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| Fetal anomalies v3.157 | PLD1 | Arina Puzriakova changed review comment from: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded.; to: Comment on list classification: This Green gene was signed off in Mar 2023 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.157 | PLD1 | Arina Puzriakova Added comment: Comment on list classification: This Green gene was signed off in Nov 2022 but now flagging for another review by the GMS specialist group in the context of the conflicting Red review by Jesse Hayesmoore (Oxford Regional Genetics Laboratory) to determine whether this gene should be downgraded. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v3.156 | PLD1 |
Arina Puzriakova commented on gene: PLD1: Copied review from Paediatric or syndromic cardiomyopathy (749) v3.43 panel: Jesse Hayesmoore (Oxford Regional Genetics Laboratory) Red List (low evidence) "On the basis of functional data described in PMIDs: 27799408 and 33645542, PLD1 certainly seems to be a plausible functional candidate for causality of cardiac valvular defects. The main paper linking this gene with congenital heart disease / cardiomyopathy is Lahrouchi et al. (2021; PMID: 33645542; note this also includes the same 2 cases as described in Ta-Shma et al. 2017 PMID: 27799408). The paper presents 19 families with severe fetal- / neonatal-onset congenital heart (mainly valvular) defects and 2 with cardiomyopathy where affected babies were homozygous or compound heterozygous for PLD1 variants. The paper also provides some functional analysis of missense variants detected, showing that many but not all of them result significant loss of PLD1 function. Unfortunately, the paper does not include a LOD score, and there is very little cosegregation data presented for any of the variants. In addition, 4 of the 31 variants they promote as pathogenic for autosomal recessive disease are detected in multiple homozygous individuals on gnomAD, which I think provides significant evidence that they might not be pathogenic for a severe autosomal recessive condition. Most notably, 1 of the variants (i.e. I668F), which the authors promote as a pathogenic Ashkenazi Jewish founder variant (but which is also fairly frequent in non-Finnish Europeans) is detected in 7 homozygotes on gnomAD and was found to have ~80% loss of PLD1 function in their assay. This suggests that significant loss of function of this gene (i.e. down to 20%) might not be causative of a severe recessive condition (that is not to say that total or near total loss of function is not causative). Three other of the variants promoted as pathogenic in this article are also detected in homozygotes on gnomAD. I think one of the major pieces of missing information required to make a full assessment of this gene’s linkage to disease is that is unknown how frequent biallelic (apparently loss of function) variant genotypes are in the general population or in healthy control individuals. Although homozygosity for any one variant can be determined from gnomAD, compound heterozygosity (which is likely to represent the vast majority of biallelic genotypes) cannot be assessed on gnomAD, and I can find no record in the literature of this being assessed in a normal control cohort. Without this information, we cannot know whether biallelic PLD1 genotypes are specific to babies with this severe phenotype. Without knowing this, and in the absence of any significant cosegregation data for any variant, there is no reasonable basis upon which one can conclude that this is a valid autosomal recessive gene for the phenotype. Without such validation, PVS1 cannot be applied for any apparent loss of function variant. Given this, and the general lack of cosegregation data for any one variant, I do not believe there is any PLD1 variant reported in the literature that could be classified as anything but uncertain significance (if not benign or likely benign) on the basis of current variant classification guidelines. Also, there are only two cases of biallelic variants in neonates where the primary phenotype is cardiomyopathy, and of these only one was dilated cardiomyopathy (the other was histiocytoid cardiomyopathy). Hence, the evidence linking this gene to cardiomyopathy is even weaker than it is for valvular defects. I, therefore, do not feel there is sufficient evidence to justify this gene being tested as part of the R135 paediatric cardiomyopathy gene panel. Other papers (e.g. PMIDs: 33142350, 35380090, 36923242, 37770978) reporting a link between PLD1 genotypes and early onset cardiac disease (not cardiomyopathy) have been published. However, again, I do not think there is sufficient data in the articles to allow any of the variants detected to be confidently classified as anything but VUS according to current variant classification guidelines." Created: 31 Jan 2024, 12:04 p.m. | Last Modified: 31 Jan 2024, 12:17 p.m |
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| Fetal anomalies v3.109 | ESAM |
Julia Baptista gene: ESAM was added gene: ESAM was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ESAM were set to PMID: 36996813 Phenotypes for gene: ESAM were set to intracranial hemorrhage; cerebral anomalies Review for gene: ESAM was set to GREEN Added comment: Four fetuses from three unrelated families (different LOF biallelic variants) with fetal intracranial hemorrhage. Fetal brain tissue from one of the affected individuals at 31 weeks' gestational age showed lack of ESAM staining in the capillary endothelial cells, thus confirming loss of ESAM. Another individual had an abnormal prenatal ultrasound and the pregnancy was terminated at 32 weeks' gestation, but no DNA was available to test for the familial variant. Neurodevelopmental disorder with cerebral calcifications, hydrocephalus, focal white matter lesions, retina anomalies and dysmorphic features. Sources: Literature |
