4.15 CHD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are four unrelated cases presenting with either cleft palate and/or bifid uvula, this phenotype is not consistently found in patients with monoallelic CHD4 variants. Hence, this gene should be rated amber.
Clefting v4.15 CHD4 Achchuthan Shanmugasundram Gene: chd4 has been classified as Amber List (Moderate Evidence).
Clefting v4.14 CHD4 Achchuthan Shanmugasundram Classified gene: CHD4 as Amber List (moderate evidence)
Clefting v4.14 CHD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are four unrelated cases presenting with either cleft palate and/or bifid uvula, this phenotype is not consistently found in patients with monoallelic CHD4 variants. Hence, this gene should be rated amber.
Clefting v4.14 CHD4 Achchuthan Shanmugasundram Gene: chd4 has been classified as Amber List (Moderate Evidence).
Clefting v4.13 CHD4 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.13 CHD4 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CHD4.
Clefting v4.13 CHD4 Achchuthan Shanmugasundram edited their review of gene: CHD4: Changed rating: AMBER
Clefting v4.13 CHD4 Achchuthan Shanmugasundram changed review comment from: PMID:31388190 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Literature; to: PMID:31388190 reported 32 patients with heterozygous variants in CHD4 gene, of which one patient (p.Gln715Ter) had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, 2 out of 10 patients with pathogenic/ likely pathogenic heterozygous variants from the DDD study were reported with cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Literature
Clefting v4.13 CHD4 Achchuthan Shanmugasundram changed review comment from: PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Literature; to: PMID:31388190 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Literature
Clefting v4.13 B4GALT7 Achchuthan Shanmugasundram Publications for gene: B4GALT7 were set to 24755949
Clefting v4.12 B4GALT7 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: B4GALT7.
Clefting v4.12 B4GALT7 Achchuthan Shanmugasundram changed review comment from: PMID:24755949 - One of 22 patients identified with homozygous p.Arg270Cys variant in B4GALT7 gene had a cleft palate.
PMID:26940150 - One of two patients reported in this publication from DDD study with compound heterozygous variants (p.His93Profds*73 & p.Cys2145Tyr) had cleft palate.
PMID:31278392 - One patient and affected third pregnancy with compound heterozygous variants (p.Gln133Arg & p.Arg270Cys) and cleft palate was reported in this family.; to: Cleft palate is not a consistent feature that is reported in patients with biallelic variants in B4GALT7 gene. However, there are three unrelated cases reported with cleft palate.

PMID:24755949 - One of 22 patients identified with homozygous p.Arg270Cys variant in B4GALT7 gene had a cleft palate.
PMID:26940150 - One of two patients reported in this publication from DDD study with compound heterozygous variants (p.His93Profds*73 & p.Cys2145Tyr) had cleft palate.
PMID:31278392 - One patient and affected third pregnancy with compound heterozygous variants (p.Gln133Arg & p.Arg270Cys) and cleft palate was reported in this family.
Clefting v4.12 B4GALT7 Achchuthan Shanmugasundram edited their review of gene: B4GALT7: Changed rating: AMBER
Clefting v4.12 B4GALT7 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.12 B4GALT7 Achchuthan Shanmugasundram changed review comment from: PMID:24755949 - One of 22 patients identified with with homozygous p.Arg270Cys variant in B4GALT7 gene had a cleft palate.
PMID:26940150 - One of two patients reported in this publication from DDD study with compound heterozygous variants (p.His93Profds*73 & p.Cys2145Tyr) had cleft palate.
PMID:31278392 - One patient and affected third pregnancy with compound heterozygous variants (p.Gln133Arg & p.Arg270Cys) and cleft palate was reported in this family.; to: PMID:24755949 - One of 22 patients identified with homozygous p.Arg270Cys variant in B4GALT7 gene had a cleft palate.
PMID:26940150 - One of two patients reported in this publication from DDD study with compound heterozygous variants (p.His93Profds*73 & p.Cys2145Tyr) had cleft palate.
PMID:31278392 - One patient and affected third pregnancy with compound heterozygous variants (p.Gln133Arg & p.Arg270Cys) and cleft palate was reported in this family.
Clefting v4.12 DDX3X Achchuthan Shanmugasundram changed review comment from: PMID:26235985 - Patients with DDX3X variants reported from multiple studies including the Deciphering Developmental Disorders (DDD) study, of which three females had cleft lip and/ or palate (one from the DDD study) and one male had bifid uvula.

PMID:27159028 - A female patient with DDX3X variant (c.856G>A/ p.Gly286Ser) and reported with severe ID and ataxic gait also had cleft uvula.; to: PMID:26235985 - 38 female and three male patients with DDX3X variants were reported from multiple studies including the Deciphering Developmental Disorders (DDD) study, of which three females had cleft lip and/ or palate (one from the DDD study) and one male had bifid uvula.

PMID:27159028 - Two female patients were reported with DDX3X variants, of which one of them reported with severe ID and ataxic gait (c.856G>A/ p.Gly286Ser) also had cleft uvula.
Clefting v4.12 DDX3X Achchuthan Shanmugasundram edited their review of gene: DDX3X: Changed rating: AMBER
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Deleted their comment
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DDX3X.
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Deleted their comment
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Classified gene: DDX3X as Amber List (moderate evidence)
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated cases associating this gene with cleft lip and/ or palate. Hence, this gene can be promoted to green rating at the next major update.
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Gene: ddx3x has been classified as Amber List (Moderate Evidence).
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Classified gene: DDX3X as Amber List (moderate evidence)
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated cases associating this gene with cleft lip and/ or palate. Hence, this gene can be promoted to green rating at the next major update.
Clefting v4.12 DDX3X Achchuthan Shanmugasundram Gene: ddx3x has been classified as Amber List (Moderate Evidence).
Clefting v4.11 DDX3X Achchuthan Shanmugasundram Publications for gene: DDX3X were set to 26235985; 27159028; 37010288
Clefting v4.11 DDX3X Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DDX3X.
Clefting v4.11 DDX3X Achchuthan Shanmugasundram Publications for gene: DDX3X were set to 26235985; 27159028; 37010288
Clefting v4.11 DDX3X Achchuthan Shanmugasundram Publications for gene: DDX3X were set to 26235985; 27159028; 37010288
Clefting v4.11 DDX3X Achchuthan Shanmugasundram Publications for gene: DDX3X were set to
Clefting v4.10 DDX3X Achchuthan Shanmugasundram reviewed gene: DDX3X: Rating: GREEN; Mode of pathogenicity: None; Publications: 26235985, 27159028, 37010288; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v4.10 CNTNAP1 Achchuthan Shanmugasundram Classified gene: CNTNAP1 as Amber List (moderate evidence)
Clefting v4.10 CNTNAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) for the association of biallelic variants from this gene with cleft palate. Hence, it can be promoted to green rating at the next major update.
Clefting v4.10 CNTNAP1 Achchuthan Shanmugasundram Gene: cntnap1 has been classified as Amber List (Moderate Evidence).
Clefting v4.9 CNTNAP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: CNTNAP1.
Clefting v4.9 CNTNAP1 Achchuthan Shanmugasundram gene: CNTNAP1 was added
gene: CNTNAP1 was added to Clefting. Sources: Literature
Mode of inheritance for gene: CNTNAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTNAP1 were set to 28374019; 29511323; 29882456; 37010288
Phenotypes for gene: CNTNAP1 were set to Hypomyelinating neuropathy, congenital, 3, OMIM:618186
Review for gene: CNTNAP1 was set to GREEN
Added comment: PMID:28374019 - Cleft palate was reported in two children from a large Israeli consanguineous family of Palestinian ancestry with a homozygous stop-gain variant in CNTNAP1(c.2015G>A/ p.Trp672Ter).

PMID:29511323/ 37010288 - There is one patient reported with compound heterozygous stop gain variants in CNTNAP1 (c.2687G​>A/ p.Trp896Ter & c.1861C​>T/ p.Arg621Ter) had cleft palate from DECIPHER database.

PMID:29882456 - An eight year old American male patient with a homozygous CNTNAP1 variant (c.1163G>C/ p.Arg388Pro) had cleft palate.
Sources: Literature
Clefting v4.8 ARID1B Achchuthan Shanmugasundram Classified gene: ARID1B as Amber List (moderate evidence)
Clefting v4.8 ARID1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least three unrelated cases) for this gene to be promoted to green rating at the next major review.
Clefting v4.8 ARID1B Achchuthan Shanmugasundram Gene: arid1b has been classified as Amber List (Moderate Evidence).
Clefting v4.7 ARID1B Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: ARID1B.
Clefting v4.7 ARID1B Achchuthan Shanmugasundram edited their review of gene: ARID1B: Changed rating: GREEN
Clefting v4.7 ARID1B Achchuthan Shanmugasundram changed review comment from: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

One patient was reported with submucous cleft soft palate and two patients were reported with bifid uvula in DECIPHER database.
Sources: Literature; to: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

One patient with ARID1B variant (c.3183_3184​insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients with ARID1B variants (c.4155_4156​insA/ p.Asn1386LysfsTer18 & c.2620+5G​>A) were reported with bifid uvula in DECIPHER database.
Sources: Literature
Clefting v4.7 ARID1B Achchuthan Shanmugasundram changed review comment from: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

There is only one patient reported with pathogenic variant in ARID1B gene and submucous cleft soft palate in DECIPHER database.
Sources: Literature; to: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

One patient was reported with submucous cleft soft palate and two patients were reported with bifid uvula in DECIPHER database.
Sources: Literature
Clefting v4.7 ARID1B Achchuthan Shanmugasundram gene: ARID1B was added
gene: ARID1B was added to Clefting. Sources: Literature
Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1B were set to 30349098; 37010288
Phenotypes for gene: ARID1B were set to Coffin-Siris syndrome 1, OMIM:135900
Review for gene: ARID1B was set to AMBER
Added comment: PMID:30349098 - On this web-based survey based on previously reported features of patients with variants in ARID1B gene (143 patients in total), which also included submissions to DECIPHER database, two patients were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available.

There is only one patient reported with pathogenic variant in ARID1B gene and submucous cleft soft palate in DECIPHER database.
Sources: Literature
Clefting v4.6 CHD4 Achchuthan Shanmugasundram changed review comment from: PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288)
Sources: Literature; to: PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Sources: Literature
Clefting v4.6 CHD4 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: CHD4.
Clefting v4.6 CHD4 Achchuthan Shanmugasundram Classified gene: CHD4 as Amber List (moderate evidence)
Clefting v4.6 CHD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases presenting with either cleft palate and/or bifid uvula. Hence, this gene can be promoted to green at the next major review.
Clefting v4.6 CHD4 Achchuthan Shanmugasundram Gene: chd4 has been classified as Amber List (Moderate Evidence).
Clefting v4.5 CHD4 Achchuthan Shanmugasundram gene: CHD4 was added
gene: CHD4 was added to Clefting. Sources: Literature
Mode of inheritance for gene: CHD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD4 were set to 31388190; 37010288
Phenotypes for gene: CHD4 were set to Sifrim-Hitz-Weiss syndrome, OMIM:617159
Review for gene: CHD4 was set to GREEN
Added comment: PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288)
Sources: Literature
Clefting v4.4 B4GALT7 Achchuthan Shanmugasundram Deleted their comment
Clefting v4.4 B4GALT7 Achchuthan Shanmugasundram Classified gene: B4GALT7 as Amber List (moderate evidence)
Clefting v4.4 B4GALT7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) for this gene to be promoted to Green rating at the next major review.
Clefting v4.4 B4GALT7 Achchuthan Shanmugasundram Gene: b4galt7 has been classified as Amber List (Moderate Evidence).
Clefting v4.3 B4GALT7 Achchuthan Shanmugasundram Classified gene: B4GALT7 as Amber List (moderate evidence)
Clefting v4.3 B4GALT7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) for this gene to be promoted to Green rating at the next major review.
Clefting v4.3 B4GALT7 Achchuthan Shanmugasundram Gene: b4galt7 has been classified as Amber List (Moderate Evidence).
Clefting v4.2 B4GALT7 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: B4GALT7.
Clefting v4.2 B4GALT7 Achchuthan Shanmugasundram reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: 24755949, 26940150, 31278392; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, OMIM:130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v4.2 UQCC2 Arina Puzriakova Phenotypes for gene: UQCC2 were changed from MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 7; MC3DN7 to Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824
Clefting v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Clefting v4.0 Arina Puzriakova promoted panel to version 4.0
Clefting v3.9 TBX1 Arina Puzriakova Classified gene: TBX1 as Amber List (moderate evidence)
Clefting v3.9 TBX1 Arina Puzriakova Added comment: Comment on list classification: Following consultation with Helen Brittain (Genomics England Clinical Team) it was agreed that there is sufficient evidence to promote this gene to Green on this panel (at least three cases of palatal involvement) at the next GMS panel update.
Clefting v3.9 TBX1 Arina Puzriakova Gene: tbx1 has been classified as Amber List (Moderate Evidence).
Clefting v3.8 TBX1 Arina Puzriakova Phenotypes for gene: TBX1 were changed from CONOTRUNCAL HEART MALFORMATIONS; CTHM; Cleft palate to DiGeorge syndrome, OMIM:188400; Conotruncal anomaly face syndrome, OMIM:217095; Velocardiofacial syndrome, OMIM:192430
Clefting v3.7 TBX1 Arina Puzriakova Publications for gene: TBX1 were set to
Clefting v3.6 TBX1 Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: TBX1.
Clefting v3.6 TBX1 Arina Puzriakova reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14585638, 17273972, 30137364; Phenotypes: DiGeorge syndrome, OMIM:188400, Conotruncal anomaly face syndrome, OMIM:217095, Velocardiofacial syndrome, OMIM:192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v3.6 MED12 Eleanor Williams commented on gene: MED12: The mode of inheritance has been left as 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' with agreement from the Genomics Unit at NHSE.
Clefting v3.6 ISCA-46303-Loss Arina Puzriakova reviewed Region: ISCA-46303-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Clefting v3.6 ISCA-37423-Gain Arina Puzriakova edited their review of Region: ISCA-37423-Gain: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates and triplosensitivity score (from 3 to 2) of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022). Regardless of the change in triplosensitivity score, it was deemed appropriate for this regions to remain green as evidence to support pathogenicity remains.; Changed rating: GREEN
Clefting v3.6 ISCA-46303-Loss Arina Puzriakova Region: ISCA-46303-Loss was added
Region: ISCA-46303-Loss was added to Clefting. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46303-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46303-Loss were set to 24934569; 26663529; 19234473
Clefting v3.6 ISCA-37423-Gain Arina Puzriakova GRCh38 position for ISCA-37423-Gain was changed from 8261773-11908210 to 8242542-11908820.
Triplosensitivity Score for ISCA-37423-Gain was changed from 3 to 2.
Clefting v3.5 MED12 Achchuthan Shanmugasundram Tag Q3_21_MOI was removed from gene: MED12.
Clefting v3.5 SF3B2 Achchuthan Shanmugasundram Tag Q4_21_rating was removed from gene: SF3B2.
Clefting v3.5 PLCB4 Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: PLCB4.
Clefting v3.5 GDF11 Achchuthan Shanmugasundram Tag Q4_21_rating was removed from gene: GDF11.
Clefting v3.5 SEPT9 Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: SEPT9.
Clefting v3.5 MED12 Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: MED12.
Tag Q3_21_expert_review was removed from gene: MED12.
Clefting v3.5 SF3B2 Achchuthan Shanmugasundram reviewed gene: SF3B2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v3.5 PLCB4 Achchuthan Shanmugasundram reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v3.5 GDF11 Achchuthan Shanmugasundram reviewed gene: GDF11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v3.5 SEPT9 Achchuthan Shanmugasundram reviewed gene: SEPT9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v3.5 MED12 Achchuthan Shanmugasundram reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v3.4 SF3B2 Achchuthan Shanmugasundram Source NHS GMS was added to SF3B2.
Source Expert Review Green was added to SF3B2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v3.4 SEPT9 Achchuthan Shanmugasundram Source Expert Review Amber was added to SEPT9.
Source NHS GMS was added to SEPT9.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Clefting v3.4 PLCB4 Achchuthan Shanmugasundram Source NHS GMS was added to PLCB4.
Source Expert Review Green was added to PLCB4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v3.4 MED12 Achchuthan Shanmugasundram Source NHS GMS was added to MED12.
Source Expert Review Green was added to MED12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v3.4 GDF11 Achchuthan Shanmugasundram Source NHS GMS was added to GDF11.
Source Expert Review Green was added to GDF11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v3.3 DDX3X Arina Puzriakova Phenotypes for gene: DDX3X were changed from MENTAL RETARDATION, X-LINKED 102; MRX102 to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958
Clefting v3.2 MYCN Achchuthan Shanmugasundram gene: MYCN was added
gene: MYCN was added to Clefting. Sources: Literature
Mode of inheritance for gene: MYCN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYCN were set to 34590686
Phenotypes for gene: MYCN were set to Cleft lip with or without cleft palate, MONDO:0016034
Review for gene: MYCN was set to RED
Added comment: Comment on classification of this gene: This gene has been added with a RED rating to this panel, as identified from one case and supported by functional studies with mouse model.

