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| Fetal anomalies v1.905 | WNT7B |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Julia Baptista. There is sufficient evidence to promote this gene to Green at the next GMS panel update. Three families reported with fetuses with multiple congenital anomalies (PMID: 35790350). Biallelic variants were identified in probands of two families and parents in third family were both heterozygous for a variant found in one of the other families. Although the fetus was not available for testing, the genotype can be inferred as homozygous for the variant given the consistent phenotype between cases. Supportive zebrafish model supports pathogenicity. |
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| Fetal anomalies v1.617 | SLC20A1 |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Rating Amber but there is sufficient evidence to promote to Green. At least three unrelated families with a BEEC phenotype (fetally-relevant) and different heterozygous variants in this gene (PMID: 32850778). In vitro assays and zebrafish model support pathogenicity. |
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| Fetal anomalies v1.165 | NUP88 |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Julia Baptista (Royal Devon and Exeter NHS Foundation Trust). Two unrelated families with lethal FADS and different biallelic variants in the NUP88 gene (PMID: 30543681). Zebrafish model recapitulated some human phenotypes such as locomotor and neuromuscular junction defects. NUP88 is associated with a relevant phenotype in OMIM but is not currently in Gene2Phenotype. Fetally-relevant phenotype but additional cases required prior to inclusion as diagnostic-grade. Added 'watchlist' tag. |
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| Fetal anomalies v1.143 | KIF14 |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Associated with relevant phenotype in OMIM and Gene2Phenotype. At least 13 unrelated families reported with most cases being of fetal relevance. Phenotypes within the spectrum of fetal forms of ciliopathies (MKS) as well as severe primary microcephaly. Also supportive zebrafish model. Rating Amber but should be promoted to Green at the next GMS panel update (added 'for-review' tag) |
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| Fetal anomalies v1.95 | KIF14 |
Rhiannon Mellis gene: KIF14 was added gene: KIF14 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF14 were set to PMID: 24128419; 30388224; 28892560; 29343805 Phenotypes for gene: KIF14 were set to ?Meckel syndrome 12; Microcephaly 20, primary Review for gene: KIF14 was set to GREEN gene: KIF14 was marked as current diagnostic Added comment: Two fetuses in one family with complex multiple congenital anomalies consistent with ciliopathy phenotype. (PMID: 24128419) Four more families with fetuses with similar phenotype (microcephaly, brain malformations and renal agenesis or hypodysplasia). Also functional (zebrafish) studies. Authors conclude that LOF variants cause the above syndromic phenotype while hypomorphic variants cause microcephaly without kidney defects. (PMID: 30388224) Four unrelated families with AR primary microcephaly and biallelic KIF14 pathogenic variants (PMID: 28892560) Four more unrelated families with AR primary microcephaly and biallelic KIF14 pathogenic variants. Two sibs from one of the families were fetuses with severe microcephaly detected prenatally and leading to termination of pregnancy. (PMID: 29343805) Sources: Literature |
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| Fetal anomalies v1.74 | AMBRA1 |
Zornitza Stark gene: AMBRA1 was added gene: AMBRA1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: AMBRA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AMBRA1 were set to 17589504; 32333458 Phenotypes for gene: AMBRA1 were set to Neural tube defects Review for gene: AMBRA1 was set to GREEN gene: AMBRA1 was marked as current diagnostic Added comment: 5 rare missense variants were identified in 6 cases from a neural tube defect cohort, and 4 (p.Thr80Met, p.Leu274Phe, p.Ser743Phe, and p.Met884Val) of them were functionally validated to affect autophagy regulation in vitro or zebrafish embryo development in vivo. There is also null mouse model with neural tube defects. Sources: Literature |
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| Fetal anomalies v1.73 | CFAP53 |
Rhiannon Mellis gene: CFAP53 was added gene: CFAP53 was added to Fetal anomalies. Sources: Literature,Expert Review Mode of inheritance for gene: CFAP53 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP53 were set to PMID: 22577226; PMID: 25504577; PMID: 26531781 Phenotypes for gene: CFAP53 were set to Heterotaxy, visceral, 6, autosomal recessive; Dextrocardia; Transposition of the great arteries; gut malrotation; midline liver; inverted spleen Review for gene: CFAP53 was set to GREEN Added comment: Literature reports 6 individuals from 4 families and a zebrafish model PMID: 22577226, PMID: 25504577, PMID: 26531781 Reviewed for fetally relevant phenotype by Prof Lyn Chitty (yes). This gene appears on our local heterotaxy panel (NETRGL) and on the Panelapp laterality disorders and non-syndromic CHD panels (Green) Sources: Literature, Expert Review |
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| Fetal anomalies v0.218 | MYT1 | Rebecca Foulger commented on gene: MYT1: Lopez et al 2016 (PMID:27358179) identified a heterozgous MYT1 de novo nonsense variant in one patient (c.25C>T, p.Arg9*) and one heterozygous inherited missense variant in second patient (c.314C>T, p.Ser105Leu) in a cohort of 169patients with OAVS. Functional studies by transient knockdown of myt1a in zebrafish, led to specific craniofacial cartilage alterations. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.183 | BRAF | Rebecca Foulger edited their review of gene: BRAF: Added comment: Additional evidence from PAGE study: Diagnostic Heterozygous variant identified in BRAF from fetalexome sequencing inLord et al., 2019 (PMID:30712880).; Changed publications: 30712880 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.134 | BRAF | Rebecca Foulger edited their review of gene: BRAF: 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 v0.32 | TRIP4 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Rated Green on relevant V1 panel(s) PLUS phenotype (Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures) appropriate for fetal panel, as noted by Helen Brittain and Anna de Burca (Genomics England Clinical team). Rated Green on 'Paediatric motor neuronopathies' panel based on sufficient cases, zebrafish model and Green review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | BRAF | Rebecca Foulger commented on gene: BRAF: DDG2P rating in original PAGE list: Confirmed for NOONAN SYNDROME TYPE 7, Confirmed for LEOPARD SYNDROME TYPE 3, and Confirmed for CARDIOFACIOCUTANEOUS SYNDROME. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3 | BRAF | Rebecca Foulger reviewed gene: BRAF: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | BRAF | Rebecca Foulger Added phenotypes CARDIOFACIOCUTANEOUS SYNDROME for gene: BRAF | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | BRAF | Rebecca Foulger Added phenotypes LEOPARD SYNDROME TYPE 3 for gene: BRAF | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | BRAF |
Rebecca Foulger gene: BRAF was added gene: BRAF was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: BRAF were set to NOONAN SYNDROME TYPE 7 |
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