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Skeletal dysplasia v1.145 CA2 Eleanor Williams Source NHS GMS was added to CA2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 C2CD3 Eleanor Williams Source NHS GMS was added to C2CD3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 BMPR1B Eleanor Williams Source NHS GMS was added to BMPR1B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 BMPER Eleanor Williams Source NHS GMS was added to BMPER.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 BMP2 Eleanor Williams Source NHS GMS was added to BMP2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 BMP1 Eleanor Williams Source NHS GMS was added to BMP1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 BHLHA9 Eleanor Williams Source NHS GMS was added to BHLHA9.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 B9D1 Eleanor Williams Source NHS GMS was added to B9D1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 B4GALT7 Eleanor Williams Source NHS GMS was added to B4GALT7.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 B3GAT3 Eleanor Williams Source NHS GMS was added to B3GAT3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 B3GALT6 Eleanor Williams Source NHS GMS was added to B3GALT6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ATP7A Eleanor Williams Source NHS GMS was added to ATP7A.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ATP6V0A2 Eleanor Williams Source NHS GMS was added to ATP6V0A2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ASXL2 Eleanor Williams Source NHS GMS was added to ASXL2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ASXL1 Eleanor Williams Source NHS GMS was added to ASXL1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ARSE Eleanor Williams Source NHS GMS was added to ARSE.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ARSB Eleanor Williams Source NHS GMS was added to ARSB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ARID1B Eleanor Williams Source NHS GMS was added to ARID1B.
Skeletal dysplasia v1.145 ARHGAP31 Eleanor Williams Source NHS GMS was added to ARHGAP31.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ANTXR2 Eleanor Williams Source NHS GMS was added to ANTXR2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ANO5 Eleanor Williams Source NHS GMS was added to ANO5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ANKRD11 Eleanor Williams Source NHS GMS was added to ANKRD11.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ANKH Eleanor Williams Source NHS GMS was added to ANKH.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 AMER1 Eleanor Williams Source NHS GMS was added to AMER1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ALX4 Eleanor Williams Source NHS GMS was added to ALX4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ALX3 Eleanor Williams Source NHS GMS was added to ALX3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ALX1 Eleanor Williams Source NHS GMS was added to ALX1.
Skeletal dysplasia v1.145 ALPL Eleanor Williams Source NHS GMS was added to ALPL.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ALG9 Eleanor Williams Source NHS GMS was added to ALG9.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ALG3 Eleanor Williams Source NHS GMS was added to ALG3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ALG12 Eleanor Williams Source NHS GMS was added to ALG12.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 AKT1 Eleanor Williams Source NHS GMS was added to AKT1.
Skeletal dysplasia v1.145 AGPS Eleanor Williams Source NHS GMS was added to AGPS.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 AGA Eleanor Williams Source NHS GMS was added to AGA.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ADAMTSL2 Eleanor Williams Source NHS GMS was added to ADAMTSL2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ADAMTS17 Eleanor Williams gene: ADAMTS17 was added
gene: ADAMTS17 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: ADAMTS17 was set to
Skeletal dysplasia v1.145 ADAMTS10 Eleanor Williams gene: ADAMTS10 was added
gene: ADAMTS10 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: ADAMTS10 was set to
Skeletal dysplasia v1.145 ACVR1 Eleanor Williams Source NHS GMS was added to ACVR1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ACP5 Eleanor Williams Source NHS GMS was added to ACP5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ACAN Eleanor Williams Source NHS GMS was added to ACAN.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.145 ABL1 Eleanor Williams Source NHS GMS was added to ABL1.
Skeletal dysplasia v1.145 ABCC9 Eleanor Williams Source NHS GMS was added to ABCC9.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.143 ISCA-37501-Loss Louise Daugherty Triplosensitivity Score for ISCA-37501-Loss was changed from 2 to None.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Skeletal dysplasia v1.142 ISCA-37501-Loss Louise Daugherty Classified Region: ISCA-37501-Loss as Green List (high evidence)
Skeletal dysplasia v1.142 ISCA-37501-Loss Louise Daugherty Region: isca-37501-loss has been classified as Green List (High Evidence).
Skeletal dysplasia v1.141 ISCA-37501-Loss Louise Daugherty Region: ISCA-37501-Loss was added
Region: ISCA-37501-Loss was added to Skeletal dysplasia. Sources: Expert list
Mode of inheritance for Region: ISCA-37501-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37501-Loss were set to 20206336; 22052739
Phenotypes for Region: ISCA-37501-Loss were set to Chromosome 17q23.1-q23.2 deletion syndrome, 613355; PMID:20206336 mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, hand, foot and limb abnormalities; PMID: 22052739 Developmental delay, heart defects, microcephaly, postnatal growth retardation, hand, foot and limb abnormalities, sensorineural hearing loss
Review for Region: ISCA-37501-Loss was set to GREEN
Added comment: Sources: Expert list
Skeletal dysplasia v1.140 TRPV6 Helen Brittain Marked gene: TRPV6 as ready
Skeletal dysplasia v1.140 TRPV6 Helen Brittain Added comment: Comment when marking as ready: Sufficient cases, relevant phenotype. Therefore considered green. Also I will add it to the thoracic dystrophies and OI panels in view of the presentation with small chest / respiratory distress and fractures.