Out of the 104 multiplex families with Mendelian non-syndromic cleft lip with or without cleft palate (NSCL/P), a novel pathogenic variant (c.703G>C/ p.A235P) has been identified in MYCN gene from one family. This variant was found in the proband and his affected mother and absent in the unaffected sister, showing co-segregation with phenotype in this family.

In addition, experimental evidence from conditional knockout mouse model showed that these mice displayed cleft palate, microglossia and micrognathia, resembling the Pierre Robin sequence (PRS) in humans.

This gene has not yet been associated with clefting either in OMIM or in Gene2Phenotype.
Sources: Literature
Clefting v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Clefting v3.0 Arina Puzriakova promoted panel to version 3.0
Clefting v2.73 RAD21 Arina Puzriakova Classified gene: RAD21 as Amber List (moderate evidence)
Clefting v2.73 RAD21 Arina Puzriakova Gene: rad21 has been classified as Amber List (Moderate Evidence).
Clefting v2.72 RAD21 Arina Puzriakova gene: RAD21 was added
gene: RAD21 was added to Clefting. Sources: Literature
Q4_22_promote_green tags were added to gene: RAD21.
Mode of inheritance for gene: RAD21 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAD21 were set to 22633399; 27882533; 31334757; 32193685
Phenotypes for gene: RAD21 were set to Cornelia de Lange syndrome 4, OMIM:614701
Review for gene: RAD21 was set to GREEN
Added comment: At least 33 unrelated families published with RAD21 alterations. Of these, 6 cases presented with cleft palate or submucous cleft palate. Although only displayed by a subset of patients, clefting is a congenital anomaly that may aid earlier diagnosis if other features such as ID have not yet become apparent. Therefore there would be value in including RAD21 on this panel with a Green rating.
Sources: Literature
Clefting v2.71 ROR2 Arina Puzriakova Phenotypes for gene: ROR2 were changed from ROBINOW SYNDROME, AUTOSOMAL RECESSIVE; RRS to Robinow syndrome, autosomal recessive, OMIM:268310
Clefting v2.70 ISCA-37423-Gain Arina Puzriakova edited their review of Region: ISCA-37423-Gain: Added comment: Only two cases with clefting have been reported to date. Following consultation with Clinical team, decided to maintain Green rating as CNVs with variable penetrance are reported in clinical practice and can be relevant diagnostically; however, adding watchlist tag to monitor for clear evidence of particularly reduced penetrance at which stage the rating may be reviewed.; Changed phenotypes to: 26097203
Clefting v2.70 ISCA-37423-Gain Arina Puzriakova Tag watchlist tag was added to Region: ISCA-37423-Gain.
Clefting v2.70 MED13L Arina Puzriakova Phenotypes for gene: MED13L were changed from Mental retardation and distinctive facial features with or without cardiac defects, 616789; MRFACD; Cleft palate to Impaired intellectual development and distinctive facial features with or without cardiac defects, OMIM:616789; MRFACD; Cleft palate
Clefting v2.69 POLR1D Arina Puzriakova commented on gene: POLR1D
Clefting v2.69 COL2A1 Arina Puzriakova commented on gene: COL2A1
Clefting v2.69 COL11A2 Arina Puzriakova commented on gene: COL11A2
Clefting v2.69 COL11A1 Arina Puzriakova commented on gene: COL11A1
Clefting v2.68 PLCB4 Eleanor Williams Tag Q2_22_rating tag was added to gene: PLCB4.
Clefting v2.68 PLCB4 Eleanor Williams edited their review of gene: PLCB4: Added comment: PMID: 28328130 - Romanelli-Tavares et al 2017 - report 2 patients (1 sporadic, 1 familial) with previous published phenotypic descriptions of Auriculocondylar syndrome in which heterozygous missense variants were found in PLCB4 after sequencing PLCB4, GNAI3,and EDN1. Cleft palate was noted in 2/7 members of the familial case.

This is a 3rd case in which cleft palate is reported in association with PLCB4 variants and therefore there is sufficient evidence to promote this gene to green following GMS review.; Changed rating: GREEN; Changed publications to: 28328130
Clefting v2.68 PLCB4 Eleanor Williams Publications for gene: PLCB4 were set to 16114046; 32201334; 27007857; 23913798; 2560091; 23315542
Clefting v2.67 IMPAD1 Arina Puzriakova commented on gene: IMPAD1
Clefting v2.67 IMPAD1 Arina Puzriakova Tag new-gene-name tag was added to gene: IMPAD1.
Clefting v2.67 HYAL2 Arina Puzriakova Tag gene-checked tag was added to gene: HYAL2.
Clefting v2.67 ARHGAP29 Sarah Leigh Tag gene-checked tag was added to gene: ARHGAP29.
Clefting v2.67 MSX1 Arina Puzriakova Phenotypes for gene: MSX1 were changed from Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600; CLP with dental anomalies; Cleft lip to Orofacial cleft 5, OMIM:608874; Tooth agenesis, selective, 1, with or without orofacial cleft, OMIM:106600
Clefting v2.66 ISCA-37423-Gain Arina Puzriakova commented on Region: ISCA-37423-Gain
Clefting v2.66 ISCA-37467-Gain Arina Puzriakova commented on Region: ISCA-37467-Gain
Clefting v2.66 ISCA-37446-Loss Eleanor Williams commented on Region: ISCA-37446-Loss
Clefting v2.66 ISCA-37433-Loss Arina Puzriakova commented on Region: ISCA-37433-Loss
Clefting v2.66 ISCA-37393-Gain Ivone Leong commented on Region: ISCA-37393-Gain
Clefting v2.66 ISCA-37423-Gain Arina Puzriakova Required Overlap Percentage for ISCA-37423-Gain was changed from 80 to 60.
Clefting v2.66 ISCA-37467-Gain Arina Puzriakova Required Overlap Percentage for ISCA-37467-Gain was changed from 80 to 60.
Clefting v2.66 ISCA-37393-Gain Arina Puzriakova Required Overlap Percentage for ISCA-37393-Gain was changed from 80 to 60.
Clefting v2.66 ISCA-37446-Loss Arina Puzriakova GRCh38 position for ISCA-37446-Loss was changed from 18924718-21111384 to 18924718-21111383.
Required Overlap Percentage for ISCA-37446-Loss was changed from 80 to 60.
Clefting v2.66 ISCA-37433-Loss Arina Puzriakova GRCh38 position for ISCA-37433-Loss was changed from 18924718-20299686 to 18924718-20299685.
Required Overlap Percentage for ISCA-37433-Loss was changed from 80 to 60.
Clefting v2.65 POLR1D Eleanor Williams commented on gene: POLR1D
Clefting v2.65 COL2A1 Eleanor Williams commented on gene: COL2A1
Clefting v2.65 COL11A2 Eleanor Williams commented on gene: COL11A2
Clefting v2.65 COL11A1 Eleanor Williams commented on gene: COL11A1
Clefting v2.64 POLR1D Eleanor Williams Mode of inheritance for gene POLR1D was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting v2.64 COL2A1 Eleanor Williams Mode of inheritance for gene COL2A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting v2.64 COL11A2 Eleanor Williams Mode of inheritance for gene COL11A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting v2.64 COL11A1 Eleanor Williams Mode of inheritance for gene COL11A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting v2.63 POLR1B Eleanor Williams Tag for-review was removed from gene: POLR1B.
Clefting v2.63 MED25 Eleanor Williams Tag for-review was removed from gene: MED25.
Clefting v2.63 HYAL2 Eleanor Williams Tag for-review was removed from gene: HYAL2.
Clefting v2.63 MAPRE2 Eleanor Williams commented on gene: MAPRE2
Clefting v2.63 POLR1B Eleanor Williams commented on gene: POLR1B: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Clefting v2.63 MED25 Eleanor Williams commented on gene: MED25: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Clefting v2.63 HYAL2 Eleanor Williams commented on gene: HYAL2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Clefting v2.62 MAPRE2 Eleanor Williams Source Expert list was added to MAPRE2.
Clefting v2.62 POLR1B Eleanor Williams Source Expert Review Green was added to POLR1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v2.62 MED25 Eleanor Williams Source Expert Review Green was added to MED25.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v2.62 HYAL2 Eleanor Williams Source Expert Review Green was added to HYAL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v2.61 POLR1D Arina Puzriakova Phenotypes for gene: POLR1D were changed from TREACHER COLLINS SYNDROME 2; TCS2 to Treacher Collins syndrome 2, OMIM:613717
Clefting v2.60 COL9A2 Arina Puzriakova Phenotypes for gene: COL9A2 were changed from ?Stickler syndrome type V, 614284; Orofacial Clefting with skeletal features; Stickler syndrome; Cleft palate to Stickler syndrome, type V, OMIM:614284
Clefting v2.59 COL9A1 Arina Puzriakova Phenotypes for gene: COL9A1 were changed from Stickler syndrome, type IV (ophthalmological: myopia, retinal detachment and cataracts, orofacial: micrognathia, midface hypoplasia and cleft palate, auditory:sensorineural hearing loss and articular: epiphyseal dysplasia) symptoms; Autosomal recessive Stickler syndrome; Orofacial Clefting with skeletal features; Cleft palate to Stickler syndrome, type IV, OMIM:614134
Clefting v2.58 COL11A1 Arina Puzriakova Phenotypes for gene: COL11A1 were changed from Orofacial Clefting with skeletal features; Stickler Syndrome; Cleft palate to Marshall Syndrome, OMIM:154780; Stickler syndrome, type II, OMIM:604841
Clefting v2.57 SCUBE3 Sarah Leigh Phenotypes for gene: SCUBE3 were changed from Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies OMIM:619184 to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies OMIM:619184; short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2 MONDO:0030953
Clefting v2.56 SCUBE3 Sarah Leigh Deleted their comment
Clefting v2.56 SCUBE3 Sarah Leigh edited their review of gene: SCUBE3: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. PMID 33308444 reports eight SCUBE variants in nine unrelated families, including eighteen affected members. In vtro studies demonstrated a variable impact of disease-causing variants on transcript processing, protein secretion and function, resulting in dysregulation on bone morphogenetic protein (BMP) signaling and a Scube3−/− mouse showed shared phenotypic features with OMIM:619184. Clefting was evident in 3/14 cases examined.; Changed rating: AMBER
Clefting v2.56 SCUBE3 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. PMID 33308444 reports eight SCUBE variants in nine unrelated families, including eighteen affected members. In vtro studies demonstrated a variable impact of disease-causing variants on transcript processing, protein secretion and function, resulting in dysregulation on bone morphogenetic protein (BMP) signaling and a Scube3−/− mouse showed shared phenotypic features with OMIM:619184. Clefting was evident in 3/14 cases examined; to: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. PMID 33308444 reports eight SCUBE variants in nine unrelated families, including eighteen affected members. In vtro studies demonstrated a variable impact of disease-causing variants on transcript processing, protein secretion and function, resulting in dysregulation on bone morphogenetic protein (BMP) signaling and a Scube3−/− mouse showed shared phenotypic features with OMIM:619184. Clefting was evident in 3/14 cases examined.
Clefting v2.56 SCUBE3 Sarah Leigh Deleted their comment
Clefting v2.56 SCUBE3 Sarah Leigh Tag Q2_21_rating was removed from gene: SCUBE3.
Clefting v2.56 SCUBE3 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 5 variants reported in 5 unrelated cases, together with supportive functional and mouse model studies (PMID 33308444).; to: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. PMID 33308444 reports eight SCUBE variants in nine unrelated families, including eighteen affected members. In vtro studies demonstrated a variable impact of disease-causing variants on transcript processing, protein secretion and function, resulting in dysregulation on bone morphogenetic protein (BMP) signaling and a Scube3−/− mouse showed shared phenotypic features with OMIM:619184. Clefting was evident in 3/14 cases examined
Clefting v2.56 SCUBE3 Sarah Leigh Entity copied from Skeletal dysplasia v2.136
Clefting v2.56 SCUBE3 Sarah Leigh gene: SCUBE3 was added
gene: SCUBE3 was added to Clefting. Sources: Expert Review Amber,Other
Q2_21_rating tags were added to gene: SCUBE3.
Mode of inheritance for gene: SCUBE3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCUBE3 were set to 33308444
Phenotypes for gene: SCUBE3 were set to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies OMIM:619184
Penetrance for gene: SCUBE3 were set to unknown
Clefting v2.55 BMP2 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the mode of inheritance as monoallelic. OMIM also reports the biallelic phenotype of {HFE hemochromatosis, modifier of} but this is not relevant to this panel.
Clefting v2.55 BMP2 Eleanor Williams Mode of inheritance for gene: BMP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v2.54 GDF11 Eleanor Williams Classified gene: GDF11 as Amber List (moderate evidence)
Clefting v2.54 GDF11 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber but with a recommendation for green rating following GMS review. 2 cases plus mouse model data.
Clefting v2.54 GDF11 Eleanor Williams Gene: gdf11 has been classified as Amber List (Moderate Evidence).
Clefting v2.53 GDF11 Eleanor Williams Phenotypes for gene: GDF11 were changed from Vertebral hypersegmentation and orofacial anomalies (VHO), OMIM #619122 to Vertebral hypersegmentation and orofacial anomalies (VHO), OMIM:619122
Clefting v2.52 GDF11 Eleanor Williams Publications for gene: GDF11 were set to 31215115; 34113007
Clefting v2.51 GDF11 Eleanor Williams Tag Q4_21_rating tag was added to gene: GDF11.
Clefting v2.51 GDF11 Eleanor Williams reviewed gene: GDF11: Rating: ; Mode of pathogenicity: None; Publications: 3411300, 31215115, 10391213; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v2.51 GDF11 Zornitza Stark gene: GDF11 was added
gene: GDF11 was added to Clefting. Sources: Literature
Mode of inheritance for gene: GDF11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GDF11 were set to 31215115; 34113007
Phenotypes for gene: GDF11 were set to Vertebral hypersegmentation and orofacial anomalies (VHO), OMIM #619122
Review for gene: GDF11 was set to GREEN
Added comment: PMID 34113007: Ravenscroft et al. (2021) report 6 probands who presented with craniofacial (5/6), vertebral (5/6), neurological (6/6), visual (4/6), cardiac (3/6), auditory (3/6), and connective tissue abnormalities (3/6). They found de novo and inherited variants in GDF11. gdf11 mutant zebrafish showed craniofacial abnormalities and body segmentation defects that matched some patient phenotypes. Expression of the patients’ variants in the fly showed that one nonsense variant in GDF11 is a severe loss-of-function (LOF) allele whereas the missense variants are partial LOF variants.

