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Fetal anomalies v1.313 SENP7 Bryony Thompson Classified gene: SENP7 as Green List (high evidence)
Fetal anomalies v1.313 SENP7 Bryony Thompson Gene: senp7 has been classified as Green List (High Evidence).
Fetal anomalies v1.312 SENP7 Bryony Thompson reviewed gene: SENP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 37460201, 39763084, 38972567; Phenotypes: Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.312 ITGAV Zornitza Stark Marked gene: ITGAV as ready
Fetal anomalies v1.312 ITGAV Zornitza Stark Gene: itgav has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.312 ITGAV Zornitza Stark Classified gene: ITGAV as Amber List (moderate evidence)
Fetal anomalies v1.312 ITGAV Zornitza Stark Gene: itgav has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.311 ITGAV Zornitza Stark gene: ITGAV was added
gene: ITGAV was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ITGAV was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGAV were set to 39526957
Phenotypes for gene: ITGAV were set to Syndromic disease, MONDO:0002254, ITGAV-related
Review for gene: ITGAV was set to AMBER
Added comment: Three unrelated families reported: two with affected children (one hmz missense; other compound het LoF with missense) and one family with four affected fetuses. Clinical features included brain and eye anomalies and IBD/immune dysregulation. TGF-beta signalling pathway affected. The deletion of itgav in zebrafish recapitulated patient phenotypes including retinal and brain defects and the loss of microglia in early development as well as colitis in juvenile zebrafish with reduced SMAD3 expression and transcriptional regulation.
Sources: Literature
Fetal anomalies v1.310 C1orf127 Zornitza Stark Marked gene: C1orf127 as ready
Fetal anomalies v1.310 C1orf127 Zornitza Stark Gene: c1orf127 has been classified as Green List (High Evidence).
Fetal anomalies v1.310 C1orf127 Zornitza Stark Classified gene: C1orf127 as Green List (high evidence)
Fetal anomalies v1.310 C1orf127 Zornitza Stark Gene: c1orf127 has been classified as Green List (High Evidence).
Fetal anomalies v1.309 C1orf127 Zornitza Stark gene: C1orf127 was added
gene: C1orf127 was added to Fetal anomalies. Sources: Literature
new gene name tags were added to gene: C1orf127.
Mode of inheritance for gene: C1orf127 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1orf127 were set to 39753129
Phenotypes for gene: C1orf127 were set to Heterotaxy, visceral, MONDO:0018677, CIROZ-related
Review for gene: C1orf127 was set to GREEN
Added comment: 16 individuals from 10 families reported with bi-allelic variants in this gene and heterotaxy, including CHD. Supportive mouse model. CIROZ is absent or obsolete in select animals with motile cilia at their left-right organiser, including Carnivora, Atherinomorpha fish, or jawless vertebrates. Knockouts in zebrafish and Xenopus did not have observable LR anomalies. Approved HGNC name is CIROZ.
Sources: Literature
Fetal anomalies v1.308 PPFIBP1 Krithika Murali Marked gene: PPFIBP1 as ready
Fetal anomalies v1.308 PPFIBP1 Krithika Murali Gene: ppfibp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.308 PPFIBP1 Krithika Murali Classified gene: PPFIBP1 as Green List (high evidence)
Fetal anomalies v1.308 PPFIBP1 Krithika Murali Gene: ppfibp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.308 PPFIBP1 Krithika Murali Classified gene: PPFIBP1 as Green List (high evidence)
Fetal anomalies v1.308 PPFIBP1 Krithika Murali Gene: ppfibp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.307 PPFIBP1 Krithika Murali changed review comment from: Fetal microcephaly and IUGR are reported features.
Sources: Literature; to: Fetal microcephaly and IUGR are reported features.
Sources: Literature
Fetal anomalies v1.307 PPFIBP1 Krithika Murali gene: PPFIBP1 was added
gene: PPFIBP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPFIBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPFIBP1 were set to PMID: 35830857; PMID: 37229200
Phenotypes for gene: PPFIBP1 were set to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities - MIM#620024
Review for gene: PPFIBP1 was set to GREEN
Added comment: Fetal microcephaly and IUGR are reported features.
Sources: Literature
Fetal anomalies v1.306 HYAL2 Zornitza Stark Phenotypes for gene: HYAL2 were changed from Cleft lip and palate; cor triatriatum; congenital cardiac malformations to Muggenthaler-Chowdhury-Chioza syndrome, MIM# 621063
Fetal anomalies v1.305 PIGL Michelle Torres reviewed gene: PIGL: Rating: GREEN; Mode of pathogenicity: None; Publications: 22444671, 31535386, 30023290, 29473937, 28371479, 25706356; Phenotypes: CHIME syndrome MIM#280000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.305 KDM6B Zornitza Stark Marked gene: KDM6B as ready
Fetal anomalies v1.305 KDM6B Zornitza Stark Gene: kdm6b has been classified as Green List (High Evidence).
Fetal anomalies v1.305 KDM6B Zornitza Stark Classified gene: KDM6B as Green List (high evidence)
Fetal anomalies v1.305 KDM6B Zornitza Stark Gene: kdm6b has been classified as Green List (High Evidence).
Fetal anomalies v1.304 KDM6B Zornitza Stark gene: KDM6B was added
gene: KDM6B was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: KDM6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KDM6B were set to Stolerman neurodevelopmental syndrome, MIM# 618505
Review for gene: KDM6B was set to GREEN
Added comment: Well established gene-disease association. A proportion of individuals have congenital anomalies, including cleft palate, skeletal anomalies and congenital heart disease.
Sources: Expert Review
Fetal anomalies v1.303 LDB1 Zornitza Stark Marked gene: LDB1 as ready
Fetal anomalies v1.303 LDB1 Zornitza Stark Gene: ldb1 has been classified as Green List (High Evidence).
Fetal anomalies v1.303 LDB1 Zornitza Stark Classified gene: LDB1 as Green List (high evidence)
Fetal anomalies v1.303 LDB1 Zornitza Stark Gene: ldb1 has been classified as Green List (High Evidence).
Fetal anomalies v1.302 LDB1 Zornitza Stark gene: LDB1 was added
gene: LDB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LDB1 were set to 39680505
Phenotypes for gene: LDB1 were set to Congenital hydrocephalus MONDO:0016349
Review for gene: LDB1 was set to GREEN
Added comment: Exome-wide significant enrichment of LDB1 protein-altering de novo variants (p = 1.11 x 10-15) in a large cerebral ventriculomegaly cohort (>2,697 parent-proband trios). 8 unrelated cases with ventriculomegaly, developmental delay, and dysmorphic features with de novo variants (7 LoF variants truncate LDB1's carboxy-terminal LIM interaction domain & 1 missense).
Sources: Literature
Fetal anomalies v1.301 PDE12 Zornitza Stark Marked gene: PDE12 as ready
Fetal anomalies v1.301 PDE12 Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence).
Fetal anomalies v1.301 PDE12 Zornitza Stark Classified gene: PDE12 as Green List (high evidence)
Fetal anomalies v1.301 PDE12 Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence).
Fetal anomalies v1.300 PDE12 Zornitza Stark gene: PDE12 was added
gene: PDE12 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE12 were set to 39567835
Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970, PDE12-related
Review for gene: PDE12 was set to GREEN
Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death).
-Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle.
-Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron
transfer chain activities in fibroblasts.
-Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V).

WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity.

PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein.
Sources: Literature
Fetal anomalies v1.299 RBFOX2 Ain Roesley Phenotypes for gene: RBFOX2 were changed from Congenital heart disease MONDO:0005453, RBFOX2-related to RBFOX2-related congenital heart disorder (MONDO:0100557)
Fetal anomalies v1.298 RBFOX2 Zornitza Stark Phenotypes for gene: RBFOX2 were changed from to Congenital heart disease MONDO:0005453, RBFOX2-related
Fetal anomalies v1.297 RBFOX2 Zornitza Stark Classified gene: RBFOX2 as Green List (high evidence)
Fetal anomalies v1.297 RBFOX2 Zornitza Stark Gene: rbfox2 has been classified as Green List (High Evidence).
Fetal anomalies v1.296 RBFOX2 Zornitza Stark reviewed gene: RBFOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital heart disease MONDO:0005453, RBFOX2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.296 FRYL Zornitza Stark Phenotypes for gene: FRYL were changed from neurodevelopmental disorder MONDO:0700092, FRYL-related to Pan-Chung-Bellen syndrome, MIM# 621049
Fetal anomalies v1.295 FRYL Zornitza Stark edited their review of gene: FRYL: Changed phenotypes: Pan-Chung-Bellen syndrome, MIM# 621049
Fetal anomalies v1.295 RFWD3 Bryony Thompson Classified gene: RFWD3 as Amber List (moderate evidence)
Fetal anomalies v1.295 RFWD3 Bryony Thompson Gene: rfwd3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.294 RFWD3 Bryony Thompson reviewed gene: RFWD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 28691929, 38058754; Phenotypes: Fanconi anemia MONDO:0019391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.294 DHRSX Zornitza Stark Phenotypes for gene: DHRSX were changed from congenital disorder of glycosylation, MONDO:0015286, DHRSX-related to Congenital disorder of glycosylation, type 1DD, MIM# 301133
Fetal anomalies v1.293 DHRSX Zornitza Stark edited their review of gene: DHRSX: Changed phenotypes: Congenital disorder of glycosylation, type 1DD, MIM# 301133
Fetal anomalies v1.293 GON4L Bryony Thompson Marked gene: GON4L as ready
Fetal anomalies v1.293 GON4L Bryony Thompson Gene: gon4l has been classified as Green List (High Evidence).
Fetal anomalies v1.293 GON4L Bryony Thompson Classified gene: GON4L as Green List (high evidence)
Fetal anomalies v1.293 GON4L Bryony Thompson Gene: gon4l has been classified as Green List (High Evidence).
Fetal anomalies v1.292 GON4L Bryony Thompson gene: GON4L was added
gene: GON4L was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GON4L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GON4L were set to 39500882; 21937992
Phenotypes for gene: GON4L were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: GON4L was set to GREEN
Added comment: 2 LoF variants in 4 cases from 3 unrelated consanguineous families, and supporting null zebrafish model
PMID: 39500882 - 2 homozygous truncating GON4L variants [NM_001282860.2: c.62_63del, p.(Gln21Argfs*12) and c.5517+1G>A] in 3 patients from 2 consanguineous families with prenatal-onset growth impairment, developmental delay, mild intellectual disability, speech impairment, progressive and disproportionate microcephaly, facial asymmetry, congenital heart anomaly, and brain structure abnormalities.
Null zebrafish model had distinct morphological and size abnormalities in the craniofacial cartilage of zebrafish larvae
Heterozygous carriers in biallelic families were unaffected
PMID: 21937992 - a case from Iran from a consanguineous family homozygous for c.5517+1G>A with syndromic ID. No other clinical details provided
Sources: Literature
Fetal anomalies v1.291 LAMA3 Ain Roesley Phenotypes for gene: LAMA3 were changed from Epidermolysis bullosa, junctional, Herlitz type (MIM#226700) to Epidermolysis bullosa, junctional 2A, intermediate MIM#619783; Epidermolysis bullosa, junctional 2B, severe MIM#619784; Epidermolysis bullosa, junctional 2C, laryngoonychocutaneous MIM#245660
Fetal anomalies v1.290 SRPK3 Zornitza Stark Phenotypes for gene: SRPK3 were changed from Neurodevelopmental disorder, MONDO:0700092, SRPK3-related to Intellectual developmental disorder, X-linked, 114, MIM#301134
Fetal anomalies v1.289 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed phenotypes: Intellectual developmental disorder, X-linked, 114, MIM#301134
Fetal anomalies v1.289 ZRSR2 Zornitza Stark Phenotypes for gene: ZRSR2 were changed from Orofacialdigital syndrome MONDO:0015375, ZRSR2-related to Orofaciodigital syndrome XXI, MIM# 301132
Fetal anomalies v1.288 ZRSR2 Zornitza Stark reviewed gene: ZRSR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome XXI, MIM# 301132; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.288 RREB1 Krithika Murali Marked gene: RREB1 as ready
Fetal anomalies v1.288 RREB1 Krithika Murali Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.288 RREB1 Krithika Murali Publications for gene: RREB1 were set to 32938917; 38332451
Fetal anomalies v1.287 RREB1 Krithika Murali Publications for gene: RREB1 were set to PMID: 32938917; 38332451
Fetal anomalies v1.286 RREB1 Krithika Murali Classified gene: RREB1 as Amber List (moderate evidence)
Fetal anomalies v1.286 RREB1 Krithika Murali Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.285 RREB1 Krithika Murali gene: RREB1 was added
gene: RREB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RREB1 were set to PMID: 32938917; 38332451
Phenotypes for gene: RREB1 were set to Rasopathy, MONDO:0021060, RREB1-related
Review for gene: RREB1 was set to AMBER
Added comment: PMID 38332451: de novo LoF variant in an individual with Noonan syndrome-like features. No prenatal phenotype reported in this individual, however, prenatal phenotype has been reported with other RASopathies.
Sources: Literature
Fetal anomalies v1.284 DHRSX Zornitza Stark Marked gene: DHRSX as ready
Fetal anomalies v1.284 DHRSX Zornitza Stark Gene: dhrsx has been classified as Green List (High Evidence).
Fetal anomalies v1.284 DHRSX Zornitza Stark Classified gene: DHRSX as Green List (high evidence)
Fetal anomalies v1.284 DHRSX Zornitza Stark Gene: dhrsx has been classified as Green List (High Evidence).
Fetal anomalies v1.283 DHRSX Zornitza Stark gene: DHRSX was added
gene: DHRSX was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DHRSX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHRSX were set to 38821050
Phenotypes for gene: DHRSX were set to congenital disorder of glycosylation, MONDO:0015286, DHRSX-related
Review for gene: DHRSX was set to GREEN
Added comment: PMID:38821050 reported the identification of biallelic missense variants in DHRSX gene in four patients from three unrelated families with a congenital disorder of glycosylation. They displayed distinct facial features, severe neurological involvement including hypotonia, scoliosis, contractures, profound intellectual disability, epilepsy, and sensorineural hearing loss. These patients also experienced severe failure to thrive (requiring tube feeding); variable respiratory insufficiency; and involvement of the eyes, the gastrointestinal system, and other organs.

In PAR.

Contractures and brain anomalies may be detectable antenatally.
Sources: Literature
Fetal anomalies v1.282 FLVCR1 Zornitza Stark Phenotypes for gene: FLVCR1 were changed from Ataxia, posterior column, with retinitis pigmentosa, MIM#609033 to neurodevelopmental disorder MONDO:0700092, FLVCR1-related; Ataxia, posterior column, with retinitis pigmentosa, MIM#609033
Fetal anomalies v1.281 FLVCR1 Zornitza Stark Publications for gene: FLVCR1 were set to
Fetal anomalies v1.280 FLVCR1 Zornitza Stark Classified gene: FLVCR1 as Green List (high evidence)
Fetal anomalies v1.280 FLVCR1 Zornitza Stark Gene: flvcr1 has been classified as Green List (High Evidence).
Fetal anomalies v1.279 FLVCR1 Zornitza Stark edited their review of gene: FLVCR1: Added comment: PMID 39306721: A new study with 30 patients from 23 unrelated families with biallelic ultra-rare missense and predicted loss-of-function variants in FLVCR1 with a novel FLVCR1-related phenotype characterised by severe developmental disorders with profound developmental delay, microcephaly, brain malformations, epilepsy, spasticity, and premature death. Optic disk atrophy, limb and digital malformations, and macrocytic anaemia can be present.

Included here as brain, limb and digital malformations can present antenatally.; Changed rating: GREEN; Changed publications: 39306721; Changed phenotypes: neurodevelopmental disorder MONDO:0700092, FLVCR1-related, Ataxia, posterior column, with retinitis pigmentosa, MIM#609033
Fetal anomalies v1.279 KLF1 Zornitza Stark Phenotypes for gene: KLF1 were changed from Dyserythropoietic anaemia, congenital, type IV MIM#613673 to Dyserythropoietic anaemia, congenital, type IV MIM#613673; Anaemia, congenital dyserythropoietic, type IVb, MIM#620969
Fetal anomalies v1.278 KLF1 Zornitza Stark Publications for gene: KLF1 were set to 28361594; 25724378
Fetal anomalies v1.277 KLF1 Zornitza Stark Mode of inheritance for gene: KLF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.276 KLF1 Zornitza Stark reviewed gene: KLF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24443441, 25724378, 28361594, 34554218; Phenotypes: Anaemia, congenital dyserythropoietic, type IVb, MIM#620969; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.276 RPL26 Zornitza Stark Marked gene: RPL26 as ready
Fetal anomalies v1.276 RPL26 Zornitza Stark Gene: rpl26 has been classified as Green List (High Evidence).
Fetal anomalies v1.276 RPL26 Zornitza Stark Classified gene: RPL26 as Green List (high evidence)
Fetal anomalies v1.276 RPL26 Zornitza Stark Gene: rpl26 has been classified as Green List (High Evidence).
Fetal anomalies v1.275 RPL26 Zornitza Stark gene: RPL26 was added
gene: RPL26 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RPL26 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL26 were set to 22431104; 39268718
Phenotypes for gene: RPL26 were set to Diamond-Blackfan anaemia 11, MIM# 614900
Review for gene: RPL26 was set to GREEN
Added comment: Four unrelated families reported, radial ray defects are part of the phenotype.
Sources: Literature
Fetal anomalies v1.274 GMPPA Ain Roesley Phenotypes for gene: GMPPA were changed from Alacrima, achalasia, and mental retardation syndrome (MIM# 615510) to Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510)
Fetal anomalies v1.273 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968) to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Fetal anomalies v1.272 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Sphingosine Phosphate Lyase Insufficiency Syndrome; Nephrotic syndrome, type 14, MIM#617575 to Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575)
Fetal anomalies v1.271 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Mental retardation, autosomal dominant 35, MIM#616355 to Houge-Janssens syndrome 1, MIM#616355
Fetal anomalies v1.270 KBTBD2 Ain Roesley Marked gene: KBTBD2 as ready
Fetal anomalies v1.270 KBTBD2 Ain Roesley Gene: kbtbd2 has been classified as Green List (High Evidence).
Fetal anomalies v1.270 KBTBD2 Ain Roesley Classified gene: KBTBD2 as Green List (high evidence)
Fetal anomalies v1.270 KBTBD2 Ain Roesley Gene: kbtbd2 has been classified as Green List (High Evidence).
Fetal anomalies v1.269 KBTBD2 Ain Roesley gene: KBTBD2 was added
gene: KBTBD2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KBTBD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KBTBD2 were set to 39313616
Phenotypes for gene: KBTBD2 were set to neurodevelopmental disorder MONDO:0700092, KBTBD2-related
Review for gene: KBTBD2 was set to GREEN
gene: KBTBD2 was marked as current diagnostic
Added comment: 3 families - 2 compound hets and 1 hom

phenotypes include:
Microcephaly, hypotonia, failure to thrive, IUGR, delayed gross motor development, dysmorphism
Sources: Literature
Fetal anomalies v1.268 EXOC3L2 Zornitza Stark Phenotypes for gene: EXOC3L2 were changed from Dandy-Walker malformation, MONDO:0009072; Meckel-Gruber-like syndrome to Brain malformation renal syndrome, MIM# 620943
Fetal anomalies v1.267 EXOC3L2 Zornitza Stark reviewed gene: EXOC3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain malformation renal syndrome, MIM# 620943; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.267 NME8 Achchuthan Shanmugasundram changed review comment from: The phenotype listed in the review below, namely, CINCA syndrome, OMIM:607115 is associated with NLRP3 gene rather than NME8 in OMIM. The publications listed below (PMIDs: 12032915, 12483741, 12928894) also reports cases with NLRP3 variants (gene alias: CIAS1) rather than NME8 variants. Hence, this gene should be demoted from green rating and NLRP3 should be added to this panel.; to: The phenotype listed in the review below, namely, CINCA syndrome, OMIM:607115 is associated with NLRP3 gene rather than NME8 in OMIM. The publications listed below (PMIDs: 12032915, 12483741, 12928894) also report cases with NLRP3 variants (gene alias: CIAS1) rather than NME8 variants. Hence, this gene should be demoted from green rating and NLRP3 should be added to this panel.
Fetal anomalies v1.267 MYBBP1A Zornitza Stark Marked gene: MYBBP1A as ready
Fetal anomalies v1.267 MYBBP1A Zornitza Stark Gene: mybbp1a has been classified as Green List (High Evidence).
Fetal anomalies v1.267 MYBBP1A Zornitza Stark Classified gene: MYBBP1A as Green List (high evidence)
Fetal anomalies v1.267 MYBBP1A Zornitza Stark Gene: mybbp1a has been classified as Green List (High Evidence).
Fetal anomalies v1.266 MYBBP1A Zornitza Stark gene: MYBBP1A was added
gene: MYBBP1A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MYBBP1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBBP1A were set to 39191491; 28425981
Phenotypes for gene: MYBBP1A were set to Hydrops fetalis, MONDO:0015193, MYBBP1A-related
Review for gene: MYBBP1A was set to GREEN
Added comment: Three unrelated fetuses with bi-allelic variants in this gene and severe hydrops.
Sources: Literature
Fetal anomalies v1.265 LAMA5 Tashunka Taylor-Miller reviewed gene: LAMA5: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36322204; Phenotypes: cleft lip, cleft palate; Mode of inheritance: Unknown
Fetal anomalies v1.265 NME8 Achchuthan Shanmugasundram reviewed gene: NME8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v1.265 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Fetal anomalies v1.265 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.265 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Fetal anomalies v1.265 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.264 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID: 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: Prenatal features reported include polyhydramnios, IUGR, preterm labour. Other reported features such as brain anomalies, arthrogryposis have the potential to be ascertained prenatally also.
--
PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Fetal anomalies v1.263 FZD6 Zornitza Stark Marked gene: FZD6 as ready
Fetal anomalies v1.263 FZD6 Zornitza Stark Gene: fzd6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.263 FZD6 Zornitza Stark Classified gene: FZD6 as Amber List (moderate evidence)
Fetal anomalies v1.263 FZD6 Zornitza Stark Gene: fzd6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.262 FZD6 Zornitza Stark gene: FZD6 was added
gene: FZD6 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: FZD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FZD6 were set to 33082562; 26036949; 28425981
Phenotypes for gene: FZD6 were set to Hydrops fetalis, MONDO:0015193, FZD6-related
Review for gene: FZD6 was set to AMBER
Added comment: Three FZD6 variants have been associated with two unrelated cases of fetal hyrdrops.
Sources: Expert list
Fetal anomalies v1.261 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Amber List (moderate evidence)
Fetal anomalies v1.261 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.260 TBC1D7 Zornitza Stark Publications for gene: TBC1D7 were set to 23687350; 24515783
Fetal anomalies v1.259 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Green List (high evidence)
Fetal anomalies v1.259 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Green List (High Evidence).
Fetal anomalies v1.258 TBC1D7 Zornitza Stark reviewed gene: TBC1D7: Rating: GREEN; Mode of pathogenicity: None; Publications: 36669495; Phenotypes: Macrocephaly/megalencephaly syndrome, autosomal recessive - MIM#248000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.258 GLIS2 Zornitza Stark Classified gene: GLIS2 as Green List (high evidence)
Fetal anomalies v1.258 GLIS2 Zornitza Stark Gene: glis2 has been classified as Green List (High Evidence).
Fetal anomalies v1.257 GLIS2 Zornitza Stark edited their review of gene: GLIS2: Added comment: Five individuals from three unrelated families reported, albeit with homozygous variants. Functional data.; Changed rating: GREEN; Changed publications: 31676329, 17618285, 23559409
Fetal anomalies v1.257 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Fetal anomalies v1.257 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.257 SRPK3 Zornitza Stark Classified gene: SRPK3 as Amber List (moderate evidence)
Fetal anomalies v1.257 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.256 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 39073169
Phenotypes for gene: SRPK3 were set to Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Review for gene: SRPK3 was set to AMBER
Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish).
Sources: Literature
Fetal anomalies v1.255 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Fetal anomalies v1.255 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Fetal anomalies v1.255 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Fetal anomalies v1.255 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Fetal anomalies v1.255 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Fetal anomalies v1.255 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Fetal anomalies v1.255 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Fetal anomalies v1.255 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Fetal anomalies v1.254 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Fetal anomalies v1.253 VPS50 Ain Roesley Publications for gene: VPS50 were set to PMID: 34037727
Fetal anomalies v1.252 VPS50 Ain Roesley reviewed gene: VPS50: Rating: AMBER; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.252 SERPINA11 Ain Roesley Marked gene: SERPINA11 as ready
Fetal anomalies v1.252 SERPINA11 Ain Roesley Gene: serpina11 has been classified as Red List (Low Evidence).
Fetal anomalies v1.252 SERPINA11 Ain Roesley gene: SERPINA11 was added
gene: SERPINA11 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SERPINA11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINA11 were set to 38831697
Phenotypes for gene: SERPINA11 were set to pericardial effusion; pleural effusion
Review for gene: SERPINA11 was set to RED
gene: SERPINA11 was marked as current diagnostic
Added comment: 1 family with 2 fetuses.

1st fetus presented with isolated pericardial effusion and a TOP was opted.
post mortem:
mild subcutaneous edema with subtle facial dysmorphic features
small gelatinous glistening cyst on the right pericardium. Bilateral pleural effusion and multiple similar cysts were noted on the lung surfaces

2nd fetus also presented with pleural and pericardial effusion and a TOP was opted
post mortem findings were similar to fetus#1

homozygous nonsense variant in SERPINA11 was found p.(Tyr224*)

Immunofluorescence of lung sections from fetus#1 and a gestation-matched fetus as a control demonstrated undetectable levels of SERPINA11 in the bronchiolar epithelium
Sources: Literature
Fetal anomalies v1.251 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from MYH10-related Multiple congenital anomalies; Bilateral ventriculomegaly; aqueductal stenosis; Microcephaly; Hip dysplasia to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Fetal anomalies v1.250 FUZ Zornitza Stark Mode of inheritance for gene: FUZ was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.249 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from Neural tube defects 182940 to Neural tube defects 182940; Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy
Fetal anomalies v1.248 FUZ Zornitza Stark Publications for gene: FUZ were set to 21840926
Fetal anomalies v1.247 FUZ Zornitza Stark Mode of inheritance for gene: FUZ was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.246 FUZ Chirag Patel Classified gene: FUZ as Green List (high evidence)
Fetal anomalies v1.246 FUZ Chirag Patel Gene: fuz has been classified as Green List (High Evidence).
Fetal anomalies v1.245 FUZ Chirag Patel reviewed gene: FUZ: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38702430, 29068549, 34719684; Phenotypes: Ciliopathy_MONDO_0005308, skeletal ciliopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.245 LIG4 Santosh Varughese reviewed gene: LIG4: 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: 15333585, 20133615, 32534991, 11779494, 16088910; Phenotypes: LIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.245 BCORL1 Zornitza Stark Marked gene: BCORL1 as ready
Fetal anomalies v1.245 BCORL1 Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.245 BCORL1 Zornitza Stark Classified gene: BCORL1 as Amber List (moderate evidence)
Fetal anomalies v1.245 BCORL1 Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.244 BCORL1 Zornitza Stark gene: BCORL1 was added
gene: BCORL1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: BCORL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: BCORL1 were set to Congenital anomaly of the kidney and urinary tract, MONDO:0019719, BCORL1-related
Review for gene: BCORL1 was set to AMBER
Added comment: Emerging evidence of disease association.
Sources: Expert Review
Fetal anomalies v1.243 CCDC114 Zornitza Stark Tag new gene name tag was added to gene: CCDC114.
Fetal anomalies v1.243 ARMC4 Zornitza Stark Tag new gene name tag was added to gene: ARMC4.
Fetal anomalies v1.243 CCDC151 Zornitza Stark Tag new gene name tag was added to gene: CCDC151.
Fetal anomalies v1.243 TTC25 Zornitza Stark Tag new gene name tag was added to gene: TTC25.
Fetal anomalies v1.243 BRWD1 Zornitza Stark changed review comment from: Single individual with situs inversus.; to: Single individual with situs inversus.

Whole gene-disease relationship assessed as DISPUTED by ClinGen.
Fetal anomalies v1.243 BRWD1 Zornitza Stark Tag disputed tag was added to gene: BRWD1.
Fetal anomalies v1.243 HOXD12 Zornitza Stark Marked gene: HOXD12 as ready
Fetal anomalies v1.243 HOXD12 Zornitza Stark Gene: hoxd12 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.243 HOXD12 Zornitza Stark Classified gene: HOXD12 as Amber List (moderate evidence)
Fetal anomalies v1.243 HOXD12 Zornitza Stark Gene: hoxd12 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.242 HOXD12 Zornitza Stark gene: HOXD12 was added
gene: HOXD12 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HOXD12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HOXD12 were set to 38663984
Phenotypes for gene: HOXD12 were set to Clubfoot (non-syndromic) MONDO:0007342
Review for gene: HOXD12 was set to AMBER
Added comment: Identified as a candidate gene in a large cohort due to enrichment of rare variants.


PMID: 38663984
Around 9 individuals from 4 unrelated families have been reported with clubfoot and the variants were shown to segregate. Cohort of over 1000 individuals, with several novel candidates identified.