Skeletal dysplasia v1.140 TRPV6 Helen Brittain Gene: trpv6 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.140 TRPV6 Helen Brittain Classified gene: TRPV6 as Green List (high evidence)
Skeletal dysplasia v1.140 TRPV6 Helen Brittain Added comment: Comment on list classification: Sufficient cases, relevant phenotype
Skeletal dysplasia v1.140 TRPV6 Helen Brittain Gene: trpv6 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.139 TRPV6 Helen Brittain gene: TRPV6 was added
gene: TRPV6 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: TRPV6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPV6 were set to 29861107
Phenotypes for gene: TRPV6 were set to Hyperparathyroidism, transient neonatal, 618188
Penetrance for gene: TRPV6 were set to unknown
Review for gene: TRPV6 was set to GREEN
Added comment: 6 unrelated children with skeletal abnormalities detected in the third trimester of pregnancy, who presented at birth with elevated serum PTH and alkaline phosphatase activity, with normal or low ionized calcium. Skeletal anomalies included generalized osteopenia, narrow chest, short ribs with multiple healing fractures, and bowing or fractures of long bones. All affected individuals experienced postnatal respiratory difficulties requiring ventilatory support in the first few weeks to months of life. In addition, most showed poor feeding, with some requiring tube feeding.
Sources: Literature
Skeletal dysplasia v1.138 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel
Skeletal dysplasia v1.137 Louise Daugherty List of related panels changed from Unexplained skeletal dysplasia; Skeletal dysplasia; GMS R104 to Unexplained skeletal dysplasia; Skeletal dysplasia
Skeletal dysplasia v1.135 ATXN10_ATTCT Louise Daugherty Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia 603516 to Spinocerebellar ataxia 10 603516
Skeletal dysplasia v1.134 ATXN10_ATTCT Louise Daugherty Phenotypes for STR: ATXN10_ATTCT were changed from Spinocerebellar ataxia , 603516 to Spinocerebellar ataxia 603516
Skeletal dysplasia v1.133 ABL1 Rebecca Foulger Added comment: Comment on mode of pathogenicity: Seleced 'LOF do not cause this phenotype' on advice from Helen Brittain, Clinical Fellow, in view of the postulated gain of function mechanism (two recurent missense variants in PMID:28288113).
Skeletal dysplasia v1.133 ABL1 Rebecca Foulger Mode of pathogenicity for gene: ABL1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Skeletal dysplasia v1.132 ABL1 Rebecca Foulger Classified gene: ABL1 as Amber List (moderate evidence)
Skeletal dysplasia v1.132 ABL1 Rebecca Foulger Gene: abl1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.131 ABL1 Rebecca Foulger gene: ABL1 was added
gene: ABL1 was added to Skeletal dysplasia. Sources: Literature
missense tags were added to gene: ABL1.
Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ABL1 were set to 28288113
Phenotypes for gene: ABL1 were set to Congenital heart defects and skeletal malformations syndrome, 617602
Mode of pathogenicity for gene: ABL1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added comment: Added to Skeletal dysplasia panel with Amber rating as suggested by Helen Brittain. Wang et al, 2017 (PMID:28288113) report ABL1 germline variants cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. They report 2 variants in 4 families (6 individuals). Helen Brittain, clinical fellow, notes that: "the broader skeletal manifestations (scoliosis / pectus) are classically thought of as part of the Marfan / FTAAD spectrum rather than a skeletal dysplasia. Therefore do not think that skeletal dysplasia (or limb panel) would be the primary route for diagnosis here and would opt for amber on the basis that we need to see the phenotype across other cases first."
Sources: Literature
Skeletal dysplasia v1.130 ATXN10_ATTCT Louise Daugherty Classified STR: ATXN10_ATTCT as No list
Skeletal dysplasia v1.130 ATXN10_ATTCT Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Skeletal dysplasia v1.130 ATXN10_ATTCT Louise Daugherty Str: atxn10_attct has been removed from the panel.
Skeletal dysplasia v1.129 Ellen McDonagh List of related panels changed from Unexplained skeletal dysplasia to Unexplained skeletal dysplasia; Skeletal dysplasia; GMS R104
Skeletal dysplasia v1.128 Ellen McDonagh Panel name changed from Unexplained skeletal dysplasia to Skeletal dysplasia
List of related panels changed from Skeletal dysplasia to Unexplained skeletal dysplasia
Skeletal dysplasia v1.127 WISP3 Louise Daugherty commented on gene: WISP3
Skeletal dysplasia v1.127 WISP3 Louise Daugherty Tag new-gene-name tag was added to gene: WISP3.
