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Fetal anomalies v3.163 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Fetal anomalies v3.111 PC Sarah Leigh Tag Q2_23_promote_green was removed from gene: PC.
Tag Q2_23_NHS_review was removed from gene: PC.
Fetal anomalies v3.111 PC Sarah Leigh reviewed gene: PC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.110 PC Sarah Leigh Source Expert Review Green was added to PC.
Source NHS GMS was added to PC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.44 PC Arina Puzriakova Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency, OMIM:266150; PYRUVATE CARBOXYLASE DEFICIENCY to Pyruvate carboxylase deficiency, OMIM:266150
Fetal anomalies v3.43 PC Arina Puzriakova Publications for gene: PC were set to
Fetal anomalies v3.42 PC Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: PC.
Tag Q2_23_NHS_review tag was added to gene: PC.
Fetal anomalies v3.27 MPC2 Arina Puzriakova Publications for gene: MPC2 were set to
Fetal anomalies v3.26 MPC1 Arina Puzriakova Publications for gene: MPC1 were set to
Fetal anomalies v3.8 PC Stephanie Allen commented on gene: PC: This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Fetal anomalies v3.8 MPC2 Stephanie Allen commented on gene: MPC2: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 MPC1 Stephanie Allen commented on gene: MPC1: This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Amber gene.
Fetal anomalies v3.8 PC Stephanie Allen reviewed gene: PC: Rating: GREEN; Mode of pathogenicity: ; Publications: 30870574, 29752808, 34485016, 10323732; Phenotypes: Pyruvate carboxylase deficiency, OMIM:266150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 MPC2 Stephanie Allen reviewed gene: MPC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 36417180; Phenotypes: Mitochondrial pyruvate carrier deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.8 MPC1 Stephanie Allen reviewed gene: MPC1: Rating: AMBER; Mode of pathogenicity: ; Publications: 34873722, 31145700; Phenotypes: Mitochondrial pyruvate carrier deficiency, OMIM:614741; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.7 PC Arina Puzriakova Source Expert Review Amber was added to PC.
Added phenotypes Pyruvate carboxylase deficiency, OMIM:266150 for gene: PC
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v3.7 MPC2 Arina Puzriakova gene: MPC2 was added
gene: MPC2 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: MPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MPC2 were set to Mitochondrial pyruvate carrier deficiency
Fetal anomalies v3.7 MPC1 Arina Puzriakova gene: MPC1 was added
gene: MPC1 was added to Fetal anomalies. Sources: Expert Review Amber
Mode of inheritance for gene: MPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MPC1 were set to Mitochondrial pyruvate carrier deficiency, OMIM:614741
Fetal anomalies v1.945 MYBPC3 Arina Puzriakova Classified gene: MYBPC3 as Amber List (moderate evidence)
Fetal anomalies v1.945 MYBPC3 Arina Puzriakova Gene: mybpc3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.944 MYBPC3 Arina Puzriakova Publications for gene: MYBPC3 were set to PMID: 28749478; 19858127
Fetal anomalies v1.900 MYBPC3 Rhiannon Mellis gene: MYBPC3 was added
gene: MYBPC3 was added to Fetal anomalies. Sources: Expert Review,Literature
Mode of inheritance for gene: MYBPC3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MYBPC3 were set to PMID: 28749478; 19858127
Phenotypes for gene: MYBPC3 were set to Cardiomyopathy; ?Congenital myopathy
Review for gene: MYBPC3 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 pending more evidence.

Currently rated Green on the following other PanelApp panel(s): Various cardiomyopathy panels. Amber on congenital myopathy panel.

Details of review:
Previously only one (AR) case with skeletal muscle phenotype, although is a known cardiomyopathy gene (PMID: 19858127). One fetal case reported by Shamseldin et al 2018 (PMID: 28749478) with hydrops.
Sources: Expert Review, Literature
Fetal anomalies v1.836 TRAPPC12 Arina Puzriakova edited their review of gene: TRAPPC12: Changed rating: GREEN
Fetal anomalies v1.836 TRAPPC12 Arina Puzriakova Tag watchlist was removed from gene: TRAPPC12.
Fetal anomalies v1.836 GPC6 Arina Puzriakova Tag for-review was removed from gene: GPC6.