PMID 31215115: In 5 affected members over 3 generations of a family segregating vertebral hypersegmentation and orofacial anomalies, Cox et al. (2019) identified heterozygosity for a missense mutation in the GDF11 gene (R298Q) that was not found in unaffected family members or in public variant databases. Functional analysis demonstrated that the R298Q substitution prevents cleavage to the active form of the protein, resulting in loss of function.
Sources: Literature
Clefting v2.51 SF3B2 Eleanor Williams Classified gene: SF3B2 as Amber List (moderate evidence)
Clefting v2.51 SF3B2 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber but with a green recommendation following GMS review. 4 families reported in which lateral oral clefting is part of the phenotype. Supportive Xenopus data.
Clefting v2.51 SF3B2 Eleanor Williams Gene: sf3b2 has been classified as Amber List (Moderate Evidence).
Clefting v2.50 SF3B2 Eleanor Williams Tag Q4_21_rating tag was added to gene: SF3B2.
Clefting v2.50 SF3B2 Eleanor Williams commented on gene: SF3B2
Clefting v2.50 MED12 Eleanor Williams Tag Q3_21_MOI tag was added to gene: MED12.
Clefting v2.50 MED12 Eleanor Williams Tag Skewed X-inactivation tag was added to gene: MED12.
Clefting v2.50 MED12 Eleanor Williams Added comment: Comment on mode of inheritance: X-linked hemizygous mutation in males, monoallelic mutations in females is the appropriate mode of inheritance for Hardikar syndrome but there are carrier implications for the male-only phenotypes associated with this gene (e.g. Lujan-Fryns syndrome, Ohdo syndrome, X-linked and Opitz-Kaveggia syndrome) in female cases.
Clefting v2.50 MED12 Eleanor Williams Mode of inheritance for gene: MED12 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v2.49 MED12 Eleanor Williams Tag Q3_21_expert_review tag was added to gene: MED12.
Clefting v2.49 GNB1 Sarah Leigh Added comment: Comment on mode of pathogenicity: Gen2Phen entry for GNB1 (https://www.ebi.ac.uk/gene2phenotype/gfd?dbID=2121) lists the mutation consequence summary as Activating
Clefting v2.49 GNB1 Sarah Leigh Mode of pathogenicity for gene: GNB1 was changed from to Other
Clefting v2.48 GNB1 Sarah Leigh Phenotypes for gene: GNB1 were changed from Mental retardation, autosomal dominant 42, 616973 to Mental retardation, autosomal dominant 42 OMIM:616973; intellectual disability, autosomal dominant 42 MONDO:0014855
Clefting v2.47 GJA1 Arina Puzriakova Phenotypes for gene: GJA1 were changed from Oculodentodigital dysplasia,164200; ODDD to Oculodentodigital dysplasia, OMIM:164200
Clefting v2.46 SF3B2 Zornitza Stark gene: SF3B2 was added
gene: SF3B2 was added to Clefting. 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
gene: SF3B2 was marked as current diagnostic
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
Clefting v2.46 SF3B4 Zornitza Stark Deleted their review
Clefting v2.46 SF3B4 Zornitza Stark reviewed gene: SF3B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 34344887; Phenotypes: Craniofacial microsomia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v2.46 SEPT9 Eleanor Williams Classified gene: SEPT9 as Green List (high evidence)
Clefting v2.46 SEPT9 Eleanor Williams Added comment: Comment on list classification: There is only 1 report of clefting in a patient with a variant in SEPT9 and a diagnosis of HNA. Other reports of clefting are in patients in which the molecular cause of the disease were not established. Therefore, the recommendation is to demote this gene from green to amber following GMS review.
Clefting v2.46 SEPT9 Eleanor Williams Gene: sept9 has been classified as Green List (High Evidence).
Clefting v2.45 SEPT9 Eleanor Williams Publications for gene: SEPT9 were set to
Clefting v2.44 SEPT9 Eleanor Williams Tag Q3_21_rating tag was added to gene: SEPT9.
Clefting v2.44 SEPT9 Eleanor Williams reviewed gene: SEPT9: Rating: AMBER; Mode of pathogenicity: None; Publications: 11739810, 18492087, 30019529, 31619932, 28503616, 20019224, 19939853, 19451530, 19139049, 16186812; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v2.44 MED12 Eleanor Williams Phenotypes for gene: MED12 were changed from Lujan-Fryns syndrome, 309520; Opitz-Kaveggia syndrome, 305450; OKS; submucous cleft palate to Hardikar syndrome, OMIM:612726; cholestasis-pigmentary retinopathy-cleft palate syndrome, MONDO:0012997
Clefting v2.43 MED12 Eleanor Williams Publications for gene: MED12 were set to 12784307
Clefting v2.42 MED12 Eleanor Williams Mode of inheritance for gene: MED12 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v2.41 MED12 Eleanor Williams Classified gene: MED12 as Amber List (moderate evidence)
Clefting v2.41 MED12 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber with the recommendation of a green rating following GMS review. There are 7 reported cases with cleft lip/palate and a variant identified in MED12.
Clefting v2.41 MED12 Eleanor Williams Gene: med12 has been classified as Amber List (Moderate Evidence).
Clefting v2.40 MED12 Eleanor Williams Tag Q3_21_rating tag was added to gene: MED12.
Clefting v2.40 MED12 Eleanor Williams reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: 33244166; Phenotypes: Hardikar syndrome, OMIM:612726, cholestasis-pigmentary retinopathy-cleft palate syndrome, MONDO:0012997; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v2.40 ESCO2 Eleanor Williams Classified gene: ESCO2 as Green List (high evidence)
Clefting v2.40 ESCO2 Eleanor Williams Added comment: Comment on list classification: Leaving rating as green. Sufficient cases reported with clefting a feature in Roberts-SC phocomelia syndrome. Additionally 2 (likely founder) cases reported with clefting in probands with Juberg-Hayward syndrome.
Clefting v2.40 ESCO2 Eleanor Williams Gene: esco2 has been classified as Green List (High Evidence).
Clefting v2.39 ESCO2 Eleanor Williams Phenotypes for gene: ESCO2 were changed from ROBERTS SYNDROME; RBS, SC PHOCOMELIA SYNDROME to Roberts-SC phocomelia syndrome, OMIM:268300; Roberts-SC phocomelia syndrome, MONDO:0100253
Clefting v2.38 ESCO2 Eleanor Williams Publications for gene: ESCO2 were set to
Clefting v2.37 ESCO2 Eleanor Williams reviewed gene: ESCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32977150, 32255174, 15821733, 16380922, 18411254, 24864645; Phenotypes: Roberts-SC phocomelia syndrome, OMIM:268300, Roberts-SC phocomelia syndrome, MONDO:0100253; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v2.37 PLCB4 Eleanor Williams Phenotypes for gene: PLCB4 were changed from Cleft palate to Auriculocondylar syndrome 2, OMIM:614669; auriculocondylar syndrome 2, MONDO:0013845
Clefting v2.36 PLCB4 Eleanor Williams Publications for gene: PLCB4 were set to
Clefting v2.35 PLCB4 Eleanor Williams Mode of inheritance for gene: PLCB4 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting v2.34 PLCB4 Eleanor Williams Classified gene: PLCB4 as Amber List (moderate evidence)
Clefting v2.34 PLCB4 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber as there are two cases of auriculocondylar syndrome 2 associated with variants in this gene where cleft palate is part of the phenotype.
Clefting v2.34 PLCB4 Eleanor Williams Gene: plcb4 has been classified as Amber List (Moderate Evidence).
Clefting v2.33 PLCB4 Eleanor Williams edited their review of gene: PLCB4: Changed rating: AMBER; Changed publications to: 16114046, 32201334, 27007857, 23913798, 2560091, 23315542; Changed phenotypes to: Auriculocondylar syndrome 2, OMIM:614669, auriculocondylar syndrome 2, MONDO:0013845; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting v2.33 PLCB4 Eleanor Williams commented on gene: PLCB4
Clefting v2.33 FLNA Arina Puzriakova Phenotypes for gene: FLNA were changed from Orofacial Clefting with skeletal anomalies; Otopalatodigital syndrome, type I, 311300 (includes clefting); Otopalatodigital syndrome, type II, 304120 (includes clefting); Melnick-Needles syndrome, 309350 (includes clefting); OTOPALATODIGITAL SYNDROME, TYPE I; OPD1, OTOPALATODIGITAL SYNDROME, TYPE II; OPD2, FRONTOMETAPHYSEAL DYSPLASIA 1; FMD1 to Frontometaphyseal dysplasia 1, OMIM:305620; Melnick-Needles syndrome, OMIM:309350; Otopalatodigital syndrome, type I, OMIM:311300; Otopalatodigital syndrome, type II, OMIM:304120
Clefting v2.32 RERE Catherine Snow Classified gene: RERE as Amber List (moderate evidence)
Clefting v2.32 RERE Catherine Snow Gene: rere has been classified as Amber List (Moderate Evidence).
Clefting v2.31 RERE Catherine Snow gene: RERE was added
gene: RERE was added to Clefting. Sources: Literature
Mode of inheritance for gene: RERE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RERE were set to PMID: 33772547
Phenotypes for gene: RERE were set to clefting
Review for gene: RERE was set to AMBER
Added comment: Expansion of phenotype. RERE associated with neurodevelopmental disorder with or without anomalies of the brain, eye or heart (NEDBEH)
A pathogenic, de novo c.4313_4318dupTCCACC proband had cleft palate, incomplete penetrance as other individuals with NEDBEH and same variant (PMID: 27087320 PMID: 29330883) did not display clefting phenotype. There is functional support in mouse models as RERE-deficient embryos have cleft palate. Previously one patient (subject 7) with NEDBEH has been described to have a cleft lip (PMID: 27087320) Therefore rating as Amber
Sources: Literature
Clefting v2.30 TRAPPC9 Arina Puzriakova Publications for gene: TRAPPC9 were set to 20004764
Clefting v2.29 TRAPPC9 Arina Puzriakova Phenotypes for gene: TRAPPC9 were changed from MENTAL RETARDATION, AUTOSOMAL RECESSIVE 13; MRT13 to Mental retardation, autosomal recessive 13, OMIM:613192
Clefting v2.28 SEPT9 Zornitza Stark reviewed gene: SEPT9: Rating: AMBER; Mode of pathogenicity: None; Publications: 18492087; Phenotypes: Amyotrophy, hereditary neuralgic, MIM# 162100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting v2.28 ACBD5 Arina Puzriakova Classified gene: ACBD5 as Red List (low evidence)
Clefting v2.28 ACBD5 Arina Puzriakova Added comment: Comment on list classification: Only a single patient reported with a cleft palate to date, and therefore rating Red on this panel.
Clefting v2.28 ACBD5 Arina Puzriakova Gene: acbd5 has been classified as Red List (Low Evidence).
Clefting v2.27 ACBD5 Arina Puzriakova Phenotypes for gene: ACBD5 were changed from Cleft palate to Retinal dystrophy with leukodystrophy, OMIM:618863
Clefting v2.26 ACBD5 Arina Puzriakova Publications for gene: ACBD5 were set to
Clefting v2.25 ACBD5 Arina Puzriakova Mode of inheritance for gene: ACBD5 was changed from to BIALLELIC, autosomal or pseudoautosomal
Clefting v2.24 MED12 Zornitza Stark reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: 33244166; Phenotypes: Hardikar syndrome, OMIM #612726; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Clefting v2.24 ESCO2 Zornitza Stark reviewed gene: ESCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32977150; Phenotypes: Juberg-Hayward syndrome, MIM# 216100, Roberts-SC phocomelia syndrome, MIM#268300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v2.24 FSHMD1A Arina Puzriakova Tag curated_removed tag was added to gene: FSHMD1A.
Clefting v2.24 ACBD5 Zornitza Stark reviewed gene: ACBD5: Rating: RED; Mode of pathogenicity: None; Publications: 27799409, 23105016, 33427402; Phenotypes: Retinal dystrophy with leukodystrophy, MIM# 618863; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v2.24 MYMK Arina Puzriakova Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome 254940 to Carey-Fineman-Ziter syndrome, OMIM:254940; Carey-Fineman-Ziter syndrome, MONDO:0009700
Clefting v2.23 MEIS2 Arina Puzriakova Phenotypes for gene: MEIS2 were changed from Orofacial clefting; cardiac defects; intellectual disability; Cleft palate to Cleft palate, cardiac defects, and mental retardation, OMIM:600987; Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies, MONDO:0010970
Clefting v2.22 IFT52 Arina Puzriakova Phenotypes for gene: IFT52 were changed from SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY; SRTD16 to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Clefting v2.21 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia, 612651 (includes cleft lip, cleft palate); ECO to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Clefting v2.20 PLCB4 Zornitza Stark reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23315542; Phenotypes: Auriculocondylar syndrome 2, MIM# 614669; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting v2.20 HYAL2 Ivone Leong Tag for-review tag was added to gene: HYAL2.
Clefting v2.20 POLR1B Eleanor Williams changed review comment from: Comment on list classification: Promoting from red to amber but with green recommendation. 3 cases reported in which cleft palate was a feature.; to: Comment on list classification: Promoting from red to amber but with green recommendation following phenotype review by the GMS. 3 cases reported in which cleft palate was a feature.
Clefting v2.20 POLR1B Eleanor Williams Classified gene: POLR1B as Amber List (moderate evidence)
Clefting v2.20 POLR1B Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber but with green recommendation. 3 cases reported in which cleft palate was a feature.
Clefting v2.20 POLR1B Eleanor Williams Gene: polr1b has been classified as Amber List (Moderate Evidence).
Clefting v2.19 POLR1B Eleanor Williams Tag for-review tag was added to gene: POLR1B.
Clefting v2.19 POLR1B Eleanor Williams changed review comment from: Associated with Treacher-Collins syndrome 4 #618939 (AD) in OMIM