Skeletal dysplasia v1.127 SLC10A7 Ellen McDonagh commented on gene: SLC10A7: This gene is not related to a disease in OMIM or Gene2Phenotype.
Skeletal dysplasia v1.127 SLC10A7 Ellen McDonagh gene: SLC10A7 was added
gene: SLC10A7 was added to Unexplained skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: SLC10A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC10A7 were set to 30082715
Phenotypes for gene: SLC10A7 were set to skeletal dysplasia and amelogenesis imperfecta
Added comment: PMID: 30082715 reports five different SLC10A7 variants in four patients from four unrelated families and two patients from two distantly related families. The study states that the variants segregated according to a recessive mode of inheritance, however the genotype was not shown on the pedigree diagram. Further evidence was provided in a knockout mouse model that displayed abnormal development of skeletal structures and teeth anomalies.
Sources: Literature
Skeletal dysplasia v1.126 PDE3A Louise Daugherty Phenotypes for gene: PDE3A were changed from Hypertension and brachydactyly syndrome 112410 to Hypertension and brachydactyly syndrome, 112410
Skeletal dysplasia v1.125 PDE3A Louise Daugherty Publications for gene: PDE3A were set to PMID: 25961942; 9696728
Skeletal dysplasia v1.124 DLL4 Louise Daugherty Phenotypes for gene: DLL4 were changed from Adams-Oliver syndrome 6 616589 to Adams-Oliver syndrome 6, 616589
Skeletal dysplasia v1.123 DVL3 Louise Daugherty Phenotypes for gene: DVL3 were changed from Robinow syndrome, autosomal dominant 3 616894 to Robinow syndrome, autosomal dominant 3, 616894
Skeletal dysplasia v1.122 BMP2 Eleanor Williams commented on gene: BMP2: More than 3 families/cases reported in PMID: 29198724 for monoallelic variants in this gene and Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies.
Skeletal dysplasia v1.122 BMP2 Eleanor Williams Publications for gene: BMP2 were set to 19327734; 21357617
Skeletal dysplasia v1.121 BMP2 Eleanor Williams Classified gene: BMP2 as Green List (high evidence)
Skeletal dysplasia v1.121 BMP2 Eleanor Williams Added comment: Comment on list classification: Rating green based on publication (PMID: 29198724) reporting sufficient cases associated with a relevant phenotype. Rating has been checked with Genomics England clinical team.
Skeletal dysplasia v1.121 BMP2 Eleanor Williams Gene: bmp2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.120 CCDC8 Louise Daugherty Classified gene: CCDC8 as Green List (high evidence)
Skeletal dysplasia v1.120 CCDC8 Louise Daugherty Added comment: Comment on list classification: Changed from Red to Green. Sufficient unrelated cases and more than one causative variant, and variants in this gene are currently reported in an external diagnostic lab
Skeletal dysplasia v1.120 CCDC8 Louise Daugherty Gene: ccdc8 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.119 CCDC8 Louise Daugherty Phenotypes for gene: CCDC8 were changed from 3-M syndrome 3 614205 to 3-M syndrome 3, 614205
Skeletal dysplasia v1.118 CCDC8 Louise Daugherty Added comment: Comment on publications: added publication to support gene-disease
Skeletal dysplasia v1.118 CCDC8 Louise Daugherty Publications for gene: CCDC8 were set to
Skeletal dysplasia v1.117 NOTCH1 Eleanor Williams Classified gene: NOTCH1 as Green List (high evidence)
Skeletal dysplasia v1.117 NOTCH1 Eleanor Williams Added comment: Comment on list classification: Rated as green as there are sufficient number of cases/families and Genomics England clinical team have reviewed as being relevant to this panel.
Skeletal dysplasia v1.117 NOTCH1 Eleanor Williams Gene: notch1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.116 SMOC1 Eleanor Williams Classified gene: SMOC1 as Green List (high evidence)
Skeletal dysplasia v1.116 SMOC1 Eleanor Williams Added comment: Comment on list classification: Rated green as sufficient number of cases/families. Reviewed by Genomics England clinical team as appropriate for this panel.
Skeletal dysplasia v1.116 SMOC1 Eleanor Williams Gene: smoc1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.115 SMOC1 Eleanor Williams gene: SMOC1 was added
gene: SMOC1 was added to Unexplained skeletal dysplasia. Sources: Expert Review
Mode of inheritance for gene: SMOC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMOC1 were set to 21194678; 21194680
Phenotypes for gene: SMOC1 were set to Ophthalmo-acromelic syndrome; Microphthalmia with limb anomalies 206920; Polydactyly
Review for gene: SMOC1 was set to GREEN
Added comment: Sourced from Genetic Home Reference. >3 cases/family reports for homozygous loss of function variants in this gene, in affacted individuals with microphthalmia with limb anomalies (see publications). This is a confirmed DD gene for OPHTHALMOACROMELIC SYNDROME. HPO terms from Gene2Phenotype include
Camptodactyly of 2nd-5th fingers, Foot oligodactyly, Hand oligodactyly, Postaxial foot polydactyly, Postaxial hand polydactyly, Toe syndactyly.