N-terminal region and C-terminal homeobox domain of HOXD12 are known to be clusters for pathogenic variants related to clubfoot.
Loss of function variants are less likely to contribute to clubfoot pathogenesis therefore mechanism of disease is suggested as dominant negative but is not confirmed.
Sources: Literature
Fetal anomalies v1.241 EHBP1L1 Ain Roesley Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related to non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related
Fetal anomalies v1.240 PIP5K1C Zornitza Stark Publications for gene: PIP5K1C were set to 17701898
Fetal anomalies v1.239 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Green List (high evidence)
Fetal anomalies v1.239 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Fetal anomalies v1.238 PIP5K1C Zornitza Stark reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 38491417; Phenotypes: Lethal congenital contractural syndrome 3, OMIM:611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.238 EHBP1L1 Zornitza Stark Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis MONDO:0009369 to Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related
Fetal anomalies v1.237 EHBP1L1 Zornitza Stark Classified gene: EHBP1L1 as Green List (high evidence)
Fetal anomalies v1.237 EHBP1L1 Zornitza Stark Gene: ehbp1l1 has been classified as Green List (High Evidence).
Fetal anomalies v1.236 EHBP1L1 Zornitza Stark reviewed gene: EHBP1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.236 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Fetal anomalies v1.235 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.235 CNOT1 Zornitza Stark Classified gene: CNOT1 as Amber List (moderate evidence)
Fetal anomalies v1.235 CNOT1 Zornitza Stark Gene: cnot1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.234 CNOT1 Zornitza Stark edited their review of gene: CNOT1: Added comment: LIMITED by ClinGen for holoprosencephaly 12 with or without pancreatic agenesis, MONDO:0032787

ClinGen curation: CNOT1 was originally reported in cases of holoprosencephaly and/or pancreatic agenesis/insufficiency in 2019 (PMID: 31006513, 31006510). One of the papers included 3 individuals with heterozygous p.Arg535Cys (PMID: 31006513), confirmed to be de novo in 2 individuals. One of these individuals was not scored due to a lack of documentation of holoprosencephaly. The other paper included 2 individuals with de novo p.Arg535Cys, both of whom with holoprosencephaly. A knock-in mouse model of this variant showed neurological and pancreatic abnormalities at E14.5, and this evidence was used to augment the genetic evidence. A mouse brain expression study (PMID: 31006510) was scored as functional evidence. In total, there is Limited evidence to support the gene-disease relationship between CNOT1 and holoprosencephaly with or without pancreatic agenesis. Of note, this gene has also been implicated in Vissers-Bodmer syndrome, which is characterized by global developmental delay and behavioral abnormalities apparent from infancy. As the condition is clinically distinct from holoprosencephaly and/or pancreatic agenesis/insufficiency, lacks specific structural brain anomalies, and likely has different molecular mechanisms, this will be/have been assessed separately.; Changed rating: AMBER; Changed phenotypes: Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787
Fetal anomalies v1.234 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Fetal anomalies v1.233 PURA Ain Roesley Phenotypes for gene: PURA were changed from Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158) to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Fetal anomalies v1.232 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Fetal anomalies v1.231 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related to ANeuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Fetal anomalies v1.230 FILIP1 Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.230 FRYL Zornitza Stark Classified gene: FRYL as Green List (high evidence)
Fetal anomalies v1.230 FRYL Zornitza Stark Gene: fryl has been classified as Green List (High Evidence).
Fetal anomalies v1.229 FRYL Zornitza Stark reviewed gene: FRYL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, FRYL-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.229 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly, MONDO:0016296 to Holoprosencephaly (MONDO:0016296), DISP1-related
Fetal anomalies v1.228 DISP1 Zornitza Stark Publications for gene: DISP1 were set to 27363716; 19184110; 26748417; 23542665
Fetal anomalies v1.227 DISP1 Zornitza Stark Mode of inheritance for gene: DISP1 was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.226 DISP1 Zornitza Stark Classified gene: DISP1 as Green List (high evidence)
Fetal anomalies v1.226 DISP1 Zornitza Stark Gene: disp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.225 DISP1 Zornitza Stark edited their review of gene: DISP1: Added comment: PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.; Changed rating: GREEN; Changed publications: 19184110, 26748417, 23542665, 38529886; Changed phenotypes: Holoprosencephaly (MONDO:0016296), DISP1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.225 FRYL Ain Roesley Marked gene: FRYL as ready
Fetal anomalies v1.225 FRYL Ain Roesley Gene: fryl has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.225 FRYL Ain Roesley Classified gene: FRYL as Amber List (moderate evidence)
Fetal anomalies v1.225 FRYL Ain Roesley Gene: fryl has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.224 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to AMBER
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

7/14 with cardiac anomalies

Of interest to this panel: 1x tetralogy of fallot (TOF) with pulmonary atresia (PA), 2x dextrocardia, 1x hypoplastic left heart syndrome

Other reported features AVSD, VSD, PDA
Sources: Literature
Fetal anomalies v1.223 MAP3K20 Zornitza Stark edited their review of gene: MAP3K20: Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.; Changed publications: 38451290; Changed phenotypes: Syndromic disease, MONDO:0002254, MAP3K20-related, Centronuclear myopathy 6 with fiber-type disproportion MIM#617760, Split-foot malformation with mesoaxial polydactyly MIM#616890; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.223 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Fetal anomalies v1.223 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Fetal anomalies v1.223 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Fetal anomalies v1.222 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.222 USP14 Zornitza Stark Publications for gene: USP14 were set to PMID: 35066879
Fetal anomalies v1.221 USP14 Zornitza Stark Classified gene: USP14 as Green List (high evidence)
Fetal anomalies v1.221 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Fetal anomalies v1.220 USP14 Zornitza Stark reviewed gene: USP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 38469793; Phenotypes: Syndromic disease MONDO:0002254, USP14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.220 PRDM6 Ain Roesley Classified gene: PRDM6 as Amber List (moderate evidence)
Fetal anomalies v1.220 PRDM6 Ain Roesley Gene: prdm6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.219 PRDM6 Ain Roesley edited their review of gene: PRDM6: Changed rating: AMBER; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.219 WASHC5 Ain Roesley Classified gene: WASHC5 as Green List (high evidence)
Fetal anomalies v1.219 WASHC5 Ain Roesley Gene: washc5 has been classified as Green List (High Evidence).
Fetal anomalies v1.218 WASHC5 Ain Roesley reviewed gene: WASHC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ritscher-Schinzel syndrome 1 MIM#220210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.218 SLC37A4 Ain Roesley Classified gene: SLC37A4 as Amber List (moderate evidence)
Fetal anomalies v1.218 SLC37A4 Ain Roesley Gene: slc37a4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.217 SLC37A4 Ain Roesley reviewed gene: SLC37A4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v1.217 RBFOX2 Ain Roesley Marked gene: RBFOX2 as ready
Fetal anomalies v1.217 RBFOX2 Ain Roesley Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.217 RBFOX2 Ain Roesley Classified gene: RBFOX2 as Amber List (moderate evidence)
Fetal anomalies v1.217 RBFOX2 Ain Roesley Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.216 RBFOX2 Ain Roesley gene: RBFOX2 was added
gene: RBFOX2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RBFOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX2 were set to 26785492; 27670201; 27485310; 25205790; 35137168; 26785492; 37165897
Review for gene: RBFOX2 was set to AMBER
gene: RBFOX2 was marked as current diagnostic
Added comment: PMID: 37165897
1x 'splice altering' de novo in in an individual with HLSH + AVSD

- PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.
Sources: Literature
Fetal anomalies v1.215 PRDM6 Ain Roesley reviewed gene: PRDM6: Rating: ; Mode of pathogenicity: None; Publications: 38071433; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v1.215 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Fetal anomalies v1.215 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Fetal anomalies v1.214 KDR Ain Roesley Marked gene: KDR as ready
Fetal anomalies v1.214 KDR Ain Roesley Gene: kdr has been classified as Red List (Low Evidence).
Fetal anomalies v1.214 KDR Ain Roesley Publications for gene: KDR were set to 34113005; 30232381
Fetal anomalies v1.213 KDR Ain Roesley Mode of inheritance for gene: KDR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.212 KDR Ain Roesley edited their review of gene: KDR: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.212 KDR Ain Roesley edited their review of gene: KDR: Changed rating: GREEN; Changed publications: 34113005, 30232381, 28991257, 30232381; Set current diagnostic: yes
Fetal anomalies v1.212 KDR Ain Roesley changed review comment from: PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense
Sources: Literature; to: GREEN for AD
RED for AR

PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID: 34328347;
cohort of ToF, looking into LoF variants
4x identified + 1x classified as VUS (stop gain in penultimate exon)
1x stop gain citing PMID: 28991257

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense



Sources: Literature
Fetal anomalies v1.212 KDR Ain Roesley gene: KDR was added
gene: KDR was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KDR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KDR were set to 34113005; 30232381
Phenotypes for gene: KDR were set to Tetralogy of Fallot
Added comment: PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense
Sources: Literature
Fetal anomalies v1.211 IRX4 Ain Roesley Marked gene: IRX4 as ready
Fetal anomalies v1.211 IRX4 Ain Roesley Gene: irx4 has been classified as Red List (Low Evidence).
Fetal anomalies v1.211 IRX4 Ain Roesley gene: IRX4 was added
gene: IRX4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: IRX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRX4 were set to 21544582
Phenotypes for gene: IRX4 were set to Ventricular septal defect
Review for gene: IRX4 was set to RED
gene: IRX4 was marked as current diagnostic
Added comment: Two individuals with novel missense variants identified in a large cohort in 2011.

nothing new in punned
Sources: Literature
Fetal anomalies v1.210 HEY2 Ain Roesley Marked gene: HEY2 as ready
Fetal anomalies v1.210 HEY2 Ain Roesley Gene: hey2 has been classified as Red List (Low Evidence).
Fetal anomalies v1.210 HEY2 Ain Roesley gene: HEY2 was added
gene: HEY2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HEY2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: HEY2 were set to 32820247
Phenotypes for gene: HEY2 were set to congenital heart defects and thoracic aortic aneurysms
Review for gene: HEY2 was set to RED
gene: HEY2 was marked as current diagnostic
Added comment: A very large family affected by CHD and familial thoracic aortic aneurysms. Trio genome sequencing was carried out in an index patient with critical CHD, and family members had either exome or Sanger sequencing. Identified homozygous loss-of-function variant (c.318_319delAG, p.G108*) in HEY2 in 3 individuals in family with critical CHD, whereas the 20 heterozygous carriers show a spectrum of CVDs (CHD and FTAA, but varying expressivity and incomplete penetrance).

Other studies show that knockout of HEY2 in mice results in cardiovascular defects (CVDs), including septal defects, cardiomyopathy, a thin-walled aorta, and valve anomalies.
Sources: Literature
Fetal anomalies v1.209 DOHH Ain Roesley Marked gene: DOHH as ready
Fetal anomalies v1.209 DOHH Ain Roesley Gene: dohh has been classified as Green List (High Evidence).
Fetal anomalies v1.209 DOHH Ain Roesley Classified gene: DOHH as Green List (high evidence)
Fetal anomalies v1.209 DOHH Ain Roesley Gene: dohh has been classified as Green List (High Evidence).
Fetal anomalies v1.208 DOHH Ain Roesley changed review comment from: 4 families - 5 affecteds

1x cardiomyopathy at prenatal examination
4/5 presented with CHD post-natally - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

microcephaly was post-natal
Sources: Literature; to: 4 families - 5 affecteds

prenatal examination:
1x cardiomyopathy
1x increased nuchal translucency; chylothorax

post-natal:
4/5 presented with CHD - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

5/5 microcephaly
Fetal anomalies v1.208 DOHH Ain Roesley gene: DOHH was added
gene: DOHH was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, MIM# 620066
Review for gene: DOHH was set to GREEN
gene: DOHH was marked as current diagnostic
Added comment: 4 families - 5 affecteds

1x cardiomyopathy at prenatal examination
4/5 presented with CHD post-natally - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

microcephaly was post-natal
Sources: Literature
Fetal anomalies v1.207 AMOTL1 Ain Roesley Marked gene: AMOTL1 as ready
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.207 AMOTL1 Ain Roesley Classified gene: AMOTL1 as Green List (high evidence)
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.207 AMOTL1 Ain Roesley Classified gene: AMOTL1 as Green List (high evidence)
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.206 AMOTL1 Ain Roesley gene: AMOTL1 was added
gene: AMOTL1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMOTL1 were set to 36751037
Phenotypes for gene: AMOTL1 were set to Orofacial clefting syndrome, MONDO:0015335, AMOTL1-related
Review for gene: AMOTL1 was set to GREEN
gene: AMOTL1 was marked as current diagnostic
Added comment: PMID: 36751037- 16 individuals from 12 families with orofacial clefting syndrome and het variants in AMOTL1. Many in 1 hotspot: 5 individuals from 3 families have R157C, 6 individuals from another 4 families have R157H, 1 has P160L, and another has Q161R. Out of this hostpaot- 1 with P368A, 1 with E507K, 1 with E579K. 7 are de novo. All but 2 have clefting, 7 are dysmorphic, 5 have hearing loss, 9 have CHD, 7 have tall stature, 6 have dev delay. Other features include liver disease, myopia, scoliosis and immune involvement.

Another 2 families have been previously reported (described in the panelapp review below) with variants in this hotspot 1 has 2 individuals with R157C, the other has 1 individual with P160L. All hotspot are absent from gnomad v2.
Sources: Literature
Fetal anomalies v1.205 AL117258.1 Ain Roesley Marked gene: AL117258.1 as ready
Fetal anomalies v1.205 AL117258.1 Ain Roesley Gene: al117258.1 has been classified as Green List (High Evidence).
Fetal anomalies v1.205 AL117258.1 Ain Roesley Classified gene: AL117258.1 as Green List (high evidence)
Fetal anomalies v1.205 AL117258.1 Ain Roesley Gene: al117258.1 has been classified as Green List (High Evidence).
Fetal anomalies v1.204 AL117258.1 Ain Roesley gene: AL117258.1 was added
gene: AL117258.1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892
Phenotypes for gene: AL117258.1 were set to Heterotaxy; congenital heart defects
Review for gene: AL117258.1 was set to GREEN
gene: AL117258.1 was marked as current diagnostic
Added comment: Gene also known as CIROP and LMLN2

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Sources: Literature
Fetal anomalies v1.203 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Feingold syndrome 1 (MIM#164280); Neurodevelopmental disorder (MONDO:0700092), MYCN-related to Feingold syndrome 1 (MIM#164280); Megalencephaly-polydactyly syndrome, MIM# 620748
Fetal anomalies v1.202 MYCN Zornitza Stark edited their review of gene: MYCN: Changed phenotypes: Feingold syndrome 1, MIM# 164280, Megalencephaly-polydactyly syndrome, MIM# 620748
Fetal anomalies v1.202 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Fetal anomalies v1.202 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Fetal anomalies v1.202 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Fetal anomalies v1.202 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Fetal anomalies v1.201 CELSR3 Zornitza Stark edited their review of gene: CELSR3: Changed rating: GREEN
Fetal anomalies v1.201 CELSR3 Zornitza Stark gene: CELSR3 was added
gene: CELSR3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals
Sources: Literature
Fetal anomalies v1.200 NARS Zornitza Stark edited their review of gene: NARS: Changed rating: GREEN
Fetal anomalies v1.200 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Fetal anomalies v1.200 HSPG2 Ain Roesley Phenotypes for gene: HSPG2 were changed from Schwartz-Jampel syndrome, MONDO:0009717; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140; Schwartz-Jampel syndrome, type 1, OMIM:255800; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410 to Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Schwartz-Jampel syndrome, MONDO:0009717; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140; Schwartz-Jampel syndrome, type 1, OMIM:255800; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410
Fetal anomalies v1.199 HSPG2 Ain Roesley Publications for gene: HSPG2 were set to
Fetal anomalies v1.198 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.198 NARS Zornitza Stark reviewed gene: NARS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, MIM# 619091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.198 THSD1 Zornitza Stark Marked gene: THSD1 as ready
Fetal anomalies v1.198 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.198 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Fetal anomalies v1.198 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.197 THSD1 Zornitza Stark gene: THSD1 was added
gene: THSD1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: THSD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THSD1 were set to 33569873; 27895300
Phenotypes for gene: THSD1 were set to Lymphatic malformation 13, MIM# 620244
Review for gene: THSD1 was set to GREEN
Added comment: PMID: 33569873 - 1 fetus with a homozygous PTC and nonimmune hydrops fetalis (NIHF), congenital heart disease and hemangiomas. FHx of 1/3 triplets with severe hydrops fetalis, not sequenced.
- Paper reviews previous NIHF cases and reports another homozygous PTC in two families ( and a recurring homozygous missense (p.Cys206Tyr) in three families.


PMID: 27895300- Mouse model has hydrocephaly with poor perfusion.
Sources: Expert Review
Fetal anomalies v1.196 FZD5 Zornitza Stark Phenotypes for gene: FZD5 were changed from Autosomal Dominant Coloboma to Microphthalmia/coloboma 11, MIM# 620731
Fetal anomalies v1.195 FZD5 Zornitza Stark Classified gene: FZD5 as Amber List (moderate evidence)
Fetal anomalies v1.195 FZD5 Zornitza Stark Gene: fzd5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.194 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed rating: AMBER
Fetal anomalies v1.194 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed phenotypes: Microphthalmia/coloboma 11, MIM# 620731
Fetal anomalies v1.194 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100
Fetal anomalies v1.193 NEK1 Zornitza Stark Publications for gene: NEK1 were set to 21211617; 22499340; 25492405; 28123176
Fetal anomalies v1.192 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: Single family with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100
Fetal anomalies v1.192 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Fetal anomalies v1.191 THOC2 Zornitza Stark Phenotypes for gene: THOC2 were changed from Mental retardation, X-linked 12/35 MIM#300957 to Mental retardation, X-linked 12/35 MIM#300957; Arthrogryposis (MONDO:0008779), THOC2-related
Fetal anomalies v1.190 THOC2 Zornitza Stark Publications for gene: THOC2 were set to 26166480; 32116545; 29851191; 32960281
Fetal anomalies v1.189 THOC2 Zornitza Stark edited their review of gene: THOC2: Added comment: PMID: 34976470 - arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family, caused by splice deletion c.2482-1_2484delGTCA which was mat inherited. No splice studies conducted, mother was normal. Postulate that amorphic or severe null pathogenic variants (possible complete loss of function) lead to AMC phenotype

PMID: 37945483 - a proband with AMC and the same splice site mutation ^ above, but de novo. Cytoplasmic bodies also detected in muscle; Changed publications: 29851191, 34976470, 37945483; Changed phenotypes: Mental retardation, X-linked 12/35 MIM#300957, Arthrogryposis (MONDO:0008779), THOC2-related
Fetal anomalies v1.189 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Fetal anomalies v1.188 MAX Zornitza Stark reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polydactyly-macrocephaly syndrome, MIM# 620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.188 NARS Zornitza Stark Marked gene: NARS as ready
Fetal anomalies v1.188 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Fetal anomalies v1.188 NARS Zornitza Stark Classified gene: NARS as Green List (high evidence)
Fetal anomalies v1.188 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Fetal anomalies v1.187 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Fetal anomalies v1.187 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Fetal anomalies v1.187 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Fetal anomalies v1.187 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Fetal anomalies v1.186 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert Review
Fetal anomalies v1.185 MYMK Zornitza Stark Deleted their comment
Fetal anomalies v1.185 MYMK Zornitza Stark Classified gene: MYMK as Green List (high evidence)
Fetal anomalies v1.185 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Fetal anomalies v1.184 MYMK Zornitza Stark edited their review of gene: MYMK: Added comment: Cleft palate, micrognathia, microcephaly, talipes are features detectable on fetal ultrasound.; Changed rating: GREEN
Fetal anomalies v1.184 CELSR1 Chern Lim edited their review of gene: CELSR1: Changed rating: GREEN
Fetal anomalies v1.184 PIEZO1 Naomi Baker reviewed gene: PIEZO1: Rating: RED; Mode of pathogenicity: None; Publications: PMID:38184690; Phenotypes: Prune belly syndrome (MONDO:0007032), PIEZO1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.184 WDR44 Seb Lunke Marked gene: WDR44 as ready
Fetal anomalies v1.184 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well established.
Fetal anomalies v1.184 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.184 CELSR1 Ain Roesley Publications for gene: CELSR1 were set to 31215153; 31403174; 26855770
Fetal anomalies v1.184 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Fetal anomalies v1.184 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.183 CELSR1 Ain Roesley Classified gene: CELSR1 as Green List (high evidence)
Fetal anomalies v1.183 CELSR1 Ain Roesley Gene: celsr1 has been classified as Green List (High Evidence).
Fetal anomalies v1.182 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Fetal anomalies v1.182 CELSR1 Chern Lim reviewed gene: CELSR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38272662; Phenotypes: hydrops fetalis (MONDO:0015193), CELSR1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v1.182 MAX Zornitza Stark Marked gene: MAX as ready
Fetal anomalies v1.182 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Fetal anomalies v1.182 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Fetal anomalies v1.182 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Fetal anomalies v1.180 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Fetal anomalies v1.180 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.180 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Fetal anomalies v1.180 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.179 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Fetal anomalies v1.179 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Fetal anomalies v1.179 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: PMID: 38158856 - Six affected individuals from four unrelated families with homozygous CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant). Excluding the two fatal cases, all other were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Seizure was reported in one case. Whole exome sequencing identified bi-allelic loss of function variants in the CACHD1 gene. In vitro human neural models of CACHD1 depletion displayed dysregulated of Wnt signaling in the developing brain.
Sources: Literature
Fetal anomalies v1.179 NUDT2 Zornitza Stark Marked gene: NUDT2 as ready
Fetal anomalies v1.179 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Fetal anomalies v1.179 NUDT2 Zornitza Stark Classified gene: NUDT2 as Green List (high evidence)
Fetal anomalies v1.179 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Fetal anomalies v1.178 NUDT2 Lilian Downie gene: NUDT2 was added
gene: NUDT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to PMID: 38141063
Phenotypes for gene: NUDT2 were set to Intellectual developmental disorder with or without peripheral neuropathy MIM#619844
Review for gene: NUDT2 was set to GREEN
Added comment: 9 individuals with partial agenesis or hypoplasia of the corpus callosum
Sources: Literature
Fetal anomalies v1.178 CNOT2 Zornitza Stark Marked gene: CNOT2 as ready
Fetal anomalies v1.178 CNOT2 Zornitza Stark Gene: cnot2 has been classified as Green List (High Evidence).
Fetal anomalies v1.178 CNOT2 Zornitza Stark Classified gene: CNOT2 as Green List (high evidence)
Fetal anomalies v1.178 CNOT2 Zornitza Stark Gene: cnot2 has been classified as Green List (High Evidence).
Fetal anomalies v1.177 CNOT2 Zornitza Stark gene: CNOT2 was added
gene: CNOT2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: CNOT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT2 were set to 31512373; 31145527; 28135719
Phenotypes for gene: CNOT2 were set to Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies 618608
Review for gene: CNOT2 was set to GREEN
Added comment: Congenital heart disease and poor growth may be detectable prenatally.
Sources: Expert Review
Fetal anomalies v1.176 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510) to Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663
Fetal anomalies v1.175 ERI1 Zornitza Stark Mode of inheritance for gene: ERI1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.174 ERI1 Zornitza Stark edited their review of gene: ERI1: Changed phenotypes: Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.174 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Fetal anomalies v1.173 RAP1B Zornitza Stark reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.173 CASP2 Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Fetal anomalies v1.172 CASP2 Zornitza Stark edited their review of gene: CASP2: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Fetal anomalies v1.172 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Fetal anomalies v1.171 MMP13 Zornitza Stark Classified gene: MMP13 as Red List (low evidence)
Fetal anomalies v1.171 MMP13 Zornitza Stark Gene: mmp13 has been classified as Red List (Low Evidence).
Fetal anomalies v1.170 MMP13 Zornitza Stark reviewed gene: MMP13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Metaphyseal anadysplasia 1 (MIM#602111), Metaphyseal dysplasia, Spahr type (MIM#250400); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.170 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Fetal anomalies v1.170 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Fetal anomalies v1.170 WBP4 Zornitza Stark Classified gene: WBP4 as Green List (high evidence)
Fetal anomalies v1.170 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Fetal anomalies v1.169 PKP2 Zornitza Stark Marked gene: PKP2 as ready
Fetal anomalies v1.169 PKP2 Zornitza Stark Gene: pkp2 has been classified as Green List (High Evidence).
Fetal anomalies v1.169 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction to Dilated cardiomyopathy, MONDO:0005021, PKP2-related; dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction
Fetal anomalies v1.168 PKP2 Zornitza Stark reviewed gene: PKP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dilated cardiomyopathy, MONDO:0005021, PKP2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.168 PKP2 Seb Lunke Marked gene: PKP2 as ready
Fetal anomalies v1.168 PKP2 Seb Lunke Gene: pkp2 has been classified as Green List (High Evidence).
Fetal anomalies v1.168 PKP2 Seb Lunke Classified gene: PKP2 as Green List (high evidence)
Fetal anomalies v1.168 PKP2 Seb Lunke Gene: pkp2 has been classified as Green List (High Evidence).
Fetal anomalies v1.167 PKP2 Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Sources: Literature; to: PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Sources: Literature
Fetal anomalies v1.167 PKP2 Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature; to: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Sources: Literature
Fetal anomalies v1.167 PKP2 Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In cases, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature; to: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature
Fetal anomalies v1.167 PKP2 Suliman Khan gene: PKP2 was added
gene: PKP2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PKP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKP2 were set to PMID: 30562116; PMID: 35059364; PMID: 38050058
Phenotypes for gene: PKP2 were set to dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction
Penetrance for gene: PKP2 were set to unknown
Review for gene: PKP2 was set to GREEN
Added comment: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In cases, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature
Fetal anomalies v1.167 WBP4 Lilian Downie gene: WBP4 was added
gene: WBP4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WBP4 were set to PMID: 37425688
Phenotypes for gene: WBP4 were set to Neurodevelopmental disorder, MONDO:0700092, WBP4-related
Review for gene: WBP4 was set to GREEN
Added comment: 11 individuals, with dysmorphic ID
3 presented in utero 2x IUGR, 1x ventriculomegaly and polyhydramnios
5 with brain anomalies (corpus callosum and cortical)
Sources: Literature
Fetal anomalies v1.167 EFCAB1 Zornitza Stark Phenotypes for gene: EFCAB1 were changed from Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related to Ciliary dyskinesia, primary, 53, MIM# 620642
Fetal anomalies v1.166 EFCAB1 Zornitza Stark Tag new gene name tag was added to gene: EFCAB1.
Fetal anomalies v1.166 EFCAB1 Zornitza Stark edited their review of gene: EFCAB1: Added comment: HGNC approved name is CLXN; Changed phenotypes: Ciliary dyskinesia, primary, 53, MIM# 620642
Fetal anomalies v1.166 PLS3 Zornitza Stark Phenotypes for gene: PLS3 were changed from Bone mineral density QTL18, osteoporosis - MIM#300910; congenital diaphragmatic hernia MONDO:0005711, PLS3-related to Bone mineral density QTL18, osteoporosis - MIM#300910; Diaphragmatic hernia 5, X-linked, MIM# 306950
Fetal anomalies v1.165 PLS3 Zornitza Stark reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 5, X-linked, MIM# 306950; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.165 TRIT1 Zornitza Stark Marked gene: TRIT1 as ready
Fetal anomalies v1.165 TRIT1 Zornitza Stark Gene: trit1 has been classified as Green List (High Evidence).
Fetal anomalies v1.165 TRIT1 Zornitza Stark Classified gene: TRIT1 as Green List (high evidence)
Fetal anomalies v1.165 TRIT1 Zornitza Stark Gene: trit1 has been classified as Green List (High Evidence).
Fetal anomalies v1.164 TRIT1 Zornitza Stark gene: TRIT1 was added
gene: TRIT1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: TRIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIT1 were set to 36049610; 32088416
Phenotypes for gene: TRIT1 were set to Combined oxidative phosphorylation deficiency 35, MIM#617873
Review for gene: TRIT1 was set to GREEN
Added comment: Presentations with IUGR reported.
Sources: Expert Review
Fetal anomalies v1.163 CASP2 Zornitza Stark Marked gene: CASP2 as ready
Fetal anomalies v1.163 CASP2 Zornitza Stark Gene: casp2 has been classified as Green List (High Evidence).
Fetal anomalies v1.163 CASP2 Zornitza Stark Classified gene: CASP2 as Green List (high evidence)
Fetal anomalies v1.163 CASP2 Zornitza Stark Gene: casp2 has been classified as Green List (High Evidence).
Fetal anomalies v1.162 CASP2 Zornitza Stark gene: CASP2 was added
gene: CASP2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CASP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP2 were set to 37880421
Phenotypes for gene: CASP2 were set to neurodevelopmental disorder MONDO:0700092, CASP2-related
Review for gene: CASP2 was set to GREEN
Added comment: 7 individuals from 5 families:
- 4 families homozygous for PTC.
- 1 family compound heterozygote for splice site + PTC. RNA studies indicate usage of 2 cryptic splice donor sites.