PMID: 31649276 - Sanchez et al 2020 - using exome sequencing they identified 6 patients (5 unrelated families) with heterozygous missense variants in POLR1B. In 3 cases the variants were de novo. One was inherited from the mother, and one from the father who was mosaic for the variant. 3 different variants are reported. The clinical phenotype was variable but all patients were reported with downward slanting palpebral fissures, Malar hypoplasia, and Conductive deafness, and 3 individuals from 3 different families had dleft palate. Morphilino knockdown of polr1b showed abnormal craniofacial development of zebrafish embryos
Sources: Literature; to: Associated with Treacher-Collins syndrome 4 #618939 (AD) in OMIM

PMID: 31649276 - Sanchez et al 2020 - using exome sequencing they identified 6 patients (5 unrelated families) with heterozygous missense variants in POLR1B. In 3 cases the variants were de novo. One was inherited from the mother, and one from the father who was mosaic for the variant. 3 different variants are reported. The clinical phenotype was variable but all patients were reported with downward slanting palpebral fissures, Malar hypoplasia, and Conductive deafness, and 3 individuals from 3 different families had cleft palate. Morphilino knockdown of polr1b showed abnormal craniofacial development of zebrafish embryos
Sources: Literature
Clefting v2.19 POLR1B Eleanor Williams gene: POLR1B was added
gene: POLR1B was added to Clefting. Sources: Literature
Mode of inheritance for gene: POLR1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR1B were set to 31649276
Phenotypes for gene: POLR1B were set to Treacher-Collins syndrome 4 OMIM:618939; treacher collins syndrome 4 MONDO:0030067
Review for gene: POLR1B was set to GREEN
Added comment: Associated with Treacher-Collins syndrome 4 #618939 (AD) in OMIM

PMID: 31649276 - Sanchez et al 2020 - using exome sequencing they identified 6 patients (5 unrelated families) with heterozygous missense variants in POLR1B. In 3 cases the variants were de novo. One was inherited from the mother, and one from the father who was mosaic for the variant. 3 different variants are reported. The clinical phenotype was variable but all patients were reported with downward slanting palpebral fissures, Malar hypoplasia, and Conductive deafness, and 3 individuals from 3 different families had dleft palate. Morphilino knockdown of polr1b showed abnormal craniofacial development of zebrafish embryos
Sources: Literature
Clefting v2.18 AMOTL1 Eleanor Williams Classified gene: AMOTL1 as Red List (low evidence)
Clefting v2.18 AMOTL1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to red. 2 cases but mouse model does not recapitulate the phenotype.
Clefting v2.18 AMOTL1 Eleanor Williams Gene: amotl1 has been classified as Red List (Low Evidence).
Clefting v2.17 AMOTL1 Eleanor Williams Phenotypes for gene: AMOTL1 were changed from Cleft lip and palate; imperforate anus; dysmorphism to cleft lip/palate MONDO:0016044; imperforate anus; dysmorphism
Clefting v2.16 AMOTL1 Eleanor Williams Publications for gene: AMOTL1 were set to 33026150
Clefting v2.15 AMOTL1 Eleanor Williams edited their review of gene: AMOTL1: Changed rating: RED
Clefting v2.15 AMOTL1 Eleanor Williams reviewed gene: AMOTL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33026150, 30375152; Phenotypes: cleft lip/palate MONDO:0016044; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v2.15 HYAL2 Eleanor Williams Phenotypes for gene: HYAL2 were changed from Cleft lip and palate, cor triatriatum to cleft lip/palate MONDO:0016044; triatrial heart MONDO:0015450
Clefting v2.14 HYAL2 Eleanor Williams Classified gene: HYAL2 as Amber List (moderate evidence)
Clefting v2.14 HYAL2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber but with recommendation for green rating following GMS review. This is based on 2 reported unrelated cases with different proposed causative variants in HYAL2, plus a mouse knockout model which replicates the human phenotype and some functional data reporting the effect of patient variants on protein levels.
Clefting v2.14 HYAL2 Eleanor Williams Gene: hyal2 has been classified as Amber List (Moderate Evidence).
Clefting v2.13 HYAL2 Eleanor Williams edited their review of gene: HYAL2: Changed rating: GREEN
Clefting v2.13 HYAL2 Eleanor Williams reviewed gene: HYAL2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28081210; Phenotypes: cleft lip/palate MONDO:0016044; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v2.13 SMC1A Arina Puzriakova Phenotypes for gene: SMC1A were changed from CORNELIA DE LANGE SYNDROME 2; CDLS2 to Cornelia de Lange syndrome 2, OMIM:300590; Cornelia de Lange syndrome 2, MONDO:0010370; Developmental and epileptic encephalopathy 85, with or without midline brain defects, OMIM:301044; Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771
Clefting v2.12 KCNJ2 Arina Puzriakova Phenotypes for gene: KCNJ2 were changed from ANDERSEN CARDIODYSRHYTHMIC PERIODIC PARALYSIS; Cleft palate to Andersen syndrome, OMIM:170390; Andersen-Tawil syndrome, MONDO:0008222
Clefting v2.11 MED25 Eleanor Williams Phenotypes for gene: MED25 were changed from BASEL-VANAGAITE-SMIRIN-YOSEF SYNDROME; BVSYS to Basel-Vanagait-Smirin-Yosef syndrome OMIM:616449
Clefting v2.10 MED25 Eleanor Williams Publications for gene: MED25 were set to 25792360
Clefting v2.9 MED25 Eleanor Williams Classified gene: MED25 as Amber List (moderate evidence)
Clefting v2.9 MED25 Eleanor Williams Added comment: Comment on list classification: Leaving the rating as Amber for now, but there are sufficient cases with clefting to promote this gene to green on this panel after the next GMS review.
Clefting v2.9 MED25 Eleanor Williams Gene: med25 has been classified as Amber List (Moderate Evidence).
Clefting v2.8 MED25 Eleanor Williams Tag for-review tag was added to gene: MED25.
Clefting v2.8 MED25 Eleanor Williams reviewed gene: MED25: Rating: ; Mode of pathogenicity: None; Publications: 31602195, 32324310, 32816121; Phenotypes: Basel-Vanagait-Smirin-Yosef syndrome OMIM:616449; Mode of inheritance: None
Clefting v2.8 MAPRE2 Arina Puzriakova Phenotypes for gene: MAPRE2 were changed from SKIN CREASES, CONGENITAL SYMMETRIC CIRCUMFERENTIAL, 2; CSCSC2 to Symmetric circumferential skin creases, congenital, 2, 616734
Clefting v2.7 MAPRE2 Arina Puzriakova Publications for gene: MAPRE2 were set to
Clefting v2.6 MAPRE2 Arina Puzriakova Mode of inheritance for gene: MAPRE2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting v2.5 AMOTL1 Zornitza Stark gene: AMOTL1 was added
gene: AMOTL1 was added to Clefting. Sources: Literature
Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMOTL1 were set to 33026150
Phenotypes for gene: AMOTL1 were set to Cleft lip and palate; imperforate anus; dysmorphism
Review for gene: AMOTL1 was set to RED
Added comment: Two unrelated families reported. In one, the variant was identified in parent and child who had orofacial cleft and cardiac abnormalities. Second report in PMID 33026150, de novo missense variant and cleft lip/palate, imperforate anus and dysmorphism. Mouse model does not recapitulate phenotype.
Sources: Literature
Clefting v2.5 KAT5 Arina Puzriakova Classified gene: KAT5 as Amber List (moderate evidence)
Clefting v2.5 KAT5 Arina Puzriakova Added comment: Comment on list classification: New gene added by Konstantinos Varvagiannis. Two unrelated cases reported in PMID:32822602 and additional cases required before inclusion on a diagnostic panel.

Rating Amber, awaiting further publications/clinical evidence to corroborate the association with this phenotype.
Clefting v2.5 KAT5 Arina Puzriakova Gene: kat5 has been classified as Amber List (Moderate Evidence).
Clefting v2.4 CTNND1 Eleanor Williams Publications for gene: CTNND1 were set to 28301459
Clefting v2.3 HYAL2 Aleš Maver changed review comment from: This entry is based on finding of homozygous HYAL2 variants in two inbred families with cleft lip and palate (CLP) in PMID:28081210. Five Amish individuals aged 4–16 years affected by a syndromic form of CLP were reported with a homozygous variant K148R variant in HYAL2 gene and two children aged 7 and 12 years from an extended consanguineous Arab family were reported with a homozygous P250L variant in HYAL2 gene. Reduced expression of the HYAL2 protein consequental to the two missense variants was shown in functional assays (PMID:28081210). Study of Hyal2 knock-out mice has also shown underdeveloped central palate bones and absence/reduction of ethmoid bone.
The entry is based on this single study, therefore currently leaving this at Red level of evidence.
Sources: Literature; to: This entry is based on finding of homozygous HYAL2 variants in two inbred families with cleft lip and palate (CLP) in PMID:28081210. Five Amish individuals aged 4–16 years affected by a syndromic form of CLP were reported with a homozygous variant K148R in HYAL2 gene and two children aged 7 and 12 years from an extended consanguineous Arab family were reported with a homozygous P250L variant in HYAL2 gene. Reduced expression of the HYAL2 protein consequental to the two missense variants was shown in functional assays (PMID:28081210). Study of Hyal2 knock-out mice has also shown underdeveloped central palate bones and absence/reduction of ethmoid bone.
The entry is based on this single study, therefore currently leaving this at Red level of evidence.
Sources: Literature
Clefting v2.3 HYAL2 Aleš Maver changed review comment from: This entry is based on finding of homozygous HYAL2 variants in two inbred families with cleft lip and palate (CLP) in PMID:28081210. Five Amish individuals aged 4–16 years affected by a syndromic form of CLP were reported with a homozygous variant K148R variant in HYAL2 gene and two children aged 7 and 12 years from an extended consanguineous Arab family were reported with a homozygous P250L variant in HYAL2 gene. Reduced expression of the HYAL2 protein consequental to the two missense vairants was shown in functional assays (PMID:28081210). Study of Hyal2 knock-out mice has also shown underdeveloped central palate bones and absence/reduction of ethmoid bone.
The entry is based on this single study, therefore currently leaving this at Red level of evidence.
Sources: Literature; to: This entry is based on finding of homozygous HYAL2 variants in two inbred families with cleft lip and palate (CLP) in PMID:28081210. Five Amish individuals aged 4–16 years affected by a syndromic form of CLP were reported with a homozygous variant K148R variant in HYAL2 gene and two children aged 7 and 12 years from an extended consanguineous Arab family were reported with a homozygous P250L variant in HYAL2 gene. Reduced expression of the HYAL2 protein consequental to the two missense variants was shown in functional assays (PMID:28081210). Study of Hyal2 knock-out mice has also shown underdeveloped central palate bones and absence/reduction of ethmoid bone.
The entry is based on this single study, therefore currently leaving this at Red level of evidence.
Sources: Literature
Clefting v2.3 HYAL2 Aleš Maver changed review comment from: This entry is based on finding of homozygous HYAL2 variants in two inbred families with cleft lip and palate (CLP). Five Amish individuals aged 4–16 years affected by a syndromic form of CLP were reported with a homozygous variant K148R variant in HYAL2 gene and two children aged 7 and 12 years from an extended consanguineous Arab family were reported with a homozygous P250L variant in HYAL2 gene. Reduced expression of the HYAL2 protein consequental to the two missense vairants was shown in functional assays (PMID:28081210). Study of Hyal2 knock-out mice has also shown underdeveloped central palate bones and absence/reduction of ethmoid bone.
The entry is based on this single study, therefore currently leaving this at Red level of evidence.
Sources: Literature; to: This entry is based on finding of homozygous HYAL2 variants in two inbred families with cleft lip and palate (CLP) in PMID:28081210. Five Amish individuals aged 4–16 years affected by a syndromic form of CLP were reported with a homozygous variant K148R variant in HYAL2 gene and two children aged 7 and 12 years from an extended consanguineous Arab family were reported with a homozygous P250L variant in HYAL2 gene. Reduced expression of the HYAL2 protein consequental to the two missense vairants was shown in functional assays (PMID:28081210). Study of Hyal2 knock-out mice has also shown underdeveloped central palate bones and absence/reduction of ethmoid bone.
The entry is based on this single study, therefore currently leaving this at Red level of evidence.
Sources: Literature
Clefting v2.3 HYAL2 Aleš Maver gene: HYAL2 was added
gene: HYAL2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: HYAL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYAL2 were set to 28081210
Phenotypes for gene: HYAL2 were set to Cleft lip and palate, cor triatriatum
Penetrance for gene: HYAL2 were set to unknown
Review for gene: HYAL2 was set to RED
Added comment: This entry is based on finding of homozygous HYAL2 variants in two inbred families with cleft lip and palate (CLP). Five Amish individuals aged 4–16 years affected by a syndromic form of CLP were reported with a homozygous variant K148R variant in HYAL2 gene and two children aged 7 and 12 years from an extended consanguineous Arab family were reported with a homozygous P250L variant in HYAL2 gene. Reduced expression of the HYAL2 protein consequental to the two missense vairants was shown in functional assays (PMID:28081210). Study of Hyal2 knock-out mice has also shown underdeveloped central palate bones and absence/reduction of ethmoid bone.
The entry is based on this single study, therefore currently leaving this at Red level of evidence.
Sources: Literature
Clefting v2.3 CTNND1 Eleanor Williams changed review comment from: PMID: 32196547 - Alharatani et al 2020 - report an expanded phenotype for CTNND1 patients. They report 13 individuals from nine families with novel protein-truncating variants in CTNND1 identified by WES. The mutations were not previously described in blepharocheilodontic (BCD), orofacial cleft cases nor in gnomAD. 8 patients had de novo variants, 2 inherited from affected parents, 2 participants inherited a variant from a parent with a mild phenotype. Additional phenotypic features seen include mild limb phenotypes (9/13), cardiovascular anomalies (6/13) and Developmental delay and other neurodevelopmental problems (8/13).; to: PMID: 32196547 - Alharatani et al 2020 - report an expanded phenotype for CTNND1 patients. They report 13 individuals from nine families with novel protein-truncating variants in CTNND1 identified by WES. The mutations were not previously described in blepharocheilodontic (BCD), orofacial cleft cases nor in gnomAD. 8 patients had de novo variants, 2 inherited from affected parents, 2 participants inherited a variant from a parent with a mild phenotype. 8/13 patients showed cleft palate. Additional phenotypic features seen include mild limb phenotypes (9/13), cardiovascular anomalies (6/13) and Developmental delay and other neurodevelopmental problems (8/13).
Clefting v2.3 CTNND1 Eleanor Williams reviewed gene: CTNND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32196547; Phenotypes: ; Mode of inheritance: None
Clefting v2.3 KAT5 Konstantinos Varvagiannis gene: KAT5 was added
gene: KAT5 was added to Clefting. Sources: Literature
Mode of inheritance for gene: KAT5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KAT5 were set to 32822602
Phenotypes for gene: KAT5 were set to Severe global developmental delay; Intellectual disability; Seizures; Microcephaly; Behavioral abnormality; Sleep disturbance; Morphological abnormality of the central nervous system; Short stature; Oral cleft; Abnormality of the face
Mode of pathogenicity for gene: KAT5 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: KAT5 was set to AMBER
Added comment: Humbert el al (2020 - PMID: 32822602) report 3 individuals with de novo missense KAT5 variants.