Sources: Expert Review
Skeletal dysplasia v1.114 NOTCH1 Eleanor Williams gene: NOTCH1 was added
gene: NOTCH1 was added to Unexplained skeletal dysplasia. Sources: Expert Review
Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NOTCH1 were set to 25132448; 25963545; 27077170; 25132448
Phenotypes for gene: NOTCH1 were set to Adams-Oliver syndrome 5, 616028; Combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly); AOS; Limb, scalp and skull defects
Review for gene: NOTCH1 was set to GREEN
Added comment: There are more than three unrelated cases reported for variants in NOTCH1 causing Adams-Oliver type 5 syndrome
Sources: Expert Review
Skeletal dysplasia v1.113 DVL3 Sarah Leigh Publications for gene: DVL3 were set to PMID: 26924530
Skeletal dysplasia v1.113 DVL3 Sarah Leigh Classified gene: DVL3 as Green List (high evidence)
Skeletal dysplasia v1.113 DVL3 Sarah Leigh Gene: dvl3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.112 DLL4 Sarah Leigh Publications for gene: DLL4 were set to PMID: 26299364
Skeletal dysplasia v1.111 DLL4 Sarah Leigh Classified gene: DLL4 as Green List (high evidence)
Skeletal dysplasia v1.111 DLL4 Sarah Leigh Gene: dll4 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.110 PDE3A Sarah Leigh Publications for gene: PDE3A were set to PMID: 25961942; 9696728
Skeletal dysplasia v1.110 PDE3A Sarah Leigh Classified gene: PDE3A as Green List (high evidence)
Skeletal dysplasia v1.110 PDE3A Sarah Leigh Gene: pde3a has been classified as Green List (High Evidence).
Skeletal dysplasia v1.109 DVL3 Rachel Jones gene: DVL3 was added
gene: DVL3 was added to Unexplained skeletal dysplasia. Sources: Other
Mode of inheritance for gene: DVL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DVL3 were set to PMID: 26924530
Phenotypes for gene: DVL3 were set to Robinow syndrome, autosomal dominant 3 616894
Penetrance for gene: DVL3 were set to unknown
Review for gene: DVL3 was set to GREEN
Added comment: 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
Skeletal dysplasia v1.108 DLL4 Rachel Jones gene: DLL4 was added
gene: DLL4 was added to Unexplained skeletal dysplasia. Sources: Other
Mode of inheritance for gene: DLL4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLL4 were set to PMID: 26299364
Phenotypes for gene: DLL4 were set to Adams-Oliver syndrome 6 616589
Penetrance for gene: DLL4 were set to Incomplete
Review for gene: DLL4 was set to GREEN
Added comment: Meester et al PMID: 26299364 using candidate gene approach identified 9 heterozygous mutations in DLL4 (which is a NOTCH ligand) from 91 families - same pathway as other genes previously idetified to cause Adams Oliver syndrome.

No functional studies were performed, but software predicted pathogenicity of missense mutations.

Evidence of non penetrance in the paper - affected siblings inheriting mutation from seemingly unaffected parent.
Sources: Other
Skeletal dysplasia v1.107 PDE3A Rachel Jones gene: PDE3A was added
gene: PDE3A was added to Unexplained skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PDE3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDE3A were set to PMID: 25961942; 9696728
Phenotypes for gene: PDE3A were set to Hypertension and brachydactyly syndrome 112410
Penetrance for gene: PDE3A were set to Complete
Mode of pathogenicity for gene: PDE3A 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: PDE3A was set to GREEN
Added comment: Mutations appear to be gain of function missense as per PMID 25961942*. 6 missense variants identified in unrelated families with dominant hypertension with brachydactyly (HTNB)
*Article link https://www.nature.com/articles/ng.3302

The article PMID: 9696728 gives more information about the clinical phenotype - their Canadian and American families showed linkage to an area of chromosome 12p containing PDE3A, as had a previous Turkish family.
http://annals.org/aim/fullarticle/711593/families-autosomal-dominant-brachydactyly-type-e-short-stature-severe-hypertension.