5/5 have ID/dev delay
1/5 seizures
2/5 hypotonia
3/5 Lissencephaly (pachygyria + cortical thickening)
Sources: Literature
Fetal anomalies v1.161 HIST1H4C Zornitza Stark Tag new gene name tag was added to gene: HIST1H4C.
Fetal anomalies v1.161 MFN2 Elena Savva Marked gene: MFN2 as ready
Fetal anomalies v1.161 MFN2 Elena Savva Gene: mfn2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.161 MFN2 Elena Savva Classified gene: MFN2 as Amber List (moderate evidence)
Fetal anomalies v1.161 MFN2 Elena Savva Gene: mfn2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.160 MFN2 Andrew Fennell gene: MFN2 was added
gene: MFN2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MFN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MFN2 were set to PMID: 37804319
Phenotypes for gene: MFN2 were set to Mitochondrial disease, MONDO:0044970, MFN2-related
Review for gene: MFN2 was set to AMBER
Added comment: A single report of fetus with severe antenatal encephalopathy with lissencephaly, polymicrogyria, and cerebellar atrophy. The authors identified a homozygous in-frame deletion leading to exon 16 skipping and in-frame loss of 50 amino acids 13 (p.Gln574_Val624del). Functional evidence of mitochondrial dysfunction (clumping) and respiratory chain complex deficiencies.
Sources: Literature
Fetal anomalies v1.160 HAND2 Zornitza Stark Phenotypes for gene: HAND2 were changed from Congenital heart defects to Congenital heart disease, MONDO:0005453, HAND2-related
Fetal anomalies v1.159 ADAMTS15 Zornitza Stark Phenotypes for gene: ADAMTS15 were changed from Arthrogryposis (MONDO:0008779), ADMATS15-related to Arthrogryposis, distal, type 12, MIM# 620545
Fetal anomalies v1.158 ADAMTS15 Zornitza Stark edited their review of gene: ADAMTS15: Changed phenotypes: Arthrogryposis, distal, type 12, MIM# 620545
Fetal anomalies v1.158 KDM2B Ain Roesley edited their review of gene: KDM2B: Changed phenotypes: neurodevelopmental disorder MONDO#0700092, KDM2B-related
Fetal anomalies v1.158 KDM2B Ain Roesley Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder MONDO#070009, KDM2B-related to neurodevelopmental disorder MONDO#0700092, KDM2B-related
Fetal anomalies v1.157 ENO1 Zornitza Stark Phenotypes for gene: ENO1 were changed from Polymicrogyria; microcephaly to Polymicrogyria, MONDO:0000087, ENO1-related
Fetal anomalies v1.156 DYNC1I1 Zornitza Stark Phenotypes for gene: DYNC1I1 were changed from Split-hand/split-foot malformation (SHFM) to Split-hand/split-foot malformation (SHFM) MONDO:0016576, DYNC1I1-related
Fetal anomalies v1.155 PLS3 Ain Roesley Phenotypes for gene: PLS3 were changed from Bone mineral density QTL18, osteoporosis - MIM#300910 to Bone mineral density QTL18, osteoporosis - MIM#300910; congenital diaphragmatic hernia MONDO:0005711, PLS3-related
Fetal anomalies v1.154 PLS3 Ain Roesley Publications for gene: PLS3 were set to 32655496; 25209159; 29736964; 29884797; 28777485; 24088043
Fetal anomalies v1.153 PLS3 Ain Roesley Classified gene: PLS3 as Green List (high evidence)
Fetal anomalies v1.153 PLS3 Ain Roesley Gene: pls3 has been classified as Green List (High Evidence).
Fetal anomalies v1.152 PLS3 Lauren Rogers reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37751738; Phenotypes: congenital diaphragmatic hernia MONDO:0005711, PLS3-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.152 MYCN Elena Savva Phenotypes for gene: MYCN were changed from Feingold syndrome 1 (MIM#164280); eurodevelopmental disorder (MONDO:0700092), MYCN-related to Feingold syndrome 1 (MIM#164280); Neurodevelopmental disorder (MONDO:0700092), MYCN-related
Fetal anomalies v1.151 MYCN Elena Savva Added comment: Comment on phenotypes: Three individuals now reported with gain-of-function missense variants (identical variant in two individuals). Clinical presentation includes megalencephaly, hypoplastic corpus callosum, postaxial polydactyly, intellectual disability and motor delay. Knock-in mouse model showed morphological manifestations in multiple tissues including digits, female reproductive system and kidney.
Fetal anomalies v1.151 MYCN Elena Savva Phenotypes for gene: MYCN were changed from Feingold syndrome 1 (MIM#164280) to Feingold syndrome 1 (MIM#164280); eurodevelopmental disorder (MONDO:0700092), MYCN-related
Fetal anomalies v1.150 MYCN Elena Savva Publications for gene: MYCN were set to 18470948
Fetal anomalies v1.149 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040 to ATR-X-related syndrome MONDO:0016980
Fetal anomalies v1.148 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy; Cleft lip and palate to Arrhythmogenic cardiomyopathy with or without ectodermal abnormalities, MIM#620519
Fetal anomalies v1.147 GNPNAT1 Zornitza Stark Marked gene: GNPNAT1 as ready
Fetal anomalies v1.147 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.147 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Amber List (moderate evidence)
Fetal anomalies v1.147 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.146 GNPNAT1 Zornitza Stark gene: GNPNAT1 was added
gene: GNPNAT1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: GNPNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPNAT1 were set to 36097642; 35427807; 32591345
Phenotypes for gene: GNPNAT1 were set to Rhizomelic dysplasia, Ain-Naz type, MIM#619598
Review for gene: GNPNAT1 was set to AMBER
Added comment: 3 unrelated families reported with a skeletal dysplasia characterised by severe short stature and rhizomelic shortening. No antenatal features reported. The parents in PMID 36097642 had a medical termination of pregnancy at 4 months gestation for a fetus with skeletal anomalies - not genotyped.
Sources: Expert Review
Fetal anomalies v1.145 ARHGAP29 Zornitza Stark Phenotypes for gene: ARHGAP29 were changed from Cleft palate; cleft lip with or without cleft palate to Clefting disorder, MONDO:0000358, ARHGAP29-related
Fetal anomalies v1.144 SCAF4 Zornitza Stark Phenotypes for gene: SCAF4 were changed from Neurodevelopmental disorder MONDO#0700092, SCAF4-related to Fliedner-Zweier syndrome, MIM#620511
Fetal anomalies v1.143 SCAF4 Zornitza Stark reviewed gene: SCAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fliedner-Zweier syndrome, MIM#620511; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.143 DBR1 Zornitza Stark Tag founder tag was added to gene: DBR1.
Fetal anomalies v1.143 DBR1 Seb Lunke Marked gene: DBR1 as ready
Fetal anomalies v1.143 DBR1 Seb Lunke Gene: dbr1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.143 DBR1 Seb Lunke Phenotypes for gene: DBR1 were changed from Prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation, and death before the first year of life to Ichthyosis (MONDO#0019269), DBR1-related
Fetal anomalies v1.142 DBR1 Chern Lim Deleted their comment
Fetal anomalies v1.142 DBR1 Chern Lim edited their review of gene: DBR1: Added comment: PMID: 37656279:
- A homozygous missense as a founder recessive DBR1 variant in four consanguineous families.
- Total of 7 affected children. WES done for one proband from each family.
- Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life.
- RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample.
- Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant.
- Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency.; Changed phenotypes: Ichthyosis (MONDO#0019269), DBR1-related
Fetal anomalies v1.142 LNPK Zornitza Stark Marked gene: LNPK as ready
Fetal anomalies v1.142 LNPK Zornitza Stark Gene: lnpk has been classified as Green List (High Evidence).
Fetal anomalies v1.142 LNPK Zornitza Stark Classified gene: LNPK as Green List (high evidence)
Fetal anomalies v1.142 LNPK Zornitza Stark Gene: lnpk has been classified as Green List (High Evidence).
Fetal anomalies v1.141 DBR1 Seb Lunke Classified gene: DBR1 as Amber List (moderate evidence)
Fetal anomalies v1.141 DBR1 Seb Lunke Gene: dbr1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.140 LNPK Lilian Downie gene: LNPK was added
gene: LNPK was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LNPK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LNPK were set to PMID: 30032983, PMID:35599435, https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcad222/7243438?login=true
Phenotypes for gene: LNPK were set to Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum MIM#618090
Review for gene: LNPK was set to GREEN
Added comment: Moderate to severe ID, majority of patients 10/15 have period of regression
Epilepsy (myoclonic frequently)
Structural brain anomalies 'ear of the lynx sign', callosal hypoplasia, mild brain including cerebellar atrophy.
Microcephaly, macrocephaly and normal head circumference described.
Sources: Literature
Fetal anomalies v1.140 DBR1 Chern Lim gene: DBR1 was added
gene: DBR1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBR1 were set to 37656279
Phenotypes for gene: DBR1 were set to Prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation, and death before the first year of life
Review for gene: DBR1 was set to AMBER
gene: DBR1 was marked as current diagnostic
Added comment: PMID: 37656279:
- A homozygous missense as a founder recessive DBR1 variant in four consanguineous families.
- Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life.
- RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample.
- Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant.
- Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency.
Sources: Literature
Fetal anomalies v1.140 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Fetal anomalies v1.140 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Fetal anomalies v1.140 CUL3 Zornitza Stark Classified gene: CUL3 as Green List (high evidence)
Fetal anomalies v1.140 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Fetal anomalies v1.139 CUL3 Lucy Spencer gene: CUL3 was added
gene: CUL3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUL3 were set to 37665043
Phenotypes for gene: CUL3 were set to Neurodevelopmental disorder with or without autism or seizures (MIM#619239); Pseudohypoaldosteronism, type IIE (MIM#614496)
Review for gene: CUL3 was set to GREEN
Added comment: PMID: 37665043
1 case study and a review of the literature. 5 patients with de novo variants (PTCs and missense) in CUL3 who have various cardiac phenotypes: atrial septal defects, left ventricular outflow tract obstruction. Hypertrophic right ventricle pulmonary atresia, and other congenital heart defects. 2 of these patients have a neurological phenotype as well, while the other three are not reported to have one (but at least one was a terminated pregnancy).
Sources: Literature
Fetal anomalies v1.139 SOX11 Zornitza Stark reviewed gene: SOX11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29459093, 24886874, 33086258, 33785884, 35642566, 35341651; Phenotypes: Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.139 ATP5O Zornitza Stark Marked gene: ATP5O as ready
Fetal anomalies v1.139 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Fetal anomalies v1.139 ATP5O Zornitza Stark Classified gene: ATP5O as Green List (high evidence)
Fetal anomalies v1.139 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Fetal anomalies v1.138 ATP5O Zornitza Stark gene: ATP5O was added
gene: ATP5O was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5O were set to 35621276; 34954817
Phenotypes for gene: ATP5O were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359
Review for gene: ATP5O was set to GREEN
Added comment: Prenatal phenotypes reported (IUGR, CHD, oligohydramnios)
Sources: Expert list
Fetal anomalies v1.137 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic intellectual disability; short stature to Syndromic disease, MONDO:0002254, RAP1B-related
Fetal anomalies v1.136 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669 to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Fetal anomalies v1.135 PLCB4 Zornitza Stark reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Auriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.135 PHF5A Zornitza Stark Marked gene: PHF5A as ready
Fetal anomalies v1.135 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Fetal anomalies v1.135 PHF5A Zornitza Stark Phenotypes for gene: PHF5A were changed from PMID: 37422718 to Neurodevelopmental disorder (MONDO#0700092), PHF5A-related
Fetal anomalies v1.134 PHF5A Zornitza Stark Publications for gene: PHF5A were set to
Fetal anomalies v1.133 PHF5A Zornitza Stark Classified gene: PHF5A as Green List (high evidence)
Fetal anomalies v1.133 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Fetal anomalies v1.132 PHF5A Daniel Flanagan reviewed gene: PHF5A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37422718; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PHF5A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.132 PHF5A Daniel Flanagan Deleted their review
Fetal anomalies v1.132 PHF5A Daniel Flanagan gene: PHF5A was added
gene: PHF5A was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PHF5A were set to PMID: 37422718
Review for gene: PHF5A was set to GREEN
Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects and heart defects, inguinal hernia, and sacral dimple in three subjects. Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects.
Sources: Expert list
Fetal anomalies v1.132 SENP7 Elena Savva Marked gene: SENP7 as ready
Fetal anomalies v1.132 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.132 SENP7 Elena Savva Classified gene: SENP7 as Amber List (moderate evidence)
Fetal anomalies v1.132 SENP7 Elena Savva Gene: senp7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.131 SENP7 Elena Savva gene: SENP7 was added
gene: SENP7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SENP7 were set to PMID: 37460201
Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related
Review for gene: SENP7 was set to AMBER
Added comment: PMID: 37460201
- 1 family (4 affecteds, sibling pair and 1st cousin) with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia. Fetus could not be tested, so 3 confirmed genetically.
- Homozygous for a PTC, decreased mRNA from one sample supports an NMD outcome.
- Additional studies performed supporting downstream proteins expression being affected
- Neutropenia observed in 2/3 patients
Sources: Literature
Fetal anomalies v1.130 STX5 Ain Roesley Marked gene: STX5 as ready
Fetal anomalies v1.130 STX5 Ain Roesley Gene: stx5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.130 STX5 Ain Roesley Classified gene: STX5 as Amber List (moderate evidence)
Fetal anomalies v1.130 STX5 Ain Roesley Gene: stx5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.129 STX5 Ain Roesley gene: STX5 was added
gene: STX5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: STX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STX5 were set to 34711829
Phenotypes for gene: STX5 were set to congenital disorder of glycosylation MONDO#0015286, STX5-related
Review for gene: STX5 was set to AMBER
gene: STX5 was marked as current diagnostic
Added comment: 1x family with 3x deceased shortly after death + 3x spontaneous abortions + 2x abortions due to abnormal fatal ultrasound (US).
Hom for NM_003164.4:c.163 A > G p.(Met55Val), which results in complete loss of short isoform (which uses Met55 as the start)

phenotype: short long bones on US, dysmorphism, skeletal dysplasia, profound hypotonia, hepatomegaly elevated cholesterol.
Post-natally they died of progressive liver failure with cholestasis and hyperinsulinemic hypoglycemias

Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking
Sources: Literature
Fetal anomalies v1.128 INTS13 Zornitza Stark Marked gene: INTS13 as ready
Fetal anomalies v1.128 INTS13 Zornitza Stark Gene: ints13 has been classified as Green List (High Evidence).
Fetal anomalies v1.128 INTS13 Zornitza Stark Phenotypes for gene: INTS13 were changed from Oral-facial-digital syndrome to Oral-facial-digital syndrome, MONDO:0015375, INTS13-related
Fetal anomalies v1.127 SLC20A1 Zornitza Stark Phenotypes for gene: SLC20A1 were changed from Bladder-Exstrophy-Epispadias Complex (BEEC) to Bladder-Exstrophy-Epispadias Complex (BEEC), MONDO:0017919, SLC20A1-related
Fetal anomalies v1.126 DCAF15 Zornitza Stark Marked gene: DCAF15 as ready
Fetal anomalies v1.126 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.126 DCAF15 Zornitza Stark Phenotypes for gene: DCAF15 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033, DCAF15-related
Fetal anomalies v1.125 INTS13 Chirag Patel Classified gene: INTS13 as Green List (high evidence)
Fetal anomalies v1.125 INTS13 Chirag Patel Gene: ints13 has been classified as Green List (High Evidence).
Fetal anomalies v1.124 INTS13 Chirag Patel gene: INTS13 was added
gene: INTS13 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: INTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS13 were set to PMID: 36229431
Phenotypes for gene: INTS13 were set to Oral-facial-digital syndrome
Review for gene: INTS13 was set to GREEN
gene: INTS13 was marked as current diagnostic
Added comment: 2 families with 4 affected individuals with Oral-facial-digital (OFD) phenotype. Homozygosity mapping and WES found 2 homozygous variants in INTS13 gene. This is a subunit of the Integrator complex, which associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. Variants segregated with disease. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Knockdown in Xenopus embryos leads to motile cilia anomalies.
Sources: Literature
Fetal anomalies v1.123 PTCH1 Chirag Patel reviewed gene: PTCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bladder exstrophy and epispadias complex (BEEC); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.123 DCAF15 Chirag Patel Classified gene: DCAF15 as Amber List (moderate evidence)
Fetal anomalies v1.123 DCAF15 Chirag Patel Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.122 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Fetal anomalies. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Fetal anomalies v1.121 ERI1 Zornitza Stark Marked gene: ERI1 as ready
Fetal anomalies v1.121 ERI1 Zornitza Stark Gene: eri1 has been classified as Green List (High Evidence).
Fetal anomalies v1.121 ERI1 Zornitza Stark Classified gene: ERI1 as Green List (high evidence)
Fetal anomalies v1.121 ERI1 Zornitza Stark Gene: eri1 has been classified as Green List (High Evidence).
Fetal anomalies v1.120 ERI1 Zornitza Stark gene: ERI1 was added
gene: ERI1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia (MONDO#0100510)
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Fetal anomalies v1.119 NUDCD2 Seb Lunke Marked gene: NUDCD2 as ready
Fetal anomalies v1.119 NUDCD2 Seb Lunke Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.119 NUDCD2 Seb Lunke Classified gene: NUDCD2 as Amber List (moderate evidence)
Fetal anomalies v1.119 NUDCD2 Seb Lunke Gene: nudcd2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.118 NUDCD2 Ee Ming Wong gene: NUDCD2 was added
gene: NUDCD2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NUDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDCD2 were set to 37272762
Phenotypes for gene: NUDCD2 were set to Multiple congenital anomalies (MONDO:0019042), NUDCD2-related
Penetrance for gene: NUDCD2 were set to unknown
Review for gene: NUDCD2 was set to AMBER
gene: NUDCD2 was marked as current diagnostic
Added comment: - Two unrelated probands, each biallelic for two variants in NUDCD2 (total 3x LoF variants, 1x missense variant)
- Immunoblotting of proteins extracted from the primary fibroblasts of one proband with 2x LoF variants demonstrated markedly reduced NUDCD2 levels compared to healthy individuals
Sources: Literature
Fetal anomalies v1.118 RAB34 Elena Savva Marked gene: RAB34 as ready
Fetal anomalies v1.118 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Fetal anomalies v1.118 RAB34 Elena Savva Phenotypes for gene: RAB34 were changed from Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Fetal anomalies v1.117 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Fetal anomalies v1.117 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Fetal anomalies v1.116 DRG1 Krithika Murali Marked gene: DRG1 as ready
Fetal anomalies v1.116 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Fetal anomalies v1.116 DRG1 Krithika Murali Publications for gene: DRG1 were set to PMID: 37179472
Fetal anomalies v1.115 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Fetal anomalies v1.115 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Fetal anomalies v1.114 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Fetal anomalies v1.114 RAB34 Sarah Pantaleo gene: RAB34 was added
gene: RAB34 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37384395
Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies
Penetrance for gene: RAB34 were set to Complete
Review for gene: RAB34 was set to GREEN
Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS.

Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher).

Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects.

RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function.

Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands.

In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth.

All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities.

All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance.
Sources: Literature
Fetal anomalies v1.114 BRWD1 Zornitza Stark Phenotypes for gene: BRWD1 were changed from Situs inversus; primary ciliary dyskinesia like to Situs inversus; Ciliary dyskinesia, primary, 51, MIM# 620438
Fetal anomalies v1.113 KIF26A Zornitza Stark Marked gene: KIF26A as ready
Fetal anomalies v1.113 KIF26A Zornitza Stark Gene: kif26a has been classified as Green List (High Evidence).
Fetal anomalies v1.113 KIF26A Zornitza Stark Classified gene: KIF26A as Green List (high evidence)
Fetal anomalies v1.113 KIF26A Zornitza Stark Gene: kif26a has been classified as Green List (High Evidence).
Fetal anomalies v1.112 KIF26A Zornitza Stark gene: KIF26A was added
gene: KIF26A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF26A were set to 36564622
Phenotypes for gene: KIF26A were set to Cortical dysplasia, complex, with other brain malformations 11, MIM# 620156
Review for gene: KIF26A was set to GREEN
Added comment: Five individuals from two families each with a different homozygous truncating variant in KIF26A segregating with profound ENS dysfunction that manifested clinically like Hirschsprung’s disease despite normal ganglionosis. Moreover, they all have neurological involvement with brain malformations ranging from ventriculomegaly to severe congenital hydrocephalus in two siblings who died early in life. Clinically, they displayed developmental delay and, in the longest surviving individual, spastic paraplegia.

Brain abnormalities may be detectable antenatally.
Sources: Literature
Fetal anomalies v1.111 MAP4K4 Zornitza Stark Marked gene: MAP4K4 as ready
Fetal anomalies v1.111 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Fetal anomalies v1.111 MAP4K4 Zornitza Stark Classified gene: MAP4K4 as Green List (high evidence)
Fetal anomalies v1.111 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Fetal anomalies v1.110 MAP4K4 Zornitza Stark gene: MAP4K4 was added
gene: MAP4K4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MAP4K4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP4K4 were set to 37126546
Phenotypes for gene: MAP4K4 were set to RASopathy, MONDO:0021060, MAP4K4-related
Review for gene: MAP4K4 was set to GREEN
Added comment: 26 individuals from 21 families reported with Rasopathy-like phenotype, comprising ID/DD, dysmorphic features and congenital anomalies.
Sources: Literature
Fetal anomalies v1.109 RASA1 Zornitza Stark Publications for gene: RASA1 were set to 33461977
Fetal anomalies v1.108 RASA1 Zornitza Stark edited their review of gene: RASA1: Added comment: PMID 36980822: 21 cases presenting with hydrops.; Changed publications: 33461977, 36980822
Fetal anomalies v1.108 SCN4A Zornitza Stark Phenotypes for gene: SCN4A were changed from Congenital myopathy; Myasthenic syndrome, congenital, 16 MIM#614198 to Congenital myopathy 22B, severe fetal, MIM# 620369; Myasthenic syndrome, congenital, 16 MIM#614198
Fetal anomalies v1.107 SCN4A Zornitza Stark reviewed gene: SCN4A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myopathy 22B, severe fetal, MIM# 620369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.107 ESAM Zornitza Stark Phenotypes for gene: ESAM were changed from Neurodevelopmental disorder (MONDO#0700092), ESAM-related to Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371
Fetal anomalies v1.106 ESAM Zornitza Stark reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.106 GATAD2A Zornitza Stark Marked gene: GATAD2A as ready
Fetal anomalies v1.106 GATAD2A Zornitza Stark Gene: gatad2a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.106 GATAD2A Zornitza Stark Classified gene: GATAD2A as Amber List (moderate evidence)
Fetal anomalies v1.106 GATAD2A Zornitza Stark Gene: gatad2a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.105 GATAD2A Zornitza Stark gene: GATAD2A was added
gene: GATAD2A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GATAD2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATAD2A were set to https://doi.org/10.1016/j.xhgg.2023.100198; 17565372
Phenotypes for gene: GATAD2A were set to Neurodevelopmental disorder, MONDO:0700092, GATAD2A-related
Review for gene: GATAD2A was set to AMBER
Added comment: Inconsistent pattern of congenital abnormalities.

https://doi.org/10.1016/j.xhgg.2023.100198 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5
PMID: 17565372 - null mouse model is embryonic lethal.
Sources: Literature
Fetal anomalies v1.104 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from Developmental and epileptic encephalopathy 31, OMIM:616346 to Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346; Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Fetal anomalies v1.103 DNM1 Zornitza Stark edited their review of gene: DNM1: Changed phenotypes: Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346, Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Fetal anomalies v1.103 MED11 Zornitza Stark Phenotypes for gene: MED11 were changed from neurodevelopmental disorder MONDO#0700092, MED11-related to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327
Fetal anomalies v1.102 KIF21A Chirag Patel Classified gene: KIF21A as Amber List (moderate evidence)
Fetal anomalies v1.102 KIF21A Chirag Patel Gene: kif21a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.101 KIF21A Chirag Patel gene: KIF21A was added
gene: KIF21A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIF21A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF21A were set to PMID: 34740919
Phenotypes for gene: KIF21A were set to Severe fetal akinesia with arthrogryposis multiplex
Review for gene: KIF21A was set to AMBER
Added comment: 2 unrelated consanguineous Turkish families with 5 affected fetuses with severe fetal akinesia with arthrogryposis multiplex. WES identified different homozygous LOF variants in KIF21A gene (p.Leu449* and p.Arg791Glufs*8). Parents and a healthy sibling were heterozygous carriers. No functional studies.
Sources: Literature
Fetal anomalies v1.100 C16orf62 Chirag Patel Classified gene: C16orf62 as Green List (high evidence)
Fetal anomalies v1.100 C16orf62 Chirag Patel Gene: c16orf62 has been classified as Green List (High Evidence).
Fetal anomalies v1.99 C16orf62 Chirag Patel reviewed gene: C16orf62: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36113987; Phenotypes: Ritscher-Schinzel syndrome-3 (RTSC3), MIM#619135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.99 FILIP1 Zornitza Stark Marked gene: FILIP1 as ready
Fetal anomalies v1.99 FILIP1 Zornitza Stark Gene: filip1 has been classified as Green List (High Evidence).
Fetal anomalies v1.99 FILIP1 Zornitza Stark Classified gene: FILIP1 as Green List (high evidence)
Fetal anomalies v1.99 FILIP1 Zornitza Stark Gene: filip1 has been classified as Green List (High Evidence).
Fetal anomalies v1.98 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168 to Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related
Fetal anomalies v1.97 ESAM Seb Lunke Marked gene: ESAM as ready
Fetal anomalies v1.97 ESAM Seb Lunke Gene: esam has been classified as Green List (High Evidence).
Fetal anomalies v1.97 ESAM Seb Lunke Classified gene: ESAM as Green List (high evidence)
Fetal anomalies v1.97 ESAM Seb Lunke Gene: esam has been classified as Green List (High Evidence).
Fetal anomalies v1.96 CRIPT Zornitza Stark Phenotypes for gene: CRIPT were changed from Short stature with microcephaly and distinctive facies, 615789 to Short stature with microcephaly and distinctive facies (MIM#615789); Rothmund-Thomson syndrome MONDO:0010002
Fetal anomalies v1.95 CRIPT Zornitza Stark Publications for gene: CRIPT were set to 24389050; 27250922
Fetal anomalies v1.94 CRIPT Zornitza Stark Classified gene: CRIPT as Green List (high evidence)
Fetal anomalies v1.94 CRIPT Zornitza Stark Gene: cript has been classified as Green List (High Evidence).
Fetal anomalies v1.93 CRIPT Karina Sandoval reviewed gene: CRIPT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37013901; Phenotypes: Short stature with microcephaly and distinctive facies (MIM#615789), Rothmund-Thomson syndrome MONDO:0010002; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.93 ACTC1 Lilian Downie reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36945405; Phenotypes: Atrial septal defect 5 MIM#612794, Cardiomyopathy, dilated, 1R MIM#613424, Cardiomyopathy, hypertrophic, 11 MIM#612098, ACTC1 related distal arthrogryposis MONDO:0019942; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.93 ESAM Chern Lim 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 36996813
Phenotypes for gene: ESAM were set to Neurodevelopmental disorder (MONDO#0700092), ESAM-related
Review for gene: ESAM was set to GREEN
gene: ESAM was marked as current diagnostic
Added comment: PMID 36996813
- Thirteen affected individuals, including four fetuses, from eight unrelated families, with homozygous loss-of-function-type variants in ESAM – 2 of the variants are frameshifts, 1x nonsense, 1x canonical splice.
- Affected individuals have profound global developmental delay/unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/cerebral calcifications, the latter being also observed in the fetuses.
- One of the frameshift variant c.115del (p.Arg39Glyfs*33), was detected in six individuals from four unrelated families from the same geographic region in Turkey (southeastern Anatolia), suggesting a founder effect.
- The c.451+1G>A variant was detected in three individuals from two independent families with the same ethnic origin (Arab Bedouin)
Sources: Literature
Fetal anomalies v1.93 FILIP1 Paul De Fazio edited their review of gene: FILIP1: Changed phenotypes: Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related
Fetal anomalies v1.93 FILIP1 Paul De Fazio gene: FILIP1 was added
gene: FILIP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FILIP1 were set to 36943452
Phenotypes for gene: FILIP1 were set to Arthrogryposis multiplex congenita MONDO:0015168
Penetrance for gene: FILIP1 were set to unknown
Review for gene: FILIP1 was set to GREEN
gene: FILIP1 was marked as current diagnostic
Added comment: 3 families, all consanguineous, reported with 3 different homozygous loss of function variants (2x NMD-predicted nonsense, 1x intragenic deletion of exons 3-6 of 6). In one family, the variant segregated in 3 affected siblings.

Phenotypes consist of congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly (-1.5 to -4 SD), and facial dysmorphism.
Sources: Literature
Fetal anomalies v1.93 CRIPT Suliman Khan edited their review of gene: CRIPT: Changed rating: AMBER
Fetal anomalies v1.93 SLC31A1 Zornitza Stark Phenotypes for gene: SLC31A1 were changed from Neurodevelopmental disorder, SLC31A1-related (MONDO#0700092) to Neurodegeneration and seizures due to copper transport defect, MIM# 620306
Fetal anomalies v1.92 SLC31A1 Zornitza Stark reviewed gene: SLC31A1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration and seizures due to copper transport defect, MIM# 620306; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.92 PLXND1 Zornitza Stark Phenotypes for gene: PLXND1 were changed from Congenital heart disease, MONDO:0005453, PLXND1-related to Congenital heart defects, multiple types, 9, MIM# 620294
Fetal anomalies v1.91 PLXND1 Zornitza Stark edited their review of gene: PLXND1: Changed phenotypes: Congenital heart defects, multiple types, 9, MIM# 620294
Fetal anomalies v1.91 PLXND1 Zornitza Stark Marked gene: PLXND1 as ready
Fetal anomalies v1.91 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.91 PLXND1 Zornitza Stark Classified gene: PLXND1 as Green List (high evidence)
Fetal anomalies v1.91 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.90 PLXND1 Zornitza Stark gene: PLXND1 was added
gene: PLXND1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLXND1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXND1 were set to 35396997
Phenotypes for gene: PLXND1 were set to Congenital heart disease, MONDO:0005453, PLXND1-related
Review for gene: PLXND1 was set to GREEN
Added comment: 10 individuals including four fetal cases from five unrelated families were identified with biallelic variants in PLXND1 gene and they presented with cardiac defects. The most frequent defect is common arterial trunk (CAT)/truncus arteriosus.
Sources: Literature
Fetal anomalies v1.89 HMGB1 Ain Roesley Phenotypes for gene: HMGB1 were changed from Neurodevelopmental disorder MONDO:0700092, HMGB1-related; microcephaly; intellectual disability to Neurodevelopmental disorder MONDO:0700092, HMGB1-related; microcephaly; intellectual disability; brachyphalangy, polydactyly, and tibial aplasia/hypoplasia MIM#163905
Fetal anomalies v1.89 HMGB1 Ain Roesley Publications for gene: HMGB1 were set to 34164801
Fetal anomalies v1.88 HMGB1 Ain Roesley reviewed gene: HMGB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36755093, 34159400; Phenotypes: brachyphalangy, polydactyly, and tibial aplasia/hypoplasia MIM#163905; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v1.88 CRIPT Suliman Khan reviewed gene: CRIPT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36630262; Phenotypes: Short stature with microcephaly and distinctive facies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.88 EFCAB1 Zornitza Stark Marked gene: EFCAB1 as ready
Fetal anomalies v1.88 EFCAB1 Zornitza Stark Gene: efcab1 has been classified as Green List (High Evidence).
Fetal anomalies v1.88 EFCAB1 Zornitza Stark Classified gene: EFCAB1 as Green List (high evidence)
Fetal anomalies v1.88 EFCAB1 Zornitza Stark Gene: efcab1 has been classified as Green List (High Evidence).
Fetal anomalies v1.87 EFCAB1 Zornitza Stark gene: EFCAB1 was added
gene: EFCAB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EFCAB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFCAB1 were set to 36727596
Phenotypes for gene: EFCAB1 were set to Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related
Review for gene: EFCAB1 was set to GREEN
Added comment: WES in 3 individuals with laterality defects and respiratory symptoms, identified homozygous pathogenic variants in CLXN (EFCAB1). They found Clxn expressed in mice left-right organizer. Transmission electron microscopy depicted outer dynein arm (ODA) defects in distal ciliary axonemes. Immunofluorescence microscopy revealed absence of CLXN from the ciliary axonemes, absence of the ODA components DNAH5, DNAI1 and DNAI2 from the distal axonemes, as well as mislocalization or absence of DNAH9. Additionally, CLXN is undetectable in ciliary axonemes of individuals with defects in the outer dynein arm docking (ODA-DC) machinery: ODAD1, ODAD2, ODAD3 and ODAD4. Moreover, SMED-EFCAB1-deficient planaria displayed ciliary dysmotility.
Sources: Literature
Fetal anomalies v1.86 ATP9A Zornitza Stark Phenotypes for gene: ATP9A were changed from neurodevelopmental disorder, ATP9A-related MONDO#0700092 to Neurodevelopmental disorder with poor growth and behavioural abnormalities, MIM# 620242
Fetal anomalies v1.85 GOLGA2 Zornitza Stark Phenotypes for gene: GOLGA2 were changed from neuromuscular disease, GOLGA2-related MONDO#0019056 to Developmental delay with hypotonia, myopathy, and brain abnormalities, MIM 620240
Fetal anomalies v1.84 GOLGA2 Zornitza Stark edited their review of gene: GOLGA2: Added comment: Third family reported but again hypoplasia of CC which may be difficult to detect. Onset of microcephaly uncertain.; Changed publications: 34424553; Changed phenotypes: Developmental delay with hypotonia, myopathy, and brain abnormalities, MIM 620240
Fetal anomalies v1.84 ZNF668 Zornitza Stark Phenotypes for gene: ZNF668 were changed from DNA damage repair defect; microcephaly; growth deficiency; severe global developmental delay; brain malformation; facial dysmorphism to Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies, MIM# 620194
Fetal anomalies v1.83 SLC31A1 Zornitza Stark Marked gene: SLC31A1 as ready
Fetal anomalies v1.83 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.83 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Amber List (moderate evidence)
Fetal anomalies v1.83 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.82 SLC31A1 Daniel Flanagan gene: SLC31A1 was added
gene: SLC31A1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: SLC31A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC31A1 were set to PMID: 35913762; 36562171
Phenotypes for gene: SLC31A1 were set to Neurodevelopmental disorder, SLC31A1-related (MONDO#0700092)
Review for gene: SLC31A1 was set to AMBER
Added comment: PMID:36562171
Homozygous c.236T>C; p.(Leu79Pro) identified in a newborn of consanguineous parents. Variant absent from gnomAD. Prenatal ultrasound showed a male fetus with short femoral bones, an apparently enlarged heart-to-thorax ratio, and a wide cisterna magna. The infant was born with pulmonary hypoplasia. At 2 weeks of age, multifocal brain hemorrhages were diagnosed and the infant developed seizures. The infant died at 1 month of age. The Mother had three healthy children while nine pregnancies had been extrauterine gravidities or ended in first or mid-trimester spontaneous abortions.

PMID: 35913762
SLC31A1 is also referred to as CTR1.
Monozygotic twins with hypotonia, global developmental delay, seizures, and rapid brain atrophy, consistent with profound central nervous system copper deficiency. Homozygous for a novel missense variant (p.(Arg95His)) in copper transporter CTR1, both parents heterozygous. A mouse knock-out model of CTR1 deficiency resulted in prenatal lethality.
Sources: Expert list
Fetal anomalies v1.82 TGFBR1 Alison Yeung reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36584339; Phenotypes: Loeys-Dietz syndrome 1, MIM# 609192; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v1.82 TGFBR1 Alison Yeung Mode of inheritance for gene: TGFBR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v1.81 CDK5 Zornitza Stark Publications for gene: CDK5 were set to 25560765
Fetal anomalies v1.80 CDK5 Zornitza Stark Classified gene: CDK5 as Amber List (moderate evidence)
Fetal anomalies v1.80 CDK5 Zornitza Stark Gene: cdk5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.79 CDK5 Zornitza Stark reviewed gene: CDK5: Rating: AMBER; Mode of pathogenicity: None; Publications: 25560765, 32273484, 32097629, 28854363, 7490100; Phenotypes: Lissencephaly 7 with cerebellar hypoplasia, MIM# 616342; Mode of inheritance: None
Fetal anomalies v1.79 KDM2B Ain Roesley Marked gene: KDM2B as ready
Fetal anomalies v1.79 KDM2B Ain Roesley Gene: kdm2b has been classified as Green List (High Evidence).
Fetal anomalies v1.79 KDM2B Ain Roesley Classified gene: KDM2B as Green List (high evidence)
Fetal anomalies v1.79 KDM2B Ain Roesley Gene: kdm2b has been classified as Green List (High Evidence).
Fetal anomalies v1.78 KDM2B Ain Roesley gene: KDM2B was added
gene: KDM2B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KDM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM2B were set to 36322151
Phenotypes for gene: KDM2B were set to neurodevelopmental disorder MONDO#070009, KDM2B-related
Review for gene: KDM2B was set to GREEN
gene: KDM2B was marked as current diagnostic
Added comment: 27 individuals from 22 families were recruited
13 SNV classified LP/P, all de novo except 2 familial cases
5 variants were classified as VUS if more than 1 het is present in gnomAD or does result in a KDM2B-specific episignature (therefore suggesting normal function)

14 families with SNVs and a variety of cardiac anomalies including ASD, VSD, MR, PDA, PFO, Atrial septal aneurysm and Mild mitral insufficiency
Sources: Literature
Fetal anomalies v1.77 SHROOM4 Alison Yeung Classified gene: SHROOM4 as Green List (high evidence)
Fetal anomalies v1.77 SHROOM4 Alison Yeung Gene: shroom4 has been classified as Green List (High Evidence).
Fetal anomalies v1.76 SHROOM4 Alison Yeung reviewed gene: SHROOM4: Rating: GREEN; Mode of pathogenicity: None; Publications: 36379543; Phenotypes: Congenital anomaly of the kidney and urinary tracy (CAKUT), SHROOM4-related, MONDO:0019719; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.76 PDIA6 Chirag Patel reviewed gene: PDIA6: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35856135; Phenotypes: Polycystic kidney disease, infancy-onset diabetes, and microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.76 MBTPS1 Krithika Murali reviewed gene: MBTPS1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Spondyloepiphyseal dysplasia, Kondo-Fu type - MIM#618392; Mode of inheritance: None
Fetal anomalies v1.76 FRA10AC1 Zornitza Stark Phenotypes for gene: FRA10AC1 were changed from Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related to Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113
Fetal anomalies v1.75 FRA10AC1 Zornitza Stark reviewed gene: FRA10AC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.75 KCNK3 Zornitza Stark Marked gene: KCNK3 as ready
Fetal anomalies v1.75 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Green List (High Evidence).
Fetal anomalies v1.75 KCNK3 Zornitza Stark Classified gene: KCNK3 as Green List (high evidence)
Fetal anomalies v1.75 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Green List (High Evidence).
Fetal anomalies v1.74 MED11 Ain Roesley Marked gene: MED11 as ready
Fetal anomalies v1.74 MED11 Ain Roesley Gene: med11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.74 MED11 Ain Roesley Classified gene: MED11 as Amber List (moderate evidence)
Fetal anomalies v1.74 MED11 Ain Roesley Gene: med11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.73 MED11 Ain Roesley gene: MED11 was added
gene: MED11 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED11 were set to 36001086
Phenotypes for gene: MED11 were set to neurodevelopmental disorder MONDO#0700092, MED11-related
Review for gene: MED11 was set to AMBER
gene: MED11 was marked as current diagnostic
Added comment: 7 affected from 5 families (3x consang) with the same recurrent variant of p.(Arg109*).