Features included severe DD (3/3) and ID (2/2 - the 3rd was 18m on last examination), microcephaly (2/3), behavioral anomalies (3/3) including severe sleep disorder (3/3 - table S1 / night walking, sleep onset delay, excessive daytime sleepiness), seizures (3/3 - variable type and age of onset), brain MRI abnormalities (3/3 - CC, cerebellar atrophy each in 2 subjects, focal polymicrogyria in 1), various genitourinary anomalies (3/3). All had moderately short stature (-1.95 SD to -2.9SD). Cleft LP and submucous cleft P were observed in 2/3. Facial features included round face, flat profile, depressed nasal bridge, downturned corners of mouth and prognathism (each in at least 2 subjects).

KAT5 encodes a lysine acetyltransferase involved in gene expression, DNA repair, chromatine remodeling, apoptosis and cell proliferation. It is part of the NuA4 histone acetyltransferase (HAT) complex also called TIP60/p400 (TIP60 being another name for KAT5). Regulation by histone acetylation is important for proper development.

3 missense KAT5 SNVs were identified, one within the chromobarrel domain (aa 7-65 / NM_006388.3) and 2 in the acetyl-CoA binding domain (aa 365-420).

Following generation of K562 cells expressing either WT or variants, it was demonstrated that wt/mt KAT5 assemble normally into NuA4/TIP60 complexes. Histone acetyltransferase activity was however impaired for all variants, suggesting a partial loss of function mechanism.

As Humbert et al comment, it is possible that KAT5 haploinsufficiency does not lead to a
syndrome. Over 10 high-confidence LoF variants are listed in gnomAD. Heterozygous Kat5 ko mice have normal development, growth and fertility. Homozygous ko mice are embryonic lethal. In haploinsufficient mice, reduction of mRNA to 50% has been shown to be compensated at the protein level in adipose and/or other tissues (several studies cited).

RNA-Seq in fibroblasts from 2 affected individuals revealed dysregulation of highly relevant genes (e.g. for neurodevelopment, circadian clock, etc).

Mutations in KAT6A/B, encoding two other acetyltransferases cause neurodevelopmental disorders with features overlapping those observed in individuals with KAT5 variants (e.g. DD/ID, microcephaly, seizures, sleep disturbance, clefts, CC or genital anomalies).

Consider inclusion in the ID and epilepsy panels with green rating as well as the gene panel for clefting with amber.
Sources: Literature
Clefting v2.3 FSHMD1A Eleanor Williams Tag ensembl_ids_known_missing tag was added to gene: FSHMD1A.
Clefting v2.3 PIGA Sarah Leigh Tag Skewed X-inactivation tag was added to gene: PIGA.
Clefting v2.3 WDR34 Catherine Snow commented on gene: WDR34
Clefting v2.3 WDR34 Catherine Snow Tag new-gene-name tag was added to gene: WDR34.
Clefting v2.3 WDR60 Catherine Snow commented on gene: WDR60
Clefting v2.3 WDR60 Catherine Snow Tag new-gene-name tag was added to gene: WDR60.
Clefting v2.3 Eleanor Williams Panel version has been signed off
Clefting v2.0 Eleanor Williams promoted panel to version 2.0
Clefting v1.61 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Clefting v1.60 ARHGAP29 Catherine Snow Classified gene: ARHGAP29 as Green List (high evidence)
Clefting v1.60 ARHGAP29 Catherine Snow Gene: arhgap29 has been classified as Green List (High Evidence).
Clefting v1.59 ARHGAP29 Catherine Snow reviewed gene: ARHGAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Clefting v1.59 ALX1 Eleanor Williams commented on gene: ALX1: Amber rating confirmed by Genomics England clinical team.
Clefting v1.59 ICK Eleanor Williams commented on gene: ICK
Clefting v1.59 ICK Eleanor Williams Tag new-gene-name tag was added to gene: ICK.
Clefting v1.59 KIF1BP Louise Daugherty Tag new-gene-name tag was added to gene: KIF1BP.
Clefting v1.59 KIF1BP Louise Daugherty commented on gene: KIF1BP
Clefting v1.59 FBXO11 Eleanor Williams Classified gene: FBXO11 as Amber List (moderate evidence)
Clefting v1.59 FBXO11 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber as there are some cases reported, but the incidence of clefting is low and in one paper they felt the clefting phenotype was not related to the main phenotype of developmental delay.
Clefting v1.59 FBXO11 Eleanor Williams Gene: fbxo11 has been classified as Amber List (Moderate Evidence).
Clefting v1.58 EIF4A3 Louise Daugherty Mode of inheritance for gene: EIF4A3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Clefting v1.57 FBXO11 Catherine Snow Publications for gene: FBXO11 were set to 30057029; 30679813; 17035249
Clefting v1.57 FBXO11 Catherine Snow Publications for gene: FBXO11 were set to 30057029; 30679813
Clefting v1.56 FBXO11 Catherine Snow edited their review of gene: FBXO11: Added comment: PMID:30057029 reports on 20 individuals with a variable neurodevelopmental disorder all with de novo variants in FBXO11. Three of the individuals had clefting phenotypes. One had a cleft lip (c.1825_ 1829del (p.Glu609*), one had a cleft palate (c.2729A>G (p.Asp910Gly) and one had a bifid uvula (c.1868C>G (p.Thr623Arg)). All individuals had developmental delay.

PMID:30679813 reports on 24 individuals with de novo variants in FBXO11, one individual had a submucosal cleft palate, although the authors feel that this was not related to the phenotype of DD/ID that was found in all the individuals.

PMID:17035249 - A mutation in the F-box gene, Fbxo11 causes otitis media in the Jeff mouse found that homozygous Fbxo11 mutants all have clefting of the hard or soft palate as well as facial clefting. Hetrozygous mouse had no clefting phenotypes.; Changed publications: 30057029, 30679813, 17035249
Clefting v1.56 FBXO11 Catherine Snow gene: FBXO11 was added
gene: FBXO11 was added to Clefting. Sources: Expert list
Mode of inheritance for gene: FBXO11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FBXO11 were set to 30057029; 30679813
Phenotypes for gene: FBXO11 were set to cleft lip; Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, 618089
Review for gene: FBXO11 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Clefting v1.55 EIF4A3 Catherine Snow Phenotypes for gene: EIF4A3 were changed from Cleft palate to Cleft palate; Robin sequence with cleft mandible and limb anomalies, 268305; Richieri-Costa-Pereira syndrome
Clefting v1.54 EIF4A3 Catherine Snow Publications for gene: EIF4A3 were set to
Clefting v1.53 EIF4A3 Catherine Snow Classified gene: EIF4A3 as Green List (high evidence)
Clefting v1.53 EIF4A3 Catherine Snow Gene: eif4a3 has been classified as Green List (High Evidence).
Clefting v1.52 POLR1A Catherine Snow Phenotypes for gene: POLR1A were changed from cleft lip to cleft palte
Clefting v1.51 POLR1A Catherine Snow Classified gene: POLR1A as Amber List (moderate evidence)
Clefting v1.51 POLR1A Catherine Snow Gene: polr1a has been classified as Amber List (Moderate Evidence).
Clefting v1.50 POLR1A Catherine Snow commented on gene: POLR1A: PMID: 25913037 : Acrofacial Dysostosis, Cincinnati Type, a Mandibulofacial Dysostosis Syndrome with Limb Anomalies identified POLR1A in three unrelated individuals. One individual had a cleft palate, the other individuals had craniofacial features but not specifically a cleft palate.
POLR1A is associated with cleft palate in OMIM based on this paper and is in Gene2Phenotype as a DD Gene, associated with Disease: ACROFACIAL DYSOSTOSIS, CINCINNATI TYPE.
As insufficient number of cases, classifying as Amber.
Clefting v1.50 POLR1A Catherine Snow gene: POLR1A was added
gene: POLR1A was added to Clefting. Sources: Expert list
Mode of inheritance for gene: POLR1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR1A were set to 25913037
Phenotypes for gene: POLR1A were set to cleft lip
Review for gene: POLR1A was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Clefting v1.49 PLEKHA7 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic variant (chr11:g.16838582C>T;p.Gly544Asp) was identified in one family. Further analysis of 497 individuals identified a further likely pathogenic variant and another variant of unknown significance both variants were found in the same family (chr11:g.16838676G>A;p.Arg513Trp and chr11:g.16834682T>C;p.Asp662Gly), a further variant of unknown significance was identified in another family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic variant (chr11:g.16838582C>T;p.Gly544Asp) was identified in one family. Further analysis of 497 individuals identified a likely pathogenic variant and another variant of unknown significance both variants were found in the same family (chr11:g.16838676G>A;p.Arg513Trp and chr11:g.16834682T>C;p.Asp662Gly), a further variant of unknown significance was identified in another family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Clefting v1.49 PLEKHA7 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant (chr11:g.16838582C>T;p.Gly544Asp) was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family (chr11:g.16838676G>A;p.Arg513Trp and chr11:g.16834682T>C;p.Asp662Gly), a further variant of unknown significance was identified in another family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic variant (chr11:g.16838582C>T;p.Gly544Asp) was identified in one family. Further analysis of 497 individuals identified a further likely pathogenic variant and another variant of unknown significance both variants were found in the same family (chr11:g.16838676G>A;p.Arg513Trp and chr11:g.16834682T>C;p.Asp662Gly), a further variant of unknown significance was identified in another family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Clefting v1.49 PLEKHA5 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA5 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic de novo variant was identified in one family (chr12:g.19440414A>G;p.Tyr590Cys). Further analysis of 497 individuals identified 5 variants of unknown significance. PLEKHA5 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA5 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic de novo variant was identified in one family (chr12:g.19440414A>G;p.Tyr590Cys). Further analysis of 497 individuals identified 5 variants of unknown significance. PLEKHA5 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Clefting v1.49 PLEKHA5 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA5 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family (chr12:g.19440414A>G;p.Tyr590Cys). Further analysis of 497 individuals identified 5 variants of unknown significance. PLEKHA5 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA5 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic de novo variant was identified in one family (chr12:g.19440414A>G;p.Tyr590Cys). Further analysis of 497 individuals identified 5 variants of unknown significance. PLEKHA5 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Clefting v1.49 ESRP2 Catherine Snow Classified gene: ESRP2 as Amber List (moderate evidence)
Clefting v1.49 ESRP2 Catherine Snow Gene: esrp2 has been classified as Amber List (Moderate Evidence).
Clefting v1.49 ESRP2 Catherine Snow Classified gene: ESRP2 as Amber List (moderate evidence)
Clefting v1.49 ESRP2 Catherine Snow Gene: esrp2 has been classified as Amber List (Moderate Evidence).
Clefting v1.48 ESRP2 Catherine Snow edited their review of gene: ESRP2: Changed rating: AMBER
Clefting v1.48 ESRP2 Catherine Snow edited their review of gene: ESRP2: Added comment: PMID: 29805042 Cox et al. Identified ESRP2 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic variant (chr16:g.68266284C>T;p.Arg315) was identified in one family. Further analysis of 497 individuals identified a further likely pathogenic variant (chr16:g.68265234G>A;p.Arg520*) in another family. ESRP2 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; Changed rating: RED
Clefting v1.48 ESRP2 Catherine Snow gene: ESRP2 was added
gene: ESRP2 was added to Clefting. Sources: Expert list
Mode of inheritance for gene: ESRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ESRP2 were set to 29805042
Phenotypes for gene: ESRP2 were set to cleft lip
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Clefting v1.47 PLEKHA7 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family, a further variant of unknown significance was identified in a family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant (chr11:g.16838582C>T;p.Gly544Asp) was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family (chr11:g.16838676G>A;p.Arg513Trp and chr11:g.16834682T>C;p.Asp662Gly), a further variant of unknown significance was identified in another family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Clefting v1.47 PLEKHA5 Catherine Snow edited their review of gene: PLEKHA5: Added comment: PMID: 29805042 Cox et al. Identified PLEKHA5 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family (chr12:g.19440414A>G;p.Tyr590Cys). Further analysis of 497 individuals identified 5 variants of unknown significance. PLEKHA5 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; Changed rating: RED
Clefting v1.47 PLEKHA7 Catherine Snow changed review comment from: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.; to: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family, a further variant of unknown significance was identified in a family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Clefting v1.47 PLEKHA5 Catherine Snow gene: PLEKHA5 was added
gene: PLEKHA5 was added to Clefting. Sources: Expert list
Mode of inheritance for gene: PLEKHA5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEKHA5 were set to 29805042
Phenotypes for gene: PLEKHA5 were set to cleft lip
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Clefting v1.46 PLEKHA7 Catherine Snow Classified gene: PLEKHA7 as Amber List (moderate evidence)
Clefting v1.46 PLEKHA7 Catherine Snow Gene: plekha7 has been classified as Amber List (Moderate Evidence).
Clefting v1.45 PLEKHA7 Catherine Snow commented on gene: PLEKHA7: PMID: 29805042 Cox et al. Identified PLEKHA7 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 pathogenic variant was identified in one family. Further analysis of 497 individuals identified a further pathogenic variant and another variant of unknown significance both variants were found in the same family. PLEKHA7 has no phenotypes associated in OMIM or disease association in Gene2Phenotype.
Clefting v1.45 PLEKHA7 Catherine Snow gene: PLEKHA7 was added
gene: PLEKHA7 was added to Clefting. Sources: Expert list
Mode of inheritance for gene: PLEKHA7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEKHA7 were set to 29805042
Phenotypes for gene: PLEKHA7 were set to cleft lip
Review for gene: PLEKHA7 was set to AMBER
Added comment: Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Clefting v1.44 ALX1 Catherine Snow Classified gene: ALX1 as Amber List (moderate evidence)
Clefting v1.44 ALX1 Catherine Snow Added comment: Comment on list classification: Changed to Amber based on Eleanor Williams review.
Clefting v1.44 ALX1 Catherine Snow Gene: alx1 has been classified as Amber List (Moderate Evidence).
Clefting v1.43 EIF4A3 Catherine Snow reviewed gene: EIF4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10594883, 29922329, 29112243; Phenotypes: Robin sequence with cleft mandible and limb anomalies, 268305, Richieri-Costa-Pereira syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting v1.43 BMP2 Catherine Snow Phenotypes for gene: BMP2 were changed from Cleft palate to Cleft palate; Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies, 617877
Clefting v1.42 BMP2 Catherine Snow Publications for gene: BMP2 were set to
Clefting v1.41 BMP2 Catherine Snow Mode of inheritance for gene: BMP2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v1.40 BMP2 Catherine Snow Classified gene: BMP2 as Green List (high evidence)
Clefting v1.40 BMP2 Catherine Snow Gene: bmp2 has been classified as Green List (High Evidence).
Clefting v1.39 BMP2 Catherine Snow reviewed gene: BMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21671386, 29198724; Phenotypes: Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies, 617877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v1.39 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel
Clefting v1.37 ALX1 Eleanor Williams Phenotypes for gene: ALX1 were changed from to ?Frontonasal dysplasia 3, 613456
Clefting v1.36 ALX1 Eleanor Williams Publications for gene: ALX1 were set to
Clefting v1.35 ALX1 Eleanor Williams commented on gene: ALX1: This gene is provisionally associated with ?Frontonasal dysplasia 3 (#613456) in OMIM.