Fetal anomalies v1.836 TRAPPC12 Arina Puzriakova commented on gene: TRAPPC12: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Fetal anomalies v1.836 GPC6 Arina Puzriakova commented on gene: GPC6: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Fetal anomalies v1.835 TRAPPC12 Arina Puzriakova Source Expert Review Green was added to TRAPPC12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v1.835 GPC6 Arina Puzriakova Source Expert Review Green was added to GPC6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v1.668 MYBPC2 Arina Puzriakova gene: MYBPC2 was added
gene: MYBPC2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MYBPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBPC2 were set to 32732226
Phenotypes for gene: MYBPC2 were set to Fetal akinesia; Hydrops; Hygroma; Multiple pterygium
Review for gene: MYBPC2 was set to RED
Added comment: Novel candidate gene identified in a fetus with fetal akinesia detected by ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, hygroma, multiple pterygium. A homozygous variant (c.3394G>A/ p.Glu1132Lys) in MYBPC2 was found by exome sequencing with concordant segregation among one affected sib and two unaffected sibs.
Sources: Literature
Fetal anomalies v1.423 GPC6 Arina Puzriakova Phenotypes for gene: GPC6 were changed from OMODYSPLASIA TYPE 1 (OMOD1) [ to Omodysplasia 1, OMIM:258315; Autosomal recessive omodysplasia, MONDO:0009779
Fetal anomalies v1.421 GPC6 Arina Puzriakova Classified gene: GPC6 as Amber List (moderate evidence)
Fetal anomalies v1.421 GPC6 Arina Puzriakova Gene: gpc6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.420 GPC6 Arina Puzriakova Tag for-review tag was added to gene: GPC6.
Fetal anomalies v1.214 GPC6 Rhiannon Mellis reviewed gene: GPC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Omodysplasia 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.195 SCLT1 Rhiannon Mellis gene: SCLT1 was added
gene: SCLT1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SCLT1 were set to No OMIM phenotype; Oro-facio-digital syndrome type IX; Senior-Løken Syndrome
Review for gene: SCLT1 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): Rare multisystem ciliopathy Super panel


Copied from rare multisystem ciliopathies panel:
PMID: 24285566 - Adly et al 2014 - 1 case with index patient with consanguineous Saudi parents and a severe ciliopathy phenotype. He had severe midline cleft lip and palate, microcephaly and choanal atresia. He also had significant eye involvement in the form of severe coloboma, and congenital heart disease (ASD and VSD). He had micropenis. Brain imaging revealed pachygyria and absent corpus callosum. He had abnormal inner ear structures. A splicing mutation was identified in SCLT1 (, NM_144643.2:exon5:c.290+2T>C). This mutation completely abolishes the consensus donor site of exon 5 as confirmed by RTPCR, which showed complete skipping of exon 5 resulting in a frameshift and introduction of a premature stop codon (p.Lys79Valfs*4),

PMID: 28005958 - de Castro-Miró et al 2016 - A cohort of 33 pedigrees affected with a variety of retinal disorders was analysed by WES. 1 case with compound heterozygosity (one missense and one splicing altering mutations) in SCLT1 that segregates with the condition in the family (2 affected siblings). Proposed to be causative of early-onset Retinitis Pigmentosa. SCLT1 is a member of the centrosomal/ciliary protein family.

PMID: 28486600 - Li et al 2017 - report a mouse model with mutated Sclt1 gene. The Sclt1-/- mice exhibit typical ciliopathy phenotypes, including cystic kidney, cleft palate and polydactyly.

PMID: 30425282 - Katagiri et al 2018 - a patient with Senior Løken syndrome and her unaffected parents revealed that the patient had infantile-onset retinal dystrophy and juvenile-onset nephronophthisis. Other systemic abnormalities included hepatic dysfunction, megacystis, mild learning disability, autism, obesity, and hyperinsulinemia. Whole-exome sequencing identified compound heterozygous SCLT1 variants (c.1218 + 3insT and c.1631A > G) in the patient. The unaffected parents were heterozygous for each variant. Transcript analysis using reverse transcription PCR demonstrated that the c.1218 + 3insT variant leads to exon 14 skipping (p.V383_M406del), while the other variant (c.1631A > G) primarily leads to exon 17 skipping (p.D480EfsX11) as well as minor amounts of two transcripts. Immunohistochemical analysis demonstrated that the Sclt1 protein was localized to the distal appendage of the photoreceptor basal body, indicating a ciliary protein.

= 3 cases plus a mouse model and functional evidence that the protein is a ciliary protein.