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| Fetal anomalies v3.73 | MYL9 | Arina Puzriakova commented on gene: MYL9: Third family reported by Billon et al. 2020 (PMID: 32621347) with the same homozygous exon 4 deletion of MYL9 as the one detected by Moreno et al. 2018 (PMID: 29453416) in an unrelated case. Family includes three sibs affected with megacystis, intestinal malrotation, small and thin colon, as well as some dysmorphic features. Fetopathological examination confirmed the diagnosis of MMIHS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v2.12 | CHAMP1 | Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from INTELLECTUAL DISABILITY to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v2.8 | KIF21A |
Hannah Robinson gene: KIF21A was added gene: KIF21A was added to Fetal anomalies. Sources: Literature,NHS GMS Mode of inheritance for gene: KIF21A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF21A were set to 34740919 Phenotypes for gene: KIF21A were set to Arthrogryposis; fetal akinesia Penetrance for gene: KIF21A were set to unknown Review for gene: KIF21A was set to GREEN gene: KIF21A was marked as current diagnostic Added comment: Falb et al 2023 (PMID: 34740919) describe two unrelated families in which biallelic loss of function variants segregated with a severe form of fetal akinesia characterised by arthrogryposis multiplex, pulmonary hypoplasia and variable facial dysmorphisms. Exeter Genomics Laboratory has identified an unrelated third case homozygous for a nonsense variant in KIF21A. The patient had an antenatal diagnosis of talipes, arthrogryposis, polyhydramnios and lack of fetal movements. At birth, all joints displayed fixed flexion deformities, no primitive reflexes, poor muscle bulk and care was re-oriented shortly after birth. Taken together, three unrelated cases including segregation evidence in the published families provides sufficient evidence for the gene-disease association. Sources: Literature, NHS GMS |
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| Fetal anomalies v1.966 | SETD2 | Arina Puzriakova Phenotypes for gene: SETD2 were changed from SETD2-associated Overgrowth Syndrome to microcephaly; profound intellectual disability; congenital anomalies; dysmorphic facial features | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.964 | SETD2 | Rhiannon Mellis reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 32710489, 33255631; Phenotypes: microcephaly, profound intellectual disability, congenital anomalies, dysmorphic facial features; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.900 | MRPS16 |
Rhiannon Mellis gene: MRPS16 was added gene: MRPS16 was added to Fetal anomalies. Sources: Expert Review,Literature Mode of inheritance for gene: MRPS16 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPS16 were set to PMID: 28749478 Phenotypes for gene: MRPS16 were set to Combined oxidative phosphorylation deficiency 2 Review for gene: MRPS16 was set to AMBER Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene. Details of review: Amber on mitochondrial/inborn errors of metabolism etc. Not Green on any panel. One previous case reported with "agenesis of the corpus callosum, dysmorphism, and fatal neonatal lactic acidosis. The patient was small at birth, with dysmorphic facies, low-set ears, nonpitting edema of the limbs, brachydactyly, and redundant skin over the neck. She died of intractable metabolic acidosis at age 3 days." PMID:15505824 (2004). One further fetal case reported by Shamseldin et al. 2018 (PMID: 28749478) with hydrops, very short long bones, and partial ACC Sources: Expert Review, Literature |
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| Fetal anomalies v1.900 | CACNA1S |
Rhiannon Mellis gene: CACNA1S was added gene: CACNA1S was added to Fetal anomalies. Sources: Expert Review,Literature Mode of inheritance for gene: CACNA1S was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CACNA1S were set to PMID: 33060286; 28012042 Phenotypes for gene: CACNA1S were set to Congenital myopathy; arthrogryposis Review for gene: CACNA1S was set to AMBER Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene. Details of review: Previously only monoallelic variants reported associated with malignant hyperthermia and periodic paralysis but more recently biallelic variants have been associated with congenital myopathy. In Ravenscroft et al 2020 (PMID: 33060286) the reported biallelic variants were VUS but strong suspicion of causality: the proband had polyhydramnios, scalp oedema, bilateral wrist contractures, bilateral talipes and reduced fetal movements, ToP at 26/40. Mild facial dysmorphic features were noted on autopsy, including low anterior hairline, mild hypertelorism and moderate retrognathia. A previous pregnancy was affected with polyhydramnios and reduced fetal movements, delivered at 32/40 due to placental abruption and died at 10 days. On photos the baby had ptosis and broad nasal tip. The biallelic variants segregated within the family (parents and the 2 unaffected sibs all het). No cell lines available for functional studies. Another study (PMID: 28012042) reports 7 families with congenital myopathy and CACNA1S mutations (both recessive and dominant), of whom 3 had cases with antenatal onset (reduced fetal movements). Sources: Expert Review, Literature |
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| Fetal anomalies v1.900 | FTO |