Protein truncating, NOT NMD as proven by RT-PCR and western blot. Zebrafish knockout model recapitulates key clinical phenotypes

NO evidence of founder effect from haplotype analysis

7/7 cerebral dysgyria, cortical atrophy
5/7 limb contracture
4/7 epilepsy
3/7 families with IUGR
3/7 GDD
3/7 hearing loss
3/7 undescended testis
2/7 nystagmus
1/7 congenital cataract
Sources: Literature
Fetal anomalies v1.72 FOSL2 Zornitza Stark Marked gene: FOSL2 as ready
Fetal anomalies v1.72 FOSL2 Zornitza Stark Gene: fosl2 has been classified as Green List (High Evidence).
Fetal anomalies v1.72 FOSL2 Zornitza Stark Classified gene: FOSL2 as Green List (high evidence)
Fetal anomalies v1.72 FOSL2 Zornitza Stark Gene: fosl2 has been classified as Green List (High Evidence).
Fetal anomalies v1.71 FOSL2 Krithika Murali gene: FOSL2 was added
gene: FOSL2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FOSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOSL2 were set to 36197437
Phenotypes for gene: FOSL2 were set to Neurodevelopmental disorder, MONDO:0700092, FOSL2-related
Review for gene: FOSL2 was set to GREEN
Added comment: PMID 36197437 Cospain et al 2022 report 11 individuals from 10 families with heterozygous PTC variants in exon 4/4 of the FOSL2 gene. All variants were predicted to escape NMD resulting in a truncated protein, with the truncation occurring proximal to the C-terminal domain (supportive functional studies).

In 10/11 families the variant occurred de novo in a single affected proband. In one family with 2 affected siblings, the variant was present in the siblings but absent in the unaffected parent likely due to gonadal mosaicism.

Clinical features included:
- Cutis aplasia congenital of the scalp (10/11)
- Tooth enamel hypoplasia and discolouration (8/9)
- Multiple other ectodermal features also noted e.g. small brittle nails, hypotrichosis/hypertrichosis, lichen sclerosis
- 5 individuals had cataracts (mostly bilateral, congenital/early childhood onset)
- 6/9 IUGR
- 5/9 postnatal growth restriction
- 7/9 developmental delay/ID
- 5/7 ADHD/ASD
- 2/9 seizures
Sources: Literature
Fetal anomalies v1.71 KCNK3 Krithika Murali gene: KCNK3 was added
gene: KCNK3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KCNK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNK3 were set to 36195757
Phenotypes for gene: KCNK3 were set to Neurodevelopmental disorder, MONDO:0700092, KCNK3-related; developmental delay with sleep apnoea (DDSA)
Review for gene: KCNK3 was set to GREEN
Added comment: PMID 36195757 Sörmann et al 2022 report 9 unrelated individuals with de novo heterozygous KCNK3 missense variants (21 weeks to 25 years old). All 8 living probands (3-25 years) had hypotonia, global developmental delay, central and/or obstructive sleep apnoea and feeding difficulties. 7/9 probands had additional anomalies including microcephaly (at least 3/9), arthrogryposis/flexion contractures/foot deformities (7/9), scoliosis, cleft palate (2/9), and ambiguous genitalia/undescended testes (5/6) and dysmorphism. IUGR reported in 3/9 probands and polyhdramnios in 2/9.

KCNK3 encodes the TASK-1 K2P channel expressed throughout the central nervous system. All identified variants clustered near the X-gate and are involved in inter- or intra-subunit interaction likely to hold the X-gate closed. Individuals with variants located in the M2 transmembrane helix had a more severe phenotype than those with variants in the M4 helix. Functional studies support a gain of function disease mechanism with increased channel activation. TASK-1 K+ channel inhibitors (some in clinical use) have been raised as a possible therapeutic strategy.

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Heterozygous LoF variants associated with a different disorder - primary pulmonary arterial hypertension
Sources: Literature
Fetal anomalies v1.71 ADAMTS19 Zornitza Stark Phenotypes for gene: ADAMTS19 were changed from Heart valve disorder, MONDO:0002869 to Cardiac valvular dysplasia 2, MIM# 620067
Fetal anomalies v1.70 ADAMTS19 Zornitza Stark edited their review of gene: ADAMTS19: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.70 ADAMTS19 Zornitza Stark reviewed gene: ADAMTS19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiac valvular dysplasia 2, MIM# 620067; Mode of inheritance: None
Fetal anomalies v1.70 ACVR1 Zornitza Stark Tag clinical trial tag was added to gene: ACVR1.
Fetal anomalies v1.70 ATP7A Zornitza Stark changed review comment from: Well established gene-disease association, IUGR is a feature.; to: Well established gene-disease association, IUGR is a feature.

Treatment: subcutaneous injections of copper histidine or copper chloride

ClinGen has assessed as moderate evidence for actionability.

Neonatal treatment with subcutaneous copper-histidine (initiated before 30 days of life) is recommended for asymptomatic males with a diagnosis of MD, but is not recommended for symptomatic boys or after 30 days of life. Treatment should be continued indefinitely. In an open-label clinical trial, 12 patients with MD treated with copper-histidine within 22 days of life had 92% survival after a mean follow-up of 4.6 years compared to 13% in a historical control group of 15 patients treated after a late diagnosis (mean age at diagnosis: 163 ± 113 days, range: 42 to 390). Two of the 12 patients with earlier treatment had normal neurological development. A second open-label trial of 35 presymptomatic patients receiving copper-histidine at less than a month of age reported significant improvement of four major neurodevelopmental (gross motor, fine motor/adaptive, personal/social, and language) domains and a non-significant lower mortality (28.5% vs 50%) at age of 3 years (or age of death) compared to 22 patients treated later and after onset of symptoms.
Fetal anomalies v1.70 ATP7A Zornitza Stark Tag treatable tag was added to gene: ATP7A.
Fetal anomalies v1.70 PDCD6IP Zornitza Stark Phenotypes for gene: PDCD6IP were changed from Primary microcephaly to Microcephaly 29, primary, autosomal recessive, MIM# 620047
Fetal anomalies v1.69 PDCD6IP Zornitza Stark reviewed gene: PDCD6IP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly 29, primary, autosomal recessive, MIM# 620047; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.69 USP9X Krithika Murali Deleted their review
Fetal anomalies v1.69 USP9X Krithika Murali reviewed gene: USP9X: Rating: GREEN; Mode of pathogenicity: None; Publications: 31443933, 26833328; Phenotypes: Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v1.69 NODAL Zornitza Stark Publications for gene: NODAL were set to 9354794; 19064609
Fetal anomalies v1.68 NODAL Zornitza Stark Classified gene: NODAL as Amber List (moderate evidence)
Fetal anomalies v1.68 NODAL Zornitza Stark Gene: nodal has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.67 NODAL Zornitza Stark edited their review of gene: NODAL: Added comment: NODAL is a good biological candidate for heterotaxy disorders, and this is supported by animal models. The gene is depleted for LoF variants in gnomad.

The missense variants reported in PMIDs 9354794 and 19064609 are present at a high population frequency in gnomad, including some in homozygous case: their association with disease is DISPUTED.

A total of at least 7 families reported with severe CHD and high impact variants (stop gain, frameshift and canonical splice site). However, almost invariably these were inherited from unaffected or questionably affected parents (e.g. self reports of heart murmur in childhood), raising questions about whether these variants contribute to disease under a monogenic or polygenic model and/or about penetrance.

Discussed at GenCC on 13/9/2022 and agreed on MODERATE assessment.; Changed rating: AMBER; Changed publications: 9354794, 19064609, 29368431, 19933292, 11311163, 30293987
Fetal anomalies v1.67 ALDH1A2 Zornitza Stark Phenotypes for gene: ALDH1A2 were changed from Multiple congenital anomalies, ALDH1A2-related, MONDO:0019042 to Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025
Fetal anomalies v1.66 ALDH1A2 Zornitza Stark reviewed gene: ALDH1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.66 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from neurodevelopmental disorder, CHKA-related MONDO#0700092 to Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023
Fetal anomalies v1.65 CHKA Zornitza Stark reviewed gene: CHKA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.65 ADAMTS15 Zornitza Stark Marked gene: ADAMTS15 as ready
Fetal anomalies v1.65 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Fetal anomalies v1.65 ADAMTS15 Zornitza Stark Classified gene: ADAMTS15 as Green List (high evidence)
Fetal anomalies v1.65 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Fetal anomalies v1.64 ADAMTS15 Zornitza Stark gene: ADAMTS15 was added
gene: ADAMTS15 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS15 were set to 35962790
Phenotypes for gene: ADAMTS15 were set to Arthrogryposis (MONDO:0008779), ADMATS15-related
Review for gene: ADAMTS15 was set to GREEN
Added comment: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: contractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature
Fetal anomalies v1.63 NPNT Zornitza Stark Marked gene: NPNT as ready
Fetal anomalies v1.63 NPNT Zornitza Stark Gene: npnt has been classified as Green List (High Evidence).
Fetal anomalies v1.63 NPNT Zornitza Stark Phenotypes for gene: NPNT were changed from Renal agenesis, no OMIM # to Renal agenesis, MONDO:0018470, NPNT-related
Fetal anomalies v1.62 NPNT Zornitza Stark Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792
Fetal anomalies v1.61 NPNT Zornitza Stark reviewed gene: NPNT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal agenesis, MONDO:0018470, NPNT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.61 NPNT Chirag Patel Classified gene: NPNT as Green List (high evidence)
Fetal anomalies v1.61 NPNT Chirag Patel Gene: npnt has been classified as Green List (High Evidence).
Fetal anomalies v1.60 NPNT Chirag Patel gene: NPNT was added
gene: NPNT was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NPNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792
Phenotypes for gene: NPNT were set to Renal agenesis, no OMIM #
Review for gene: NPNT was set to GREEN
Added comment: 3 consanguineous families with multiple affecteds with bilateral renal agenesis. Whole-exome sequencing (WES)-based homozygosity mapping identified 2 homozygous truncating variants. Reverse transcription polymerase chain reaction data showing complete nonsense-mediated decay of the NPNT transcript. Loss of nephronectin (NPNT) is known to lead to failure of metanephric kidney development with resulting renal agenesis in murine models.
Sources: Literature
Fetal anomalies v1.59 KIF5B Chirag Patel Classified gene: KIF5B as Green List (high evidence)
Fetal anomalies v1.59 KIF5B Chirag Patel Gene: kif5b has been classified as Green List (High Evidence).
Fetal anomalies v1.58 KIF5B Chirag Patel gene: KIF5B was added
gene: KIF5B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to PMID: 35342932
Phenotypes for gene: KIF5B were set to Kyphomelic dysplasia, no OMIM #
Review for gene: KIF5B was set to GREEN
Added comment: 4 individuals with Kyphomelic dysplasia (severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. WES found de novo heterozygous missense variants in KIF5B encoding kinesin-1 heavy chain. All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. No functional studies of variants.

Previously 2 animal model experiments showed that loss of function of KIF5B can cause kyphomelic dysplasia. First, chondrocyte-specific knockout of Kif5b in mice was shown to produce a disorganized growth plate, leading to bone deformity. Second, double mutants disrupting the two zebrafish kif5b caused abnormal skeletal morphogenesis and the curvature of Meckel's and ceratohyal cartilages.
Sources: Literature
Fetal anomalies v1.57 MDFIC Zornitza Stark Phenotypes for gene: MDFIC were changed from Hydrops fetalis MONDO:0015193 to Lymphatic malformation 12, MIM# 620014
Fetal anomalies v1.56 MDFIC Zornitza Stark reviewed gene: MDFIC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lymphatic malformation 12, MIM# 620014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.56 SETD5 Zornitza Stark Mode of inheritance for gene: SETD5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.55 SETD5 Zornitza Stark reviewed gene: SETD5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, autosomal dominant 23 (MIM # 615761); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.55 ZMYND8 Zornitza Stark Marked gene: ZMYND8 as ready
Fetal anomalies v1.55 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Fetal anomalies v1.55 ZMYND8 Zornitza Stark Classified gene: ZMYND8 as Green List (high evidence)
Fetal anomalies v1.55 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Fetal anomalies v1.54 ZMYND8 Zornitza Stark gene: ZMYND8 was added
gene: ZMYND8 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND8 were set to 35916866; 32530565
Phenotypes for gene: ZMYND8 were set to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures
Review for gene: ZMYND8 was set to GREEN
Added comment: Dias et al (2022 - PMID: 35916866) describe the phenotype of 11 unrelated individuals with monoallelic de novo (or suspected de novo) missense (N=9) or truncating (N=2) ZMYND8 variants. One of these subjects was previously reported by Suzuki et al (2020 - PMID: 32530565).

Features included speech delay/language difficulties (9/11), motor delay (9/11), ID (in 10/11 - profound in 1, moderate in 2), CHD (7/11 - PDA, VSD, ASD, pulmonary stenosis, etc), hearing or vision impairment (7/11). Seizures were reported in few (in text 5/11, table 2/11). Variable non-familial facial features were present in (9/11).

As the authors discuss, ZMYND8 encodes a multidomain protein playing a role in transcription regulation, chromatin remodeling, regulation of super enhancers, DNA damage response/tumor suppression.

The protein is broadly expressed in brain and shows highest expression in early development.

Molecular modeling and/or a yeast two-hybrid system were suggestive of disrupted interaction of ZMYND8 with Drebrin (missense variants in PWWP domain) or GATAD2A (variants in MYND domain).

Neuronal Zmynd8 knockdown in Drosophila resulted in deficits in habituation learning.
Sources: Expert Review
Fetal anomalies v1.53 PRIM1 Zornitza Stark Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Fetal anomalies v1.52 PRIM1 Zornitza Stark Tag deep intronic tag was added to gene: PRIM1.
Tag founder tag was added to gene: PRIM1.
Fetal anomalies v1.52 PRIM1 Zornitza Stark reviewed gene: PRIM1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005; Mode of inheritance: None
Fetal anomalies v1.52 BMP3 Seb Lunke Marked gene: BMP3 as ready
Fetal anomalies v1.52 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.52 BMP3 Seb Lunke Classified gene: BMP3 as Amber List (moderate evidence)
Fetal anomalies v1.52 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.51 BMP3 Seb Lunke gene: BMP3 was added
gene: BMP3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: BMP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP3 were set to 35089417
Phenotypes for gene: BMP3 were set to coloboma, MONDO:0001476; microphthalmia, MONDO:0021129
Added comment: Single missense variant identified segregating with disease following WES screen in a family with coloboma and/or microphthalmia in BMP3. Two additional unrelated patients identified with different missense in BMP3. Pathogenicity however largely on in-silicos, with one of the 3 missense having 29 hets in gnomAD. Additional functional work in bmp3 -/- zebra fish and some supporting evidence but not conclusive.
Sources: Literature
Fetal anomalies v1.50 SPTA1 Zornitza Stark Marked gene: SPTA1 as ready
Fetal anomalies v1.50 SPTA1 Zornitza Stark Gene: spta1 has been classified as Green List (High Evidence).
Fetal anomalies v1.50 SPTA1 Zornitza Stark Classified gene: SPTA1 as Green List (high evidence)
Fetal anomalies v1.50 SPTA1 Zornitza Stark Gene: spta1 has been classified as Green List (High Evidence).
Fetal anomalies v1.49 SPTA1 Zornitza Stark gene: SPTA1 was added
gene: SPTA1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: SPTA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPTA1 were set to 34132406; 35483216; 31333484; 29594000
Phenotypes for gene: SPTA1 were set to Spherocytosis type 3 #270970; Elliptocytosis-2 #130600; pyropoikilocytosis #266140
Review for gene: SPTA1 was set to GREEN
Added comment: Severe presentations with hydrops reported.
Sources: Expert Review
Fetal anomalies v1.48 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy; Cleft lip and palate to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy; Cleft lip and palate
Fetal anomalies v1.47 PPP1R13L Krithika Murali edited their review of gene: PPP1R13L: Changed phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related disorder, Dilated cardiomyopathy, onset in infancy, Cleft lip and palate
Fetal anomalies v1.47 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Fetal anomalies v1.46 UBA2 Zornitza Stark Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Fetal anomalies v1.45 UBA2 Zornitza Stark Publications for gene: UBA2 were set to PMID: 31332306; 31587267
Fetal anomalies v1.44 TTC25 Zornitza Stark Publications for gene: TTC25 were set to 27486780
Fetal anomalies v1.43 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Fetal anomalies v1.43 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Fetal anomalies v1.42 TTC25 Zornitza Stark edited their review of gene: TTC25: Added comment: At least 7 families reported now.; Changed rating: GREEN; Changed publications: 27486780, 31765523, 33715250, 33746037, 34215651
Fetal anomalies v1.42 WNT7B Zornitza Stark Marked gene: WNT7B as ready
Fetal anomalies v1.42 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Fetal anomalies v1.42 WNT7B Zornitza Stark Classified gene: WNT7B as Green List (high evidence)
Fetal anomalies v1.42 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Fetal anomalies v1.41 WNT7B Zornitza Stark gene: WNT7B was added
gene: WNT7B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT7B were set to 35790350
Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related
Review for gene: WNT7B was set to GREEN
Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model.
Sources: Literature
Fetal anomalies v1.40 PAN2 Zornitza Stark Marked gene: PAN2 as ready
Fetal anomalies v1.40 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Fetal anomalies v1.40 PAN2 Zornitza Stark Classified gene: PAN2 as Green List (high evidence)
Fetal anomalies v1.40 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Fetal anomalies v1.39 PAN2 Zornitza Stark reviewed gene: PAN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disease MONDO:0002254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.39 PAN2 Naomi Baker gene: PAN2 was added
gene: PAN2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAN2 were set to PMID:35304602; 29620724
Phenotypes for gene: PAN2 were set to Syndromic disease MONDO:0002254
Added comment: PMID:35304602 reports five individuals from 3 families with biallelic (homozygous) loss-of-function variants. Clinical presentation incudes mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck.

PMID:29620724 reports one individual with biallelic (homozygous) loss-of-function variant who presented with global developmental delay, mild hypotonia, craniosynostosis, severe early-onset scoliosis, imperforate anus, and double urinary collecting system.
Sources: Literature
Fetal anomalies v1.39 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from Growth delay, microcephaly and intellectual disability to Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758
Fetal anomalies v1.38 HIST1H4C Zornitza Stark edited their review of gene: HIST1H4C: Changed phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758
Fetal anomalies v1.38 ETV2 Zornitza Stark Marked gene: ETV2 as ready
Fetal anomalies v1.38 ETV2 Zornitza Stark Gene: etv2 has been classified as Red List (Low Evidence).
Fetal anomalies v1.38 ETV2 Zornitza Stark gene: ETV2 was added
gene: ETV2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: ETV2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETV2 were set to 33359164
Phenotypes for gene: ETV2 were set to multiple fetal anomalies; congenital heart disease MONDO:000545, ETV2-related; vertebral malformations
Review for gene: ETV2 was set to RED
Added comment: 1 family with 4 fetus-es all cHet for a fs (NMD-predicted) and a missense

3/4 vertebral malformations
2/4 Tetralogy of Fallot
1/4 arterial septal defect
1/4 ventricular septal defect, aortic dilatation
1/4 pre-axial polydactyly
Sources: Expert Review
Fetal anomalies v1.37 ADD1 Zornitza Stark Marked gene: ADD1 as ready
Fetal anomalies v1.37 ADD1 Zornitza Stark Gene: add1 has been classified as Green List (High Evidence).
Fetal anomalies v1.37 ADD1 Zornitza Stark Classified gene: ADD1 as Green List (high evidence)
Fetal anomalies v1.37 ADD1 Zornitza Stark Gene: add1 has been classified as Green List (High Evidence).
Fetal anomalies v1.36 ADD1 Zornitza Stark gene: ADD1 was added
gene: ADD1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: ADD1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ADD1 were set to 34906466
Phenotypes for gene: ADD1 were set to Neurodevelopmental disorder MONDO:0700092, ADD1-related
Review for gene: ADD1 was set to GREEN
Added comment: 4 unrelated individuals affected by ID and/or complete or partial agenesis of corpus callosum, and enlarged lateral ventricles. WES found loss-of-function variants - 1 recessive missense variant and 3 de novo variants. The recessive variant is associated with ACC and enlarged lateral ventricles, and the de novo variants were associated with complete or partial agenesis of corpus callosum, mild ID and attention deficit. Human variants impair ADD1 protein expression and/or dimerization with ADD2. Add1 knockout mice recapitulate corpus callosum dysgenesis and ventriculomegaly phenotypes. Three adducin genes (ADD1, ADD2, and ADD3) encode cytoskeleton proteins that are critical for osmotic rigidity and cell shape. ADD1, ADD2, and ADD3 form heterodimers (ADD1/ADD2, ADD1/ADD3), which further form heterotetramers. Adducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown
Sources: Expert Review
Fetal anomalies v1.35 PLCH1 Zornitza Stark Phenotypes for gene: PLCH1 were changed from Holoprosencephaly spectrum; Severe developmental delay; Brain malformations to Holoprosencephaly 14, MIM# 619895
Fetal anomalies v1.34 PLCH1 Zornitza Stark reviewed gene: PLCH1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Holoprosencephaly 14, MIM# 619895; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.34 MYO9A Zornitza Stark Publications for gene: MYO9A were set to 27259756; 29462312; 26752647
Fetal anomalies v1.33 MYO9A Zornitza Stark Classified gene: MYO9A as Amber List (moderate evidence)
Fetal anomalies v1.33 MYO9A Zornitza Stark Gene: myo9a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.32 MYO9A Zornitza Stark changed review comment from: This gene-disease association has been reviewed as part of GenCC discordance resolution: note at least two of the variants reported have homozygotes with gnomad, which would be out of keeping for a severe paediatric disorder.; to: This gene-disease association has been reviewed as part of GenCC discordance resolution: note at least two of the variants reported have homozygotes with gnomad, which would be out of keeping for a severe paediatric disorder.

However, also note reports of fetal akinesia and hydrocephalus, which are pertinent to this panel.
Fetal anomalies v1.32 MYO9A Zornitza Stark edited their review of gene: MYO9A: Changed publications: 31130284, 30237576
Fetal anomalies v1.32 MYO9A Zornitza Stark edited their review of gene: MYO9A: Added comment: This gene-disease association has been reviewed as part of GenCC discordance resolution: note at least two of the variants reported have homozygotes with gnomad, which would be out of keeping for a severe paediatric disorder.; Changed rating: AMBER
Fetal anomalies v1.32 GFRA1 Zornitza Stark Phenotypes for gene: GFRA1 were changed from Renal agenesis to Renal hypodysplasia/aplasia 4, MIM# 619887
Fetal anomalies v1.31 GFRA1 Zornitza Stark reviewed gene: GFRA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal hypodysplasia/aplasia 4, MIM# 619887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.31 USP14 Zornitza Stark Marked gene: USP14 as ready
Fetal anomalies v1.31 USP14 Zornitza Stark Gene: usp14 has been classified as Red List (Low Evidence).
Fetal anomalies v1.31 USP14 Zornitza Stark Phenotypes for gene: USP14 were changed from Distal arthrogryposis, corpus callosum anomalies, and dysmorphic features; no OMIM # to Syndromic disease MONDO:0002254, USP14-related; Distal arthrogryposis, corpus callosum anomalies, and dysmorphic features
Fetal anomalies v1.30 ZNF526 Zornitza Stark Phenotypes for gene: ZNF526 were changed from Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia to Dentici-Novelli neurodevelopmental syndrome, MIM# 619877
Fetal anomalies v1.29 ZNF526 Zornitza Stark reviewed gene: ZNF526: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dentici-Novelli neurodevelopmental syndrome, MIM# 619877; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.29 USP14 Chirag Patel gene: USP14 was added
gene: USP14 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to PMID: 35066879
Phenotypes for gene: USP14 were set to Distal arthrogryposis, corpus callosum anomalies, and dysmorphic features; no OMIM #
Review for gene: USP14 was set to RED
Added comment: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay.
Sources: Literature
Fetal anomalies v1.28 TXNDC15 Zornitza Stark Phenotypes for gene: TXNDC15 were changed from Meckel Gruber syndrome, MONDO:0018921 to Meckel syndrome 14, MIM# 619879
Fetal anomalies v1.27 TXNDC15 Zornitza Stark edited their review of gene: TXNDC15: Changed phenotypes: Meckel syndrome 14, MIM# 619879
Fetal anomalies v1.27 FTO Bryony Thompson Publications for gene: FTO were set to 19559399; 26378117
Fetal anomalies v1.26 FTO Bryony Thompson Classified gene: FTO as Green List (high evidence)
Fetal anomalies v1.26 FTO Bryony Thompson Gene: fto has been classified as Green List (High Evidence).
Fetal anomalies v1.25 FTO Bryony Thompson reviewed gene: FTO: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234441, 19559399, 26378117, 26697951, 26378117, 26740239; Phenotypes: Growth retardation, developmental delay, facial dysmorphism MIM#612938; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.25 ODC1 Lucy Spencer gene: ODC1 was added
gene: ODC1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ODC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ODC1 were set to 30475435; 30239107
Phenotypes for gene: ODC1 were set to Bachmann-Bupp syndrome (MIM#619075)
Review for gene: ODC1 was set to GREEN
Added comment: Polyhydraminos are a common prenatal finding in individuals with ODC1 variants. Malformations of cortical development and intracranial calcification have also been reported.
Sources: Literature
Fetal anomalies v1.25 MAPKAPK5 Zornitza Stark Phenotypes for gene: MAPKAPK5 were changed from Developmental delay, variable brain anomalies, congenital heart defects, dysmorphic to Neurocardiofaciodigital syndrome, MIM# 619869
Fetal anomalies v1.24 MAPKAPK5 Zornitza Stark edited their review of gene: MAPKAPK5: Changed phenotypes: Neurocardiofaciodigital syndrome, MIM# 619869
Fetal anomalies v1.24 COASY Ain Roesley Publications for gene: COASY were set to 30089828
Fetal anomalies v1.23 COASY Ain Roesley Classified gene: COASY as Green List (high evidence)
Fetal anomalies v1.23 COASY Ain Roesley Gene: coasy has been classified as Green List (High Evidence).
Fetal anomalies v1.22 COASY Ain Roesley edited their review of gene: COASY: Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.22 COASY Ain Roesley reviewed gene: COASY: Rating: ; Mode of pathogenicity: None; Publications: 35499143; Phenotypes: Pontocerebellar hypoplasia, type 12, MIM#618266; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v1.22 ATP11A Zornitza Stark Phenotypes for gene: ATP11A were changed from Ventriculomegaly; cerebral atrophy; hypoplasia corpus callosum to Leukodystrophy, hypomyelinating, 24 , MIM# 619851
Fetal anomalies v1.21 ATP11A Zornitza Stark reviewed gene: ATP11A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 24 , MIM# 619851; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.21 PIDD1 Zornitza Stark Phenotypes for gene: PIDD1 were changed from Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum to Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM# 619827; Pachygyria; Lissencephaly; Abnormality of the corpus callosum
Fetal anomalies v1.20 PIDD1 Zornitza Stark edited their review of gene: PIDD1: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM# 619827, Pachygyria, Lissencephaly, Abnormality of the corpus callosum
Fetal anomalies v1.20 CDK10 Ain Roesley Marked gene: CDK10 as ready
Fetal anomalies v1.20 CDK10 Ain Roesley Gene: cdk10 has been classified as Green List (High Evidence).
Fetal anomalies v1.20 CDK10 Ain Roesley Classified gene: CDK10 as Green List (high evidence)
Fetal anomalies v1.20 CDK10 Ain Roesley Gene: cdk10 has been classified as Green List (High Evidence).
Fetal anomalies v1.19 CDK10 Ain Roesley gene: CDK10 was added
gene: CDK10 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CDK10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK10 were set to 28886341; 34974531
Phenotypes for gene: CDK10 were set to Al Kaissi syndrome MIM#617694
Review for gene: CDK10 was set to GREEN
gene: CDK10 was marked as current diagnostic
Added comment: 6 families reported

1x with IUGR, 1x hydrocephalus and 1x with fetal hydrops, hydrocephalus, multicystic, dysplastic kidneys, lung hypoplasia, cardiomyopathy, retrognathia

Small birth weight/sizes reported in all
Sources: Literature
Fetal anomalies v1.18 RSPO2 Zornitza Stark Marked gene: RSPO2 as ready
Fetal anomalies v1.18 RSPO2 Zornitza Stark Gene: rspo2 has been classified as Green List (High Evidence).
Fetal anomalies v1.18 RSPO2 Zornitza Stark Classified gene: RSPO2 as Green List (high evidence)
Fetal anomalies v1.18 RSPO2 Zornitza Stark Gene: rspo2 has been classified as Green List (High Evidence).
Fetal anomalies v1.17 RSPO2 Zornitza Stark gene: RSPO2 was added
gene: RSPO2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: RSPO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RSPO2 were set to 29769720; 32457899
Phenotypes for gene: RSPO2 were set to Tetraamelia syndrome 2, MIM# 618021
Review for gene: RSPO2 was set to GREEN
Added comment: Tetraamelia syndrome-2 (TETAMS2) is characterized by rudimentary appendages or complete absence of the limbs, usually symmetric, as well as bilateral agenesis of the lungs. There are abnormalities of the pulmonary vasculature and dysmorphic features, including bilateral cleft lip/palate, ankyloglossia, mandibular hypoplasia, microretrognathia, and labioscrotal fold aplasia. Four unrelated families and functional data including animal model.
Sources: Expert Review
Fetal anomalies v1.16 MDFIC Zornitza Stark Marked gene: MDFIC as ready
Fetal anomalies v1.16 MDFIC Zornitza Stark Gene: mdfic has been classified as Green List (High Evidence).
Fetal anomalies v1.16 MDFIC Zornitza Stark Classified gene: MDFIC as Green List (high evidence)
Fetal anomalies v1.16 MDFIC Zornitza Stark Gene: mdfic has been classified as Green List (High Evidence).
Fetal anomalies v1.15 MDFIC Belinda Chong gene: MDFIC was added
gene: MDFIC was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MDFIC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDFIC were set to 35235341
Phenotypes for gene: MDFIC were set to Hydrops fetalis MONDO:0015193
Review for gene: MDFIC was set to GREEN
Added comment: Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise.

Seven individuals with CCLA from six independent families. Clinical manifestations of affected fetuses and children included nonimmune hydrops fetalis (NIHF), pleural and pericardial effusions, and lymphedema. Generation of a mouse model of human MDFIC truncation variants revealed that homozygous mutant mice died perinatally exhibiting chylothorax.
Sources: Literature
Fetal anomalies v1.15 TNNI1 Zornitza Stark Marked gene: TNNI1 as ready
Fetal anomalies v1.15 TNNI1 Zornitza Stark Gene: tnni1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.15 TNNI1 Zornitza Stark Classified gene: TNNI1 as Amber List (moderate evidence)
Fetal anomalies v1.15 TNNI1 Zornitza Stark Gene: tnni1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.14 TNNI1 Zornitza Stark Phenotypes for gene: TNNI1 were changed from arthrogryposis; joint contractures to Arthrogryposis MONDO:0008779, TNNI1-related
Fetal anomalies v1.13 TNNI1 Krithika Murali gene: TNNI1 was added
gene: TNNI1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TNNI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNI1 were set to 34934811
Phenotypes for gene: TNNI1 were set to arthrogryposis; joint contractures
Review for gene: TNNI1 was set to AMBER
Added comment: No OMIM gene disease association reported

PMID 34934811 Nishimori et al report 2 individuals from a Japanese family with joint contractures, elevated CK and a novel heterozygous TNNI1 variant.

The proband was born with clasped thumbs (gestational age not stated) requiring surgical correction at 5 months of age. At age 14 was diagnosed with contractures of the neck, trunk, hip and knee with elevated serum CK (1689 IU/L). No muscle weakness noted. Muscle biopsy showed moth-eaten appearance of type I fibres and electron microscopy showed type 1 fibre Z disk streaming.

Trio exome sequencing identified a paternally heterozygous nonsense TNNI1 variant (c.523A>T p.K175*). The proband's father and paternal grandfather (not genotyped) also have a history of joint contractures with elevated CK.