PMID: 20451171 - Uz et al. (2010) - 2 families presenting with autosomal-recessive frontonasal dysplasia (FND) characterized by bilateral extreme microphthalmia, bilateral oblique facial cleft, complete cleft palate, hypertelorism, wide nasal bridge with hypoplasia of the ala nasi, and low-set, posteriorly rotated ears in two distinct families. In one family they found a three siblings were affected, and CNV analysis of the critical region showed a homozygous 3.7 Mb deletion containing the ALX1 (CART1) gene. In the second family a homozygous donor-splice-site mutation (c.531+1G > A) in the ALX1 gene was found.

PMID: 27324866 - Ullah et al 2017 - report a consanguineous family from Pakistan with four individuals presenting a milder form of Frontonasal dysplasia. Using exome sequencing, a homozygous splice acceptor site variant has been identified in the ALX1 gene. NO CLEFTING REPORTED.
Clefting v1.35 ALX1 Eleanor Williams gene: ALX1 was added
gene: ALX1 was added to Clefting. Sources: Expert list
Mode of inheritance for gene: ALX1 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: ALX1 was set to AMBER
Added comment: Gene suggested by Andrew Wilkie, University of Oxford
Sources: Expert list
Clefting v1.34 SEPT9 Louise Daugherty Tag new-gene-name tag was added to gene: SEPT9.
Clefting v1.34 SEPT9 Louise Daugherty commented on gene: SEPT9
Clefting v1.34 CHD1 Ellen McDonagh commented on gene: CHD1
Clefting v1.33 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Clefting v1.32 DVL3 Louise Daugherty Classified gene: DVL3 as Green List (high evidence)
Clefting v1.32 DVL3 Louise Daugherty Added comment: Comment on list classification: changed rating from Red to Green. There is enough evidence to support the upgrading of the rating of this gene
Clefting v1.32 DVL3 Louise Daugherty Gene: dvl3 has been classified as Green List (High Evidence).
Clefting v1.31 DVL3 Louise Daugherty gene: DVL3 was added
gene: DVL3 was added to Clefting. Sources: Other
Mode of inheritance for gene: DVL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DVL3 were set to 26924530; 29575616
Phenotypes for gene: DVL3 were set to Robinow syndrome, autosomal dominant 3, 616894
Review for gene: DVL3 was set to GREEN
Added comment: PMID: 26924530 White et al. (2016) described five patients with Robinow syndrome-3 and identified heterozygosity for mutations in DVL3, all predicted to result in a frameshift to the -1 reading frame and a premature termination codon in the last exon.
From Gel clinical team: Stittrich et al (PMID: 26924530 ) looked for variants in DVL3 in patients with Robinow syndrome and no previously identified mutation; because mutations had previously described in DVL1 and there was functional redundancy between the genes. They identified 4 de novo frameshift variants in their cohort of 17 patients. Danyal et al (PMID: 29575616) identified a frame shift variant in a further patient with Robinow syndrome.
Sources: Other
Clefting v1.30 TGFB2 Louise Daugherty Phenotypes for gene: TGFB2 were changed from Loeys-Dietz syndrome to Loeys-Dietz syndrome 4, 614816
Clefting v1.29 TGFB2 Anna de Burca gene: TGFB2 was added
gene: TGFB2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: TGFB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFB2 were set to 29392890
Phenotypes for gene: TGFB2 were set to Loeys-Dietz syndrome
Review for gene: TGFB2 was set to AMBER
Added comment: Recently described as a cause of Loeys-Dietz syndrome. Only a small number of cases have been described in the literature, but clefting has been a feature in some cases.
Sources: Literature
Clefting v1.28 SMAD2 Anna de Burca gene: SMAD2 was added
gene: SMAD2 was added to Clefting. Sources: Literature
Mode of inheritance for gene: SMAD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD2 were set to 29967133; 29392890
Phenotypes for gene: SMAD2 were set to Loeys-Dietz syndrome
Review for gene: SMAD2 was set to AMBER
Added comment: Variants in this gene have recently been associated with Loeys-Dietz syndrome. Since only a small number of cases have been described to date, further work is required to determine whether individuals with variants in SMAD2 commonly present with the craniofacial features associated with this condition.
Sources: Literature
Clefting v1.27 ISCA-37433-Loss Louise Daugherty 22q11.2 recurrent (DGS/VCFS) region (proximal region, LCR22-A to -B) Loss was changed to 22q11.2 recurrent (DGS/VCFS) region (proximal, A-B) (includes TBX1) Loss
Added phenotypes 188400; immune deficiency; renal anomalies; 22q11.2 deletion syndrome; 192430; facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay; polyhydramnios; Velocardiofacial syndrome; Learning difficulties; diaphragmatic hernia; DiGeorge syndrome; congenital heart disease; cleft palate, polydactyly for Region: ISCA-37433-Loss
Publications for Region: ISCA-37433-Loss were changed from 15545748; 15889418; 20301696 to 15889418; 20301696; 15545748
Clefting v1.27 ISCA-37446-Loss Louise Daugherty 22q11.2 recurrent (DGS/VCFS) region (proximal region, LCR22-A to -D) Loss was changed to 22q11.2 recurrent (DGS/VCFS) region (proximal, A-D) (includes TBX1) Loss
Added phenotypes 188400; neonatal hypocalcemia, which may present as tetany or seizures, due to hypoplasia of the parathyroid glands, and susceptibility to infection due to a deficit of T cells; micrognathia; clefting; Hearing deficits; Velocardiofacial syndrome; cardiac malformations; DiGeorge syndrome for Region: ISCA-37446-Loss
Clefting v1.26 ISCA-37433-Loss Louise Daugherty GRCh38 position for ISCA-37433-Loss was changed from 18178958-20324381 to 18924718-20299686.
Clefting v1.26 ISCA-37446-Loss Louise Daugherty GRCh38 position for ISCA-37446-Loss was changed from 18178958-21207225 to 18924718-21111384.
Clefting v1.25 ISCA-37423-Gain Louise Daugherty Region: ISCA-37423-Gain was added
Region: ISCA-37423-Gain was added to Clefting. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37423-Gain was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37423-Gain were set to 21933911; 23345203
Phenotypes for Region: ISCA-37423-Gain were set to Behavioral problems, cleft lip and/or palate, macrocephaly, and seizures were confirmed as additional features among the new patients, and novel features included neonatal respiratory distress, attention deficit hyperactivity disorder (ADHD), ocular anomalies, balance problems, hypotonia, and hydrocele.; mild to moderate developmental delay, intellectual disability, mild facial dysmorphism (incl. prominent forehead, arched eyebrows, broad nasal bridge, upturned nares, cleft lip and/or palate) and congenital cardiac anomalies (e.g., atrioventricular septal defect). Other reported features include macrocephaly, behavioral abnormalities (e.g., attention deficit disorder), seizures, hypotonia and ocular and digital anomalies (poly/syndactyly); congenital heart disease; 8p23.1 duplication syndrome
Clefting v1.25 ISCA-37433-Loss Louise Daugherty Region: ISCA-37433-Loss was added
Region: ISCA-37433-Loss was added to Clefting. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37433-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37433-Loss were set to 15545748; 15889418; 20301696
Phenotypes for Region: ISCA-37433-Loss were set to facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay; diaphragmatic hernia; Learning difficulties; 192430; immune deficiency; congenital heart disease; 22q11.2 deletion syndrome; Velocardiofacial syndrome; DiGeorge syndrome; cleft palate, polydactyly; polyhydramnios; 188400; renal anomalies
Clefting v1.25 ISCA-37446-Loss Louise Daugherty Region: ISCA-37446-Loss was added
Region: ISCA-37446-Loss was added to Clefting. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37446-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37446-Loss were set to cardiac malformations; clefting; neonatal hypocalcemia, which may present as tetany or seizures, due to hypoplasia of the parathyroid glands, and susceptibility to infection due to a deficit of T cells; Velocardiofacial syndrome; DiGeorge syndrome; micrognathia; Hearing deficits; 188400
Clefting v1.25 ISCA-37467-Gain Louise Daugherty Region: ISCA-37467-Gain was added
Region: ISCA-37467-Gain was added to Clefting. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37467-Gain was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37467-Gain were set to 19291772; 18417549; 18178630
Phenotypes for Region: ISCA-37467-Gain were set to human triphalangeal thumb and polysyndactyly (TPT-PS) phenotype; 174500; Triphalangeal thumbpolysyndactyly syndrome; syndactyly type IV with tibial hypoplasia
Clefting v1.25 ISCA-37393-Gain Louise Daugherty Region: ISCA-37393-Gain was added
Region: ISCA-37393-Gain was added to Clefting. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37393-Gain was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37393-Gain were set to 11693792; 22890013; 22495764
Phenotypes for Region: ISCA-37393-Gain were set to PMID 22890013: variable phenotype including developmental delay, ocular coloboma, preauricular tags/pits, cleft palate, skeletal defects, heart defects, urogenital defect, anal defect, hearing loss, clinodactyly of fifth fingers, umbilical hernia, accessory spleen, strabismus, shortening of the fifth finger. PMID 22495764: Inter and intra individual variability of phenotype, mosaic. PMID 11693792: preauricular skin tags and pits, downslanting palpebral fissures, hypertelorism, ectopic anus, hypospadias, and hypoplastic left heart syndrome; 115470
Clefting TGFBR2 Louise Daugherty classified TGFBR2 as Green List (high evidence)
Clefting TSR2 Ellen McDonagh Added gene to panel
Clefting TFAP2B Ellen McDonagh Added gene to panel
Clefting SELENOI Ellen McDonagh Added gene to panel
Clefting RSPO2 Ellen McDonagh Added gene to panel
Clefting RPL11 Ellen McDonagh Added gene to panel
Clefting PLCB4 Ellen McDonagh Added gene to panel
Clefting PGM1 Ellen McDonagh Added gene to panel
Clefting INTS1 Ellen McDonagh Added gene to panel
Clefting GNAI3 Ellen McDonagh Added gene to panel
Clefting FOXE1 Ellen McDonagh Added gene to panel
Clefting EIF4A3 Ellen McDonagh Added gene to panel
Clefting EDN1 Ellen McDonagh Added gene to panel
Clefting COL9A3 Ellen McDonagh Added gene to panel
Clefting CHD1 Ellen McDonagh Added gene to panel
Clefting BMP2 Ellen McDonagh Added gene to panel