Rhiannon Mellis gene: FTO was added gene: FTO was added to Fetal anomalies. Sources: Expert Review,Literature Mode of inheritance for gene: FTO was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FTO were set to PMID: 31130284; 19559399; 26378117 Phenotypes for gene: FTO were set to Growth retardation, developmental delay, facial dysmorphism Review for gene: FTO was set to AMBER Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene. Details of review: Not Green on any panels (only 2 families reported to date). On OMIM: Growth retardation, developmental delay, facial dysmorphism. One fetal case reported by Monies et al 2019 (PMID: 31130284) with Dandy-Walker malformation, IUGR, and polyhydramnios. This fits with the phenotype reported in one consanguineous family with 9 affected individuals reported by Boissel 2009 PMID: 19559399. The other reported case is PMID: 26378117 - a homozygous missense variant in FTO was identified in a 21-month old girl who presented with growth retardation, failure to thrive, severely delayed development, Dysmorphic facial features, decreased brain parenchyma, delayed myelination, and a thin corpus callosum. Sources: Expert Review, Literature |
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| Fetal anomalies v1.900 | LOX |
Rhiannon Mellis gene: LOX was added gene: LOX was added to Fetal anomalies. Sources: Expert Review,Literature Mode of inheritance for gene: LOX was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LOX were set to PMID: 31742715 Phenotypes for gene: LOX were set to Aortopathy Review for gene: LOX was set to AMBER Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene. Currently rated Green on the following other PanelApp panel(s): familial thoracic aortic aneurysm Details of review: Reported as a novel genotype-phenotype association in Aggarwal et al 2020 (PMID: 31742715), in a fetus with homozygous missense variants. Heterozygous variants in this gene are known to cause thoracic aortic aneurysm. The fetus presented with unexplained IUD and on post-mortem had: Excessive skin folds, emphysematous bullae on lung surface, Facial dysmorphism, distal joint contractures, internal haemorrhages. Histopathology and special stains confirmed degradation of collagen and elastin in the aorta, pleura and skin. If we are going to add to panel suggest putting MOI as biallelic only (and accept that this would be an incidental finding for carrier parents that would lead to them needing monitoring for aortic aneurysm) Sources: Expert Review, Literature |
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| Fetal anomalies v1.880 | MED13L | Rhiannon Mellis reviewed gene: MED13L: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33142350, PMID: 32058062; Phenotypes: Intellectual disability, dysmorphic features, congenital heart malformations, talipes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.851 | RAC3 | Arina Puzriakova Phenotypes for gene: RAC3 were changed from Abnormality of brain morphology; Abnormal muscle tone; Neurodevelopmental delay; Intellectual disability to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, OMIM:618577 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.836 | MSMO1 | Arina Puzriakova Tag for-review was removed from gene: MSMO1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.836 | MSMO1 | Arina Puzriakova commented on gene: MSMO1: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.835 | MSMO1 |
Arina Puzriakova Source Expert Review Green was added to MSMO1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Fetal anomalies v1.749 | CDK8 |
Rhiannon Mellis gene: CDK8 was added gene: CDK8 was added to Fetal anomalies. Sources: Literature,Expert Review Mode of inheritance for gene: CDK8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDK8 were set to PMID: 31742715; 30905399 Phenotypes for gene: CDK8 were set to Syndromic developmental disorder with hypotonia and behavioural abnormalities Review for gene: CDK8 was set to GREEN Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene. Already rated Green on the following other PanelApp panel(s): Intellectual disability; Severe paediatric disorders Details of review: Aggarwal et al 2020 report a heterozygous nonsense variant in a fetus with ventriculomegaly and Ebstein anomaly resulting in IUFD. Post-mortem found additionally congenital diaphragmatic hernia, common atrium and facial dysmorphism. This nonsense variant is at the same position as a hotspot for missense variants reported in a paediatric cohort (Calpena et al 2019, PMID: 30905399) with overlapping but milder phenotype: half of the 12 children in that cohort had cardiac defects, most had dysmorphic features - hence Aggarwal et al propose that this is a more severe (prenatal) presentation of the same multiple malformation syndrome, caused here by a nonsense rather than missense mutation. Sources: Literature, Expert Review |
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| Fetal anomalies v1.728 | 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.727 | SCUBE3 |
Sarah Leigh gene: SCUBE3 was added gene: SCUBE3 was added to Fetal anomalies. 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 |
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| Fetal anomalies v1.720 | WLS |
Zornitza Stark gene: WLS was added gene: WLS was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: WLS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WLS were set to 34587386 Phenotypes for gene: WLS were set to structural congenital anomalies Review for gene: WLS was set to GREEN Added comment: - Homozygous variants in 10 affected persons from 5 unrelated families. - Affected individuals had multiorgan defects, including microcephaly, facial dysmorphism, foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects. - The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis. Sources: Literature |