Sources: Literature
Fetal anomalies v1.162 TRAPPC12 Arina Puzriakova Classified gene: TRAPPC12 as Amber List (moderate evidence)
Fetal anomalies v1.162 TRAPPC12 Arina Puzriakova Gene: trappc12 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.161 TRAPPC12 Arina Puzriakova Publications for gene: TRAPPC12 were set to
Fetal anomalies v1.160 TRAPPC12 Arina Puzriakova Phenotypes for gene: TRAPPC12 were changed from Progressive Childhood Encephalopathy and Golgi Dysfunction to Hydrocephaly; Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, OMIM:617669; Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, MONDO:0044696
Fetal anomalies v1.159 TRAPPC12 Arina Puzriakova Mode of inheritance for gene: TRAPPC12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.158 TRAPPC12 Arina Puzriakova commented on gene: TRAPPC12: Removed 'polygenic' tag as published cases revealed no evidence to indicate polygenic inheritance
Fetal anomalies v1.158 TRAPPC12 Arina Puzriakova Tag polygenic was removed from gene: TRAPPC12.
Tag watchlist tag was added to gene: TRAPPC12.
Fetal anomalies v1.158 TRAPPC12 Arina Puzriakova reviewed gene: TRAPPC12: Rating: AMBER; Mode of pathogenicity: None; Publications: 32347653, 28777934; Phenotypes: Hydrocephaly, Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, OMIM:617669, Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, MONDO:0044696; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.108 TRAPPC12 Rhiannon Mellis reviewed gene: TRAPPC12: Rating: GREEN; Mode of pathogenicity: None; Publications: 32347653; Phenotypes: Hydrocephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.342 ANAPC1 Rebecca Foulger commented on gene: ANAPC1: Added ANAPC1 to the Fetal anomalies panel and rated Green on approval from Anna de Burca and Richard Scott (Genomics England Clinical team). Note yet associated with a disorder in OMIM but evidence comes from PMID:31303264 (Ajeawung et al., 2019) where they report 10 individuals (7 families including 3 families of Amish ancestry) with Rothmund-Thomson Syndrome Type 1 and biallelic variants in ANAPC1. Phenotype includes skeletal abnormalities and short stature. All individuals carried an intronic splicing variant (NM_022662.3:c.2705−198C>T): in 3 Amish families plus individual 4, this intronic variant was found in a homozygous state. In the remaining families, the intronic variant was found in trans with one of three other LOF variants. Therefore sufficient cases to support a Green rating plus fetally-relevant phenotype.
Fetal anomalies v0.342 ANAPC1 Rebecca Foulger reviewed gene: ANAPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.342 ANAPC1 Rebecca Foulger gene: ANAPC1 was added
gene: ANAPC1 was added to Fetal anomalies. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: ANAPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANAPC1 were set to 31303264
Phenotypes for gene: ANAPC1 were set to Rothmund-Thomson Syndrome Type 1
Fetal anomalies v0.311 PC Rebecca Foulger edited their review of gene: PC: Added comment: This gene was reviewed by Anna de Burca (Genomics England Clinical Team), and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Presentation of mitochondrial disorders can be variable, and most aren't obvious at birth. Therefore exclude unless the gene has been directly associated with a fetal presentation.; Changed rating: RED
Fetal anomalies v0.310 PC Rebecca Foulger Source Expert Review Red was added to PC.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.233 PCGF2 Rebecca Foulger Phenotypes for gene: PCGF2 were changed from INTELLECTUAL DUSBILITY; Craniofacial Neurological Cardiovascular and Skeletal Features to INTELLECTUAL DUSBILITY; Craniofacial Neurological Cardiovascular and Skeletal Features; Intellectual disability
Fetal anomalies v0.228 TRAPPC9 Rebecca Foulger edited their review of gene: TRAPPC9: 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.; Changed rating: GREEN
Fetal anomalies v0.226 PCGF2 Rebecca Foulger Source Expert Review Green was added to PCGF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v0.225 G6PC3 Rebecca Foulger edited their review of gene: G6PC3: 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: G6PC3 was originally added to the Fetal anomalies panel from the PAGE Additional gene list. G6PC3 is not yet associated with a disorder in Gene2Phenotype but is associated in OMIM with Dursun syndrome and Neutropenia, severe congenital 4, autosomal recessive (both MIM:612541). Since structural features were noted in some patients, it was decided that on balance G6PC3 should be included on the panel.; Changed rating: GREEN
Fetal anomalies v0.225 PCGF2 Rebecca Foulger edited their review of gene: PCGF2: 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.; Changed rating: GREEN
Fetal anomalies v0.188 PCGF2 Rebecca Foulger Tag watchlist tag was added to gene: PCGF2.