Clefting ACBD5 Ellen McDonagh Added gene to panel
Clefting TGFBR2 Anna de Burca Added gene to panel
Clefting USP9X Sarah Leigh classified USP9X as Green List (high evidence)
Clefting USP9X Sarah Leigh Added gene to panel
Clefting CDH1 Ellen McDonagh commented on CDH1
Clefting C5orf42 Louise Daugherty commented on C5orf42
Clefting MED25 Louise Daugherty commented on MED25
Clefting RBPJ Louise Daugherty commented on RBPJ
Clefting DLG1 Ellen McDonagh added DLG1 to panel
Clefting DLG1 Ellen McDonagh reviewed DLG1
Clefting DDX3X Louise Daugherty commented on DDX3X
Clefting TMEM8C Sarah Leigh classified TMEM8C as green
Clefting TMEM8C Sarah Leigh added TMEM8C to panel
Clefting TMEM8C Sarah Leigh reviewed TMEM8C
Clefting FSHMD1A Louise Daugherty classified FSHMD1A as grey
Clefting TGFB3 Ellen McDonagh reviewed TGFB3
Clefting ZIC3 Helen Brittain commented on ZIC3
Clefting KDM1A Louise Daugherty edited their review of KDM1A
Clefting PTDSS1 Louise Daugherty commented on PTDSS1
Clefting PTDSS1 Philip Stanier reviewed PTDSS1
Clefting Louise Daugherty promoted panel to version 1
Clefting PHGDH Louise Daugherty commented on PHGDH
Clefting PIGV Ellen McDonagh marked PIGV as ready
Clefting PIGN Ellen McDonagh marked PIGN as ready
Clefting PHGDH Ellen McDonagh commented on PHGDH
Clefting PIK3R2 Olivia Niblock reviewed PIK3R2
Clefting PIGL Olivia Niblock reviewed PIGL
Clefting PIGA Olivia Niblock reviewed PIGA
Clefting PGAP2 Olivia Niblock reviewed PGAP2
Clefting NSDHL Olivia Niblock reviewed NSDHL
Clefting GDF1 Olivia Niblock reviewed GDF1
Clefting GATA6 Olivia Niblock reviewed GATA6
Clefting NKX2-6 Olivia Niblock reviewed NKX2-6
Clefting NKX2-5 Olivia Niblock reviewed NKX2-5
Clefting PHGDH Olivia Niblock reviewed PHGDH
Clefting TBX1 Olivia Niblock reviewed TBX1
Clefting PIGV Olivia Niblock reviewed PIGV
Clefting PIGN Olivia Niblock reviewed PIGN
Clefting PTDSS1 Ellen McDonagh marked PTDSS1 as ready
Clefting PTDSS1 Ellen McDonagh classified PTDSS1 as red
Clefting PTDSS1 Ellen McDonagh classified PTDSS1 as red
Clefting PTDSS1 Ellen McDonagh added PTDSS1 to panel
Clefting PTDSS1 Ellen McDonagh reviewed PTDSS1
Clefting PSAT1 Louise Daugherty added PSAT1 to panel
Clefting PSAT1 Louise Daugherty reviewed PSAT1
Clefting POMT1 Louise Daugherty added POMT1 to panel
Clefting POMT1 Louise Daugherty reviewed POMT1
Clefting FLNA Arianna Tucci marked FLNA as ready
Clefting FLNA Arianna Tucci commented on FLNA
Clefting FLNA Arianna Tucci classified FLNA as green
Clefting COL9A2 Arianna Tucci reviewed COL9A2
Clefting PQBP1 Louise Daugherty added PQBP1 to panel
Clefting PQBP1 Louise Daugherty reviewed PQBP1
Clefting PORCN Louise Daugherty classified PORCN as green
Clefting ATR Arianna Tucci commented on ATR
Clefting ATR Arianna Tucci commented on ATR
Clefting PORCN Louise Daugherty added PORCN to panel
Clefting PORCN Louise Daugherty reviewed PORCN
Clefting BMP4 Ellen McDonagh classified BMP4 as red
Clefting BMP4 Ellen McDonagh classified BMP4 as red
Clefting CASK Ellen McDonagh reviewed CASK
Clefting CANT1 Ellen McDonagh reviewed CANT1
Clefting B3GAT3 Ellen McDonagh reviewed B3GAT3
Clefting ATRX Ellen McDonagh reviewed ATRX
Clefting ARCN1 Ellen McDonagh reviewed ARCN1
Clefting SMG9 Ellen McDonagh reviewed SMG9
Clefting BUB1B Ellen McDonagh reviewed BUB1B
Clefting BMP4 Ellen McDonagh reviewed BMP4
Clefting B4GALT7 Ellen McDonagh reviewed B4GALT7
Clefting B3GALT6 Ellen McDonagh reviewed B3GALT6
Clefting ATR Ellen McDonagh reviewed ATR
Clefting ALX3 Ellen McDonagh reviewed ALX3
Clefting BCOR Ellen McDonagh reviewed BCOR
Clefting POMT2 Louise Daugherty added POMT2 to panel
Clefting POMT2 Louise Daugherty reviewed POMT2
Clefting CKAP2L Louise Daugherty added CKAP2L to panel
Clefting CKAP2L Louise Daugherty reviewed CKAP2L
Clefting CC2D2A Louise Daugherty classified CC2D2A as green
Clefting CC2D2A Louise Daugherty added CC2D2A to panel
Clefting CC2D2A Louise Daugherty reviewed CC2D2A
Clefting CDC45 Louise Daugherty classified CDC45 as amber
Clefting CDC45 Louise Daugherty added CDC45 to panel
Clefting CDC45 Louise Daugherty reviewed CDC45
Clefting CDKN1C Louise Daugherty commented on CDKN1C
Clefting KIAA0196 Ellen McDonagh commented on KIAA0196
Clefting YAP1 Arianna Tucci reviewed YAP1
Clefting KIAA0196 Arianna Tucci reviewed KIAA0196
Clefting WNT3 Arianna Tucci reviewed WNT3
Clefting VAX1 Arianna Tucci reviewed VAX1
Clefting UQCC2 Arianna Tucci reviewed UQCC2
Clefting STXBP1 Arianna Tucci reviewed STXBP1
Clefting STRA6 Arianna Tucci reviewed STRA6
Clefting STIL Arianna Tucci reviewed STIL
Clefting LMNA Arianna Tucci reviewed LMNA
Clefting ZMPSTE24 Arianna Tucci reviewed ZMPSTE24
Clefting ZBTB24 Arianna Tucci reviewed ZBTB24
Clefting ZIC2 Arianna Tucci reviewed ZIC2
Clefting ZEB2 Arianna Tucci reviewed ZEB2
Clefting XYLT1 Arianna Tucci reviewed XYLT1
Clefting TRIM37 Arianna Tucci reviewed TRIM37
Clefting TRAPPC9 Arianna Tucci reviewed TRAPPC9
Clefting TMCO1 Arianna Tucci reviewed TMCO1
Clefting STAMBP Arianna Tucci reviewed STAMBP
Clefting KIAA1279 Ellen McDonagh commented on KIAA1279
Clefting PVRL1 Ellen McDonagh marked PVRL1 as ready
Clefting PVRL1 Ellen McDonagh commented on PVRL1
Clefting NBN Rebecca Foulger reviewed NBN
Clefting METTL23 Rebecca Foulger reviewed METTL23
Clefting MED12 Rebecca Foulger reviewed MED12
Clefting LMX1B Rebecca Foulger reviewed LMX1B
Clefting KIF22 Rebecca Foulger reviewed KIF22
Clefting KAT6B Rebecca Foulger reviewed KAT6B
Clefting KANSL1 Rebecca Foulger reviewed KANSL1
Clefting MED13L Rebecca Foulger reviewed MED13L
Clefting NECTIN1 Rebecca Foulger reviewed NECTIN1*
Clefting MKS1 Rebecca Foulger reviewed MKS1
Clefting MAP3K7 Rebecca Foulger reviewed MAP3K7
Clefting KIAA1279 Rebecca Foulger reviewed KIAA1279
Clefting IMPAD1 Rebecca Foulger reviewed IMPAD1
Clefting ICK Rebecca Foulger reviewed ICK
Clefting HYLS1 Rebecca Foulger reviewed HYLS1
Clefting CHRNG Louise Daugherty added CHRNG to panel
Clefting CHRNG Louise Daugherty reviewed CHRNG
Clefting CHSY1 Louise Daugherty classified CHSY1 as red
Clefting CHSY1 Louise Daugherty added CHSY1 to panel
Clefting CHSY1 Louise Daugherty reviewed CHSY1
Clefting FREM2 Louise Daugherty classified FREM2 as red
Clefting FREM2 Louise Daugherty edited their review of FREM2
Clefting EPG5 Louise Daugherty classified EPG5 as green
Clefting GRIP1 Louise Daugherty classified GRIP1 as red
Clefting GRIP1 Louise Daugherty edited their review of GRIP1
Clefting FANCL Louise Daugherty classified FANCL as red
Clefting FANCL Louise Daugherty edited their review of FANCL
Clefting FAM111A Louise Daugherty edited their review of FAM111A
Clefting EPG5 Louise Daugherty edited their review of EPG5
Clefting DNMT3B Louise Daugherty edited their review of DNMT3B
Clefting DIS3L2 Louise Daugherty edited their review of DIS3L2
Clefting GNB1 Louise Daugherty classified GNB1 as amber
Clefting GNB1 Louise Daugherty classified GNB1 as amber
Clefting GNB1 Louise Daugherty added GNB1 to panel
Clefting GNB1 Louise Daugherty reviewed GNB1
Clefting GMNN Louise Daugherty classified GMNN as red
Clefting GMNN Louise Daugherty classified GMNN as amber
Clefting GMNN Louise Daugherty added GMNN to panel
Clefting GMNN Louise Daugherty reviewed GMNN
Clefting GLI3 Louise Daugherty added GLI3 to panel
Clefting GLI3 Louise Daugherty reviewed GLI3
Clefting GJA1 Louise Daugherty classified GJA1 as green
Clefting KDM1A Rebecca Foulger classified KDM1A as amber
Clefting KDM1A Rebecca Foulger commented on KDM1A
Clefting GJA1 Louise Daugherty added GJA1 to panel
Clefting GJA1 Louise Daugherty reviewed GJA1
Clefting GATA3 Louise Daugherty classified GATA3 as amber
Clefting GATA3 Louise Daugherty added GATA3 to panel
Clefting GATA3 Louise Daugherty reviewed GATA3
Clefting FTO Louise Daugherty added FTO to panel
Clefting FTO Louise Daugherty reviewed FTO
Clefting FOXP2 Louise Daugherty added FOXP2 to panel
Clefting FOXP2 Louise Daugherty reviewed FOXP2
Clefting FLNB Louise Daugherty classified FLNB as green
Clefting FGFR1 Louise Daugherty added FGFR1 to panel
Clefting FGFR1 Louise Daugherty reviewed FGFR1
Clefting FREM2 Louise Daugherty commented on FREM2
Clefting FREM2 Louise Daugherty added FREM2 to panel
Clefting FREM2 Louise Daugherty reviewed FREM2
Clefting GRIP1 Louise Daugherty commented on GRIP1
Clefting GRIP1 Louise Daugherty added GRIP1 to panel
Clefting GRIP1 Louise Daugherty reviewed GRIP1
Clefting FRAS1 Louise Daugherty classified FRAS1 as green
Clefting FRAS1 Louise Daugherty added FRAS1 to panel
Clefting FRAS1 Louise Daugherty reviewed FRAS1
Clefting FANCL Louise Daugherty classified FANCL as amber
Clefting FANCL Louise Daugherty added FANCL to panel
Clefting FANCL Louise Daugherty reviewed FANCL
Clefting FAM20C Louise Daugherty classified FAM20C as green
Clefting FAM20C Louise Daugherty added FAM20C to panel
Clefting FAM20C Louise Daugherty reviewed FAM20C
Clefting FAM111A Louise Daugherty added FAM111A to panel
Clefting FAM111A Louise Daugherty reviewed FAM111A
Clefting EPG5 Louise Daugherty edited their review of EPG5
Clefting EPG5 Louise Daugherty added EPG5 to panel
Clefting EPG5 Louise Daugherty reviewed EPG5
Clefting DNMT3B Louise Daugherty edited their review of DNMT3B
Clefting DNMT3B Louise Daugherty added DNMT3B to panel
Clefting DNMT3B Louise Daugherty reviewed DNMT3B
Clefting DIS3L2 Louise Daugherty edited their review of DIS3L2
Clefting DIS3L2 Louise Daugherty added DIS3L2 to panel
Clefting DIS3L2 Louise Daugherty reviewed DIS3L2
Clefting B3GALTL Ellen McDonagh commented on B3GALTL
Clefting TWIST2 Helen Brittain reviewed TWIST2
Clefting ALG9 Helen Brittain reviewed ALG9
Clefting DLX4 Helen Brittain reviewed DLX4
Clefting DDX3X Helen Brittain reviewed DDX3X
Clefting SEC23A Helen Brittain reviewed SEC23A
Clefting TBX15 Helen Brittain reviewed TBX15
Clefting RYR1 Helen Brittain reviewed RYR1
Clefting MED25 Helen Brittain reviewed MED25
Clefting RBPJ Helen Brittain reviewed RBPJ
Clefting WDR60 Helen Brittain reviewed WDR60
Clefting WDR35 Helen Brittain reviewed WDR35
Clefting WDR19 Helen Brittain reviewed WDR19
Clefting TTC21B Helen Brittain reviewed TTC21B
Clefting IFT52 Helen Brittain reviewed IFT52
Clefting WDR34 Helen Brittain reviewed WDR34
Clefting DDX59 Helen Brittain reviewed DDX59
Clefting MEOX1 Helen Brittain reviewed MEOX1
Clefting SON Helen Brittain reviewed SON
Clefting TELO2 Helen Brittain reviewed TELO2