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| Fetal anomalies v1.693 | ASPH |
Ivone Leong Added comment: Comment on phenotypes: Previously: FACIAL DYSMORPHISM, LENS DISLOCATION, ANTERIOR SEGMENT ABNORMALITIES, AND SPONTANEOUS FILTERING BLEBS |
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| Fetal anomalies v1.693 | ASPH | Ivone Leong Phenotypes for gene: ASPH were changed from FACIAL DYSMORPHISM, LENS DISLOCATION, ANTERIOR SEGMENT ABNORMALITIES, AND SPONTANEOUS FILTERING BLEBS to Traboulsi syndrome, OMIM:601552 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.692 | MYOD1 |
Ivone Leong gene: MYOD1 was added gene: MYOD1 was added to Fetal anomalies. Sources: Expert Review Amber,Literature Q3_21_rating tags were added to gene: MYOD1. Mode of inheritance for gene: MYOD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYOD1 were set to 26733463; 30403323; 31260566 Phenotypes for gene: MYOD1 were set to Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies, OMIM:618975 |
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| Fetal anomalies v1.685 | TMEM94 | Ivone Leong Phenotypes for gene: TMEM94 were changed from Intellectual developmental disorder with cardiac defects and dysmorphic facies to Intellectual developmental disorder with cardiac defects and dysmorphic facies, OMIM:618316 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.670 | SPTBN5 |
Arina Puzriakova gene: SPTBN5 was added gene: SPTBN5 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SPTBN5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPTBN5 were set to 32732226 Phenotypes for gene: SPTBN5 were set to Multicystic kidney; Oligohydramnios Review for gene: SPTBN5 was set to RED Added comment: Novel candidate gene identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis. Compound heterozygous variants including a truncating variant were found by exome sequencing. Sources: Literature |
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| Fetal anomalies v1.663 | DPH1 |
Arina Puzriakova gene: DPH1 was added gene: DPH1 was added to Fetal anomalies. Sources: Literature Q2_21_rating tags were added to gene: DPH1. Mode of inheritance for gene: DPH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DPH1 were set to 25558065; 29362492; 30877278; 32732226 Phenotypes for gene: DPH1 were set to Developmental delay with short stature, dysmorphic facial features, and sparse hair, OMIM:616901 Review for gene: DPH1 was set to GREEN Added comment: Biallelic variants in this gene cause a neurodevelopmental disorder characterised by ID/DD, short stature, dysmorphic features, craniofacial and ectodermal anomalies. Several reports note antenatal anomalies and multiple congenital abnormalities that may conceivably be detected prenatally. Fetal ultrasound phenotypes reported in literature include IUGR, polyhydramnios, craniostenosis, cardiac abnormalities, brain anomalies, and polydactyly (PMID: 25558065; 29362492; 30877278; 32732226) Sources: Literature |
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| Fetal anomalies v1.641 | EBF3 | Sarah Leigh Added comment: Comment on phenotypes: Intellectual Disability, Ataxia, and Facial Dysmorphism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.641 | EBF3 | Sarah Leigh Phenotypes for gene: EBF3 were changed from Intellectual Disability, Ataxia, and Facial Dysmorphism to Hypotonia, ataxia, and delayed development syndrome OMIM:617330; hypotonia, ataxia, and delayed development syndrome MONDO:0015021 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.625 | OTUD5 |
Arina Puzriakova gene: OTUD5 was added gene: OTUD5 was added to Fetal anomalies. Sources: Expert Review Q2_21_rating tags were added to gene: OTUD5. Mode of inheritance for gene: OTUD5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: OTUD5 were set to 33131077; 33523931 Phenotypes for gene: OTUD5 were set to Multiple congenital anomalies-neurodevelopmental syndrome, X-linked, OMIM:301056 Review for gene: OTUD5 was set to GREEN Added comment: OTUD5 is associated with a relevant phenotype in OMIM but not yet in Gene2Phenotype. - PMID: 33131077 (2021) - 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with IUGR, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. WGS in four individuals identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals. - PMID: 33523931 (2021) - Another 10 individuals from 7 families reported. Key features include poor growth, global developmental delay with impaired intellectual development, and variable abnormalities of the cardiac, skeletal, and genitourinary systems. Most affected individuals also have hypotonia and dysmorphic craniofacial features. Brain imaging typically shows enlarged ventricles and thin corpus callosum; some have microcephaly, whereas others have hydrocephalus. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade. Sources: Expert Review |
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| Fetal anomalies v1.280 | MYO18B | Arina Puzriakova Phenotypes for gene: MYO18B were changed from Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, OMIM:616549; Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome, MONDO:0014689 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.262 | MSMO1 | Arina Puzriakova Publications for gene: MSMO1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.261 | MSMO1 | Arina Puzriakova Phenotypes for gene: MSMO1 were changed from Microcephaly, congenital cataract, and psoriasiform dermatitis to Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.260 | MSMO1 | Arina Puzriakova Classified gene: MSMO1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.260 | MSMO1 | Arina Puzriakova Gene: msmo1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.259 | MSMO1 | Arina Puzriakova Tag for-review tag was added to gene: MSMO1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.228 | CTU2 |