Fetal anomalies v0.188 PCGF2 Rebecca Foulger commented on gene: PCGF2: Added 'watchlist' tag to reflect multiple Disease confidence ratings for different disorders in Gene2Phenotype: Rated probable for INTELLECTUAL DUSBILITY. Rated confirmed for Craniofacial Neurological Cardiovascular and Skeletal.
Fetal anomalies v0.188 PCGF2 Rebecca Foulger commented on gene: PCGF2: New gene:disorder association added to DDG2P in March 2019: Craniofacial Neurological Cardiovascular and Skeletal Features. DDG2P Disease confidence: confirmed. DDG2P mode of pathogenicity/mutation consequence: all missense/in frame. DDG2P mode of inheritance: monoallelic.
Fetal anomalies v0.188 PCGF2 Rebecca Foulger Publications for gene: PCGF2 were set to
Fetal anomalies v0.187 PCGF2 Rebecca Foulger Phenotypes for gene: PCGF2 were changed from INTELLECTUAL DUSBILITY to INTELLECTUAL DUSBILITY; Craniofacial Neurological Cardiovascular and Skeletal Features
Fetal anomalies v0.167 TRAPPC2 Rebecca Foulger Source Expert Review Red was added to TRAPPC2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.166 TRAPPC2 Rebecca Foulger edited their review of gene: TRAPPC2: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: Age of onset is 5-10 years. Action taken: Demoted gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.166 HYDIN Rebecca Foulger edited their review of gene: HYDIN: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: Primary Ciliary Dyskinesia (PCD) but can exclude from causing situs defects. According to PMID:30166424 (Best et al., 2019) plus email correspondance from Hannah Mitchison (UCL), there is fairly firm evidence that mutations in HYDIN cause PCD without laterality defects/Situs Invertis. Variant flagged as Potentially Clinically Useful from PAGE study. Action taken: Demoted gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.166 GAS8 Rebecca Foulger edited their review of gene: GAS8: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: Primary Ciliary Dyskinesia (PCD) but highly unlikely to cause situs defects. According to PMID:30166424 (Best et al., 2019), GAS8 has not previously been associated with Situs defects in the literature. Plus email correspondance from Hannah Mitchison (UCL) that mutations in GAS8 are not associated with laterality defects, including in mice. Action taken: Demoted gene rating from Green to Red.; Changed rating: RED; Changed publications: 30166424
Fetal anomalies v0.166 CCDC65 Rebecca Foulger edited their review of gene: CCDC65: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: Primary Ciliary Dyskinesia (PCD) but highly unlikely to cause situs defects. According to PMID:30166424 (Best et al., 2019), CCDC65 (DRC2) has not previously been associated with Situs defects in the literature. Plus email correspondance from Hannah Mitchison (UCL) that mutations in CCDC65/DRC2 are not associated with laterality defects, including in mice. Action taken: Demoted gene rating from Green to Red.; Changed rating: RED; Changed publications: 30166424
Fetal anomalies v0.166 CCNO Rebecca Foulger edited their review of gene: CCNO: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: Primary Ciliary Dyskinesia (PCD) but can exclude from causing situs defects. According to PMID:30166424 (Best et al., 2019) plus email correspondance from Hannah Mitchison (UCL), there is fairly firm evidence that mutations in CCNO cause PCD without laterality defects/Situs Invertis. Action taken: Demoted gene rating from Green to Red.; Changed rating: RED; Changed publications: 30166424
Fetal anomalies v0.166 RSPH3 Rebecca Foulger edited their review of gene: RSPH3: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: Primary Ciliary Dyskinesia (PCD) but can exclude from causing situs defects. According to PMID:30166424 (Best et al., 2019), RSPH3 has not previously been associated with Situs defects in the literature. Plus email correspondance from Hannah Mitchison (UCL) that there is fairly firm evidence that mutations in RSPH3 cause PCD without laterality defects/Situs Invertis. Action taken: Demoted gene rating from Green to Red.; Changed rating: RED; Changed publications: 30166424
Fetal anomalies v0.166 RSPH1 Rebecca Foulger edited their review of gene: RSPH1: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: Primary Ciliary Dyskinesia (PCD) but can exclude from causing situs defects. According to PMID:30166424 (Best et al., 2019) plus email correspondance from Hannah Mitchison (UCL), there is fairly firm evidence that mutations in RSPH1 cause PCD without laterality defects/Situs Invertis. Action taken: Demoted gene rating from Green to Red.; Changed rating: RED; Changed publications: 30166424