Sources: Literature
Skeletal dysplasia v1.106 ARHGAP31 Eleanor Williams Publications for gene: ARHGAP31 were set to 21565291
Skeletal dysplasia v1.105 ARHGAP31 Eleanor Williams commented on gene: ARHGAP31
Skeletal dysplasia v1.105 ISCA-37418-Loss Louise Daugherty Region: ISCA-37418-Loss was added
Region: ISCA-37418-Loss was added to Unexplained skeletal dysplasia. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37418-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37418-Loss were set to Potocki-Lupski syndrome; hypotonia, poor feeding, failure to thrive, developmental delay particularly cognitive and language deficity, mild-moderate intellectual deficit, and neuropsychiatric disorders; Smith-Magenis syndrome; Structural cardiovascular anomalies (dilated aortic root, bicommissural aortic valve, atrial/ventricular and septal defects) and sleep disturbance; 182290; moderate intellectual disability, delayed speech and language skills, distinctive facial features, sleep disturbances, and behavioral problems; hypotonia, failure to thrive, mental retardation, pervasive developmental disorders, congenital anomalies; Dental abnormalities
Skeletal dysplasia v1.105 ISCA-37434-Loss Louise Daugherty Region: ISCA-37434-Loss was added
Region: ISCA-37434-Loss was added to Unexplained skeletal dysplasia. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37434-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37434-Loss were set to 17918734; 22766398; 18245432
Phenotypes for Region: ISCA-37434-Loss were set to posteriorly rotated, low-set, abnormal ears; brachycephaly; epicanthus; heart defects; pointed chin; deep-set eyes; microcephaly; hypotonia; seizures; poor/absent speech; central nervous system anomalies; large anterior fontanels; microbrachycephaly; mental retardation; growth impairment; large, late-closing anterior fontanel; flat nose; nasal bridge; developmental delay; hearing impairment; distinct dysmorphic features; 1p36 deletion syndrome; 607872
Skeletal dysplasia v1.105 ISCA-37441-Loss Louise Daugherty Region: ISCA-37441-Loss was added
Region: ISCA-37441-Loss was added to Unexplained skeletal dysplasia. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37441-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37441-Loss were set to 15852040; 16319823; 20140962
Phenotypes for Region: ISCA-37441-Loss were set to Potocki-Shaffer syndrome; multiple exostoses; biparietal foramina; intellectual disability; strabismus; minor craniofacial anomalies; myopia; ophthalmologic anomalies; 601224; mental retardation; enlarged anterior fontanel; genital abnormalities in males; parietal foramina; developmental delay
Skeletal dysplasia v1.105 ISCA-37394-Loss Louise Daugherty Region: ISCA-37394-Loss was added
Region: ISCA-37394-Loss was added to Unexplained skeletal dysplasia. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37394-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37394-Loss were set to 25402011; 23188045
Phenotypes for Region: ISCA-37394-Loss were set to 2q37 deletion syndrome is a condition that can affect many parts of the body. This condition is characterized by weak muscle tone (hypotonia) in infancy, mild to severe intellectual disability and developmental delay, behavioral problems, characteristic facial features, and other physical abnormalities. PMID 23188045 brachydactyly-mental retardation syndrome, Albright hereditary osteodystrophy-like syndrome, developmental delay and behavioural abnormalities in combination; 600430
Skeletal dysplasia v1.105 ISCA-37406-Loss Louise Daugherty Region: ISCA-37406-Loss was added
Region: ISCA-37406-Loss was added to Unexplained skeletal dysplasia. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37406-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37406-Loss were set to 10573006; 16783566