Rhiannon Mellis gene: CTU2 was added gene: CTU2 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, 618142 Review for gene: CTU2 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): CAKUT Sources: Expert list |
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| Fetal anomalies v1.214 | MSMO1 |
Rhiannon Mellis gene: MSMO1 was added gene: MSMO1 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: MSMO1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MSMO1 were set to Microcephaly, congenital cataract, and psoriasiform dermatitis Review for gene: MSMO1 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Severe microcephaly Sources: Expert list |
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| Fetal anomalies v1.214 | MYO18B |
Rhiannon Mellis gene: MYO18B was added gene: MYO18B was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: MYO18B was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MYO18B were set to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism Review for gene: MYO18B was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Neuromuscular disorders Sources: Expert list |
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| Fetal anomalies v1.115 | MN1 |
Rhiannon Mellis gene: MN1 was added gene: MN1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MN1 were set to 31834374; 31839203; 15870292 Phenotypes for gene: MN1 were set to CEBALID syndrome, 618774 Mode of pathogenicity for gene: MN1 was set to Other Review for gene: MN1 was set to GREEN Added comment: Copied from MN1 review on Cortical malformations panel: Associated with phenotype in OMIM, and a probable gene for MN1 C-terminal truncation syndrome in G2P. Over 20 unrelated probands reported with heterozygous MN1 truncating variants, associated with a distinct phenotype which includes DD, craniofacial abnormalities, hearing loss, and structural abnormalities in the brain (e.g. polymicrogyria, dysmorphic corpus callosum and anomalies of the cerebellum - rhombencephalosynapsis). Most variants cluster in the C-terminal, and all were predicted to escape NMD. Authors postulated that the resulting truncated protein may have a dominant-negative or gain-of-function effect. Also phenotypically supportive knockout mouse model. Sources: Literature |
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| Fetal anomalies v1.73 | TMEM94 |
Rhiannon Mellis gene: TMEM94 was added gene: TMEM94 was added to Fetal anomalies. Sources: Literature,Expert Review Mode of inheritance for gene: TMEM94 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM94 were set to PMID: 30526868 Phenotypes for gene: TMEM94 were set to Intellectual developmental disorder with cardiac defects and dysmorphic facies Review for gene: TMEM94 was set to GREEN Added comment: Literature reports 10 patients from 6 unrelated families, and a mouse model PMID: 30526868 Reviewed with Prof Lyn Chitty for fetally relevant phenotype (Yes - Congenital heart malformations including: Atrial septal defect; Ventricular septal defect; Pulmonary hypoplasia; Pulmonary atresia; Tetralogy of Fallot; Double outlet right ventricle Sources: Literature, Expert Review |
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| Fetal anomalies v1.73 | NUP88 |
Julia Baptista gene: NUP88 was added gene: NUP88 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP88 were set to PMID: 30543681 Phenotypes for gene: NUP88 were set to fetal akinesia Review for gene: NUP88 was set to RED Added comment: Bonnin et al reported biallelic variants in two unrelated families. A homozygous missense variant was identified in family A and the co-segregation data was supportive (tested 4 unaffected and 2 of the 4 affected fetuses). Compound heterozygous in-frame and nonsense variants were identified in the proband in family B (co-segregation studies in 2 unaffected sibs). The clinical features included fetal akinesia and arthrogryposis multiplex congenita. Polyhydramnios, muscle atrophy and dysmorphic features were also described. Sources: Literature |
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| Fetal anomalies v1.73 | ITGA8 | Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber awaiting GLH review. Additional phenotypes were reported in the fetuses and sibling (who died perinatally) from PMID:24439109 (clubbed feet, facial dysmorphism, pulmonary hypoplasia, bilateral cryptorchidism) although renal agenesis is the primary phenotype and only 2 families from one paper. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.49 | ALG9 |
Rebecca Foulger changed review comment from: PMID:28932688. Davis et al., 2017 review the literature for ALG9:CDG cases. They summarise 10 patients from 6 different families with one of four ALG9 variants. In addition to summarising the 3 patients from Tham et al (PMID:25966638) who died in utero , they report an additional patient with ALG9-CDH with a milder phenotype. Prenatally, dysmorphic features, renal cysts and cardiac malformations were detected. She had a homozygous variant in ALG9: p.Tyr287Cys.; to: PMID:28932688. Davis et al., 2017 review the literature for ALG9:CDG cases. They summarise 10 patients from 6 different families with one of four ALG9 variants. In addition to summarising the 3 patients from Tham et al (PMID:25966638) who died in utero, they report an additional patient with ALG9-CDH with a milder phenotype. Prenatally, dysmorphic features, renal cysts and cardiac malformations were detected. She had a homozygous variant in ALG9: p.Tyr287Cys. |