Clefting MAPRE2 Helen Brittain reviewed MAPRE2
Clefting TUBB Helen Brittain reviewed TUBB
Clefting PHF8 Helen Brittain reviewed PHF8
Clefting EIF2S3 Helen Brittain reviewed EIF2S3
Clefting KAT6A Helen Brittain reviewed KAT6A
Clefting CTCF Helen Brittain reviewed CTCF
Clefting EBP Helen Brittain reviewed EBP
Clefting MBTPS2 Helen Brittain reviewed MBTPS2
Clefting CHST14 Helen Brittain reviewed CHST14
Clefting KCNJ2 Helen Brittain reviewed KCNJ2
Clefting SEPT9 Helen Brittain reviewed SEPT9
Clefting NOTCH1 Helen Brittain reviewed NOTCH1
Clefting EOGT Helen Brittain reviewed EOGT
Clefting DOCK6 Helen Brittain reviewed DOCK6
Clefting DLL4 Helen Brittain reviewed DLL4
Clefting ARHGAP31 Helen Brittain reviewed ARHGAP31
Clefting SIX5 Helen Brittain reviewed SIX5
Clefting SIX1 Helen Brittain reviewed SIX1
Clefting EYA1 Helen Brittain reviewed EYA1
Clefting PAX3 Helen Brittain reviewed PAX3
Clefting CTNND1 Helen Brittain reviewed CTNND1
Clefting CHD1 Helen Brittain reviewed CHD1
Clefting GRHL3 Helen Brittain reviewed GRHL3
Clefting IRF6 Helen Brittain reviewed IRF6
Clefting ZIC3 Helen Brittain reviewed ZIC3
Clefting POLR1D Helen Brittain reviewed POLR1D
Clefting POLR1C Helen Brittain reviewed POLR1C
Clefting TCOF1 Helen Brittain reviewed TCOF1
Clefting COL2A1 Helen Brittain reviewed COL2A1
Clefting DHCR7 Helen Brittain reviewed DHCR7
Clefting GPC3 Helen Brittain reviewed GPC3
Clefting IFT140 Helen Brittain reviewed IFT140
Clefting NEK1 Helen Brittain reviewed NEK1
Clefting DYNC2H1 Helen Brittain reviewed DYNC2H1
Clefting IFT80 Helen Brittain reviewed IFT80
Clefting DYNC2LI1 Helen Brittain reviewed DYNC2LI1
Clefting KIAA0586 Helen Brittain reviewed KIAA0586
Clefting IFT172 Helen Brittain reviewed IFT172
Clefting ROR2 Helen Brittain reviewed ROR2
Clefting DVL1 Helen Brittain reviewed DVL1
Clefting WNT5A Helen Brittain reviewed WNT5A
Clefting ESCO2 Helen Brittain reviewed ESCO2
Clefting DHODH Helen Brittain reviewed DHODH
Clefting B3GLCT Helen Brittain reviewed B3GLCT*
Clefting FLNA Helen Brittain reviewed FLNA
Clefting AMER1 Helen Brittain reviewed AMER1
Clefting C2CD3 Helen Brittain reviewed C2CD3
Clefting C5orf42 Helen Brittain reviewed C5orf42
Clefting TCTN3 Helen Brittain reviewed TCTN3
Clefting OFD1 Helen Brittain reviewed OFD1
Clefting SPECC1L Helen Brittain reviewed SPECC1L
Clefting MID1 Helen Brittain reviewed MID1
Clefting EFTUD2 Helen Brittain reviewed EFTUD2
Clefting EDNRA Helen Brittain reviewed EDNRA
Clefting FOXC2 Helen Brittain reviewed FOXC2
Clefting TGFB3 Helen Brittain reviewed TGFB3
Clefting SMAD3 Helen Brittain reviewed SMAD3
Clefting TGFBR1 Helen Brittain reviewed TGFBR1
Clefting SALL4 Helen Brittain reviewed SALL4
Clefting EFNB1 Helen Brittain reviewed EFNB1
Clefting HDAC8 Helen Brittain reviewed HDAC8
Clefting SMC3 Helen Brittain reviewed SMC3
Clefting SMC1A Helen Brittain reviewed SMC1A
Clefting NIPBL Helen Brittain reviewed NIPBL
Clefting CHD7 Helen Brittain reviewed CHD7
Clefting SNRPB Helen Brittain reviewed SNRPB
Clefting TGDS Helen Brittain reviewed TGDS
Clefting SOX9 Helen Brittain reviewed SOX9
Clefting TXNL4A Helen Brittain reviewed TXNL4A
Clefting TFAP2A Helen Brittain reviewed TFAP2A
Clefting ASXL1 Helen Brittain reviewed ASXL1
Clefting CDKN1C Helen Brittain reviewed CDKN1C
Clefting PTCH1 Helen Brittain reviewed PTCH1
Clefting ACTG1 Helen Brittain reviewed ACTG1
Clefting ACTB Helen Brittain reviewed ACTB
Clefting PIEZO2 Helen Brittain reviewed PIEZO2
Clefting FGFR2 Helen Brittain reviewed FGFR2
Clefting TP63 Helen Brittain reviewed TP63
Clefting ZSWIM6 Helen Brittain reviewed ZSWIM6
Clefting SF3B4 Helen Brittain reviewed SF3B4
Clefting KIF7 Helen Brittain reviewed KIF7
Clefting FGD1 Helen Brittain reviewed FGD1
Clefting COLEC10 Helen Brittain reviewed COLEC10
Clefting COLEC11 Helen Brittain reviewed COLEC11
Clefting MASP1 Helen Brittain reviewed MASP1
Clefting SLC26A2 Ellen McDonagh classified SLC26A2 as green
Clefting SOX2 Helen Brittain reviewed SOX2
Clefting SMOC1 Helen Brittain reviewed SMOC1
Clefting RPS19 Helen Brittain reviewed RPS19
Clefting RPS17 Helen Brittain reviewed RPS17
Clefting RBM8A Helen Brittain reviewed RBM8A
Clefting RAI1 Helen Brittain reviewed RAI1
Clefting SMS Helen Brittain reviewed SMS
Clefting SMAD4 Helen Brittain reviewed SMAD4
Clefting SLC26A2 Helen Brittain reviewed SLC26A2
Clefting SKI Helen Brittain reviewed SKI
Clefting SIX3 Helen Brittain reviewed SIX3
Clefting SHH Helen Brittain reviewed SHH
Clefting SCARF2 Helen Brittain reviewed SCARF2
Clefting SATB2 Helen Brittain reviewed SATB2
Clefting RPS26 Helen Brittain reviewed RPS26
Clefting RPL5 Helen Brittain reviewed RPL5
Clefting RBM10 Helen Brittain reviewed RBM10
Clefting RPS28 Helen Brittain reviewed RPS28
Clefting RARB Helen Brittain reviewed RARB
Clefting SLC26A2 Louise Daugherty classified SLC26A2 as amber
Clefting HOXA2 Louise Daugherty classified HOXA2 as red
Clefting KDM1A Louise Daugherty classified KDM1A as red
Clefting HOXA2 Louise Daugherty edited their review of HOXA2
Clefting BMP4 Louise Daugherty classified BMP4 as red
Clefting MEIS2 Louise Daugherty classified MEIS2 as green
Clefting COL9A2 Louise Daugherty classified COL9A2 as amber
Clefting FLNA Louise Daugherty classified FLNA as amber
Clefting ANKRD11 Louise Daugherty classified ANKRD11 as green
Clefting NEDD4L Louise Daugherty classified NEDD4L as green
Clefting NEDD4L Louise Daugherty classified NEDD4L as green
Clefting NEDD4L Louise Daugherty commented on NEDD4L
Clefting ARHGAP29 Louise Daugherty classified ARHGAP29 as red
Clefting MEIS2 Louise Daugherty classified MEIS2 as amber
Clefting MEIS2 Louise Daugherty commented on MEIS2
Clefting KMT2D Louise Daugherty classified KMT2D as green
Clefting KMT2D Louise Daugherty commented on KMT2D
Clefting KDM6A Louise Daugherty classified KDM6A as green
Clefting KDM6A Louise Daugherty commented on KDM6A
Clefting ARHGAP29 Louise Daugherty edited their review of ARHGAP29
Clefting ARHGAP29 Louise Daugherty commented on ARHGAP29
Clefting ARHGAP29 Louise Daugherty reviewed ARHGAP29
Clefting SPECC1L Louise Daugherty commented on SPECC1L
Clefting SOX9 Louise Daugherty commented on SOX9
Clefting FSHMD1A Ellen McDonagh marked FSHMD1A as ready
Clefting SLC26A2 Louise Daugherty commented on SLC26A2
Clefting FLNA Louise Daugherty classified FLNA as amber
Clefting MSX1 Louise Daugherty classified MSX1 as green
Clefting MSX1 Louise Daugherty commented on MSX1
Clefting KDM1A Louise Daugherty classified KDM1A as amber
Clefting KDM1A Louise Daugherty commented on KDM1A
Clefting HOXA2 Louise Daugherty classified HOXA2 as amber
Clefting HOXA2 Louise Daugherty commented on HOXA2
Clefting GYPE Louise Daugherty commented on GYPE
Clefting FSHMD1A Louise Daugherty commented on FSHMD1A
Clefting FLNB Louise Daugherty classified FLNB as amber
Clefting FLNB Louise Daugherty commented on FLNB
Clefting FLNA Louise Daugherty commented on FLNA
Clefting DLX4 Louise Daugherty commented on DLX4
Clefting COL9A2 Louise Daugherty commented on COL9A2
Clefting ANKRD11 Louise Daugherty classified ANKRD11 as amber
Clefting ANKRD11 Louise Daugherty commented on ANKRD11
Clefting COL9A1 Louise Daugherty classified COL9A1 as green
Clefting COL9A1 Louise Daugherty commented on COL9A1
Clefting BMP4 Louise Daugherty edited their review of BMP4
Clefting TP63 Louise Daugherty commented on TP63
Clefting FSHMD1A Ellen McDonagh edited their review of FSHMD1A
Clefting COL2A1 Louise Daugherty classified COL2A1 as green
Clefting COL2A1 Louise Daugherty commented on COL2A1
Clefting COL11A2 Louise Daugherty classified COL11A2 as green
Clefting COL11A2 Louise Daugherty commented on COL11A2
Clefting TBX22 Louise Daugherty classified TBX22 as green
Clefting TBX22 Louise Daugherty commented on TBX22
Clefting SUMO1 Louise Daugherty classified SUMO1 as red
Clefting SUMO1 Louise Daugherty commented on SUMO1
Clefting SATB2 Louise Daugherty classified SATB2 as green
Clefting SATB2 Louise Daugherty commented on SATB2
Clefting PVRL1 Louise Daugherty classified PVRL1 as green
Clefting BMP4 Louise Daugherty commented on BMP4
Clefting COL11A1 Ellen McDonagh marked COL11A1 as ready
Clefting COL11A1 Ellen McDonagh classified COL11A1 as green
Clefting COL11A1 Ellen McDonagh commented on COL11A1
Clefting IRF6 Ellen McDonagh marked IRF6 as ready
Clefting IRF6 Ellen McDonagh classified IRF6 as green
Clefting IRF6 Ellen McDonagh commented on IRF6
Clefting IRF6 Ellen McDonagh classified IRF6 as green
Clefting ARHGAP29 Philip Stanier added ARHGAP29 to panel
Clefting ARHGAP29 Philip Stanier reviewed ARHGAP29
Clefting SUMO1 Philip Stanier reviewed SUMO1
Clefting PVRL1 Louise Daugherty commented on PVRL1
Clefting FSHMD1A Usha Kini reviewed FSHMD1A
Clefting NEDD4L Usha Kini edited their review of NEDD4L
Clefting UBB Usha Kini reviewed UBB
Clefting SPECC1L Usha Kini reviewed SPECC1L
Clefting SLC26A2 Usha Kini reviewed SLC26A2
Clefting KDM1A Usha Kini reviewed KDM1A
Clefting HOXA2 Usha Kini reviewed HOXA2
Clefting GYPE Usha Kini reviewed GYPE
Clefting FLNB Usha Kini reviewed FLNB
Clefting FLNA Usha Kini reviewed FLNA
Clefting DLX4 Usha Kini reviewed DLX4
Clefting COL9A2 Usha Kini reviewed COL9A2
Clefting COL9A1 Usha Kini reviewed COL9A1
Clefting ANKRD11 Usha Kini reviewed ANKRD11
Clefting KDM6A Usha Kini added KDM6A to panel
Clefting KDM6A Usha Kini reviewed KDM6A
Clefting KMT2D Usha Kini added KMT2D to panel
Clefting KMT2D Usha Kini reviewed KMT2D
Clefting COL11A2 Usha Kini reviewed COL11A2
Clefting COL11A1 Usha Kini reviewed COL11A1
Clefting COL2A1 Usha Kini reviewed COL2A1
Clefting MEIS2 Usha Kini added MEIS2 to panel
Clefting MEIS2 Usha Kini reviewed MEIS2
Clefting NEDD4L Usha Kini added NEDD4L to panel
Clefting NEDD4L Usha Kini reviewed NEDD4L
Clefting SUMO1 Usha Kini reviewed SUMO1
Clefting BMP4 Usha Kini reviewed BMP4
Clefting SOX9 Usha Kini reviewed SOX9
Clefting MSX1 Usha Kini reviewed MSX1
Clefting TBX22 Usha Kini reviewed TBX22
Clefting SATB2 Usha Kini reviewed SATB2
Clefting PVRL1 Usha Kini reviewed PVRL1
Clefting TP63 Usha Kini edited their review of TP63
Clefting TP63 Usha Kini reviewed TP63
Clefting IRF6 Usha Kini reviewed IRF6
Clefting FSHMD1A Ellen McDonagh commented on FSHMD1A
Clefting FSHMD1A Ellen McDonagh classified FSHMD1A as grey
Clefting SOX9 Ellen McDonagh added SOX9 to panel
Clefting SOX9 Ellen McDonagh reviewed SOX9
Clefting TBX22 Philip Stanier reviewed TBX22
Clefting Ellen McDonagh approved panel