The affected amino acid residue is in the tropomyosin binding site near the C-terminus and is highly conserved. The variant is absent from gnomAD. rt-PCR products of mRNA from the patient's muscle biopsy showed presence of both mutated and normal transcripts.
Sources: Literature
Fetal anomalies v1.13 TBL1XR1 Zornitza Stark Classified gene: TBL1XR1 as Amber List (moderate evidence)
Fetal anomalies v1.13 TBL1XR1 Zornitza Stark Gene: tbl1xr1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.12 NEXN Zornitza Stark Marked gene: NEXN as ready
Fetal anomalies v1.12 NEXN Zornitza Stark Gene: nexn has been classified as Green List (High Evidence).
Fetal anomalies v1.12 NEXN Zornitza Stark Classified gene: NEXN as Green List (high evidence)
Fetal anomalies v1.12 NEXN Zornitza Stark Gene: nexn has been classified as Green List (High Evidence).
Fetal anomalies v1.11 NEXN Krithika Murali gene: NEXN was added
gene: NEXN was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NEXN was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NEXN were set to 33947203; 33949776; 35166435; 32058062
Phenotypes for gene: NEXN were set to Lethal fetal cardiomyopathy; Hydrops fetalis; Cardiomyopathy, dilated 1CC - MIM#613122
Review for gene: NEXN was set to GREEN
Added comment: NEXN encodes cardiac Z-disc protein. Monoallelic variants associated with both paediatric and adult-onset dilated cardiomyopathy. 3 unrelated families reported with biallelic variants associated with lethal fetal cardiomyopathy.

PMID 35166435 - 3 consecutive affected pregnancies with intrauterine fetal death, dilated cardiomyopathy +/- fetal hydrops/IUGR. Autopsy findings of DCM, endomyocardial fibroelastosis. Non-consanguineous Swedish family. Homozygous variant identified - (NM_144573:c.1302del;p.(Ile435Serfs*3)). Heterozygous carriers enriched in Swedish population.


PMID: 33949776 - Report a 11 year old with mild DCM on cardiac MRI with a heterozygous paternally inherited variant (1949_1951del), father also had mild DCM. Also report a 2nd patient who presented with fetal Hydrops at 33 weeks gestation requiring emergency C-section. Homozygous c.1174C > T,p.(R392*) variants identified. Microscopic investigation showed endomyocardial fibroelastosis.

PMID: 32058062 - male fetus, compound het, DCM, MTOP; previous pregnancy with the same history.
Sources: Literature
Fetal anomalies v1.11 NDUFS4 Krithika Murali Deleted their review
Fetal anomalies v1.11 NDUFS4 Krithika Murali reviewed gene: NDUFS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11181577, 11165261, 16478720, 10944442, 24295889, 22326555; Phenotypes: Mitochondrial complex I deficiency, nuclear type 1 - MIM#252010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.11 ABCC6 Zornitza Stark Tag SV/CNV tag was added to gene: ABCC6.
Fetal anomalies v1.11 SCAF4 Zornitza Stark Marked gene: SCAF4 as ready
Fetal anomalies v1.11 SCAF4 Zornitza Stark Gene: scaf4 has been classified as Green List (High Evidence).
Fetal anomalies v1.11 SCAF4 Zornitza Stark Phenotypes for gene: SCAF4 were changed from Neurodevelopmental disorder, SCAF4-related MONDO#0700092 to Neurodevelopmental disorder MONDO#0700092, SCAF4-related
Fetal anomalies v1.10 SCAF4 Zornitza Stark Classified gene: SCAF4 as Green List (high evidence)
Fetal anomalies v1.10 SCAF4 Zornitza Stark Gene: scaf4 has been classified as Green List (High Evidence).
Fetal anomalies v1.9 SCAF4 Lucy Spencer gene: SCAF4 was added
gene: SCAF4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SCAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCAF4 were set to PMID: 32730804
Phenotypes for gene: SCAF4 were set to Neurodevelopmental disorder, SCAF4-related MONDO#0700092
Review for gene: SCAF4 was set to GREEN
Added comment: PMID: 32730804- 11 individuals with SCAF4 variants, 9 are de novo. Present with mild to severe ID/Dev delay, most have seizures, 4 have cardiac defects, 4 have renal anomalies, 3 have urogenital anomalies, 6 have skeletal anomalies, 2 have GI anomalies.
Sources: Literature
Fetal anomalies v1.9 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from Persistent Hypotonia, Encephalopathy, Growth Retardation, and Severe Intellectual Disability to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Fetal anomalies v1.8 UNC80 Zornitza Stark Classified gene: UNC80 as Amber List (moderate evidence)
Fetal anomalies v1.8 UNC80 Zornitza Stark Gene: unc80 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.7 UNC80 Ain Roesley reviewed gene: UNC80: Rating: AMBER; Mode of pathogenicity: None; Publications: 26545877; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.7 NAA15 Zornitza Stark Publications for gene: NAA15 were set to 31127942
Fetal anomalies v1.6 NAA15 Zornitza Stark Classified gene: NAA15 as Green List (high evidence)
Fetal anomalies v1.6 NAA15 Zornitza Stark Gene: naa15 has been classified as Green List (High Evidence).
Fetal anomalies v1.5 NAA15 Zornitza Stark edited their review of gene: NAA15: Changed publications: 33557580
Fetal anomalies v1.5 NAA15 Zornitza Stark changed review comment from: Typically presents post-natally.; to: Congenital heart defects in 4 of 19 individuals reported with the neurodevelopmental syndrome.

PMID 33557580 - WES of 4511 patients with CHD identified 4 subjects with a rare LoF variant (allele frequency <0.00005) in the NAA15 gene, resulting in NAA15 haploinsufficiency. Parental analyses indicated that 3 of these LoF variants (p.Ser761*, p.Lys336Lys fs*6, and p.Arg470*) arose de novo in the probands. The inheritance of the p.Ala718fs variant is uncertain, as parental samples were unavailable. The authors also reference their previous studies identifying 2 other patients with CHD and LoF NAA15 heterozygous variants.
Fetal anomalies v1.5 NAA15 Zornitza Stark edited their review of gene: NAA15: Changed rating: GREEN
Fetal anomalies v1.5 NAA15 Zornitza Stark edited their review of gene: NAA15: Changed rating: AMBER
Fetal anomalies v1.5 EFNB1 Bryony Thompson Added comment: Comment on mode of inheritance: X-LINKED: heterozygous females demonstrate more severe disease than hemizygous males
Fetal anomalies v1.5 EFNB1 Bryony Thompson Mode of inheritance for gene: EFNB1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to Other
Fetal anomalies v1.4 NARS Krithika Murali gene: NARS was added
gene: NARS was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NARS were set to 32738225; 32788587
Phenotypes for gene: NARS were set to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive - MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, autosomal dominant - MIM#619092
Review for gene: NARS was set to GREEN
Added comment: HGNC approved gene symbol - NARS1

Both mono allelic and biallelic variants associated with a progressive neurological disorder with onset in infancy. Antenatal features reported.

PMID 32738225 - reports roband with de novo heterozygous variant - IUGR and oligohydramnios noted prenatally. At birth noted to have low weight and OFC for gestational age. Proband with homozygous variant diagnosed with microcephaly, seizures and FTT in the neonatal period. Proband with compound het variants born with a low weight (-2.38 SD) and height (-3.76 SD) for gestational age. Review of supplementary material table - microcephaly at birth reported in 17 unrelated families.
Sources: Literature
Fetal anomalies v1.4 IRX5 Zornitza Stark Classified gene: IRX5 as Green List (high evidence)
Fetal anomalies v1.4 IRX5 Zornitza Stark Gene: irx5 has been classified as Green List (High Evidence).
Fetal anomalies v1.3 IRX5 Zornitza Stark edited their review of gene: IRX5: Added comment: Third family with Hamamy syndrome and homozygous missense variant reported, p.Arg168His. Two cousins, >4 meioses, good segregation data.; Changed rating: GREEN; Changed publications: 22581230, 27453922, 34899143
Fetal anomalies v1.3 ZNF335 Zornitza Stark Marked gene: ZNF335 as ready
Fetal anomalies v1.3 ZNF335 Zornitza Stark Gene: znf335 has been classified as Green List (High Evidence).
Fetal anomalies v1.3 ZNF335 Zornitza Stark Classified gene: ZNF335 as Green List (high evidence)
Fetal anomalies v1.3 ZNF335 Zornitza Stark Gene: znf335 has been classified as Green List (High Evidence).
Fetal anomalies v1.2 ZNF335 Zornitza Stark gene: ZNF335 was added
gene: ZNF335 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: ZNF335 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF335 were set to 23178126; 27540107; 29652087; 34982360
Phenotypes for gene: ZNF335 were set to Microcephaly 10, primary, autosomal recessive (MIM#615095)
Review for gene: ZNF335 was set to GREEN
Added comment: Microcephaly is generally primary, including reports of -9SD at birth.
Sources: Expert Review
Fetal anomalies v1.1 MAN2C1 Zornitza Stark Phenotypes for gene: MAN2C1 were changed from MAN2C1-related neurodevelopmental disorder MONDO:0700092 to Congenital disorder of deglycosylation 2, MIM# 619775
Fetal anomalies v1.0 MAN2C1 Zornitza Stark reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of deglycosylation 2, MIM# 619775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.0 Zornitza Stark promoted panel to version 1.0
Fetal anomalies v0.4732 OXR1 Zornitza Stark Marked gene: OXR1 as ready
Fetal anomalies v0.4732 OXR1 Zornitza Stark Gene: oxr1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4732 OXR1 Zornitza Stark Classified gene: OXR1 as Amber List (moderate evidence)
Fetal anomalies v0.4732 OXR1 Zornitza Stark Gene: oxr1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4731 OXR1 Zornitza Stark reviewed gene: OXR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar hypoplasia/atrophy, epilepsy, and global developmental delay - MIM#213000; Mode of inheritance: None
Fetal anomalies v0.4731 MED27 Zornitza Stark Marked gene: MED27 as ready
Fetal anomalies v0.4731 MED27 Zornitza Stark Gene: med27 has been classified as Green List (High Evidence).
Fetal anomalies v0.4731 MED27 Zornitza Stark Classified gene: MED27 as Green List (high evidence)
Fetal anomalies v0.4731 MED27 Zornitza Stark Gene: med27 has been classified as Green List (High Evidence).
Fetal anomalies v0.4730 EXOSC9 Zornitza Stark Marked gene: EXOSC9 as ready
Fetal anomalies v0.4730 EXOSC9 Zornitza Stark Gene: exosc9 has been classified as Green List (High Evidence).
Fetal anomalies v0.4730 EXOSC9 Zornitza Stark Classified gene: EXOSC9 as Green List (high evidence)
Fetal anomalies v0.4730 EXOSC9 Zornitza Stark Gene: exosc9 has been classified as Green List (High Evidence).
Fetal anomalies v0.4729 OXR1 Krithika Murali gene: OXR1 was added
gene: OXR1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: OXR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXR1 were set to PMID: 31785787
Phenotypes for gene: OXR1 were set to Cerebellar hypoplasia/atrophy, epilepsy, and global developmental delay - MIM#213000
Review for gene: OXR1 was set to GREEN
Added comment: Early-onset condition associated with cerebellar atrophy and severe global developmental delay. Limited antenatal information provided but affected individuals were much older at the time of formal diagnosis PMID: 31785787, antenatal detection may be possible.

---
5 individuals from 3 unrelated families reported with bi-allelic variants in this gene. Presentation was in early childhood with hypotonia, global developmental delay, delayed walking at about age 3 years, and severely impaired intellectual development with profound speech delay or even absent language. All also developed epilepsy between 7 and 10 years of age, but the seizures were controlled by medication in most. Subtle nonspecific dysmorphic features included poor overall growth, large forehead, tall face, mild hypertelorism, joint hyperlaxity, and long fingers and toes. Brain imaging in all 5 individuals showed cerebellar atrophy and dysplasia. Additional cerebellar features, such as tremor, ataxia, and nystagmus, were not noted in these individuals.
Sources: Literature
Fetal anomalies v0.4729 MED27 Krithika Murali gene: MED27 was added
gene: MED27 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED27 were set to 33443317
Phenotypes for gene: MED27 were set to Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia - MIM#619286
Review for gene: MED27 was set to GREEN
Added comment: Severe neurodevelopmental disorder with onset in infancy associated with multiple, significant brain anomalies which may be detectable antenatally (although antenatal phenotype not reported in published cases)
Sources: Literature
Fetal anomalies v0.4729 EXOSC9 Krithika Murali gene: EXOSC9 was added
gene: EXOSC9 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EXOSC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC9 were set to 33040083; 30690203; 29727687
Phenotypes for gene: EXOSC9 were set to Pontocerebellar hypoplasia, type 1D - MIM#618065
Review for gene: EXOSC9 was set to GREEN
Added comment: Multiple antenatal features reported including IUGR, reduced fetal movements, oligohydramnios, congenital fractures and contractures.
Sources: Literature
Fetal anomalies v0.4729 EXOSC8 Zornitza Stark Marked gene: EXOSC8 as ready
Fetal anomalies v0.4729 EXOSC8 Zornitza Stark Gene: exosc8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4729 EXOSC8 Zornitza Stark Classified gene: EXOSC8 as Green List (high evidence)
Fetal anomalies v0.4729 EXOSC8 Zornitza Stark Gene: exosc8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4728 EXOSC5 Zornitza Stark Marked gene: EXOSC5 as ready
Fetal anomalies v0.4728 EXOSC5 Zornitza Stark Gene: exosc5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4728 EXOSC5 Zornitza Stark Classified gene: EXOSC5 as Green List (high evidence)
Fetal anomalies v0.4728 EXOSC5 Zornitza Stark Gene: exosc5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4727 CWF19L1 Zornitza Stark Marked gene: CWF19L1 as ready
Fetal anomalies v0.4727 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4727 CWF19L1 Zornitza Stark Classified gene: CWF19L1 as Green List (high evidence)
Fetal anomalies v0.4727 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4726 RBP4 Zornitza Stark Marked gene: RBP4 as ready
Fetal anomalies v0.4726 RBP4 Zornitza Stark Gene: rbp4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4726 RBP4 Zornitza Stark Classified gene: RBP4 as Green List (high evidence)
Fetal anomalies v0.4726 RBP4 Zornitza Stark Gene: rbp4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4725 RBP4 Zornitza Stark gene: RBP4 was added
gene: RBP4 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: RBP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBP4 were set to 25910211; 29178648
Phenotypes for gene: RBP4 were set to Microphthalmia, isolated, with coloboma 10 MIM#616428
Review for gene: RBP4 was set to GREEN
Added comment: At least 3 unrelated microphthalmia, anophthalmia and coloboma families and supporting functional assays. Study established an uncharacterized mode of maternal inheritance, distinct from imprinting and oocyte-derived mRNA.
Sources: Expert Review
Fetal anomalies v0.4724 PRR12 Zornitza Stark Marked gene: PRR12 as ready
Fetal anomalies v0.4724 PRR12 Zornitza Stark Gene: prr12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4724 PRR12 Zornitza Stark Classified gene: PRR12 as Green List (high evidence)
Fetal anomalies v0.4724 PRR12 Zornitza Stark Gene: prr12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4723 PRR12 Zornitza Stark gene: PRR12 was added
gene: PRR12 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: PRR12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRR12 were set to 33314030; 29556724
Phenotypes for gene: PRR12 were set to Neuroocular syndrome, MIM#619539; Complex microphthalmia
Review for gene: PRR12 was set to GREEN
Added comment: PMID 33314030: Four unrelated families reported with unilateral or bilateral microphthalmia +/- Peters anomaly. In addition, 3 unrelated families reported with more complex phenotype including ID in PMID 29556724.
Sources: Expert Review
Fetal anomalies v0.4722 EXOSC8 Krithika Murali changed review comment from: Severe autosomal recessive neurodegenerative disorder. PMID 24989451 report polyhydramnios, vermis hypoplasia, mega cisterna magna and corpus callosum anomalies in affectd individuals
Sources: Literature; to: Severe autosomal recessive neurodegenerative disorder. PMID 24989451 (more info in supplementary material) report polyhydramnios, vermis hypoplasia, mega cisterna magna and corpus callosum anomalies in affectd individuals
Sources: Literature
Fetal anomalies v0.4722 EXOSC8 Krithika Murali gene: EXOSC8 was added
gene: EXOSC8 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EXOSC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC8 were set to 34210538; 24989451
Phenotypes for gene: EXOSC8 were set to Pontocerebellar hypoplasia, type 1C - MIM#616081
Review for gene: EXOSC8 was set to GREEN
Added comment: Severe autosomal recessive neurodegenerative disorder. PMID 24989451 report polyhydramnios, vermis hypoplasia, mega cisterna magna and corpus callosum anomalies in affectd individuals
Sources: Literature
Fetal anomalies v0.4722 MAB21L1 Zornitza Stark Marked gene: MAB21L1 as ready
Fetal anomalies v0.4722 MAB21L1 Zornitza Stark Gene: mab21l1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4722 MAB21L1 Zornitza Stark Classified gene: MAB21L1 as Green List (high evidence)
Fetal anomalies v0.4722 MAB21L1 Zornitza Stark Gene: mab21l1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4721 MAB21L1 Zornitza Stark gene: MAB21L1 was added
gene: MAB21L1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: MAB21L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAB21L1 were set to 30487245
Phenotypes for gene: MAB21L1 were set to Cerebellar, ocular, craniofacial, and genital syndrome OMIM#618479
Review for gene: MAB21L1 was set to GREEN
Added comment: Pontocerebellar hypoplasia, Dandy-Walker malformation, microcephaly reported.
Sources: Expert Review
Fetal anomalies v0.4720 FBXW11 Zornitza Stark Marked gene: FBXW11 as ready
Fetal anomalies v0.4720 FBXW11 Zornitza Stark Gene: fbxw11 has been classified as Green List (High Evidence).
Fetal anomalies v0.4720 FBXW11 Zornitza Stark Classified gene: FBXW11 as Green List (high evidence)
Fetal anomalies v0.4720 FBXW11 Zornitza Stark Gene: fbxw11 has been classified as Green List (High Evidence).
Fetal anomalies v0.4719 FBXW11 Zornitza Stark changed review comment from: 7 unrelated individuals; structural brain, eye and limb anomalies.
Sources: Expert Review; to: 7 unrelated individuals; structural brain, craniofacial, eye and limb anomalies.
Sources: Expert Review
Fetal anomalies v0.4719 FBXW11 Zornitza Stark gene: FBXW11 was added
gene: FBXW11 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: FBXW11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FBXW11 were set to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914
Review for gene: FBXW11 was set to GREEN
Added comment: 7 unrelated individuals; structural brain, eye and limb anomalies.
Sources: Expert Review
Fetal anomalies v0.4718 EXOSC5 Krithika Murali gene: EXOSC5 was added
gene: EXOSC5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EXOSC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC5 were set to 32504085; 29302074
Phenotypes for gene: EXOSC5 were set to Cerebellar ataxia, brain abnormalities, and cardiac conduction defects - MIM#619576
Review for gene: EXOSC5 was set to GREEN
Added comment: Associated with congenital anomalies
Sources: Literature
Fetal anomalies v0.4718 CAPN15 Zornitza Stark Marked gene: CAPN15 as ready
Fetal anomalies v0.4718 CAPN15 Zornitza Stark Gene: capn15 has been classified as Green List (High Evidence).
Fetal anomalies v0.4718 CAPN15 Zornitza Stark Classified gene: CAPN15 as Green List (high evidence)
Fetal anomalies v0.4718 CAPN15 Zornitza Stark Gene: capn15 has been classified as Green List (High Evidence).
Fetal anomalies v0.4717 CAPN15 Zornitza Stark gene: CAPN15 was added
gene: CAPN15 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: CAPN15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPN15 were set to 32885237
Phenotypes for gene: CAPN15 were set to Oculogastrointestinal neurodevelopmental syndrome, MIM# 619318; microphthalmia HP:0000568; coloboma HP:0000589
Review for gene: CAPN15 was set to GREEN
Added comment: PMID: 32885237 - Zha et al 2020 - report 5 individuals with microphthalmia and/or coloboma from 4 independent families who, through WES, were identified as carrying homozygous or compound heterozygous missense variants in CAPN15 that are predicted to be damanging. the variants segregated with the disease in all 4 families, with parents being unaffected heterozygous carriers. Several individuals had additional phenotypes including growth deficits (2 families), developmental delay (2 families) and hearing loss (2 families). Capn15 knockout mice showed similar severe developmental eye defects, including anophthalmia, microphthalmia and cataract, and diminished growth.
Sources: Expert Review
Fetal anomalies v0.4716 C16orf62 Zornitza Stark Marked gene: C16orf62 as ready
Fetal anomalies v0.4716 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4716 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Fetal anomalies v0.4716 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4715 C16orf62 Zornitza Stark changed review comment from: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).

Microphthalmia and multiple other anomalies.
Sources: Expert Review; to: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impaired autophagy and VPS35L knockout mouse resulted in early embryonic lethality (PMID 25434475;31712251).

Microphthalmia and multiple other anomalies.
Sources: Expert Review
Fetal anomalies v0.4715 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475; 31712251
Phenotypes for gene: C16orf62 were set to Ritscher-Schinzel syndrome-3 (RTSC3), MIM#619135
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).

Microphthalmia and multiple other anomalies.
Sources: Expert Review
Fetal anomalies v0.4714 CWF19L1 Krithika Murali gene: CWF19L1 was added
gene: CWF19L1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CWF19L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CWF19L1 were set to 27016154
Phenotypes for gene: CWF19L1 were set to Spinocerebellar ataxia, autosomal recessive 17 - MIM#616127
Review for gene: CWF19L1 was set to GREEN
Added comment: Fetal phenotype also described by 27016154 - MTOP at 22 weeks of gestation of an affected fetus due to small cerebellum and agenesis of corpus callosum. Postmortem examination showed unilateral hexadactyly and vertebral malformations.
Sources: Literature
Fetal anomalies v0.4714 TMEM218 Zornitza Stark Marked gene: TMEM218 as ready
Fetal anomalies v0.4714 TMEM218 Zornitza Stark Gene: tmem218 has been classified as Green List (High Evidence).
Fetal anomalies v0.4714 TMEM218 Zornitza Stark Classified gene: TMEM218 as Green List (high evidence)
Fetal anomalies v0.4714 TMEM218 Zornitza Stark Gene: tmem218 has been classified as Green List (High Evidence).
Fetal anomalies v0.4713 NID1 Zornitza Stark Marked gene: NID1 as ready
Fetal anomalies v0.4713 NID1 Zornitza Stark Gene: nid1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4713 NID1 Zornitza Stark Classified gene: NID1 as Green List (high evidence)
Fetal anomalies v0.4713 NID1 Zornitza Stark Gene: nid1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4712 MTX2 Zornitza Stark Marked gene: MTX2 as ready
Fetal anomalies v0.4712 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4712 MTX2 Zornitza Stark Classified gene: MTX2 as Green List (high evidence)
Fetal anomalies v0.4712 MTX2 Zornitza Stark Gene: mtx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4711 KIAA0556 Zornitza Stark Marked gene: KIAA0556 as ready
Fetal anomalies v0.4711 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Green List (High Evidence).
Fetal anomalies v0.4711 KIAA0556 Zornitza Stark Classified gene: KIAA0556 as Green List (high evidence)
Fetal anomalies v0.4711 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Green List (High Evidence).
Fetal anomalies v0.4710 KIAA0556 Zornitza Stark Tag new gene name tag was added to gene: KIAA0556.
Fetal anomalies v0.4710 BRF1 Zornitza Stark Marked gene: BRF1 as ready
Fetal anomalies v0.4710 BRF1 Zornitza Stark Gene: brf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4710 BRF1 Zornitza Stark Classified gene: BRF1 as Green List (high evidence)
Fetal anomalies v0.4710 BRF1 Zornitza Stark Gene: brf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4709 IFT74 Zornitza Stark Marked gene: IFT74 as ready
Fetal anomalies v0.4709 IFT74 Zornitza Stark Gene: ift74 has been classified as Green List (High Evidence).
Fetal anomalies v0.4709 IFT74 Zornitza Stark Phenotypes for gene: IFT74 were changed from ?Bardet-Biedl syndrome 22 - MIM#617119; Joubert syndrome 40 - MIM#619582 to Bardet-Biedl syndrome 22 - MIM#617119; Joubert syndrome 40 - MIM#619582
Fetal anomalies v0.4708 IFT74 Zornitza Stark Classified gene: IFT74 as Green List (high evidence)
Fetal anomalies v0.4708 IFT74 Zornitza Stark Gene: ift74 has been classified as Green List (High Evidence).
Fetal anomalies v0.4707 BRF1 Krithika Murali gene: BRF1 was added
gene: BRF1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: BRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRF1 were set to 25561519; 25561519; 27748960
Phenotypes for gene: BRF1 were set to Cerebellofaciodental syndrome - MIM#616202
Review for gene: BRF1 was set to GREEN
Added comment: Cerebellofaciodental syndrome is an autosomal recessive neurodevelopmental disorder characterized by delayed development, intellectual disability, abnormal facial and dental findings, and cerebellar hypoplasia.

At least 5 unrelated families and a zebrafish model.
Sources: Literature
Fetal anomalies v0.4707 FAM149B1 Zornitza Stark Marked gene: FAM149B1 as ready
Fetal anomalies v0.4707 FAM149B1 Zornitza Stark Gene: fam149b1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4707 FAM149B1 Zornitza Stark Classified gene: FAM149B1 as Green List (high evidence)
Fetal anomalies v0.4707 FAM149B1 Zornitza Stark Gene: fam149b1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4706 CCDC28B Zornitza Stark Marked gene: CCDC28B as ready
Fetal anomalies v0.4706 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4706 CCDC28B Zornitza Stark Phenotypes for gene: CCDC28B were changed from Joubert syndrome to Joubert syndrome, MONDO:0018772
Fetal anomalies v0.4705 CCDC28B Zornitza Stark Classified gene: CCDC28B as Amber List (moderate evidence)
Fetal anomalies v0.4705 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4704 ARL3 Zornitza Stark Marked gene: ARL3 as ready
Fetal anomalies v0.4704 ARL3 Zornitza Stark Gene: arl3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4704 ARL3 Zornitza Stark Classified gene: ARL3 as Green List (high evidence)
Fetal anomalies v0.4704 ARL3 Zornitza Stark Gene: arl3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4703 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Fetal anomalies v0.4702 MTX2 Krithika Murali gene: MTX2 was added
gene: MTX2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia progeroid syndrome - MIM#619127
Review for gene: MTX2 was set to GREEN
Added comment: Biallelic variants associated with severe progeroid form of MAD
Sources: Literature
Fetal anomalies v0.4702 TMEM218 Krithika Murali gene: TMEM218 was added
gene: TMEM218 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TMEM218 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM218 were set to 33791682; 25161209
Phenotypes for gene: TMEM218 were set to Joubert syndrome 39 - MIM#619562
Review for gene: TMEM218 was set to GREEN
Added comment: Associated with Jouberty syndrome. Occipital encephalocele reported in 5 fetuses.
Sources: Literature
Fetal anomalies v0.4702 NID1 Krithika Murali gene: NID1 was added
gene: NID1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NID1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NID1 were set to 23674478; 25558065; 12480912; 30773799
Phenotypes for gene: NID1 were set to Dandy-Walker malformation and occipital cephalocele; Hydrocephalus with or without seizures
Review for gene: NID1 was set to GREEN
Added comment: No OMIM gene disease association. Monoallelic variants associated with brain anomalies including hydrocephalus, Dandy Walker malformation and occipital cephalocele.
-
Sources: Literature
Fetal anomalies v0.4702 KIAA0556 Krithika Murali gene: KIAA0556 was added
gene: KIAA0556 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIAA0556 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0556 were set to 26714646; 27245168
Phenotypes for gene: KIAA0556 were set to Joubert syndrome 26 - MIM#616784
Review for gene: KIAA0556 was set to GREEN
Added comment: Associated with Joubert syndrome.

5 individuals from two families reported, supportive mouse model.

New HGNC approved name is KATNIP.
Sources: Literature
Fetal anomalies v0.4702 IFT74 Krithika Murali gene: IFT74 was added
gene: IFT74 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to 33531668; 27486776; 32144365
Phenotypes for gene: IFT74 were set to ?Bardet-Biedl syndrome 22 - MIM#617119; Joubert syndrome 40 - MIM#619582
Review for gene: IFT74 was set to GREEN
Added comment: Biallelic variants associated with both Joubert and Bardet-Biedl syndrome phenotype - multiple congenital anomalies reported.
Sources: Literature
Fetal anomalies v0.4702 FAM149B1 Krithika Murali gene: FAM149B1 was added
gene: FAM149B1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FAM149B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM149B1 were set to 30905400
Phenotypes for gene: FAM149B1 were set to Joubert syndrome 36 - MIM#618763
Review for gene: FAM149B1 was set to GREEN
Added comment: Biallelic variants associated with Joubert syndrome in 4 unrelated families. Reported characteristics in published cases includes macrocephaly, mesoaxial polydactyly and cleft lip
Sources: Literature
Fetal anomalies v0.4702 CCDC28B Krithika Murali gene: CCDC28B was added
gene: CCDC28B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CCDC28B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC28B were set to 32139166
Phenotypes for gene: CCDC28B were set to Joubert syndrome
Review for gene: CCDC28B was set to AMBER
Added comment: No new publications since last PanelApp review May 2020

---

PMID: 32139166 - Single family with Joubert syndrome. Patient was homozygous for a missense, with polydactyly, severe ID, and the molar tooth sign observed in MRI. Sibling fetus MRI showed vermis hypoplasia, and was also homozygous for the variant. Parents confirmed unaffected carriers. Knockdown of CCDC28B in human TERT retinal pigment epithelial cells reduced both the number and length of cilia 430C-T variant is postulated to be a modifier of BBS.
Sources: Literature
Fetal anomalies v0.4702 ARL3 Krithika Murali gene: ARL3 was added
gene: ARL3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ARL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL3 were set to 30269812; 16565502
Phenotypes for gene: ARL3 were set to Joubert syndrome 35- MIM#618161
Review for gene: ARL3 was set to GREEN
Added comment: Associated with Joubert syndrome with antenatally detectable features including renal and brain anomalies
Sources: Literature
Fetal anomalies v0.4702 MORC2 Zornitza Stark Marked gene: MORC2 as ready
Fetal anomalies v0.4702 MORC2 Zornitza Stark Gene: morc2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4702 MORC2 Zornitza Stark Classified gene: MORC2 as Red List (low evidence)
Fetal anomalies v0.4702 MORC2 Zornitza Stark Gene: morc2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4701 MINPP1 Zornitza Stark Marked gene: MINPP1 as ready
Fetal anomalies v0.4701 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4701 MINPP1 Zornitza Stark Classified gene: MINPP1 as Green List (high evidence)
Fetal anomalies v0.4701 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4700 MORC2 Krithika Murali gene: MORC2 was added
gene: MORC2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MORC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MORC2 were set to 32693025
Phenotypes for gene: MORC2 were set to Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy - MIM#619090
Review for gene: MORC2 was set to RED
Added comment: No new publications since last PanelApp review Dec 2020. No antenatal features reported.

---

MORC2 variants have commonly been associated with CMT, presenting axonal neuropathy with progressive weakness, muscle cramps and sensory impairment. However, Sacoto et al (2020) (PMID: 32693025) present a cohort of 20 individuals (19 kindreds) with a neurodevelopmental disorder characterised by DD, ID (18/20 - mild to severe), short stature (18/20), microcephaly (15/20) and variable craniofacial dysmorphisms. Hearing loss was observed in 11/19 subjects, primarily SNHL.
Sources: Literature
Fetal anomalies v0.4700 NCAPD2 Zornitza Stark Marked gene: NCAPD2 as ready
Fetal anomalies v0.4700 NCAPD2 Zornitza Stark Gene: ncapd2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4700 NCAPD2 Zornitza Stark Classified gene: NCAPD2 as Green List (high evidence)
Fetal anomalies v0.4700 NCAPD2 Zornitza Stark Gene: ncapd2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4699 MINPP1 Krithika Murali gene: MINPP1 was added
gene: MINPP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MINPP1 were set to 33257696; 33168985
Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia, type 16 - MIM#619527
Review for gene: MINPP1 was set to GREEN
Added comment: Biallelic LoF variants associated with pontocerebellar hypoplasia. Early-onset progressive microcephaly is a phenotypic feature with one affected individual reported to have prenatal evidence of microcephaly associated with increased thalami echogenicity (PMID 33257696)
Sources: Literature
Fetal anomalies v0.4699 NCAPD2 Zornitza Stark gene: NCAPD2 was added
gene: NCAPD2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: NCAPD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NCAPD2 were set to 31056748; 27737959; 28097321
Phenotypes for gene: NCAPD2 were set to Microcephaly 21, primary, autosomal recessive; OMIM #617983
Review for gene: NCAPD2 was set to GREEN
Added comment: Three families reported: 1 family with 2 sibs with microcephaly and ID, and homozygous NCAPD2 mutation, which segregated with disease. No functional evidence. 1 family with 1 affected and homozygous NCAPD2 mutation, which segregated with disease. Patient fibroblasts showed impaired chromosome segregation and abnormal recovery from mitotic condensation compared to controls. 1 family with 2 sibs with microcephaly, growth retardation, and ID, and homozygous NCAPD2 mutation, which segregated with disease. Functional studies of the variants and studies of patient cells were not performed.