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| Fetal anomalies v1.49 | ALG9 |
Rebecca Foulger commented on gene: ALG9: PMID:28932688. Davis et al., 2017 review the literature for ALG9:CDG cases. They summarise 10 patients from 6 different families with one of four ALG9 variants. In addition to summarising the 3 patients from Tham et al (PMID:25966638) who died in utero , they report an additional patient with ALG9-CDH with a milder phenotype. Prenatally, dysmorphic features, renal cysts and cardiac malformations were detected. She had a homozygous variant in ALG9: p.Tyr287Cys. |
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| Fetal anomalies v1.41 | SMG9 | Rebecca Foulger commented on gene: SMG9: PMID:31390136. Lecoquierre et al., 2019 performed exome sequencing in a patient with syndromic DD and diverse malformations including cleft lip and palate, facial dysmorphia, brain abnormalities, herat defect, growth retardation and severe infections. She carried a homozygous SMG9 variant, p.(Gln393*). Her unaffected parents were both heterozygous. Phenotypes were first noted in-utero: polyhydamnios, lateral cleft lip and palate, and IUGR noted on ultrasound. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.41 | SMG9 | Rebecca Foulger commented on gene: SMG9: PMID:27018474. Shaheen et al, 2016 report 2 consanguineous families with different homozygous LOF variants in SMG9 and and a similar set of congenital anomalies including craniofacial dysmorphism, and major brain and heart malformations. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.35 | CNOT3 | Rebecca Foulger Phenotypes for gene: CNOT3 were changed from CNOT3 syndrome; Intellectual developmental disorder with speech delay, 618672 autism, and dysmorphic facies to CNOT3 syndrome; Intellectual developmental disorder with speech delay, autism, and dysmorphic facies, 618672 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.34 | CNOT3 | Rebecca Foulger Phenotypes for gene: CNOT3 were changed from CNOT3 syndrome to CNOT3 syndrome; Intellectual developmental disorder with speech delay, 618672 autism, and dysmorphic facies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.22 | POLE | Rebecca Foulger Phenotypes for gene: POLE were changed from IUGR; severe growth failure of prenatal onset to IUGR; severe growth failure of prenatal onset; FILS syndrome, 615139; facial dysmorphism, immunodeficiency, livedo, and short stature (FILS) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.311 | MRPS22 | Rebecca Foulger edited their review of gene: MRPS22: Added comment: This gene was re-reviewed in a consistency check by Anna de Burca (Genomics England Clinical Team). Outcome of review: Yates et al study (PMID:28425981) pulled out a pathogenic variant in MRPS22 in a deceased fetal case with Hydrops, CNS malformations and cardiomyopathy picked up on U/S scan. Additional info from OMIM: A boy with oxidative phosphorylation defect in PMID:21189481 who had microcephaly, dysmorphic features etc at birth. 3 siblings in PMID:17873122. Therefore if include Yates et al, there are 3 cases. ; Changed rating: GREEN; Changed publications: 17873122, 21189481 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.311 | TCF20 | Rebecca Foulger edited their review of gene: TCF20: Added comment: As agreed with Anna de Burca (Genomics England Clinical team): Keep TCF20 as Amber: the structural phenotypes are variable (and largely mild). All individuals have ID/DD but the accompanying dysmorphic features are inconsistent, and the authors suggest additional genes may be responsible/modifying- some of the patients had variants in additional genes (or the phenotypes might be very very rare).; Changed publications: 30739909, 30819258 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.311 | MAN1B1 | Rebecca Foulger commented on gene: MAN1B1: This gene was reviewed by Anna de Burca (Genomics England Clinical Team) under the category of storage disorders. Outcome of review: Rate as Amber- mild dysmorphic phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.250 | TRAF7 | Rebecca Foulger Phenotypes for gene: TRAF7 were changed from Developmental Delay, Congenital Anomalies, and Dysmorphic Features to Developmental Delay, Congenital Anomalies, and Dysmorphic Features; Cardiac, facial, and digital anomalies with developmental delay, 618164 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.244 | HNRNPK | Rebecca Foulger commented on gene: HNRNPK: Au-Kline syndrome is a multiple malformation syndrome associated with intellectual disability. Patients have facial dysmorphic features and frequently have skeletal and connective tissue anomalies, craniosynostosis, congenital heart malformations, and renal anomalies (PMID:29904177). Structural phenotypes reported in the literature include talipes and partial agenesis of corpus callosum. Au et al., 2018 (PMID:29904177) report prenatal presentation with 5 patients showing increased nuchal translucency and 5 patients had hydronephrosis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.225 | CTDP1 | Rebecca Foulger edited their review of gene: CTDP1: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is fetally-relevant but limited evidence: include on the Fetal anomalies panel as an Amber gene. Additional notes from clinical review: Although CTDP1 has a 'confirmed' Disease confidence rating in DD-G2P for CONGENITAL CATARACTS FACIAL DYSMORPHISM AND NEUROPATHY SYNDROME, the disorder is prevalent in Bulagarian Gypsy populations, and is limited to a founder variant.; Changed publications: 14517542, 29174527, 20301787, 24690360 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.224 | SMO | Rebecca Foulger commented on gene: SMO: Added 'somatic' tag alonside the 'mosaicism' tag following clinical review of SMO (April 26th 2019 with Lyn Chitty, Anna de Burca, Richard Scott and Rhiannon Mellis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.224 | SMO | Rebecca Foulger Tag somatic tag was added to gene: SMO. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.222 | SMO | Rebecca Foulger edited their review of gene: SMO: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: include on the Fetal anomalies panel as a Green gene. Additional notes from clinical review: Somatic mosaic.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.166 | TMEM165 | Rebecca Foulger edited their review of gene: TMEM165: Added comment: This gene and phenotype were discussed during review of borderline cases in April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as Green. Additional notes from clinical review: OMIM phenotypes include growth retardation, and most had short stature. Other features included dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.161 | SMOC1 | Rebecca Foulger edited their review of gene: SMOC1: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.153 | QRICH1 | Rebecca Foulger edited their review of gene: QRICH1: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene. Additional notes from clinical review: Only 5 cases reported so far so phenotype is not that well-characterised yet. Some dysmorphic features may be detectable prenatally- one case had IUGR, and another had severe microcephaly.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | CREBBP | Rebecca Foulger edited their review of gene: CREBBP: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as Green. Additional notes from clinical review: Several dysmorphic features.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | CDKL5 | Rebecca Foulger edited their review of gene: CDKL5: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as Green. Additional notes from clinical review: Phenotype includes progressive microcephaly (which may or may not be detectable in a fetus) plus subtle dysmorphic features and small feet.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.115 | TRAF7 |
Rebecca Foulger gene: TRAF7 was added gene: TRAF7 was added to Fetal anomalies. Sources: DD-Gene2Phenotype,Expert Review Green Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TRAF7 were set to 29961569 Phenotypes for gene: TRAF7 were set to Developmental Delay, Congenital Anomalies, and Dysmorphic Features Mode of pathogenicity for gene: TRAF7 was set to Other - please provide details in the comments |
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| Fetal anomalies v0.9 | SMOC2 | Rebecca Foulger reviewed gene: SMOC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | SMOC1 | Rebecca Foulger reviewed gene: SMOC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | SMO | Rebecca Foulger commented on gene: SMO: DDG2P rating in original PAGE list: Confirmed for Curry-Jones Syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | RPS23 | Rebecca Foulger commented on gene: RPS23: DDG2P rating in original PAGE list: Probable for Microcephaly, hearing loss, and dysmorphic features | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | MTOR | Rebecca Foulger commented on gene: MTOR: DDG2P rating in original PAGE list: Confirmed for Smith-Kingsmore syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.8 | SUFU | Rebecca Foulger Phenotypes for gene: SUFU were changed from Medulloblastoma, desmoplastic 155255; Joubert Syndrome with Cranio-facial and Skeletal Defects; Basal cell nevus syndrome 109400 to Joubert Syndrome with Cranio-facial and Skeletal Defects; Basal cell nevus syndrome 109400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3 | SMO | Rebecca Foulger Tag mosaicism tag was added to gene: SMO. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3 | SMO | Rebecca Foulger commented on gene: SMO: Mosaicism tag added based on original PAGE file which records Mosaic MOI for Curry-Jones Syndrome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3 | SMO | Rebecca Foulger reviewed gene: SMO: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | TMCO1 |
Rebecca Foulger gene: TMCO1 was added gene: TMCO1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: TMCO1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TMCO1 were set to CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION SYNDROME |
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| Fetal anomalies v0.1 | TBX15 |
Rebecca Foulger gene: TBX15 was added gene: TBX15 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: TBX15 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TBX15 were set to Craniofacial Dysmorphism, Hypoplasia of Scapula and Pelvis, and Short Stature; Cousin Syndrome |
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| Fetal anomalies v0.1 | TBCE | Rebecca Foulger Added phenotypes HYPOPARATHYROIDISM-RETARDATION-DYSMORPHISM SYNDROME for gene: TBCE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | TAF1 |
Rebecca Foulger gene: TAF1 was added gene: TAF1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: TAF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: TAF1 were set to Dysmorphic Features, Intellectual Disability, and Neurological Manifestations |
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| Fetal anomalies v0.1 | SZT2 |
Rebecca Foulger gene: SZT2 was added gene: SZT2 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: SZT2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SZT2 were set to INFANTILE ENCEPHALOPATHY WITH EPILEPSY AND DYSMORPHIC CORPUS CALLOSUM |