Phenotypes for Region: ISCA-37406-Loss were set to PMID: 10573006 death in infancy, accessory spleens, hypoplastic left heart, abnormal pulmonary lobulation, renal agenesis (patient 1), severe neonatal seizures (patient 2). PMID 16783566: failure to thrive, life-threatening malformations, and/or critical infections, and all died in infancy (5 weeks, 7 months, and 9 months, respectivelyFrom Genetics Home Reference: short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes; 610543
Skeletal dysplasia C21orf2 Louise Daugherty commented on gene: C21orf2
Skeletal dysplasia MAP3K7 Helen Brittain marked gene: MAP3K7 as ready
Skeletal dysplasia MAP3K7 Helen Brittain classified MAP3K7 as Green List (high evidence)
Skeletal dysplasia MAP3K7 Helen Brittain Added gene to panel
Skeletal dysplasia ATXN10 Ellen McDonagh Added STR to panel
Skeletal dysplasia C2orf71 Louise Daugherty commented on gene: C2orf71
Skeletal dysplasia GREM1 Rachel Jones reviewed GREM1
Skeletal dysplasia SFRP4 Ellen McDonagh classified SFRP4 as Green List (high evidence)
Skeletal dysplasia SFRP4 Ellen McDonagh classified SFRP4 as Amber List (moderate evidence)
Skeletal dysplasia SFRP4 Ellen McDonagh Added gene to panel
Skeletal dysplasia FBLN1 Sarah Leigh classified FBLN1 as Amber List (moderate evidence)
Skeletal dysplasia FBLN1 Sarah Leigh edited their review of FBLN1
Skeletal dysplasia C5orf42 Louise Daugherty commented on C5orf42
Skeletal dysplasia MIR17HG Louise Daugherty classified MIR17HG as Amber List (moderate evidence)
Skeletal dysplasia MIR17HG Louise Daugherty commented on MIR17HG
Skeletal dysplasia MIR17HG Louise Daugherty edited their review of MIR17HG
Skeletal dysplasia MIR17HG Louise Daugherty edited their review of MIR17HG
Skeletal dysplasia LTBP3 Sarah Leigh classified LTBP3 as Green List (high evidence)
Skeletal dysplasia LTBP3 Sarah Leigh Added gene to panel
Skeletal dysplasia PRMT7 Helen Brittain marked PRMT7 as ready
Skeletal dysplasia PRMT7 Helen Brittain classified PRMT7 as Green List (high evidence)
Skeletal dysplasia PRMT7 Helen Brittain Added gene to panel
Skeletal dysplasia ASXL2 Sarah Leigh classified ASXL2 as Green List (high evidence)
Skeletal dysplasia ASXL2 Sarah Leigh Added gene to panel
Skeletal dysplasia RBPJ Louise Daugherty edited their review of RBPJ
Skeletal dysplasia RBPJ Louise Daugherty classified RBPJ as green
Skeletal dysplasia RBPJ Louise Daugherty classified RBPJ as amber
Skeletal dysplasia RBPJ Louise Daugherty commented on RBPJ
Skeletal dysplasia PUF60 Louise Daugherty classified PUF60 as green
Skeletal dysplasia PUF60 Louise Daugherty added PUF60 to panel
Skeletal dysplasia PUF60 Louise Daugherty reviewed PUF60
Skeletal dysplasia EXTL3 Ellen McDonagh classified EXTL3 as green
Skeletal dysplasia EXTL3 Ellen McDonagh added EXTL3 to panel
Skeletal dysplasia EXTL3 Ellen McDonagh reviewed EXTL3
Skeletal dysplasia EED Sarah Leigh classified EED as green
Skeletal dysplasia EED Sarah Leigh classified EED as green
Skeletal dysplasia EED Sarah Leigh added EED to panel
Skeletal dysplasia EED Sarah Leigh reviewed EED
Skeletal dysplasia GPC6 Sarah Leigh edited their review of GPC6
Skeletal dysplasia GZF1 Sarah Leigh classified GZF1 as green
Skeletal dysplasia GZF1 Sarah Leigh added GZF1 to panel
Skeletal dysplasia GZF1 Sarah Leigh reviewed GZF1
Skeletal dysplasia MCM5 Sarah Leigh added MCM5 to panel
Skeletal dysplasia MCM5 Sarah Leigh reviewed MCM5
Skeletal dysplasia YY1 Sarah Leigh classified YY1 as green
Skeletal dysplasia YY1 Sarah Leigh added YY1 to panel
Skeletal dysplasia YY1 Sarah Leigh reviewed YY1
Skeletal dysplasia DACT1 Louise Daugherty added DACT1 to panel
Skeletal dysplasia DACT1 Louise Daugherty reviewed DACT1
Skeletal dysplasia DCC Sarah Leigh classified DCC as amber
Skeletal dysplasia DCC Sarah Leigh classified DCC as amber
Skeletal dysplasia DCC Sarah Leigh added DCC to panel
Skeletal dysplasia DCC Sarah Leigh reviewed DCC
Skeletal dysplasia CTSK Ellen McDonagh commented on CTSK
Skeletal dysplasia FAM58A Louise Daugherty commented on FAM58A
Skeletal dysplasia GNAS Helen Brittain commented on GNAS