IUGR reported.
Sources: Expert Review
Fetal anomalies v0.4698 NSRP1 Zornitza Stark Marked gene: NSRP1 as ready
Fetal anomalies v0.4698 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4698 NSRP1 Zornitza Stark Classified gene: NSRP1 as Green List (high evidence)
Fetal anomalies v0.4698 NSRP1 Zornitza Stark Gene: nsrp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4697 NSRP1 Zornitza Stark gene: NSRP1 was added
gene: NSRP1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSRP1 were set to 34385670
Phenotypes for gene: NSRP1 were set to Neurodevelopmental disorder, MONDO:0700092, NSRP1-related; Epilepsy; Cerebral palsy; microcephaly; Intellectual disability
Review for gene: NSRP1 was set to GREEN
Added comment: Novel gene regulating splicing. Biallelic LoF pathogenic variants reported in 6 individuals from 3 unrelated families associated with a phenotype characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.

Structural brain abnormalities.
Sources: Expert Review
Fetal anomalies v0.4696 NUF2 Zornitza Stark Marked gene: NUF2 as ready
Fetal anomalies v0.4696 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4696 NUF2 Zornitza Stark gene: NUF2 was added
gene: NUF2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: NUF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NUF2 were set to 33721060
Phenotypes for gene: NUF2 were set to Syndromic disease, MONDO:0002254; microcephaly; short stature; bilateral vocal cord paralysis; micrognathia; atrial septal defect
Review for gene: NUF2 was set to RED
Added comment: PMID: 33721060 - de novo missense variant identified in one male patient with microcephaly and short stature, with additional features, such as bilateral vocal cord paralysis, micrognathia and atrial septal defect.
Sources: Expert Review
Fetal anomalies v0.4695 NUP188 Zornitza Stark Marked gene: NUP188 as ready
Fetal anomalies v0.4695 NUP188 Zornitza Stark Gene: nup188 has been classified as Green List (High Evidence).
Fetal anomalies v0.4695 NUP188 Zornitza Stark Classified gene: NUP188 as Green List (high evidence)
Fetal anomalies v0.4695 NUP188 Zornitza Stark Gene: nup188 has been classified as Green List (High Evidence).
Fetal anomalies v0.4694 NUP188 Zornitza Stark gene: NUP188 was added
gene: NUP188 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: NUP188 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP188 were set to 32021605; 28726809; 32275884
Phenotypes for gene: NUP188 were set to Sandestig-Stefanova syndrome, 618804; microcephaly; ID; cataract; structural brain abnormalities
Review for gene: NUP188 was set to GREEN
Added comment: 8 unrelated individuals reported.
Sources: Expert Review
Fetal anomalies v0.4693 NUP85 Zornitza Stark Marked gene: NUP85 as ready
Fetal anomalies v0.4693 NUP85 Zornitza Stark Gene: nup85 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4693 NUP85 Zornitza Stark Classified gene: NUP85 as Amber List (moderate evidence)
Fetal anomalies v0.4693 NUP85 Zornitza Stark Gene: nup85 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4692 NUP85 Zornitza Stark gene: NUP85 was added
gene: NUP85 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: NUP85 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP85 were set to 34170319
Phenotypes for gene: NUP85 were set to Microcephaly, MONDO:0001149, NUP85-related
Review for gene: NUP85 was set to AMBER
Added comment: PMID: 34170319 - Ravindran et al 2021 report two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS. In the first family, a 9 yo female, with consanguineous parents, is reported to have a missense variant in NUP85 (c.932G > A; p.R311Q). Intrauterine growth restriction was noticed. At birth microcephaly was observed (OFC < 3rd centile, < −3.6 SD) as well as hypotrophy [weight −2.8 SD), length 45 cm (−2.7 SD), both <3rd centile], facial dysmorphism, syndactyly, long and thin fingers, and bilateral pes adductus. She has severe developmental delay with strongly delayed motor milestones and absent speech. Drug-resistant, genetic epilepsy with focal-onset seizures started in the first year of life. She had no clinical, laboratory or radiological findings indicative of kidney dysfunction. In the second family, compound heterozygous missense variants in NUP85 were detected (c.1109A > G, c.1589 T > C;p.N370S, p.M530T ) in a fetus. MRI of the fetal brain at 24 + 2 GW indicated complete agenesis of the corpus callosum, abnormal sulcation in the left frontal lobe, nodularity of the frontal horn and trigone with focal puckering of the left lateral ventricle.

Variants in this gene are also associated with nephrotic syndrome.
Sources: Expert Review
Fetal anomalies v0.4691 PUS7 Zornitza Stark Marked gene: PUS7 as ready
Fetal anomalies v0.4691 PUS7 Zornitza Stark Gene: pus7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4691 PUS7 Zornitza Stark Classified gene: PUS7 as Amber List (moderate evidence)
Fetal anomalies v0.4691 PUS7 Zornitza Stark Gene: pus7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4690 PUS7 Zornitza Stark reviewed gene: PUS7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature, OMIM #618342; Mode of inheritance: None
Fetal anomalies v0.4690 PTPN23 Zornitza Stark Marked gene: PTPN23 as ready
Fetal anomalies v0.4690 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Green List (High Evidence).
Fetal anomalies v0.4690 PTPN23 Zornitza Stark Classified gene: PTPN23 as Green List (high evidence)
Fetal anomalies v0.4690 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Green List (High Evidence).
Fetal anomalies v0.4689 PUS7 Belinda Chong gene: PUS7 was added
gene: PUS7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PUS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS7 were set to 30526862; 30778726; 31583274
Phenotypes for gene: PUS7 were set to Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature; OMIM #618342
Review for gene: PUS7 was set to RED
gene: PUS7 was marked as current diagnostic
Added comment: Onset at infancy

11 patients from 6 families with ID, speech delay, short stature, microcephaly, and aggressive behavior, with homozygous PUS7 mutations, which segregated with disease.
Sources: Literature
Fetal anomalies v0.4689 PRIM1 Zornitza Stark Marked gene: PRIM1 as ready
Fetal anomalies v0.4689 PRIM1 Zornitza Stark Gene: prim1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4689 PRIM1 Zornitza Stark Classified gene: PRIM1 as Amber List (moderate evidence)
Fetal anomalies v0.4689 PRIM1 Zornitza Stark Gene: prim1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4688 PPP1R15B Zornitza Stark Marked gene: PPP1R15B as ready
Fetal anomalies v0.4688 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4688 PPP1R15B Zornitza Stark Classified gene: PPP1R15B as Amber List (moderate evidence)
Fetal anomalies v0.4688 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4687 PPIL1 Zornitza Stark Marked gene: PPIL1 as ready
Fetal anomalies v0.4687 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4687 PPIL1 Zornitza Stark Classified gene: PPIL1 as Green List (high evidence)
Fetal anomalies v0.4687 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4686 PTPN23 Belinda Chong gene: PTPN23 was added
gene: PTPN23 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PTPN23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN23 were set to 31395947; 29899372; 29090338; 27848944; 25558065
Phenotypes for gene: PTPN23 were set to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890
Review for gene: PTPN23 was set to GREEN
gene: PTPN23 was marked as current diagnostic
Added comment: Onset at birth or early infancy.

Over 10 families reported with an autosomal recessive neurologic disorder characterised by global developmental delay apparent from early infancy, poor overall growth often with microcephaly (6/10), impaired intellectual development with delayed or absent speech, axial hypotonia, and peripheral spasticity. Additional common but variable features include early-onset seizures, optic atrophy with poor visual fixation, and dysmorphic facial features. Brain imaging shows cerebral atrophy, poor or absent myelination with loss of white matter volume, and often hypoplasia of the corpus callosum and/or cerebellum.
Sources: Literature
Fetal anomalies v0.4686 PRIM1 Belinda Chong gene: PRIM1 was added
gene: PRIM1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIM1 were set to 33060134
Phenotypes for gene: PRIM1 were set to Microcephalic primordial dwarfism, MONDO:0017950
Review for gene: PRIM1 was set to AMBER
gene: PRIM1 was marked as current diagnostic
Added comment: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Fetal anomalies v0.4686 PPP1R15B Belinda Chong gene: PPP1R15B was added
gene: PPP1R15B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPP1R15B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP1R15B were set to 26159176; 26307080; 27640355
Phenotypes for gene: PPP1R15B were set to Microcephaly, short stature, and impaired glucose metabolism 2, MIM# 616817
Review for gene: PPP1R15B was set to AMBER
gene: PPP1R15B was marked as current diagnostic
Added comment: Three unrelated families reported, two with the same variant. Phenotype in family reported in PMID 27640355 included infantile cirrhosis requiring transplantation.
Sources: Literature
Fetal anomalies v0.4686 PPIL1 Belinda Chong gene: PPIL1 was added
gene: PPIL1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPIL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIL1 were set to 33220177
Phenotypes for gene: PPIL1 were set to Pontocerebellar hypoplasia, type 14, MIM# 619301; microcephaly; seizures
Review for gene: PPIL1 was set to GREEN
gene: PPIL1 was marked as current diagnostic
Added comment: The patients presented at birth with severe microcephaly (-2 to -6 SD), which progressed postnatally (-4 to -8 SD)

17 individuals from 9 unrelated families reported with bi-allelic variants in the gene and PCH, microcephaly, hypotonia, seizures, severe DD/ID. Mouse models support gene-disease association.
Sources: Literature
Fetal anomalies v0.4686 HIST1H4C Paul De Fazio reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 35202563; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758, Neurodevelopmental disorder, HIST1H4C-related MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Fetal anomalies v0.4686 SYNCRIP Zornitza Stark Marked gene: SYNCRIP as ready
Fetal anomalies v0.4686 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Red List (Low Evidence).
Fetal anomalies v0.4686 SYNCRIP Zornitza Stark gene: SYNCRIP was added
gene: SYNCRIP was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: SYNCRIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYNCRIP were set to 34157790
Phenotypes for gene: SYNCRIP were set to SYNCRIP-related neurodevelopmental disorder
Review for gene: SYNCRIP was set to RED
Added comment: One of 8 individuals reported so far had PVNH. Other features present post-natally.
Sources: Expert Review
Fetal anomalies v0.4685 PIDD1 Zornitza Stark Classified gene: PIDD1 as Green List (high evidence)
Fetal anomalies v0.4685 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4684 PIDD1 Zornitza Stark reviewed gene: PIDD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pachygyria, Lissencephaly, Abnormality of the corpus callosum; Mode of inheritance: None
Fetal anomalies v0.4684 DEPDC5 Zornitza Stark Classified gene: DEPDC5 as Green List (high evidence)
Fetal anomalies v0.4684 DEPDC5 Zornitza Stark Gene: depdc5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4683 DEPDC5 Zornitza Stark reviewed gene: DEPDC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 31444548; Phenotypes: Epilepsy, familial focal, with variable foci 1 MIM#604364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4683 AR Alison Yeung Phenotypes for gene: AR were changed from Androgen insensitivity, MIM# 300068 to Androgen insensitivity, MIM# 300068; Androgen insensitivity syndrome, MONDO:0019154
Fetal anomalies v0.4682 AR Alison Yeung reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Androgen insensitivity, MIM# 300068, Androgen insensitivity syndrome, MONDO:0019154; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.4682 AP4B1 Alison Yeung reviewed gene: AP4B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 47, autosomal recessive, MIM# 614066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4682 ANKS6 Alison Yeung reviewed gene: ANKS6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephronophthisis 16, MIM# 615382, MONDO:0014158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4682 ANGPT2 Alison Yeung Phenotypes for gene: ANGPT2 were changed from Hydrops; Lymphatic malformation-10, MIM#619369 to Hydrops fetalis, MONDO:0015193; Lymphatic malformation-10, MIM#619369
Fetal anomalies v0.4681 ALDH1A2 Alison Yeung Phenotypes for gene: ALDH1A2 were changed from Congenital heart defects; diaphragmatic eventration; pulmonary hypoplasia; thymus aplasia to Multiple congenital anomalies, ALDH1A2-related, MONDO:0019042
Fetal anomalies v0.4679 ALB Alison Yeung Phenotypes for gene: ALB were changed from Analbuminemia- MIM#616000 to Analbuminemia, MIM#616000
Fetal anomalies v0.4678 ADGRG6 Alison Yeung Phenotypes for gene: ADGRG6 were changed from Lethal congenital contracture syndrome 9; OMIM #616503 to Lethal congenital contracture syndrome 9, OMIM #616503
Fetal anomalies v0.4677 ADAMTS19 Alison Yeung Phenotypes for gene: ADAMTS19 were changed from Heart valve disease (HVD) to Heart valve disorder, MONDO:0002869
Fetal anomalies v0.4676 PLK1 Zornitza Stark Marked gene: PLK1 as ready
Fetal anomalies v0.4676 PLK1 Zornitza Stark Gene: plk1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4676 PLK1 Zornitza Stark Classified gene: PLK1 as Amber List (moderate evidence)
Fetal anomalies v0.4676 PLK1 Zornitza Stark Gene: plk1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4675 PIGH Zornitza Stark Classified gene: PIGH as Green List (high evidence)
Fetal anomalies v0.4675 PIGH Zornitza Stark Gene: pigh has been classified as Green List (High Evidence).
Fetal anomalies v0.4674 PIGH Zornitza Stark reviewed gene: PIGH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 17, MIM# 618010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4674 PIGH Zornitza Stark Marked gene: PIGH as ready
Fetal anomalies v0.4674 PIGH Zornitza Stark Gene: pigh has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4674 PIGH Zornitza Stark Classified gene: PIGH as Amber List (moderate evidence)
Fetal anomalies v0.4674 PIGH Zornitza Stark Gene: pigh has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4673 PHC1 Zornitza Stark Marked gene: PHC1 as ready
Fetal anomalies v0.4673 PHC1 Zornitza Stark Gene: phc1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4673 PHC1 Zornitza Stark Classified gene: PHC1 as Red List (low evidence)
Fetal anomalies v0.4673 PHC1 Zornitza Stark Gene: phc1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4672 ADAMTS17 Alison Yeung Phenotypes for gene: ADAMTS17 were changed from Weill-Marchesani 4 syndrome, recessive, 613195 to Weill-Marchesani 4 syndrome, recessive, MIM# 613195
Fetal anomalies v0.4671 PDCD6IP Zornitza Stark Marked gene: PDCD6IP as ready
Fetal anomalies v0.4671 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4671 PDCD6IP Zornitza Stark Classified gene: PDCD6IP as Amber List (moderate evidence)
Fetal anomalies v0.4671 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4670 PCYT2 Zornitza Stark Marked gene: PCYT2 as ready
Fetal anomalies v0.4670 PCYT2 Zornitza Stark Gene: pcyt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4670 PCYT2 Zornitza Stark Classified gene: PCYT2 as Red List (low evidence)
Fetal anomalies v0.4670 PCYT2 Zornitza Stark Gene: pcyt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4669 ACTC1 Alison Yeung Phenotypes for gene: ACTC1 were changed from Atrial septal defect 5 612794; Cardiomyopathy, hypertrophic, 11 612098 to Atrial septal defect 5, MIM# 612794; Cardiomyopathy, hypertrophic, 11 MIM# 612098
Fetal anomalies v0.4668 PCDH12 Zornitza Stark Marked gene: PCDH12 as ready
Fetal anomalies v0.4668 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4668 PCDH12 Zornitza Stark Classified gene: PCDH12 as Green List (high evidence)
Fetal anomalies v0.4668 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4667 PARP6 Zornitza Stark Marked gene: PARP6 as ready
Fetal anomalies v0.4667 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Fetal anomalies v0.4667 PARP6 Zornitza Stark Classified gene: PARP6 as Green List (high evidence)
Fetal anomalies v0.4667 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Fetal anomalies v0.4666 NKX2-5 Zornitza Stark Marked gene: NKX2-5 as ready
Fetal anomalies v0.4666 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4666 NKX2-5 Alison Yeung Marked gene: NKX2-5 as ready
Fetal anomalies v0.4666 NKX2-5 Alison Yeung Gene: nkx2-5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4666 NKX2-5 Alison Yeung Phenotypes for gene: NKX2-5 were changed from CONGENITAL HYPOTHYROIDISM NON-GOITROUS TYPE 5; TETRALOGY OF FALLOT; ATRIAL SEPTAL DEFECT WITH ATRIOVENTRICULAR CONDUCTION DEFECTS to Atrial septal defect 7, with or without AV conduction defects, MIM# 108900; Hypoplastic left heart syndrome 2, MIM# 614435; Tetralogy of Fallot, MIM# 187500; Ventricular septal defect 3, MIM# 614432; Hypothyroidism, congenital nongoitrous, 5, MIM# 225250
Fetal anomalies v0.4665 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Fetal anomalies v0.4665 NPC2 Zornitza Stark Gene: npc2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4665 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from NIEMANN-PICK DISEASE, TYPE C2 to Niemann-pick disease, type C2, MIM# 607625
Fetal anomalies v0.4664 NPC2 Zornitza Stark Publications for gene: NPC2 were set to
Fetal anomalies v0.4663 NPC2 Zornitza Stark Classified gene: NPC2 as Amber List (moderate evidence)
Fetal anomalies v0.4663 NPC2 Zornitza Stark Gene: npc2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4662 NPC2 Zornitza Stark edited their review of gene: NPC2: Changed rating: AMBER
Fetal anomalies v0.4662 NPHP1 Zornitza Stark Marked gene: NPHP1 as ready
Fetal anomalies v0.4662 NPHP1 Zornitza Stark Gene: nphp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4662 NPHP1 Zornitza Stark Phenotypes for gene: NPHP1 were changed from NEPHRONOPHTHISIS TYPE 1; JOUBERT SYNDROME TYPE 4; SENIOR-LOKEN SYNDROME TYPE 1 to Joubert syndrome 4, MIM# 609583
Fetal anomalies v0.4661 NPHP1 Zornitza Stark Publications for gene: NPHP1 were set to
Fetal anomalies v0.4660 NKX2-5 Alison Yeung Publications for gene: NKX2-5 were set to
Fetal anomalies v0.4659 NKX2-5 Alison Yeung Mode of inheritance for gene: NKX2-5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4658 NPHP3 Zornitza Stark Marked gene: NPHP3 as ready
Fetal anomalies v0.4658 NPHP3 Zornitza Stark Gene: nphp3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4658 NPHP3 Zornitza Stark Phenotypes for gene: NPHP3 were changed from RENAL-HEPATIC-PANCREATIC DYSPLASIA; NEPHRONOPHTHISIS TYPE 3; MECKEL SYNDROME TYPE 7 to Meckel syndrome 7, MIM# 267010; Nephronophthisis 3, MIM# 604387; Renal-hepatic-pancreatic dysplasia 1, MIM# 208540
Fetal anomalies v0.4657 NPHP3 Zornitza Stark Publications for gene: NPHP3 were set to
Fetal anomalies v0.4656 NIPBL Alison Yeung Marked gene: NIPBL as ready
Fetal anomalies v0.4656 NIPBL Alison Yeung Gene: nipbl has been classified as Green List (High Evidence).
Fetal anomalies v0.4656 NPHP3 Zornitza Stark edited their review of gene: NPHP3: Changed phenotypes: Meckel syndrome 7, MIM# 267010, Nephronophthisis 3, MIM# 604387, Renal-hepatic-pancreatic dysplasia 1, MIM# 208540
Fetal anomalies v0.4656 NIPBL Alison Yeung Phenotypes for gene: NIPBL were changed from CORNELIA DE LANGE SYNDROME TYPE 1 to Cornelia de Lange syndrome 1, MIM# 122470
Fetal anomalies v0.4655 NIPBL Alison Yeung Mode of inheritance for gene: NIPBL was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4654 NPHP3 Zornitza Stark edited their review of gene: NPHP3: Changed rating: GREEN
Fetal anomalies v0.4654 NIPBL Alison Yeung reviewed gene: NIPBL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 1, MIM# 122470; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4654 NPHP4 Zornitza Stark Marked gene: NPHP4 as ready
Fetal anomalies v0.4654 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4654 NPHP4 Zornitza Stark Phenotypes for gene: NPHP4 were changed from NEPHRONOPHTHISIS TYPE 4 to Nephronophthisis 4, MIM# 606966; Senior-Loken syndrome 4, MIM# 606996
Fetal anomalies v0.4653 NPHP4 Zornitza Stark Publications for gene: NPHP4 were set to
Fetal anomalies v0.4652 NRAS Zornitza Stark Marked gene: NRAS as ready
Fetal anomalies v0.4652 NRAS Zornitza Stark Gene: nras has been classified as Green List (High Evidence).
Fetal anomalies v0.4652 NRAS Zornitza Stark Phenotypes for gene: NRAS were changed from NOONAN SYNDROME TYPE 6 to Noonan syndrome 6, MIM# 613224
Fetal anomalies v0.4651 NRAS Zornitza Stark Publications for gene: NRAS were set to
Fetal anomalies v0.4650 NRAS Zornitza Stark Mode of pathogenicity for gene: NRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v0.4649 NRAS Zornitza Stark Mode of inheritance for gene: NRAS was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4648 NSD1 Zornitza Stark Marked gene: NSD1 as ready
Fetal anomalies v0.4648 NSD1 Zornitza Stark Gene: nsd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4648 NSD1 Zornitza Stark Phenotypes for gene: NSD1 were changed from BECKWITH-WIEDEMANN SYNDROME; WEAVER SYNDROME; SOTOS SYNDROME to Sotos syndrome 1, MIM# 117550
Fetal anomalies v0.4647 NSD1 Zornitza Stark Publications for gene: NSD1 were set to
Fetal anomalies v0.4646 NSD1 Zornitza Stark Mode of inheritance for gene: NSD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4645 NSD1 Zornitza Stark Deleted their comment
Fetal anomalies v0.4645 NSD1 Zornitza Stark commented on gene: NSD1: Overgrowth, congenital anomalies.
Fetal anomalies v0.4645 NSD1 Zornitza Stark edited their review of gene: NSD1: Changed rating: GREEN
Fetal anomalies v0.4645 NSDHL Zornitza Stark Marked gene: NSDHL as ready
Fetal anomalies v0.4645 NSDHL Zornitza Stark Gene: nsdhl has been classified as Green List (High Evidence).
Fetal anomalies v0.4645 NSDHL Zornitza Stark Phenotypes for gene: NSDHL were changed from CK SYNDROME; CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS to CK syndrome , MIM#300831
Fetal anomalies v0.4644 NSDHL Zornitza Stark Publications for gene: NSDHL were set to
Fetal anomalies v0.4643 NSDHL Zornitza Stark Mode of inheritance for gene: NSDHL was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.4642 NSDHL Zornitza Stark reviewed gene: NSDHL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CK syndrome , MIM#300831; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.4642 NUP107 Zornitza Stark Marked gene: NUP107 as ready
Fetal anomalies v0.4642 NUP107 Zornitza Stark Gene: nup107 has been classified as Green List (High Evidence).
Fetal anomalies v0.4642 NUP107 Zornitza Stark Phenotypes for gene: NUP107 were changed from EARLY-CHILDHOOD-ONSET STEROID-RESISTANT NEPHROTIC SYNDROME to Galloway-Mowat syndrome 7, MIM# 618348
Fetal anomalies v0.4641 NUP107 Zornitza Stark Publications for gene: NUP107 were set to
Fetal anomalies v0.4640 OCRL Zornitza Stark Marked gene: OCRL as ready
Fetal anomalies v0.4640 OCRL Zornitza Stark Gene: ocrl has been classified as Green List (High Evidence).
Fetal anomalies v0.4640 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Fetal anomalies v0.4640 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4640 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from SIMPSON-GOLABI-BEHMEL SYNDROME TYPE 2; JOUBERT SYNDROME TYPE 10; ORAL-FACIAL-DIGITAL SYNDROME TYPE 1 to Orofaciodigital syndrome I, MIM# 311200; Joubert syndrome 10, MIM# 300804
Fetal anomalies v0.4639 OFD1 Zornitza Stark changed review comment from: XLD. Polydactyly is a rare feature. Primarily facial/neurological features.; to: Well established gene-disease associations, multiple congenital anomalies.
Fetal anomalies v0.4639 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed phenotypes: Orofaciodigital syndrome I, MIM# 311200, Joubert syndrome 10, MIM# 300804
Fetal anomalies v0.4639 OFD1 Zornitza Stark edited their review of gene: OFD1: Changed rating: GREEN; Changed phenotypes: Orofaciodigital syndrome I, MIM# 311200, Joubert syndrome 10 300804; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.4639 PCGF2 Zornitza Stark Marked gene: PCGF2 as ready
Fetal anomalies v0.4639 PCGF2 Zornitza Stark Gene: pcgf2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4639 PCGF2 Zornitza Stark Phenotypes for gene: PCGF2 were changed from Craniofacial Neurological Cardiovascular and Skeletal Features; Intellectual disability; INTELLECTUAL DUSBILITY to Turnpenny-Fry syndrome, MIM# 618371
Fetal anomalies v0.4638 PCGF2 Zornitza Stark Publications for gene: PCGF2 were set to 30526864
Fetal anomalies v0.4637 PCGF2 Zornitza Stark Mode of inheritance for gene: PCGF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4636 PCNT Zornitza Stark Marked gene: PCNT as ready
Fetal anomalies v0.4636 PCNT Zornitza Stark Gene: pcnt has been classified as Green List (High Evidence).
Fetal anomalies v0.4636 PCNT Zornitza Stark Phenotypes for gene: PCNT were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II to Microcephalic osteodysplastic primordial dwarfism, type II, MIM# 210720; MONDO:0008872
Fetal anomalies v0.4635 PCNT Zornitza Stark Publications for gene: PCNT were set to
Fetal anomalies v0.4634 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
Fetal anomalies v0.4634 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4634 PDHA1 Zornitza Stark Phenotypes for gene: PDHA1 were changed from X-LINKED LEIGH SYNDROME; PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES; INTELLECTUAL DISABILTIY; Pyruvate dehydrogenase E1-alpha deficiency to Pyruvate dehydrogenase E1-alpha deficiency, MIM# 312170
Fetal anomalies v0.4633 PDHA1 Zornitza Stark Publications for gene: PDHA1 were set to 26865159
Fetal anomalies v0.4632 PDHA1 Zornitza Stark changed review comment from: Variants in this gene can cause congenital anomalies.
Sources: Literature; to: Variants in this gene can cause congenital anomalies, primarily affecting the brain. One report of CDH.
Sources: Literature
Fetal anomalies v0.4632 PDHA1 Zornitza Stark edited their review of gene: PDHA1: Changed publications: 33461977, 26865159
Fetal anomalies v0.4632 PDHA1 Zornitza Stark changed review comment from: Single individual reported as part of a cohort. Note variants in this gene can cause congenital anomalies.
Sources: Literature; to: Variants in this gene can cause congenital anomalies.
Sources: Literature
Fetal anomalies v0.4632 PDHA1 Zornitza Stark edited their review of gene: PDHA1: Changed rating: GREEN; Changed phenotypes: Pyruvate dehydrogenase E1-alpha deficiency, MIM# 312170
Fetal anomalies v0.4632 PEX1 Zornitza Stark Marked gene: PEX1 as ready
Fetal anomalies v0.4632 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4632 PEX1 Zornitza Stark Phenotypes for gene: PEX1 were changed from PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 1; INFANTILE REFSUM DISEASE; ADRENOLEUKODYSTROPHY NEONATAL to Peroxisome biogenesis disorder 1A (Zellweger) (MIM#214100)
Fetal anomalies v0.4631 PEX1 Zornitza Stark Publications for gene: PEX1 were set to
Fetal anomalies v0.4630 PEX10 Zornitza Stark Marked gene: PEX10 as ready
Fetal anomalies v0.4630 PEX10 Zornitza Stark Gene: pex10 has been classified as Green List (High Evidence).
Fetal anomalies v0.4630 PEX10 Zornitza Stark Phenotypes for gene: PEX10 were changed from ZELLWEGER SYNDROME; ADRENOLEUKODYSTROPHY NEONATAL; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 7 to Peroxisome biogenesis disorder 6A (Zellweger), MIM# 614870
Fetal anomalies v0.4629 PEX10 Zornitza Stark Publications for gene: PEX10 were set to
Fetal anomalies v0.4628 PEX10 Zornitza Stark reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger), MIM# 614870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4628 PEX11B Zornitza Stark Marked gene: PEX11B as ready
Fetal anomalies v0.4628 PEX11B Zornitza Stark Gene: pex11b has been classified as Green List (High Evidence).
Fetal anomalies v0.4628 PEX11B Zornitza Stark Phenotypes for gene: PEX11B were changed from Peroxisome biogenesis disorder 14B to Peroxisome biogenesis disorder 14B, MIM# 614920
Fetal anomalies v0.4627 PEX11B Zornitza Stark Publications for gene: PEX11B were set to
Fetal anomalies v0.4626 PEX11B Zornitza Stark changed review comment from: Congenital cataracts.; to: Congenital cataracts. Three families altogether, two published, and one internal.
Fetal anomalies v0.4626 PEX11B Zornitza Stark edited their review of gene: PEX11B: Changed rating: GREEN; Changed publications: 31724321
Fetal anomalies v0.4626 PEX11B Zornitza Stark edited their review of gene: PEX11B: Changed rating: AMBER
Fetal anomalies v0.4626 PEX11B Zornitza Stark edited their review of gene: PEX11B: Added comment: Congenital cataracts.; Changed rating: GREEN; Changed phenotypes: Peroxisome biogenesis disorder 14B, MIM# 614920; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4626 PEX12 Zornitza Stark Marked gene: PEX12 as ready
Fetal anomalies v0.4626 PEX12 Zornitza Stark Gene: pex12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4626 PEX12 Zornitza Stark Phenotypes for gene: PEX12 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 3 to Peroxisome biogenesis disorder 3A (Zellweger), MIM# 614859
Fetal anomalies v0.4625 PEX12 Zornitza Stark Publications for gene: PEX12 were set to
Fetal anomalies v0.4624 PEX12 Zornitza Stark reviewed gene: PEX12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 3A (Zellweger), MIM# 614859; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4624 PEX13 Zornitza Stark Marked gene: PEX13 as ready
Fetal anomalies v0.4624 PEX13 Zornitza Stark Gene: pex13 has been classified as Green List (High Evidence).
Fetal anomalies v0.4624 PEX13 Zornitza Stark Phenotypes for gene: PEX13 were changed from PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 13; ADRENOLEUKODYSTROPHY NEONATAL to Peroxisome biogenesis disorder 11A (Zellweger), MIM# 614883
Fetal anomalies v0.4623 PEX13 Zornitza Stark Publications for gene: PEX13 were set to
Fetal anomalies v0.4622 PEX13 Zornitza Stark reviewed gene: PEX13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 11A (Zellweger), MIM# 614883; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4622 PEX14 Zornitza Stark Marked gene: PEX14 as ready
Fetal anomalies v0.4622 PEX14 Zornitza Stark Gene: pex14 has been classified as Green List (High Evidence).
Fetal anomalies v0.4622 PEX14 Zornitza Stark Phenotypes for gene: PEX14 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP K to Peroxisome biogenesis disorder 13A (Zellweger), MIM# 614887
Fetal anomalies v0.4621 PEX14 Zornitza Stark Publications for gene: PEX14 were set to
Fetal anomalies v0.4620 PEX14 Zornitza Stark reviewed gene: PEX14: Rating: GREEN; Mode of pathogenicity: None; Publications: 26627464; Phenotypes: Peroxisome biogenesis disorder 13A (Zellweger), MIM# 614887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4620 PEX16 Zornitza Stark Marked gene: PEX16 as ready
Fetal anomalies v0.4620 PEX16 Zornitza Stark Gene: pex16 has been classified as Green List (High Evidence).
Fetal anomalies v0.4620 PEX16 Zornitza Stark Phenotypes for gene: PEX16 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 9 to Peroxisome biogenesis disorder 8A (Zellweger), MIM# 614876
Fetal anomalies v0.4619 PEX16 Zornitza Stark Publications for gene: PEX16 were set to
Fetal anomalies v0.4618 PEX16 Zornitza Stark reviewed gene: PEX16: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 8A (Zellweger), MIM# 614876; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4618 POMGNT1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association, congenital anomalies at the severe end of the spectrum.
Fetal anomalies v0.4618 POMGNT1 Zornitza Stark Marked gene: POMGNT1 as ready
Fetal anomalies v0.4618 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4618 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A3 (MDDGA3 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3, 253280
Fetal anomalies v0.4617 PEX19 Zornitza Stark Marked gene: PEX19 as ready
Fetal anomalies v0.4617 PEX19 Zornitza Stark Gene: pex19 has been classified as Green List (High Evidence).
Fetal anomalies v0.4617 PEX19 Zornitza Stark Phenotypes for gene: PEX19 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 14 to Peroxisome biogenesis disorder 12A (Zellweger), MIM# 614886
Fetal anomalies v0.4616 PEX19 Zornitza Stark Publications for gene: PEX19 were set to
Fetal anomalies v0.4615 PEX19 Zornitza Stark reviewed gene: PEX19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 12A (Zellweger), MIM# 614886; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4615 PEX2 Zornitza Stark Marked gene: PEX2 as ready
Fetal anomalies v0.4615 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4615 PEX2 Zornitza Stark Phenotypes for gene: PEX2 were changed from ZELLWEGER SYNDROME; INFANTILE REFSUM DISEASE; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 5 to Peroxisome biogenesis disorder 5A (Zellweger), MIM# 614866
Fetal anomalies v0.4614 PEX2 Zornitza Stark Publications for gene: PEX2 were set to
Fetal anomalies v0.4613 PEX2 Zornitza Stark reviewed gene: PEX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger), MIM# 614866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4613 PEX26 Zornitza Stark Marked gene: PEX26 as ready
Fetal anomalies v0.4613 PEX26 Zornitza Stark Gene: pex26 has been classified as Green List (High Evidence).
Fetal anomalies v0.4613 PEX26 Zornitza Stark Phenotypes for gene: PEX26 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 8; INFANTILE REFSUM DISEASE; ADRENOLEUKODYSTROPHY NEONATAL to Peroxisome biogenesis disorder 7A (Zellweger), MIM# 614872
Fetal anomalies v0.4612 PEX26 Zornitza Stark Publications for gene: PEX26 were set to
Fetal anomalies v0.4611 PEX26 Zornitza Stark reviewed gene: PEX26: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 7A (Zellweger), MIM# 614872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4611 PEX3 Zornitza Stark Marked gene: PEX3 as ready
Fetal anomalies v0.4611 PEX3 Zornitza Stark Gene: pex3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4611 PEX3 Zornitza Stark Phenotypes for gene: PEX3 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 12 to Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882
Fetal anomalies v0.4610 PEX3 Zornitza Stark Publications for gene: PEX3 were set to
Fetal anomalies v0.4609 PEX3 Zornitza Stark reviewed gene: PEX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4609 PEX5 Zornitza Stark Marked gene: PEX5 as ready
Fetal anomalies v0.4609 PEX5 Zornitza Stark Gene: pex5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4609 PEX5 Zornitza Stark Phenotypes for gene: PEX5 were changed from ZELLWEGER SYNDROME; INFANTILE REFSUM DISEASE; ADRENOLEUKODYSTROPHY NEONATAL to Peroxisome biogenesis disorder 2A (Zellweger), MIM# 214110
Fetal anomalies v0.4608 PEX5 Zornitza Stark Publications for gene: PEX5 were set to
Fetal anomalies v0.4607 PEX5 Zornitza Stark reviewed gene: PEX5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 2A (Zellweger), MIM# 214110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4607 NR2F2 Zornitza Stark Marked gene: NR2F2 as ready
Fetal anomalies v0.4607 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4607 NR2F2 Zornitza Stark Phenotypes for gene: NR2F2 were changed from CONGENITAL HEART DEFECTS, MULTIPLE TYPES, 4 to Congenital heart defects, multiple types, 4, MIM# 615779
Fetal anomalies v0.4606 NR2F2 Zornitza Stark Publications for gene: NR2F2 were set to
Fetal anomalies v0.4605 NR2F2 Zornitza Stark Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4604 PEX6 Zornitza Stark Marked gene: PEX6 as ready
Fetal anomalies v0.4604 PEX6 Zornitza Stark Gene: pex6 has been classified as Green List (High Evidence).
Fetal anomalies v0.4604 PEX6 Zornitza Stark Phenotypes for gene: PEX6 were changed from ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 4 to Peroxisome biogenesis disorder 4A (Zellweger) (MIM#614862)
Fetal anomalies v0.4603 PEX6 Zornitza Stark Publications for gene: PEX6 were set to
Fetal anomalies v0.4602 PGAP2 Zornitza Stark Marked gene: PGAP2 as ready
Fetal anomalies v0.4602 PGAP2 Zornitza Stark Gene: pgap2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4602 PGAP2 Zornitza Stark Phenotypes for gene: PGAP2 were changed from INTELLECTUAL DISABILITY to Hyperphosphatasia with mental retardation syndrome 3, MIM# 614207, MONDO:0013628
Fetal anomalies v0.4601 PGAP2 Zornitza Stark Publications for gene: PGAP2 were set to
Fetal anomalies v0.4600 PGAP2 Zornitza Stark changed review comment from: Bi-allelic variants in this gene are typically associated with severe DD/ID, hypotonia with very poor motor development, poor speech, and increased serum alkaline phosphatase, although presentations with milder ID have also been reported. More than 10 unrelated families reported.; to: Bi-allelic variants in this gene are typically associated with severe DD/ID, hypotonia with very poor motor development, poor speech, and increased serum alkaline phosphatase, although presentations with milder ID have also been reported. More than 10 unrelated families reported.