Fetal anomalies v0.165 XPC Rebecca Foulger Source Expert Review Red was added to XPC.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.161 XPC Rebecca Foulger edited their review of gene: XPC: 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: Phenotype is not fetally-relevant. Action taken: Demoted XPC gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.161 WDPCP Rebecca Foulger edited their review of gene: WDPCP: 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 v0.154 PCDH19 Rebecca Foulger Source Expert Review Red was added to PCDH19.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.154 PCCB Rebecca Foulger Source Expert Review Red was added to PCCB.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.154 PCCA Rebecca Foulger Source Expert Review Red was added to PCCA.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.154 PCBD1 Rebecca Foulger Source Expert Review Red was added to PCBD1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.153 PCYT1A Rebecca Foulger edited their review of gene: PCYT1A: 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 PCNT Rebecca Foulger edited their review of gene: PCNT: 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 PCDH19 Rebecca Foulger edited their review of gene: PCDH19: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: No structural phenotypes. Action taken: Demoted PCDH19 gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.153 PCCB Rebecca Foulger edited their review of gene: PCCB: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: Probably all features are secondary to the metabolite accumulation postnatally. Action taken: Demoted PCCB gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.153 PCCA Rebecca Foulger edited their review of gene: PCCA: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: Probably all features are secondary to the metabolite accumulation postnatally. Action taken: Demoted PCCA gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.153 PCBD1 Rebecca Foulger edited their review of gene: PCBD1: 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: Phenotype is not fetally-relevant. Action taken: Demoted PCBD1 gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.134 NPC2 Rebecca Foulger edited their review of gene: NPC2: 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 v0.134 NPC1 Rebecca Foulger edited their review of gene: NPC1: 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 v0.134 GPC3 Rebecca Foulger edited their review of gene: GPC3: 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 v0.134 C2orf71 Rebecca Foulger edited their review of gene: C2orf71: 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: Phenotype is not fetally-relevant. Additional notes from clinical review: Retinitis pigmentosa has adult onset with two patients reported with an earlier onset. Action taken: Demoted C2orf71 (PCARE) gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.134 MYBPC1 Rebecca Foulger edited their review of gene: MYBPC1: 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 v0.9 XPC Rebecca Foulger reviewed gene: XPC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 WDPCP Rebecca Foulger reviewed gene: WDPCP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 TRAPPC9 Rebecca Foulger reviewed gene: TRAPPC9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 TRAPPC2 Rebecca Foulger reviewed gene: TRAPPC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 TRAPPC12 Rebecca Foulger edited their review of gene: TRAPPC12: Added comment: DDG2P rating in original PAGE list: Probable for Progressive Childhood Encephalopathy and Golgi Dysfunction; Changed rating: AMBER
Fetal anomalies v0.9 TRAPPC11 Rebecca Foulger reviewed gene: TRAPPC11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 PCYT1A Rebecca Foulger reviewed gene: PCYT1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 PCNT Rebecca Foulger reviewed gene: PCNT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 PCGF2 Rebecca Foulger commented on gene: PCGF2: DDG2P rating in original PAGE list: Probable for INTELLECTUAL DUSBILITY
Fetal anomalies v0.9 PCDH19 Rebecca Foulger reviewed gene: PCDH19: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 PCCB Rebecca Foulger reviewed gene: PCCB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 PCCA Rebecca Foulger reviewed gene: PCCA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 PCBD1 Rebecca Foulger reviewed gene: PCBD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 PC Rebecca Foulger reviewed gene: PC: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 NPC2 Rebecca Foulger reviewed gene: NPC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 NPC1 Rebecca Foulger reviewed gene: NPC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 MYBPC1 Rebecca Foulger reviewed gene: MYBPC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 GPC6 Rebecca Foulger reviewed gene: GPC6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 GPC3 Rebecca Foulger reviewed gene: GPC3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 G6PC3 Rebecca Foulger reviewed gene: G6PC3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.3 TRAPPC12 Rebecca Foulger commented on gene: TRAPPC12
Fetal anomalies v0.3 TRAPPC12 Rebecca Foulger Tag polygenic tag was added to gene: TRAPPC12.
