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Fetal anomalies v3.155 GRM1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red inline with review by Zornitza Stark. Could not find any evidence of prenatal phenotypes in patients with GRM1 variants.
Fetal anomalies v3.78 WNT9B Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Not yet associated with any phenotype in OMIM or G2P. Rating Amber as to date, only two cases have been reported in one paper but with a watchlist tag to monitor for additional cases.
Fetal anomalies v1.879 LONP1 Arina Puzriakova commented on gene: LONP1: Added 'watchlist_moi' tag to monitor recently reported association with congenital diaphragmatic hernia as highlighted in review by Zornitza Stark (Australian Genomics)
Fetal anomalies v1.705 PRKD1 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI was reassessed following a recent review by Zornitza Stark highlighting the potential involvement of biallelic variants. Currently the evidence for biallelic inheritance only suffices for an Amber rating and so I have kept the MOI as monoallelic but with a 'watchlist_MOI' tag to monitor for additional evidence. The Genomics England pipeline would still pick up biallelic cases under the current MOI.
Fetal anomalies v1.692 MYOD1 Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics) on Congenital myopathy panel. This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is currently not enough evidence to support a gene-disease association on this panel (Fetal anomalies). Therefore, this gene has been given an Amber rating.
Fetal anomalies v1.645 FOXP4 Ivone Leong gene: FOXP4 was added
gene: FOXP4 was added to Fetal anomalies. Sources: Literature
Q2_21_rating, Q2_21_phenotype tags were added to gene: FOXP4.
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to AMBER
Added comment: This gene is associated with a phenotype in Gene2Phenotype but not in OMIM.

This gene is present as an Amber gene on the Intellectual disability panel (Version 3.1052) with the following reviews:

"This gene is a little bit difficult to place, may be Green on Fetal Anomalies panel? Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays, hence Amber rating here. Sources: Literature
Zornitza Stark (Australian Genomics), 4 Nov 2020"

"Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). As ID is not present in the majority of affected patients, and the affected individuals only show mild ID, this gene has been given an Amber rating.
Ivone Leong (Genomics England Curator), 4 Dec 2020"

After discussion with the Genomics England Clinical Team it was decided that this gene should be added to this panel as an Amber gene and subject to review by the GMS specialist group.
Sources: Literature
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.
Fetal anomalies v1.219 GDF2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Single family with 2 sibs affected by lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis. Homozygous truncating variant in GDF2 was detected which segregated with the disorder (PMID:32618121).

Rating Red as additional cases/functional evidence required to corroborate this gene-disease association.
Fetal anomalies v1.215 GFRA1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Two unrelated families with non-syndromic bilateral renal agenesis, detected during the prenatal period, and distinct homozygous LoF variants in GFRA1. Animal models support a role in renal morphogenesis (PMID:33020172).

Rating Amber awaiting further cases/clinical evidence prior to inclusion as diagnositc-grade.
Fetal anomalies v1.184 NUAK2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Single consanguineous family with three consecutive fetuses with anencephaly. Exome sequencing revealed a recessive 21-bp in-frame deletion in NUAK2 segregating with the disease. Pathogenicity is supported by in vitro and animal model data.

Rating Amber, awaiting further cases/clinical evidence prior to inclusion as diagnostic-grade (added 'watchlist' tag)
Fetal anomalies v1.183 AMBRA1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Sufficient unrelated cases and supportive functional data. However, only a single publication linking this gene to human disease at present (PMID:32333458). Segregation data was not provided and penetrance remains unclear. AMBRA1 was investigated by targeted sequencing and so there also is a possibility of variants in other genes.

Currently the evidence is insufficient for a Green rating, but this may be revised if further cases/clinical evidence arise (added 'watchlist' tag)
Fetal anomalies v1.180 CALCRL Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Single family with recurrent hydrops fetalis (PMID:30115739), supported by in vitro and animal model data. Rating Red as additional cases required to corroborate this gene-disease association.
Fetal anomalies v1.54 ATP1A2 Rebecca Foulger Added comment: Comment on list classification: Added to panel with Amber review by Zornitza Stark. Not yet associated with a disorder in Gene2Phenotype. 2 families reported in PMID:30690204 with a fetally-relevant phenotype (including fetal hydrops). Therefore rated Amber awaiting further cases.
Fetal anomalies v1.45 AHCY Rebecca Foulger Added comment: Comment on list classification: Added to panel and rated Amber by Zornitza Stark. Two unrelated families with hydrops reported (PMID:30121674, 20852937). Note that previous reports of AHCY deficiency do not include hydrops (e.g. PMID:15024124). Overall, phenotype is relevant to the panel but currently insufficient evidence for Green rating. Rated Amber awaiting further evidence.
Fetal anomalies v0.345 FAM58A Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from MONOALLELIC to X-linked dominant. Although monoallelic inheritance is currently listed in DDG2P for STAR SYNDROME, FAM58A (CCNQ) is an X-linked gene.
Fetal anomalies v0.161 STAR Rebecca Foulger edited their review of gene: STAR: 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 STAR Rebecca Foulger reviewed gene: STAR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 FAM58A Rebecca Foulger commented on gene: FAM58A: DDG2P rating in original PAGE list: Confirmed for STAR SYNDROME
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
Fetal anomalies v0.1 FAM58A Rebecca Foulger gene: FAM58A was added
gene: FAM58A was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: FAM58A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FAM58A were set to STAR SYNDROME