Microcephaly is a feature.
Fetal anomalies v0.4600 PGAP3 Zornitza Stark Marked gene: PGAP3 as ready
Fetal anomalies v0.4600 PGAP3 Zornitza Stark Gene: pgap3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4600 PGAP3 Zornitza Stark Phenotypes for gene: PGAP3 were changed from HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 4 to Hyperphosphatasia with mental retardation syndrome 4, MIM# 615716, MONDO:0014318
Fetal anomalies v0.4599 PGAP3 Zornitza Stark Publications for gene: PGAP3 were set to
Fetal anomalies v0.4598 PGAP3 Zornitza Stark changed review comment from: Bi-allelic variants in this gene are associated with severe DD/ID, lack of speech acquisition, seizures, and dysmorphic facial features. Laboratory studies show increased serum alkaline phosphatase. More than 15 unrelated families reported.; to: Bi-allelic variants in this gene are associated with severe DD/ID, lack of speech acquisition, seizures, and dysmorphic facial features. Laboratory studies show increased serum alkaline phosphatase. More than 15 unrelated families reported.

Microcephaly, CC abnormalities reported.
Fetal anomalies v0.4598 PGM1 Zornitza Stark Marked gene: PGM1 as ready
Fetal anomalies v0.4598 PGM1 Zornitza Stark Gene: pgm1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4598 PGM1 Zornitza Stark Phenotypes for gene: PGM1 were changed from CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IT to Congenital disorder of glycosylation, type It 614921
Fetal anomalies v0.4597 PGM1 Zornitza Stark Publications for gene: PGM1 were set to
Fetal anomalies v0.4596 PGM1 Zornitza Stark changed review comment from: The most common features include cleft lip and bifid uvula, apparent at birth, followed by hepatopathy, intermittent hypoglycemia, short stature, and exercise intolerance, often accompanied by increased serum creatine kinase. Less common features include rhabdomyolysis, dilated cardiomyopathy, and hypogonadotropic hypogonadism; to: Over 50 individuals reported. The most common features include cleft lip and bifid uvula, apparent at birth, followed by hepatopathy, intermittent hypoglycemia, short stature, and exercise intolerance, often accompanied by increased serum creatine kinase. Less common features include rhabdomyolysis, dilated cardiomyopathy, and hypogonadotropic hypogonadism
Fetal anomalies v0.4596 PGM1 Zornitza Stark edited their review of gene: PGM1: Changed publications: 24499211, 33342467
Fetal anomalies v0.4596 PGM1 Zornitza Stark commented on gene: PGM1: The most common features include cleft lip and bifid uvula, apparent at birth, followed by hepatopathy, intermittent hypoglycemia, short stature, and exercise intolerance, often accompanied by increased serum creatine kinase. Less common features include rhabdomyolysis, dilated cardiomyopathy, and hypogonadotropic hypogonadism
Fetal anomalies v0.4596 PHF8 Zornitza Stark Marked gene: PHF8 as ready
Fetal anomalies v0.4596 PHF8 Zornitza Stark Gene: phf8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4596 PHF8 Zornitza Stark Phenotypes for gene: PHF8 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED SIDERIUS TYPE to Intellectual developmental disorder, X-linked, syndromic, Siderius type, MIM# 300263
Fetal anomalies v0.4595 PHF8 Zornitza Stark Publications for gene: PHF8 were set to
Fetal anomalies v0.4594 PHF8 Zornitza Stark commented on gene: PHF8: Cleft lip/palate is a feature.
Fetal anomalies v0.4594 PHF8 Zornitza Stark edited their review of gene: PHF8: Changed phenotypes: Intellectual developmental disorder, X-linked, syndromic, Siderius type, MIM# 300263
Fetal anomalies v0.4594 PHGDH Zornitza Stark Marked gene: PHGDH as ready
Fetal anomalies v0.4594 PHGDH Zornitza Stark Gene: phgdh has been classified as Green List (High Evidence).
Fetal anomalies v0.4594 PHGDH Zornitza Stark Phenotypes for gene: PHGDH were changed from PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY; NEU-LAXOVA SYNDROME to Neu-Laxova syndrome 1, MIM# 256520
Fetal anomalies v0.4593 PHGDH Zornitza Stark Publications for gene: PHGDH were set to
Fetal anomalies v0.4592 PHIP Zornitza Stark Marked gene: PHIP as ready
Fetal anomalies v0.4592 PHIP Zornitza Stark Gene: phip has been classified as Red List (Low Evidence).
Fetal anomalies v0.4592 PHIP Zornitza Stark Phenotypes for gene: PHIP were changed from Developmental delay, ID, obesity and dysmorphic features to Chung-Jansen syndrome, MIM#617991
Fetal anomalies v0.4591 PHIP Zornitza Stark Publications for gene: PHIP were set to
Fetal anomalies v0.4590 PHIP Zornitza Stark Mode of inheritance for gene: PHIP was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4589 PHIP Zornitza Stark Classified gene: PHIP as Red List (low evidence)
Fetal anomalies v0.4589 PHIP Zornitza Stark Gene: phip has been classified as Red List (Low Evidence).
Fetal anomalies v0.4588 PHIP Zornitza Stark changed review comment from: Recent large case series describing 20 individuals; variable expressivity, some inherited from mildly affected parents, most de novo.
Sources: Expert list; to: Recent large case series describing 20 individuals; variable expressivity, some inherited from mildly affected parents, most de novo. ID, dysmorphism and obesity are the key features. Clinical presentation is typically post-natal.
Sources: Expert list
Fetal anomalies v0.4588 PHIP Zornitza Stark edited their review of gene: PHIP: Changed rating: RED
Fetal anomalies v0.4588 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
Fetal anomalies v0.4588 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4588 PIEZO2 Zornitza Stark Phenotypes for gene: PIEZO2 were changed from Ataxia, dysmetria, contractures & scoliosis with normal cognition but loss of discriminative touch perception; ARTHROGRYPOSIS, DISTAL, TYPE 3 to Marden-Walker syndrome, MIM# 248700; Arthrogryposis, distal, type 3, MIM# 114300
Fetal anomalies v0.4587 PIEZO2 Zornitza Stark Publications for gene: PIEZO2 were set to
Fetal anomalies v0.4586 PIEZO2 Zornitza Stark Mode of inheritance for gene: PIEZO2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4585 PIEZO2 Zornitza Stark changed review comment from: Gene is associated with several phenotypes. The other two DA phenotypes do not have ID as a feature. Mild ID is part of the phenotype of some individuals with DA type 3. ID is part of the phenotype of Marden-Walker, however only one individual with PIEZO2 variant has been reported to date.; to: Gene is associated with several phenotypes, contractures are a key feature.
Fetal anomalies v0.4585 PIEZO2 Zornitza Stark edited their review of gene: PIEZO2: Changed rating: GREEN
Fetal anomalies v0.4585 PIGA Zornitza Stark Marked gene: PIGA as ready
Fetal anomalies v0.4585 PIGA Zornitza Stark Gene: piga has been classified as Green List (High Evidence).
Fetal anomalies v0.4585 PIGA Zornitza Stark Phenotypes for gene: PIGA were changed from MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2 to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM#300868
Fetal anomalies v0.4584 PIGA Zornitza Stark Publications for gene: PIGA were set to
Fetal anomalies v0.4583 PIGL Zornitza Stark Marked gene: PIGL as ready
Fetal anomalies v0.4583 PIGL Zornitza Stark Gene: pigl has been classified as Green List (High Evidence).
Fetal anomalies v0.4583 PIGL Zornitza Stark Phenotypes for gene: PIGL were changed from ZUNICH NEUROECTODERMAL SYNDROME to CHIME syndrome, MIM# 280000, MONDO:0010221
Fetal anomalies v0.4582 PIGL Zornitza Stark Publications for gene: PIGL were set to
Fetal anomalies v0.4581 PIGL Zornitza Stark Tag SV/CNV tag was added to gene: PIGL.
Fetal anomalies v0.4581 PIGO Zornitza Stark Marked gene: PIGO as ready
Fetal anomalies v0.4581 PIGO Zornitza Stark Gene: pigo has been classified as Green List (High Evidence).
Fetal anomalies v0.4581 PIGO Zornitza Stark Phenotypes for gene: PIGO were changed from HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 2 to Hyperphosphatasia with mental retardation syndrome 2, MIM# 614749, MONDO:0013882
Fetal anomalies v0.4580 PIGO Zornitza Stark Publications for gene: PIGO were set to
Fetal anomalies v0.4579 PIGT Zornitza Stark Marked gene: PIGT as ready
Fetal anomalies v0.4579 PIGT Zornitza Stark Gene: pigt has been classified as Green List (High Evidence).
Fetal anomalies v0.4579 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 3 to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398, MONDO:0014165
Fetal anomalies v0.4578 PIGT Zornitza Stark Publications for gene: PIGT were set to
Fetal anomalies v0.4577 PIGV Zornitza Stark Marked gene: PIGV as ready
Fetal anomalies v0.4577 PIGV Zornitza Stark Gene: pigv has been classified as Green List (High Evidence).
Fetal anomalies v0.4577 PIGV Zornitza Stark Phenotypes for gene: PIGV were changed from HYPERPHOSPHATASIA WITH MENTAL RETARDATION to Hyperphosphatasia with mental retardation syndrome 1, MIM# 239300, MONDO:0009398
Fetal anomalies v0.4576 PIGV Zornitza Stark Publications for gene: PIGV were set to
Fetal anomalies v0.4575 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Fetal anomalies v0.4575 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Fetal anomalies v0.4575 PIK3CA Zornitza Stark Phenotypes for gene: PIK3CA were changed from CLOVES: CONGENITAL LIPOMATOUS OVERGROWTH, VASCULAR MALFORMATIONS, AND EPIDERMAL NEVI; HEMIMEGALENCEPHALY PIK3CA; MEGALENCEPHALY-CAPILLARY MALFORMATION-POLYMICROGYRIA SYNDROME, SOMATIC 3 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, MIM# 615937
Fetal anomalies v0.4574 PIK3CA Zornitza Stark Publications for gene: PIK3CA were set to 30712880; 28425981
Fetal anomalies v0.4573 PIK3CA Zornitza Stark Mode of inheritance for gene: PIK3CA was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4572 PIK3CA Zornitza Stark changed review comment from: Single case report of MCAP with fetal hydrops presentation, PIK3CA variant identified.
Sources: Expert list; to: Multiple congenital anomalies.
Sources: Expert list
Fetal anomalies v0.4572 PIK3CA Zornitza Stark edited their review of gene: PIK3CA: Changed rating: GREEN; Changed phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, MIM# 615937
Fetal anomalies v0.4572 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Fetal anomalies v0.4572 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4572 PIK3R1 Zornitza Stark Phenotypes for gene: PIK3R1 were changed from AGAMMAGLOBULINEMIA 7, AUTOSOMAL RECESSIVE; SHORT SYNDROME to SHORT syndrome, MIM#269880
Fetal anomalies v0.4571 PIK3R1 Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: IUGR.
Fetal anomalies v0.4571 PIK3R1 Zornitza Stark edited their review of gene: PIK3R1: Changed rating: GREEN
Fetal anomalies v0.4571 PIK3R2 Zornitza Stark Marked gene: PIK3R2 as ready
Fetal anomalies v0.4571 PIK3R2 Zornitza Stark Gene: pik3r2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4571 PIK3R2 Zornitza Stark Phenotypes for gene: PIK3R2 were changed from MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM# 603387
Fetal anomalies v0.4570 PIK3R2 Zornitza Stark Publications for gene: PIK3R2 were set to 28425981
Fetal anomalies v0.4569 PIK3R2 Zornitza Stark Mode of inheritance for gene: PIK3R2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4568 PITX3 Zornitza Stark Marked gene: PITX3 as ready
Fetal anomalies v0.4568 PITX3 Zornitza Stark Gene: pitx3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4568 PITX3 Zornitza Stark Phenotypes for gene: PITX3 were changed from CATARACT AUTOSOMAL DOMINANT; ANTERIOR SEGMENT MESENCHYMAL DYSGENESIS; CATARACT POSTERIOR POLAR TYPE 4 to Anterior segment dysgenesis 1, multiple subtypes, MIM# 107250; Cataract 11, multiple types, MIM# 610623; Microphthalmia
Fetal anomalies v0.4567 PITX3 Zornitza Stark Publications for gene: PITX3 were set to
Fetal anomalies v0.4566 PITX3 Zornitza Stark Mode of inheritance for gene: PITX3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4565 PKD1L1 Zornitza Stark Marked gene: PKD1L1 as ready
Fetal anomalies v0.4565 PKD1L1 Zornitza Stark Gene: pkd1l1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4565 PKD1L1 Zornitza Stark Phenotypes for gene: PKD1L1 were changed from Laterality defects to Heterotaxy, visceral, 8, autosomal (MIM#617205)
Fetal anomalies v0.4564 PKD1L1 Zornitza Stark Publications for gene: PKD1L1 were set to
Fetal anomalies v0.4563 PKHD1 Zornitza Stark Marked gene: PKHD1 as ready
Fetal anomalies v0.4563 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4563 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from POLYCYSTIC KIDNEY DISEASE, AUTOSOMAL RECESSIVE to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200
Fetal anomalies v0.4562 PKHD1 Zornitza Stark changed review comment from: Included due to possible phenotypic overlap.
Sources: Expert Review; to: Presents antenatally.
Sources: Expert Review
Fetal anomalies v0.4562 PKLR Zornitza Stark Marked gene: PKLR as ready
Fetal anomalies v0.4562 PKLR Zornitza Stark Gene: pklr has been classified as Green List (High Evidence).
Fetal anomalies v0.4562 PKLR Zornitza Stark Publications for gene: PKLR were set to
Fetal anomalies v0.4561 PMM2 Zornitza Stark Marked gene: PMM2 as ready
Fetal anomalies v0.4561 PMM2 Zornitza Stark Gene: pmm2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4561 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from CONGENITAL DISORDERS OF GLYCOSYLATION to Congenital disorder of glycosylation, type Ia , MIM#212065
Fetal anomalies v0.4560 PMM2 Zornitza Stark Publications for gene: PMM2 were set to
Fetal anomalies v0.4559 PMM2 Zornitza Stark reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ia , MIM#212065; Mode of inheritance: None
Fetal anomalies v0.4559 PNKP Zornitza Stark Marked gene: PNKP as ready
Fetal anomalies v0.4559 PNKP Zornitza Stark Gene: pnkp has been classified as Green List (High Evidence).
Fetal anomalies v0.4559 PNKP Zornitza Stark Phenotypes for gene: PNKP were changed from ATAXIA-OCULOMOTOR APRAXIA 4; EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 10 to Microcephaly, seizures, and developmental delay, MIM#613402
Fetal anomalies v0.4558 PNKP Zornitza Stark Publications for gene: PNKP were set to
Fetal anomalies v0.4557 POC1A Zornitza Stark Marked gene: POC1A as ready
Fetal anomalies v0.4557 POC1A Zornitza Stark Gene: poc1a has been classified as Green List (High Evidence).
Fetal anomalies v0.4557 POC1A Zornitza Stark Phenotypes for gene: POC1A were changed from PRIMORDIAL DWARFISM; SHORT STATURE, ONYCHODYSPLASIA, FACIAL DYSMORPHISM, AND HYPOTRICHOSIS SYNDROME to Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM#614813
Fetal anomalies v0.4556 POC1A Zornitza Stark changed review comment from: ID is not a prominent feature of the phenotype.; to: Skeletal dysplasia.
Fetal anomalies v0.4556 POC1A Zornitza Stark edited their review of gene: POC1A: Changed rating: GREEN
Fetal anomalies v0.4556 POGZ Zornitza Stark Marked gene: POGZ as ready
Fetal anomalies v0.4556 POGZ Zornitza Stark Gene: pogz has been classified as Green List (High Evidence).
Fetal anomalies v0.4556 POGZ Zornitza Stark Phenotypes for gene: POGZ were changed from INTELLECTUAL DISABILITY to White-Sutton syndrome, MIM# 616364; MONDO:0014606
Fetal anomalies v0.4555 POGZ Zornitza Stark Publications for gene: POGZ were set to
Fetal anomalies v0.4554 PLK1 Belinda Chong gene: PLK1 was added
gene: PLK1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLK1 were set to 33875846
Phenotypes for gene: PLK1 were set to Epilepsy; microcephaly; intellectual disability
Review for gene: PLK1 was set to AMBER
gene: PLK1 was marked as current diagnostic
Added comment: Five individuals reported with microcephaly. However, unclear if microcephaly is pre or post natal.
Sources: Literature
Fetal anomalies v0.4554 POGZ Zornitza Stark Mode of inheritance for gene: POGZ was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4553 POGZ Zornitza Stark changed review comment from: White-Sutton syndrome is a neurodevelopmental disorder characterized by delayed psychomotor development apparent in infancy and a characteristic constellation of dysmorphic facial features. Additional features may include hypotonia, sensorineural hearing impairment, visual defects, joint laxity, and gastrointestinal difficulties, such as poor feeding.

More than 40 individuals reported.; to: White-Sutton syndrome is a neurodevelopmental disorder characterized by delayed psychomotor development apparent in infancy and a characteristic constellation of dysmorphic facial features. Additional features may include hypotonia, sensorineural hearing impairment, visual defects, joint laxity, and gastrointestinal difficulties, such as poor feeding.

More than 40 individuals reported.

Microcephaly is a feature, congenital heart disease rarely reported.
Fetal anomalies v0.4553 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Fetal anomalies v0.4553 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Fetal anomalies v0.4553 POLR1C Zornitza Stark Phenotypes for gene: POLR1C were changed from TREACHER COLLINS SYNDROME TYPE 3 to Treacher Collins syndrome 3, MIM# 248390
Fetal anomalies v0.4552 POLR1C Zornitza Stark Publications for gene: POLR1C were set to
Fetal anomalies v0.4551 POLR1C Zornitza Stark changed review comment from: 8 unrelated individuals reported, ID is part of the phenotype.
Sources: Expert list; to: Treacher Collins more likely to be detected antenatally.

Sources: Expert list
Fetal anomalies v0.4551 POLR1C Zornitza Stark edited their review of gene: POLR1C: Changed phenotypes: Leukodystrophy, hypomyelinating, 11, MIM# 616494, Treacher Collins syndrome 3, MIM# 248390
Fetal anomalies v0.4551 POMGNT2 Zornitza Stark Marked gene: POMGNT2 as ready
Fetal anomalies v0.4551 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4551 POMGNT2 Zornitza Stark Phenotypes for gene: POMGNT2 were changed from WALKER WARBERG SYNDROME to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8, MIM# 614830
Fetal anomalies v0.4550 POMGNT2 Zornitza Stark edited their review of gene: POMGNT2: Changed phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 614830
Fetal anomalies v0.4550 POMK Zornitza Stark Marked gene: POMK as ready
Fetal anomalies v0.4550 POMK Zornitza Stark Gene: pomk has been classified as Green List (High Evidence).
Fetal anomalies v0.4550 POMT1 Zornitza Stark Marked gene: POMT1 as ready
Fetal anomalies v0.4550 POMT1 Zornitza Stark Gene: pomt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4550 POMT1 Zornitza Stark Phenotypes for gene: POMT1 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C1; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B1; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A1 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Walker-Walburg syndrome
Fetal anomalies v0.4549 POMT1 Zornitza Stark Publications for gene: POMT1 were set to
Fetal anomalies v0.4548 POMT2 Zornitza Stark Marked gene: POMT2 as ready
Fetal anomalies v0.4548 POMT2 Zornitza Stark Gene: pomt2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4548 POMT2 Zornitza Stark Phenotypes for gene: POMT2 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A2; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B2; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C2 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150
Fetal anomalies v0.4547 POMT2 Zornitza Stark Publications for gene: POMT2 were set to
Fetal anomalies v0.4546 POMT2 Zornitza Stark edited their review of gene: POMT2: Changed phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150
Fetal anomalies v0.4546 POMT2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association, multiple anomalies at the more severe end of the spectrum.
Fetal anomalies v0.4546 PIGH Belinda Chong gene: PIGH was added
gene: PIGH was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PIGH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGH were set to 29573052; 33156547; 29603516
Phenotypes for gene: PIGH were set to Glycosylphosphatidylinositol biosynthesis defect 17, MIM# 618010
Review for gene: PIGH was set to AMBER
gene: PIGH was marked as current diagnostic
Added comment: Microcephaly appears to present at postnatal in these individuals.

Three further families reported, including two sibs with microcephaly.
Sources: Literature
Fetal anomalies v0.4546 PHC1 Belinda Chong gene: PHC1 was added
gene: PHC1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PHC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHC1 were set to 23418308
Phenotypes for gene: PHC1 were set to Microcephaly 11, primary, autosomal recessive, MIM#615414
Review for gene: PHC1 was set to RED
gene: PHC1 was marked as current diagnostic
Added comment: Short stature and microcephaly, currently not enough information.

Single family reported with functional data.
Sources: Literature
Fetal anomalies v0.4546 POR Zornitza Stark Marked gene: POR as ready
Fetal anomalies v0.4546 POR Zornitza Stark Gene: por has been classified as Green List (High Evidence).
Fetal anomalies v0.4546 PORCN Zornitza Stark Marked gene: PORCN as ready
Fetal anomalies v0.4546 PORCN Zornitza Stark Gene: porcn has been classified as Green List (High Evidence).
Fetal anomalies v0.4546 PORCN Zornitza Stark Phenotypes for gene: PORCN were changed from FOCAL DERMAL HYPOPLASIA to Focal dermal hypoplasia, MIM# 305600
Fetal anomalies v0.4545 PORCN Zornitza Stark Publications for gene: PORCN were set to
Fetal anomalies v0.4544 POU1F1 Zornitza Stark Marked gene: POU1F1 as ready
Fetal anomalies v0.4544 POU1F1 Zornitza Stark Gene: pou1f1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4544 POU1F1 Zornitza Stark Phenotypes for gene: POU1F1 were changed from POU1F1-RELATED COMBINED PITUITARY HORMONE DEFICIENCY to Pituitary hormone deficiency, combined, 1, MIM# 613038
Fetal anomalies v0.4543 POU1F1 Zornitza Stark Publications for gene: POU1F1 were set to
Fetal anomalies v0.4542 POU1F1 Zornitza Stark changed review comment from: Hypotonia with untreated hypothyroidism, not truly ID.; to: Presentation with hydrops reported.
Fetal anomalies v0.4542 POU1F1 Zornitza Stark edited their review of gene: POU1F1: Changed rating: GREEN; Changed publications: 7593413
Fetal anomalies v0.4542 PPP2R1A Zornitza Stark Marked gene: PPP2R1A as ready
Fetal anomalies v0.4542 PPP2R1A Zornitza Stark Gene: ppp2r1a has been classified as Green List (High Evidence).
Fetal anomalies v0.4542 PPP2R1A Zornitza Stark Phenotypes for gene: PPP2R1A were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 36, MIM#616362; Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605
Fetal anomalies v0.4541 PPP2R1A Zornitza Stark Publications for gene: PPP2R1A were set to
Fetal anomalies v0.4540 PPP2R1A Zornitza Stark Mode of pathogenicity for gene: PPP2R1A was changed from to Other
Fetal anomalies v0.4539 PPP2R1A Zornitza Stark Mode of inheritance for gene: PPP2R1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4538 PPP2R5D Zornitza Stark Marked gene: PPP2R5D as ready
Fetal anomalies v0.4538 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Fetal anomalies v0.4538 PPP2R5D Zornitza Stark Phenotypes for gene: PPP2R5D were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 35, MIM#616355
Fetal anomalies v0.4537 PPP2R5D Zornitza Stark Publications for gene: PPP2R5D were set to
Fetal anomalies v0.4536 PPP2R5D Zornitza Stark Mode of inheritance for gene: PPP2R5D was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4535 PPP2R5D Zornitza Stark changed review comment from: (P/LP in ClinVar): >15 missense, 1 PTC DN missense mechanism suspected: Functional studies showed defective holoenzyme assembly in transfected HEK293 cells and mutant subunits hindering dephosphorylation of B56δ-anchored substrates. Moreover,. p.P53S was the only variant to not show defective binding - authors speculate an alternative mechanism. Unknown mechanism for PTCs: pLI = 1 and very few in gnomAD. Missense variants cluster p.198-207 (Decipher).; to: (P/LP in ClinVar): >15 missense, 1 PTC DN missense mechanism suspected: Functional studies showed defective holoenzyme assembly in transfected HEK293 cells and mutant subunits hindering dephosphorylation of B56δ-anchored substrates. Moreover,. p.P53S was the only variant to not show defective binding - authors speculate an alternative mechanism. Unknown mechanism for PTCs: pLI = 1 and very few in gnomAD. Missense variants cluster p.198-207 (Decipher).

Hydrocephalus reported in some.
Fetal anomalies v0.4535 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Fetal anomalies v0.4535 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Fetal anomalies v0.4535 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from Rasopathy with developmental delay, short stature and sparse slow-growing hair to Noonan syndrome-like disorder with loose anlagen hair 2, OMIM # 617506
Fetal anomalies v0.4534 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to
Fetal anomalies v0.4533 PPP1CB Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4532 PDCD6IP Belinda Chong gene: PDCD6IP was added
gene: PDCD6IP was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to 32286682
Phenotypes for gene: PDCD6IP were set to Primary microcephaly
Review for gene: PDCD6IP was set to AMBER
gene: PDCD6IP was marked as current diagnostic
Added comment: Primary microcephaly was noticed at birth and their occipital-frontal circumference (OFC) was ≤−2 standard deviations (SD), may be relevant for this panel however, currently not enough information.

One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Fetal anomalies v0.4532 PCYT2 Belinda Chong gene: PCYT2 was added
gene: PCYT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCYT2 were set to 31637422
Phenotypes for gene: PCYT2 were set to Spastic paraplegia 82, autosomal recessive MIM#618770
Review for gene: PCYT2 was set to RED
gene: PCYT2 was marked as current diagnostic
Added comment: Brain imaging shows progressive cerebral and cerebellar atrophy however, normal initially.

5 individuals from 4 families reported with progressive neurologic disorder characterized by global developmental delay apparent from infancy, significant motor impairment, and progressive spasticity mainly affecting the lower limbs. Some never achieved walking, whereas others lost the ability to walk or walk with an unsteady gait. Additional features included variably impaired intellectual development with language difficulties, ocular anomalies, such as nystagmus and visual impairment, and seizures. Brain imaging shows progressive cerebral and cerebellar atrophy, as well as white matter hyperintensities. Overall poor growth, but only one individual reported with microcephaly -3SD, and head size appears relatively spared against other reported growth parameters.
Sources: Literature
Fetal anomalies v0.4532 PCDH12 Belinda Chong gene: PCDH12 was added
gene: PCDH12 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PCDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDH12 were set to 27164683; 30178464
Phenotypes for gene: PCDH12 were set to Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280
Review for gene: PCDH12 was set to GREEN
gene: PCDH12 was marked as current diagnostic
Added comment: Brain malformations were detectable antenatally.

Diencephalic-mesencephalic junction dysplasia syndrome-1 (DMJDS1) is an autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, severely delayed or even absent psychomotor development with profound intellectual disability, and spasticity or dystonia. Some patients may have seizures and/or visual impairment. Brain imaging shows a characteristic developmental malformation of the midbrain; subtle intracranial calcifications may also be present. At least 12 families reported.
Sources: Literature
Fetal anomalies v0.4532 PARP6 Belinda Chong gene: PARP6 was added
gene: PARP6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PARP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PARP6 were set to 34067418
Phenotypes for gene: PARP6 were set to Intellectual disability; Epilepsy; Microcephaly
Review for gene: PARP6 was set to GREEN
gene: PARP6 was marked as current diagnostic
Added comment: IUGR and partial agenesis of the corpus callosum has been observed.