Fetal anomalies v0.3 C2orf71 Rebecca Foulger commented on gene: C2orf71: Added new-gene-name tag, new approved HGNC gene symbol is PCARE
Fetal anomalies v0.3 PCGF2 Rebecca Foulger reviewed gene: PCGF2: Rating: AMBER; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.1 XPC Rebecca Foulger gene: XPC was added
gene: XPC was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: XPC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: XPC were set to XERODERMA PIGMENTOSUM, GROUP C
Fetal anomalies v0.1 WDPCP Rebecca Foulger gene: WDPCP was added
gene: WDPCP was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: WDPCP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDPCP were set to BARDET-BIEDL SYNDROME TYPE 15
Fetal anomalies v0.1 TRAPPC9 Rebecca Foulger gene: TRAPPC9 was added
gene: TRAPPC9 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: TRAPPC9 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRAPPC9 were set to MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 13
Fetal anomalies v0.1 TRAPPC2 Rebecca Foulger gene: TRAPPC2 was added
gene: TRAPPC2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: TRAPPC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: TRAPPC2 were set to SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
Fetal anomalies v0.1 TRAPPC12 Rebecca Foulger gene: TRAPPC12 was added
gene: TRAPPC12 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: TRAPPC12 was set to Unknown
Phenotypes for gene: TRAPPC12 were set to Progressive Childhood Encephalopathy and Golgi Dysfunction
Fetal anomalies v0.1 TRAPPC11 Rebecca Foulger gene: TRAPPC11 was added
gene: TRAPPC11 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: TRAPPC11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRAPPC11 were set to MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2S
Fetal anomalies v0.1 PCYT1A Rebecca Foulger gene: PCYT1A was added
gene: PCYT1A was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PCYT1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCYT1A were set to SPONDYLOMETAPHYSEAL DYSPLASIA WITH CONE-ROD DYSTROPHY
Fetal anomalies v0.1 PCNT Rebecca Foulger gene: PCNT was added
gene: PCNT was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PCNT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCNT were set to MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II
Fetal anomalies v0.1 PCGF2 Rebecca Foulger gene: PCGF2 was added
gene: PCGF2 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: PCGF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PCGF2 were set to INTELLECTUAL DUSBILITY
Fetal anomalies v0.1 PCDH19 Rebecca Foulger gene: PCDH19 was added
gene: PCDH19 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PCDH19 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: PCDH19 were set to EPILEPTIC ENCEPHALOPATHY EARLY INFANTILE TYPE 9
Fetal anomalies v0.1 PCCB Rebecca Foulger gene: PCCB was added
gene: PCCB was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PCCB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCCB were set to PROPIONIC ACIDEMIA
Fetal anomalies v0.1 PCCA Rebecca Foulger gene: PCCA was added
gene: PCCA was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PCCA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCCA were set to PROPIONIC ACIDEMIA
Fetal anomalies v0.1 PCBD1 Rebecca Foulger gene: PCBD1 was added
gene: PCBD1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PCBD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PCBD1 were set to HYPERPHENYLALANINEMIA, BH4-DEFICIENT, D
Fetal anomalies v0.1 PC Rebecca Foulger gene: PC was added
gene: PC was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: PC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PC were set to PYRUVATE CARBOXYLASE DEFICIENCY
Fetal anomalies v0.1 NPC2 Rebecca Foulger gene: NPC2 was added
gene: NPC2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: NPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPC2 were set to NIEMANN-PICK DISEASE, TYPE C2
Fetal anomalies v0.1 NPC1 Rebecca Foulger gene: NPC1 was added
gene: NPC1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPC1 were set to NIEMANN-PICK DISEASE, TYPE C1
Fetal anomalies v0.1 MYBPC1 Rebecca Foulger Added phenotypes Lethal congenital contracture syndrome 4 614915 for gene: MYBPC1
Fetal anomalies v0.1 MYBPC1 Rebecca Foulger gene: MYBPC1 was added
gene: MYBPC1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List
Mode of inheritance for gene: MYBPC1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: MYBPC1 were set to Arthrogryposis, distal, type 1B 614335
Fetal anomalies v0.1 GPC6 Rebecca Foulger gene: GPC6 was added
gene: GPC6 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: GPC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPC6 were set to OMODYSPLASIA TYPE 1 (OMOD1) [
Fetal anomalies v0.1 GPC3 Rebecca Foulger gene: GPC3 was added
gene: GPC3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: GPC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: GPC3 were set to SIMPSON-GOLABI-BEHMEL SYNDROME, TYPE 1
Fetal anomalies v0.1 G6PC3 Rebecca Foulger Added phenotypes Neutropenia, severe congenital 4, autosomal recessive for gene: G6PC3
Fetal anomalies v0.1 G6PC3 Rebecca Foulger gene: G6PC3 was added
gene: G6PC3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List
Mode of inheritance for gene: G6PC3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: G6PC3 were set to Dursun syndrome