Skeletal dysplasia HNRNPK Ellen McDonagh classified HNRNPK as amber
Skeletal dysplasia HNRNPK Ellen McDonagh classified HNRNPK as amber
Skeletal dysplasia HNRNPK Ellen McDonagh added HNRNPK to panel
Skeletal dysplasia HNRNPK Ellen McDonagh reviewed HNRNPK
Skeletal dysplasia IFT52 Arianna Tucci classified IFT52 as green
Skeletal dysplasia IFT52 Arianna Tucci classified IFT52 as green
Skeletal dysplasia IFT81 Arianna Tucci classified IFT81 as green
Skeletal dysplasia IFT81 Arianna Tucci added IFT81 to panel
Skeletal dysplasia IFT81 Arianna Tucci reviewed IFT81
Skeletal dysplasia IFT52 Arianna Tucci added IFT52 to panel
Skeletal dysplasia IFT52 Arianna Tucci reviewed IFT52
Skeletal dysplasia IFT43 Arianna Tucci marked IFT43 as ready
Skeletal dysplasia IFT43 Arianna Tucci commented on IFT43
Skeletal dysplasia IFT43 Arianna Tucci classified IFT43 as green
Skeletal dysplasia DYNC2LI1 Arianna Tucci marked DYNC2LI1 as ready
Skeletal dysplasia DYNC2LI1 Arianna Tucci classified DYNC2LI1 as green
Skeletal dysplasia DYNC2LI1 Arianna Tucci classified DYNC2LI1 as green
Skeletal dysplasia DYNC2LI1 Arianna Tucci classified DYNC2LI1 as green
Skeletal dysplasia DYNC2LI1 Arianna Tucci added DYNC2LI1 to panel
Skeletal dysplasia DYNC2LI1 Arianna Tucci reviewed DYNC2LI1
Skeletal dysplasia CSPP1 Arianna Tucci classified CSPP1 as green
Skeletal dysplasia CSPP1 Arianna Tucci added CSPP1 to panel
Skeletal dysplasia CSPP1 Arianna Tucci reviewed CSPP1
Skeletal dysplasia FAM111A Louise Daugherty commented on FAM111A
Skeletal dysplasia TCTEX1D2 Helen Brittain marked TCTEX1D2 as ready
Skeletal dysplasia TCTEX1D2 Helen Brittain classified TCTEX1D2 as green
Skeletal dysplasia TCTEX1D2 Helen Brittain added TCTEX1D2 to panel
Skeletal dysplasia TCTEX1D2 Helen Brittain reviewed TCTEX1D2
Skeletal dysplasia POP1 Rebecca Foulger classified POP1 as green
Skeletal dysplasia POP1 Rebecca Foulger classified POP1 as green
Skeletal dysplasia POP1 Rebecca Foulger commented on POP1
Skeletal dysplasia POP1 Rebecca Foulger commented on POP1
Skeletal dysplasia POP1 Rebecca Foulger edited their review of POP1
Skeletal dysplasia NANS Helen Brittain marked NANS as ready
Skeletal dysplasia NANS Helen Brittain classified NANS as green
Skeletal dysplasia NANS Helen Brittain classified NANS as green
Skeletal dysplasia NANS Helen Brittain added NANS to panel
Skeletal dysplasia NANS Helen Brittain reviewed NANS
Skeletal dysplasia POP1 Rebecca Foulger commented on POP1
Skeletal dysplasia PIGT Sarah Leigh classified PIGT as green
Skeletal dysplasia PIGT Sarah Leigh classified PIGT as green
Skeletal dysplasia VAC14 Rebecca Foulger commented on VAC14
Skeletal dysplasia VAC14 Rebecca Foulger added VAC14 to panel
Skeletal dysplasia VAC14 Rebecca Foulger reviewed VAC14
Skeletal dysplasia FGF9 Sarah Leigh edited their review of FGF9
Skeletal dysplasia FGF9 Sarah Leigh classified FGF9 as red
Skeletal dysplasia FBXW4 Sarah Leigh classified FBXW4 as red
Skeletal dysplasia OFD1 Ellen McDonagh commented on OFD1
Skeletal dysplasia NSDHL Ellen McDonagh commented on NSDHL
Skeletal dysplasia FLNA Ellen McDonagh commented on FLNA
Skeletal dysplasia SHFM1 Louise Daugherty commented on SHFM1
Skeletal dysplasia SHFM1 Louise Daugherty classified SHFM1 as red
Skeletal dysplasia RNU4ATAC Ellen McDonagh commented on RNU4ATAC
Skeletal dysplasia RMRP Ellen McDonagh commented on RMRP
Skeletal dysplasia MIR17HG Ellen McDonagh commented on MIR17HG
Skeletal dysplasia DFNB31 Louise Daugherty commented on DFNB31
Skeletal dysplasia SHFM1 Louise Daugherty commented on SHFM1
Skeletal dysplasia ATXN10 Ellen McDonagh commented on ATXN10
Skeletal dysplasia Sarah Leigh promoted panel to version 1
Skeletal dysplasia IDH1 Sarah Leigh classified IDH1 as green
Skeletal dysplasia SNX10 Sarah Leigh classified SNX10 as green
Skeletal dysplasia PEX5 Sarah Leigh classified PEX5 as green
Skeletal dysplasia CREBBP Sarah Leigh marked CREBBP as ready
Skeletal dysplasia CREBBP Sarah Leigh commented on CREBBP