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| Fetal anomalies v0.1 | SUFU | Rebecca Foulger Added phenotypes Medulloblastoma, desmoplastic 155255 for gene: SUFU | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | STAR |
Rebecca Foulger gene: STAR was added gene: STAR was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: STAR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: STAR were set to CHOLESTEROL DESMOLASE-DEFICIENT CONGENITAL ADRENAL HYPERPLASIA |
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| Fetal anomalies v0.1 | SMOC2 |
Rebecca Foulger gene: SMOC2 was added gene: SMOC2 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: SMOC2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SMOC2 were set to DENTIN DYSPLASIA, TYPE I, WITH MICRODONTIA AND MISSHAPEN TEETH |
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| Fetal anomalies v0.1 | SMOC1 |
Rebecca Foulger gene: SMOC1 was added gene: SMOC1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: SMOC1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SMOC1 were set to OPHTHALMOACROMELIC SYNDROME |
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| Fetal anomalies v0.1 | SMO |
Rebecca Foulger gene: SMO was added gene: SMO was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: SMO was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SMO were set to Curry-Jones Syndrome |
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| Fetal anomalies v0.1 | RPS23 |
Rebecca Foulger gene: RPS23 was added gene: RPS23 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: RPS23 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: RPS23 were set to Microcephaly, hearing loss, and dysmorphic features |
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| Fetal anomalies v0.1 | POC1A |
Rebecca Foulger gene: POC1A was added gene: POC1A was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: POC1A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: POC1A were set to SHORT STATURE, ONYCHODYSPLASIA, FACIAL DYSMORPHISM, AND HYPOTRICHOSIS SYNDROME |
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| Fetal anomalies v0.1 | PHIP |
Rebecca Foulger gene: PHIP was added gene: PHIP was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: PHIP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: PHIP were set to Developmental delay, ID, obesity and dysmorphic features |
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| Fetal anomalies v0.1 | OTUD6B |
Rebecca Foulger gene: OTUD6B was added gene: OTUD6B was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: OTUD6B was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: OTUD6B were set to Intellectual Disability Syndrome Associated with Seizures and Dysmorphic Features |
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| Fetal anomalies v0.1 | MTOR |
Rebecca Foulger gene: MTOR was added gene: MTOR was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: MTOR was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: MTOR were set to Smith-Kingsmore syndrome |
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| Fetal anomalies v0.1 | INPPL1 |
Rebecca Foulger gene: INPPL1 was added gene: INPPL1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: INPPL1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: INPPL1 were set to OPSISMODYSPLASIA |
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| Fetal anomalies v0.1 | EBF3 |
Rebecca Foulger gene: EBF3 was added gene: EBF3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: EBF3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: EBF3 were set to Intellectual Disability, Ataxia, and Facial Dysmorphism |
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| Fetal anomalies v0.1 | DHCR24 |
Rebecca Foulger gene: DHCR24 was added gene: DHCR24 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: DHCR24 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DHCR24 were set to DESMOSTEROLOSIS |
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| Fetal anomalies v0.1 | CTDP1 |
Rebecca Foulger gene: CTDP1 was added gene: CTDP1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: CTDP1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CTDP1 were set to CONGENITAL CATARACTS FACIAL DYSMORPHISM AND NEUROPATHY SYNDROME |
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| Fetal anomalies v0.1 | BPTF |
Rebecca Foulger gene: BPTF was added gene: BPTF was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: BPTF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: BPTF were set to Developmental and Speech Delay, Postnatal Microcephaly, and Dysmorphic Features |
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| Fetal anomalies v0.1 | B3GAT3 |
Rebecca Foulger gene: B3GAT3 was added gene: B3GAT3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: B3GAT3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: B3GAT3 were set to Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects 245600 |
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| Fetal anomalies v0.1 | ASXL2 |
Rebecca Foulger gene: ASXL2 was added gene: ASXL2 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: ASXL2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ASXL2 were set to Developmental delay, macrocephaly, and dysmorphic features |
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| Fetal anomalies v0.1 | ASPH |
Rebecca Foulger gene: ASPH was added gene: ASPH was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: ASPH was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ASPH were set to FACIAL DYSMORPHISM, LENS DISLOCATION, ANTERIOR SEGMENT ABNORMALITIES, AND SPONTANEOUS FILTERING BLEBS |
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