Skeletal dysplasia CREBBP Sarah Leigh classified CREBBP as green
Skeletal dysplasia ALG9 Sarah Leigh classified ALG9 as green
Skeletal dysplasia COL9A1 Sarah Leigh classified COL9A1 as green
Skeletal dysplasia ACAN Sarah Leigh classified ACAN as green
Skeletal dysplasia SHFM1 Sarah Leigh classified SHFM1 as grey
Skeletal dysplasia USP9X Ana Beleza reviewed USP9X
Skeletal dysplasia LOXL3 Sarah Leigh marked LOXL3 as ready
Skeletal dysplasia LOXL3 Sarah Leigh commented on LOXL3
Skeletal dysplasia DOLPP1 Sarah Leigh marked DOLPP1 as ready
Skeletal dysplasia DOLPP1 Sarah Leigh commented on DOLPP1
Skeletal dysplasia RAB33B Sarah Leigh classified RAB33B as red
Skeletal dysplasia RAB33B Sarah Leigh classified RAB33B as red
Skeletal dysplasia ZBTB16 Sarah Leigh marked ZBTB16 as ready
Skeletal dysplasia ZBTB16 Sarah Leigh commented on ZBTB16
Skeletal dysplasia XYLT2 Sarah Leigh marked XYLT2 as ready
Skeletal dysplasia XYLT2 Sarah Leigh commented on XYLT2
Skeletal dysplasia XYLT2 Sarah Leigh classified XYLT2 as green
Skeletal dysplasia XRCC4 Sarah Leigh commented on XRCC4
Skeletal dysplasia XRCC4 Sarah Leigh marked XRCC4 as ready
Skeletal dysplasia XRCC4 Sarah Leigh classified XRCC4 as green
Skeletal dysplasia WNT10B Sarah Leigh marked WNT10B as ready
Skeletal dysplasia WNT10B Sarah Leigh commented on WNT10B
Skeletal dysplasia WNT10B Sarah Leigh classified WNT10B as green
Skeletal dysplasia TWIST1 Sarah Leigh marked TWIST1 as ready
Skeletal dysplasia TWIST1 Sarah Leigh commented on TWIST1
Skeletal dysplasia TWIST1 Sarah Leigh classified TWIST1 as green
Skeletal dysplasia TMEM231 Sarah Leigh commented on TMEM231
Skeletal dysplasia TMEM231 Sarah Leigh marked TMEM231 as ready
Skeletal dysplasia TMEM165 Sarah Leigh marked TMEM165 as ready
Skeletal dysplasia TMEM165 Sarah Leigh commented on TMEM165
Skeletal dysplasia TGFBR2 Sarah Leigh marked TGFBR2 as ready
Skeletal dysplasia TGFBR2 Sarah Leigh commented on TGFBR2
Skeletal dysplasia TGFBR1 Sarah Leigh marked TGFBR1 as ready
Skeletal dysplasia TGFBR1 Sarah Leigh commented on TGFBR1
Skeletal dysplasia TGFB2 Sarah Leigh marked TGFB2 as ready
Skeletal dysplasia TGFB2 Sarah Leigh commented on TGFB2
Skeletal dysplasia TERT Sarah Leigh marked TERT as ready
Skeletal dysplasia TERT Sarah Leigh classified TERT as green
Skeletal dysplasia TERT Sarah Leigh classified TERT as green
Skeletal dysplasia TERT Sarah Leigh commented on TERT
Skeletal dysplasia TCTN2 Sarah Leigh marked TCTN2 as ready
Skeletal dysplasia TCTN2 Sarah Leigh commented on TCTN2
Skeletal dysplasia TCOF1 Sarah Leigh marked TCOF1 as ready
Skeletal dysplasia TCOF1 Sarah Leigh commented on TCOF1
Skeletal dysplasia TBX4 Sarah Leigh marked TBX4 as ready
Skeletal dysplasia TBX4 Sarah Leigh commented on TBX4
Skeletal dysplasia TBX4 Sarah Leigh classified TBX4 as green
Skeletal dysplasia TALDO1 Sarah Leigh marked TALDO1 as ready
Skeletal dysplasia TALDO1 Sarah Leigh commented on TALDO1
Skeletal dysplasia TALDO1 Sarah Leigh classified TALDO1 as green
Skeletal dysplasia SUMF1 Sarah Leigh marked SUMF1 as ready
Skeletal dysplasia SUMF1 Sarah Leigh commented on SUMF1
Skeletal dysplasia SPECC1L Sarah Leigh marked SPECC1L as ready
Skeletal dysplasia SPECC1L Sarah Leigh commented on SPECC1L
Skeletal dysplasia SPARC Sarah Leigh marked SPARC as ready
Skeletal dysplasia SNX10 Sarah Leigh marked SNX10 as ready
Skeletal dysplasia SNX10 Sarah Leigh commented on SNX10
Skeletal dysplasia SNX10 Sarah Leigh classified SNX10 as red
Skeletal dysplasia SNRPB Sarah Leigh marked SNRPB as ready
Skeletal dysplasia SNRPB Sarah Leigh commented on SNRPB
Skeletal dysplasia SNRPB Sarah Leigh classified SNRPB as green
Skeletal dysplasia SMC3 Sarah Leigh marked SMC3 as ready
Skeletal dysplasia SMC3 Sarah Leigh commented on SMC3
Skeletal dysplasia SMC1A Sarah Leigh marked SMC1A as ready
Skeletal dysplasia SMC1A Sarah Leigh commented on SMC1A
Skeletal dysplasia SMAD3 Sarah Leigh marked SMAD3 as ready
Skeletal dysplasia SMAD3 Sarah Leigh commented on SMAD3