Four unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype. Supportive functional data. One pair of siblings with a homozygous missense: limited evidence for bi-allelic variants causing disease.
Sources: Literature
Fetal anomalies v0.4532 PUF60 Zornitza Stark commented on gene: PUF60: Multiple congenital anomalies.
Fetal anomalies v0.4532 PSAP Zornitza Stark Phenotypes for gene: PSAP were changed from Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722, MONDO:0012720; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, MONDO:0009590; Gaucher disease, atypical, MIM# 610539, MONDO:0012517 to Combined SAP deficiency, MIM# 611721
Fetal anomalies v0.4531 PSAP Zornitza Stark edited their review of gene: PSAP: Added comment: Hepatosplenomegaly at birth at the most severe end of the spectrum.; Changed rating: AMBER; Changed phenotypes: Combined SAP deficiency, MIM# 611721
Fetal anomalies v0.4531 PSAP Zornitza Stark Deleted their comment
Fetal anomalies v0.4531 TBC1D7 Zornitza Stark Marked gene: TBC1D7 as ready
Fetal anomalies v0.4531 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4531 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Amber List (moderate evidence)
Fetal anomalies v0.4531 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4530 TAOK1 Zornitza Stark Marked gene: TAOK1 as ready
Fetal anomalies v0.4530 TAOK1 Zornitza Stark Gene: taok1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4530 TAOK1 Zornitza Stark Classified gene: TAOK1 as Green List (high evidence)
Fetal anomalies v0.4530 TAOK1 Zornitza Stark Gene: taok1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4529 STT3A Zornitza Stark Marked gene: STT3A as ready
Fetal anomalies v0.4529 STT3A Zornitza Stark Gene: stt3a has been classified as Green List (High Evidence).
Fetal anomalies v0.4529 STT3A Zornitza Stark Classified gene: STT3A as Green List (high evidence)
Fetal anomalies v0.4529 STT3A Zornitza Stark Gene: stt3a has been classified as Green List (High Evidence).
Fetal anomalies v0.4528 RHEB Zornitza Stark Marked gene: RHEB as ready
Fetal anomalies v0.4528 RHEB Zornitza Stark Gene: rheb has been classified as Green List (High Evidence).
Fetal anomalies v0.4528 RHEB Zornitza Stark Classified gene: RHEB as Green List (high evidence)
Fetal anomalies v0.4528 RHEB Zornitza Stark Gene: rheb has been classified as Green List (High Evidence).
Fetal anomalies v0.4527 PPP2R5C Zornitza Stark Marked gene: PPP2R5C as ready
Fetal anomalies v0.4527 PPP2R5C Zornitza Stark Gene: ppp2r5c has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4527 PPP2R5C Zornitza Stark Classified gene: PPP2R5C as Amber List (moderate evidence)
Fetal anomalies v0.4527 PPP2R5C Zornitza Stark Gene: ppp2r5c has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4526 LMNB2 Zornitza Stark Marked gene: LMNB2 as ready
Fetal anomalies v0.4526 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4526 LMNB2 Zornitza Stark Classified gene: LMNB2 as Green List (high evidence)
Fetal anomalies v0.4526 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4525 MCM7 Zornitza Stark Marked gene: MCM7 as ready
Fetal anomalies v0.4525 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4525 MCM7 Zornitza Stark Classified gene: MCM7 as Amber List (moderate evidence)
Fetal anomalies v0.4525 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4524 LMNB1 Zornitza Stark Marked gene: LMNB1 as ready
Fetal anomalies v0.4524 LMNB1 Zornitza Stark Gene: lmnb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4524 LMNB1 Zornitza Stark Classified gene: LMNB1 as Green List (high evidence)
Fetal anomalies v0.4524 LMNB1 Zornitza Stark Gene: lmnb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4523 LINGO1 Zornitza Stark Marked gene: LINGO1 as ready
Fetal anomalies v0.4523 LINGO1 Zornitza Stark Gene: lingo1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4523 LINGO1 Zornitza Stark Classified gene: LINGO1 as Amber List (moderate evidence)
Fetal anomalies v0.4523 LINGO1 Zornitza Stark Gene: lingo1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4522 LAGE3 Zornitza Stark Marked gene: LAGE3 as ready
Fetal anomalies v0.4522 LAGE3 Zornitza Stark Gene: lage3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4522 LAGE3 Zornitza Stark Classified gene: LAGE3 as Green List (high evidence)
Fetal anomalies v0.4522 LAGE3 Zornitza Stark Gene: lage3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4521 KIF21B Zornitza Stark Marked gene: KIF21B as ready
Fetal anomalies v0.4521 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Fetal anomalies v0.4521 KIF21B Zornitza Stark Phenotypes for gene: KIF21B were changed from Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly to Neurodevelopmental disorder, MONDO:0700092; Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Fetal anomalies v0.4520 KIF21B Zornitza Stark Classified gene: KIF21B as Green List (high evidence)
Fetal anomalies v0.4520 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Fetal anomalies v0.4519 PQBP1 Zornitza Stark Marked gene: PQBP1 as ready
Fetal anomalies v0.4519 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4519 PQBP1 Zornitza Stark Phenotypes for gene: PQBP1 were changed from RENPENNING S(YNDROME 1 to Renpenning syndrome, MIM#309500
Fetal anomalies v0.4518 PQBP1 Zornitza Stark Publications for gene: PQBP1 were set to
Fetal anomalies v0.4517 PRKAR1A Zornitza Stark Marked gene: PRKAR1A as ready
Fetal anomalies v0.4517 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
Fetal anomalies v0.4517 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from ACRODYSOSTOSIS to Acrodysostosis 1, with or without hormone resistance, MIM#101800
Fetal anomalies v0.4516 PRKAR1A Zornitza Stark Mode of inheritance for gene: PRKAR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4515 PRKAR1A Zornitza Stark changed review comment from: Multiple phenotypes associated with this gene, but this particular OMIM condition has ID as part of the phenotype.; to: Multiple phenotypes associated with this gene, but this particular OMIM condition has prenatal growth retardation as part of the phenotype.
Fetal anomalies v0.4515 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Fetal anomalies v0.4515 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4515 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from Syndromic congenital heart defects to Congenital heart defects and ectodermal dysplasia, MIM#617364
Fetal anomalies v0.4514 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4513 PRKD1 Zornitza Stark edited their review of gene: PRKD1: Added comment: PMID: 27479907 (2016): three individuals reported, two with the c.1774G>A variant and one with the c.896T>G variant. All had congenital heart disease, two had some developmental delay, and two had variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth; the third individuals had a 'disorganized eyebrow.'

PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation.

c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.; Changed publications: 27479907, 32817298; Changed phenotypes: Congenital heart defects and ectodermal dysplasia, MIM#617364; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4513 PRKD1 Zornitza Stark Deleted their comment
Fetal anomalies v0.4513 PRKD1 Zornitza Stark Deleted their comment
Fetal anomalies v0.4513 PRSS56 Zornitza Stark Marked gene: PRSS56 as ready
Fetal anomalies v0.4513 PRSS56 Zornitza Stark Gene: prss56 has been classified as Green List (High Evidence).
Fetal anomalies v0.4513 PRSS56 Zornitza Stark Phenotypes for gene: PRSS56 were changed from MICROPHTHALMIA ISOLATED TYPE 6 to Microphthalmia, isolated 6, MIM# 613517
Fetal anomalies v0.4512 PRSS56 Zornitza Stark Publications for gene: PRSS56 were set to
Fetal anomalies v0.4511 RAB18 Zornitza Stark Marked gene: RAB18 as ready
Fetal anomalies v0.4511 RAB18 Zornitza Stark Gene: rab18 has been classified as Green List (High Evidence).
Fetal anomalies v0.4511 RAB18 Zornitza Stark Phenotypes for gene: RAB18 were changed from WARBURG MICRO SYNDROME TYPE 3 to Warburg micro syndrome 3, MIM# 614222
Fetal anomalies v0.4510 RAB18 Zornitza Stark Publications for gene: RAB18 were set to
Fetal anomalies v0.4509 RAB3GAP1 Zornitza Stark Marked gene: RAB3GAP1 as ready
Fetal anomalies v0.4509 RAB3GAP1 Zornitza Stark Gene: rab3gap1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4509 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from WARBURG MICRO SYNDROME TYPE 1 to Warburg micro syndrome 1, MIM# 600118; Martsolf syndrome 2, MIM# 619420
Fetal anomalies v0.4508 RAB3GAP1 Zornitza Stark Publications for gene: RAB3GAP1 were set to
Fetal anomalies v0.4507 RAB3GAP2 Zornitza Stark Marked gene: RAB3GAP2 as ready
Fetal anomalies v0.4507 RAB3GAP2 Zornitza Stark Gene: rab3gap2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4507 RAB3GAP2 Zornitza Stark Phenotypes for gene: RAB3GAP2 were changed from MARTSOLF SYNDROME to Warburg micro syndrome 2, MIM# 614225
Fetal anomalies v0.4506 RAB3GAP2 Zornitza Stark Publications for gene: RAB3GAP2 were set to
Fetal anomalies v0.4505 RAC1 Zornitza Stark Marked gene: RAC1 as ready
Fetal anomalies v0.4505 RAC1 Zornitza Stark Gene: rac1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4505 RAC1 Zornitza Stark Phenotypes for gene: RAC1 were changed from Developmental Disorders with Diverse Phenotypes to Mental retardation, autosomal dominant 48, MIM# 617751
Fetal anomalies v0.4504 RAC1 Zornitza Stark Publications for gene: RAC1 were set to 30712878; 28886345
Fetal anomalies v0.4503 RAC1 Zornitza Stark Mode of pathogenicity for gene: RAC1 was changed from to Other
Fetal anomalies v0.4502 RAC1 Zornitza Stark Mode of inheritance for gene: RAC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4501 RAD21 Zornitza Stark Marked gene: RAD21 as ready
Fetal anomalies v0.4501 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Fetal anomalies v0.4501 RAD21 Zornitza Stark Phenotypes for gene: RAD21 were changed from COHESINOPATHY to Cornelia de Lange syndrome 4, MIM# 614701; Holoprosencephaly
Fetal anomalies v0.4500 RAD21 Zornitza Stark Publications for gene: RAD21 were set to
Fetal anomalies v0.4499 RAD21 Zornitza Stark Mode of inheritance for gene: RAD21 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4498 RAF1 Zornitza Stark Marked gene: RAF1 as ready
Fetal anomalies v0.4498 RAF1 Zornitza Stark Gene: raf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4498 RAF1 Zornitza Stark Phenotypes for gene: RAF1 were changed from NOONAN SYNDROME 5 to Noonan syndrome 5, MIM# 611553
Fetal anomalies v0.4497 RAF1 Zornitza Stark Publications for gene: RAF1 were set to
Fetal anomalies v0.4496 RAF1 Zornitza Stark Mode of pathogenicity for gene: RAF1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v0.4495 RAF1 Zornitza Stark Mode of inheritance for gene: RAF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4494 RAI1 Zornitza Stark Marked gene: RAI1 as ready
Fetal anomalies v0.4494 RAI1 Zornitza Stark Gene: rai1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4494 RAI1 Zornitza Stark Phenotypes for gene: RAI1 were changed from SMITH-MAGENIS SYNDROME to Smith-Magenis syndrome (MIM#182290)
Fetal anomalies v0.4493 RAI1 Zornitza Stark Publications for gene: RAI1 were set to
Fetal anomalies v0.4492 RAI1 Zornitza Stark Mode of inheritance for gene: RAI1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4491 RAI1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association, multiple congenital anomalies.
Fetal anomalies v0.4491 RAPSN Zornitza Stark Marked gene: RAPSN as ready
Fetal anomalies v0.4491 RAPSN Zornitza Stark Gene: rapsn has been classified as Green List (High Evidence).
Fetal anomalies v0.4491 RAPSN Zornitza Stark Phenotypes for gene: RAPSN were changed from FETAL AKINESIA DEFORMATION SEQUENCE; CONGENITAL MYASTHENIC SYNDROME WITH ACETYLCHOLINE RECEPTOR DEFICIENCY to Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency, MIM#616326; Fetal akinesia deformation sequence 2, MIM# 618388
Fetal anomalies v0.4490 RAPSN Zornitza Stark edited their review of gene: RAPSN: Changed phenotypes: Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency, MIM#616326, Fetal akinesia deformation sequence 2, MIM# 618388
Fetal anomalies v0.4490 RAPSN Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Fetal akinesia, contractures.
Fetal anomalies v0.4490 RAPSN Zornitza Stark edited their review of gene: RAPSN: Changed rating: GREEN
Fetal anomalies v0.4490 RARB Zornitza Stark Marked gene: RARB as ready
Fetal anomalies v0.4490 RARB Zornitza Stark Gene: rarb has been classified as Green List (High Evidence).
Fetal anomalies v0.4490 RARB Zornitza Stark Phenotypes for gene: RARB were changed from MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA to Microphthalmia, syndromic 12, MIM# 615524
Fetal anomalies v0.4489 RARB Zornitza Stark Publications for gene: RARB were set to
Fetal anomalies v0.4488 RARS2 Zornitza Stark Marked gene: RARS2 as ready
Fetal anomalies v0.4488 RARS2 Zornitza Stark Gene: rars2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4488 RARS2 Zornitza Stark Phenotypes for gene: RARS2 were changed from PONTOCEREBELLAR HYPOPLASIA TYPE 6 to Pontocerebellar hypoplasia, type 6, MIM# 611523
Fetal anomalies v0.4487 RARS2 Zornitza Stark Publications for gene: RARS2 were set to 26083569
Fetal anomalies v0.4486 RARS2 Zornitza Stark changed review comment from: Progressive microcephaly is part of the phenotype. At least three unrelated families reported.; to: Progressive microcephaly, PCH. At least three unrelated families reported.
Fetal anomalies v0.4486 RASA1 Zornitza Stark Marked gene: RASA1 as ready
Fetal anomalies v0.4486 RASA1 Zornitza Stark Gene: rasa1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4486 RASA1 Zornitza Stark Phenotypes for gene: RASA1 were changed from PARKES WEBER SYNDROME; CAPILLARY MALFORMATION-ARTERIOVENOUS MALFORMATION to Capillary malformation-arteriovenous malformation 1, MIM# 608354
Fetal anomalies v0.4485 RASA1 Zornitza Stark Publications for gene: RASA1 were set to
Fetal anomalies v0.4484 RASA1 Zornitza Stark Mode of inheritance for gene: RASA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4483 RASA1 Zornitza Stark changed review comment from: Single individual reported as part of a cohort.
Sources: Literature; to: AV malformations/fistulas, which can be large.
Sources: Literature
Fetal anomalies v0.4483 RASA1 Zornitza Stark edited their review of gene: RASA1: Changed rating: GREEN; Changed phenotypes: Capillary malformation-arteriovenous malformation 1, MIM# 608354
Fetal anomalies v0.4483 RAX Zornitza Stark Marked gene: RAX as ready
Fetal anomalies v0.4483 RAX Zornitza Stark Gene: rax has been classified as Green List (High Evidence).
Fetal anomalies v0.4483 RAX Zornitza Stark Phenotypes for gene: RAX were changed from MICROPHTHALMIA ISOLATED TYPE 3 to Microphthalmia, isolated 3, MIM# 611038
Fetal anomalies v0.4482 RAX Zornitza Stark Publications for gene: RAX were set to
Fetal anomalies v0.4481 RBM8A Zornitza Stark Marked gene: RBM8A as ready
Fetal anomalies v0.4481 RBM8A Zornitza Stark Gene: rbm8a has been classified as Green List (High Evidence).
Fetal anomalies v0.4481 RBM8A Zornitza Stark Phenotypes for gene: RBM8A were changed from THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME to Thrombocytopaenia-absent radius syndrome, MIM# 274000
Fetal anomalies v0.4480 RBM8A Zornitza Stark Tag SV/CNV tag was added to gene: RBM8A.
Fetal anomalies v0.4480 RBPJ Zornitza Stark Marked gene: RBPJ as ready
Fetal anomalies v0.4480 RBPJ Zornitza Stark Gene: rbpj has been classified as Green List (High Evidence).
Fetal anomalies v0.4480 RBPJ Zornitza Stark Phenotypes for gene: RBPJ were changed from ADAMS OLIVER SYNDROME to Adams-Oliver syndrome 3, MIM#614814
Fetal anomalies v0.4479 RBPJ Zornitza Stark Mode of inheritance for gene: RBPJ was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4478 RBPJ Zornitza Stark changed review comment from: One of the original families described as having no intellectual disability and the other with mild, so I don't think ID is a core feature of the phenotype.; to: Transverse limb defects.
Fetal anomalies v0.4478 RBPJ Zornitza Stark edited their review of gene: RBPJ: Changed rating: GREEN
Fetal anomalies v0.4478 RECQL4 Zornitza Stark Marked gene: RECQL4 as ready
Fetal anomalies v0.4478 RECQL4 Zornitza Stark Gene: recql4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4478 MCM7 Krithika Murali gene: MCM7 was added
gene: MCM7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MCM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM7 were set to 33654309; 34059554
Phenotypes for gene: MCM7 were set to Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Review for gene: MCM7 was set to AMBER
Added comment: Association with congenital microcephaly. No new publications since last PanelApp review

---

MCM7 is a component of the MCM complex, a DNA helicase which is essential for DNA replication. Other components have been linked to disease with phenotypes including microcephaly and ID. MCM7 is not associated with any phenotype in OMIM or G2P at present. ------ Currently there are 3 unrelated pedigrees in literature with different biallelic MCM7 variants associated with disease (see below). Although there is some functional data in support of variant-level deleteriousness or gene-level pathogenicity, the clinical gestalt is very different between the 3 families.

- PMID: 33654309 (2021) - Two unrelated individuals with different compound het variants in MCM7 but disparate clinical features. One patient had typical Meier-Gorlin syndrome (including growth retardation, microcephaly, congenital lung emphysema, absent breast development, microtia, facial dysmorphism) whereas the second case had a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. While small at birth, the second patient did not demonstrate reduced stature or microcephaly at age 14.5 years. Both individuals had normal neurodevelopment. Functional studies using patient-derived fibroblasts demonstrate that the identified MCM7 variants were deleterious at either transcript or protein levels and through interfering with MCM complex formation, impact efficiency of S phase progression.

- PMID: 34059554 (2021) - Homozygous missense variant identified in three affected individuals from a consanguineous family with severe primary microcephaly, severe ID and behavioural abnormalities. Knockdown of Mcm7 in mouse neuroblastoma cells lead to reduced cell viability and proliferation with increased apoptosis, which were rescued by overexpression of wild-type but not mutant MCM7.
Sources: Literature
Fetal anomalies v0.4478 LMNB2 Krithika Murali gene: LMNB2 was added
gene: LMNB2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LMNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMNB2 were set to 33033404
Phenotypes for gene: LMNB2 were set to Microcephaly 27, primary, autosomal dominant - MIM#619180
Review for gene: LMNB2 was set to GREEN
Added comment: Almost all reported individuals had congenital microcephaly.
Sources: Literature
Fetal anomalies v0.4478 LMNB1 Krithika Murali gene: LMNB1 was added
gene: LMNB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LMNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMNB1 were set to 32910914
Phenotypes for gene: LMNB1 were set to Microcephaly 26, primary, autosomal dominant - MIM#619179
Review for gene: LMNB1 was set to GREEN
Added comment: Monoallelic variants associated with profound microcephaly - this was noted antenatally in 5 unrelated individuals (total of 8 individuals from 5 families reported)
Sources: Literature
Fetal anomalies v0.4478 LINGO1 Krithika Murali gene: LINGO1 was added
gene: LINGO1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LINGO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LINGO1 were set to 28837161; 31668702
Phenotypes for gene: LINGO1 were set to Mental retardation, autosomal recessive 64 - MIM#618103
Review for gene: LINGO1 was set to AMBER
Added comment: 5 individuals reported from 2 families. 4 out of the 5 individuals had microcephaly. ID, developmentatl delay, spasticity, hypertonia, feeding problems also reported features. No antenatal information or birth growth parameters provided, but it is possible that microcephaly was antenatal/congenital in onset based on other phenotypic features reported.
Sources: Literature
Fetal anomalies v0.4478 LAGE3 Krithika Murali gene: LAGE3 was added
gene: LAGE3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LAGE3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: LAGE3 were set to 31069511; 28805828
Phenotypes for gene: LAGE3 were set to Galloway-Mowat syndrome 2, X-linked - MIM#301006
Review for gene: LAGE3 was set to GREEN
Added comment: Phenotypic features detectable antenatally include microcephaly, IUGR and brain malformations.
Sources: Literature
Fetal anomalies v0.4478 KIF21B Krithika Murali gene: KIF21B was added
gene: KIF21B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF21B were set to 32415109
Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Review for gene: KIF21B was set to GREEN
Added comment: Monoallelic variants associated with a neurodevelopmental disorder. Phenotypic features include ID, corpus callosum anomalies and microcephaly. PMID 32415109 report 4 unrelated individuals, 2 had IUGR +/- oligohydramnios.
Sources: Literature
Fetal anomalies v0.4478 PSAP Seb Lunke Marked gene: PSAP as ready
Fetal anomalies v0.4478 PSAP Seb Lunke Gene: psap has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4478 PSAP Seb Lunke Phenotypes for gene: PSAP were changed from ATYPICAL KRABBE DISEASE to Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722, MONDO:0012720; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, MONDO:0009590; Gaucher disease, atypical, MIM# 610539, MONDO:0012517
Fetal anomalies v0.4477 PSAP Seb Lunke Classified gene: PSAP as Amber List (moderate evidence)
Fetal anomalies v0.4477 PSAP Seb Lunke Added comment: Comment on list classification: Onset in infancy, amber for fetal anomalies
Fetal anomalies v0.4477 PSAP Seb Lunke Gene: psap has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4476 PSAP Seb Lunke reviewed gene: PSAP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined SAP deficiency, MIM# 611721, Encephalopathy due to prosaposin deficiency, MONDO:0012719, Krabbe disease, atypical, MIM# 611722, MONDO:0012720, Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, MONDO:0009590, Gaucher disease, atypical, MIM# 610539, MONDO:0012517 Edit; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4476 PTCH1 Seb Lunke Marked gene: PTCH1 as ready
Fetal anomalies v0.4476 PTCH1 Seb Lunke Gene: ptch1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4476 PTCH1 Seb Lunke Publications for gene: PTCH1 were set to
Fetal anomalies v0.4475 PTCH1 Seb Lunke Phenotypes for gene: PTCH1 were changed from HOLOPROSENCEPHALY-7; BASAL CELL NEVUS SYNDROME to Holoprosencephaly 7, MIM# 610828
Fetal anomalies v0.4474 PTCH1 Seb Lunke Mode of inheritance for gene: PTCH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4473 PTPN11 Seb Lunke Marked gene: PTPN11 as ready
Fetal anomalies v0.4473 PTPN11 Seb Lunke Gene: ptpn11 has been classified as Green List (High Evidence).
Fetal anomalies v0.4473 PTPN11 Seb Lunke Phenotypes for gene: PTPN11 were changed from LEOPARD SYNDROME TYPE 1; NOONAN SYNDROME 1 to LEOPARD syndrome 1, AD, MIM#151100 AD; Noonan syndrome 1, AD, MIM#163950
Fetal anomalies v0.4472 PTPN11 Seb Lunke Publications for gene: PTPN11 were set to 30266093; 28425981
Fetal anomalies v0.4471 PTPN11 Seb Lunke Mode of inheritance for gene: PTPN11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4470 PUF60 Seb Lunke Marked gene: PUF60 as ready
Fetal anomalies v0.4470 PUF60 Seb Lunke Gene: puf60 has been classified as Green List (High Evidence).
Fetal anomalies v0.4470 PUF60 Seb Lunke Phenotypes for gene: PUF60 were changed from PUF60 syndrome to Verheij syndrome, MIM# 615583
Fetal anomalies v0.4469 PUF60 Seb Lunke Publications for gene: PUF60 were set to
Fetal anomalies v0.4468 PUF60 Seb Lunke Mode of inheritance for gene: PUF60 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4467 RECQL4 Seb Lunke Phenotypes for gene: RECQL4 were changed from RAPADILINO SYNDROME; ROTHMUND-THOMSON SYNDROME; BALLER-GEROLD SYNDROME to Baller-Gerold syndrome, MIM# 218600; RAPADILINO syndrome, MIM# 266280; Rothmund-Thomson syndrome, type 2,MIM#268400
Fetal anomalies v0.4466 RERE Seb Lunke Marked gene: RERE as ready
Fetal anomalies v0.4466 RERE Seb Lunke Gene: rere has been classified as Green List (High Evidence).
Fetal anomalies v0.4466 RERE Seb Lunke Phenotypes for gene: RERE were changed from Phenocopy of Proximal 1p36 Deletions to Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart, MIM# 616975
Fetal anomalies v0.4465 RERE Seb Lunke Publications for gene: RERE were set to
Fetal anomalies v0.4464 RERE Seb Lunke Mode of inheritance for gene: RERE was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4463 RET Zornitza Stark Marked gene: RET as ready
Fetal anomalies v0.4463 RET Zornitza Stark Gene: ret has been classified as Green List (High Evidence).
Fetal anomalies v0.4463 RET Zornitza Stark Phenotypes for gene: RET were changed from RENAL AGENESIS; MULTIPLE ENDOCRINE NEOPLASIA IIB to Central hypoventilation syndrome, congenital, MIM#209880; Multiple endocrine neoplasia IIA, MIM#171400; Multiple endocrine neoplasia IIB, MIM#162300
Fetal anomalies v0.4462 RET Zornitza Stark Mode of inheritance for gene: RET was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4461 SNORD118 Zornitza Stark Marked gene: SNORD118 as ready
Fetal anomalies v0.4461 SNORD118 Zornitza Stark Gene: snord118 has been classified as Green List (High Evidence).
Fetal anomalies v0.4461 SNORD118 Zornitza Stark Phenotypes for gene: SNORD118 were changed from Leukoencephalopathy with cerebral calcification & cysts to Leukoencephalopathy, brain calcifications, and cysts, MIM# 614561
Fetal anomalies v0.4460 SNORD118 Zornitza Stark Publications for gene: SNORD118 were set to
Fetal anomalies v0.4459 SNORD118 Zornitza Stark changed review comment from: Many reported individuals have ID; however overall this is a progressive neurological disorder with variable onset, including in late adulthood.; to: Variable onset, including in infancy with brain abnormalities detectable by imaging.
Fetal anomalies v0.4459 SNORD118 Zornitza Stark edited their review of gene: SNORD118: Changed rating: GREEN
Fetal anomalies v0.4459 RET Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Megacolon is a feature.
Fetal anomalies v0.4459 RET Zornitza Stark edited their review of gene: RET: Changed rating: GREEN
Fetal anomalies v0.4459 RFX6 Zornitza Stark Marked gene: RFX6 as ready
Fetal anomalies v0.4459 RFX6 Zornitza Stark Gene: rfx6 has been classified as Green List (High Evidence).
Fetal anomalies v0.4459 RFX6 Zornitza Stark Phenotypes for gene: RFX6 were changed from MARTINEZ-FRIAS SYNDROME to Mitchell-Riley syndrome, MIM#615710
Fetal anomalies v0.4458 RFX6 Zornitza Stark Publications for gene: RFX6 were set to
Fetal anomalies v0.4457 RFX6 Zornitza Stark edited their review of gene: RFX6: Changed publications: 20148032, 26264437
Fetal anomalies v0.4457 RFX6 Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Intestinal atresia.
Fetal anomalies v0.4457 RFX6 Zornitza Stark edited their review of gene: RFX6: Changed rating: GREEN
Fetal anomalies v0.4457 RIPK4 Zornitza Stark Marked gene: RIPK4 as ready
Fetal anomalies v0.4457 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4457 RIPK4 Zornitza Stark Phenotypes for gene: RIPK4 were changed from POPLITEAL PTERYGIUM SYNDROME, LETHAL TYPE to Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650
Fetal anomalies v0.4456 RIPK4 Zornitza Stark Publications for gene: RIPK4 were set to 28425981
Fetal anomalies v0.4455 RIT1 Zornitza Stark Marked gene: RIT1 as ready
Fetal anomalies v0.4455 RIT1 Zornitza Stark Gene: rit1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4455 RIT1 Zornitza Stark Phenotypes for gene: RIT1 were changed from NOONAN SYNDROME 8 to Noonan syndrome 8, MIM# 615355
Fetal anomalies v0.4454 RIT1 Zornitza Stark Publications for gene: RIT1 were set to 30712878; 28425981
Fetal anomalies v0.4453 RIT1 Zornitza Stark Mode of pathogenicity for gene: RIT1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v0.4453 RIT1 Zornitza Stark Mode of pathogenicity for gene: RIT1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v0.4452 RIT1 Zornitza Stark Mode of inheritance for gene: RIT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4451 RMRP Zornitza Stark Marked gene: RMRP as ready
Fetal anomalies v0.4451 RMRP Zornitza Stark Gene: rmrp has been classified as Green List (High Evidence).
Fetal anomalies v0.4451 RMRP Zornitza Stark Phenotypes for gene: RMRP were changed from CARTILAGE-HAIR HYPOPLASIA to Anauxetic dysplasia 1, MIM#607095
Fetal anomalies v0.4450 RMRP Zornitza Stark changed review comment from: Affected individuals are described as having mild ID; note gene is associated with two milder phenotypes, cartilage-hair hypoplasia and metaphyseal dysplasia without hypotrichosis, which are not associated with ID.; to: Skeletal abnormalities; note gene is associated with two milder phenotypes, cartilage-hair hypoplasia and metaphyseal dysplasia without hypotrichosis, which are more subtle.
Fetal anomalies v0.4450 RMRP Zornitza Stark edited their review of gene: RMRP: Changed rating: GREEN
Fetal anomalies v0.4450 RNU4ATAC Zornitza Stark changed review comment from: ID is reported as part of the phenotype. NOTE this gene codes for snRNA, not protein.; to: IUGR. NOTE this gene codes for snRNA, not protein.
Fetal anomalies v0.4450 RNU4ATAC Zornitza Stark Marked gene: RNU4ATAC as ready
Fetal anomalies v0.4450 RNU4ATAC Zornitza Stark Gene: rnu4atac has been classified as Green List (High Evidence).
Fetal anomalies v0.4450 RNU4ATAC Zornitza Stark Phenotypes for gene: RNU4ATAC were changed from MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE I to Microcephalic osteodysplastic primordial dwarfism, type I, MIM#210710; Roifman syndrome, MIM#616651
Fetal anomalies v0.4449 RNU4ATAC Zornitza Stark Mode of pathogenicity for gene: RNU4ATAC was changed from to Other
Fetal anomalies v0.4448 ROBO1 Zornitza Stark Marked gene: ROBO1 as ready
Fetal anomalies v0.4448 ROBO1 Zornitza Stark Gene: robo1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4448 ROBO1 Zornitza Stark Phenotypes for gene: ROBO1 were changed from Tetralogy of Fallot and septal defects to Tetralogy of Fallot and septal defects; Congenital heart disease, MONDO:0005453
Fetal anomalies v0.4447 ROBO1 Zornitza Stark Phenotypes for gene: ROBO1 were changed from tetralogy of Fallot and septal defects to Tetralogy of Fallot and septal defects
Fetal anomalies v0.4446 ROBO1 Zornitza Stark Mode of inheritance for gene: ROBO1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4445 ROGDI Zornitza Stark Marked gene: ROGDI as ready
Fetal anomalies v0.4445 ROGDI Zornitza Stark Gene: rogdi has been classified as Green List (High Evidence).
Fetal anomalies v0.4445 ROGDI Zornitza Stark Phenotypes for gene: ROGDI were changed from KOHLSCHAYTTER-TANZ SYNDROME to Kohlschutter-Tonz syndrome, MIM# 226750
Fetal anomalies v0.4444 ROGDI Zornitza Stark Publications for gene: ROGDI were set to
Fetal anomalies v0.4443 ROGDI Zornitza Stark changed review comment from: Kohlschutter-Tonz syndrome (KTZS) is an autosomal recessive disorder characterized by severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting both primary and secondary teeth and causing yellow or brown discolouration of the teeth. More than 10 families reported.; to: Kohlschutter-Tonz syndrome (KTZS) is an autosomal recessive disorder characterized by severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting both primary and secondary teeth and causing yellow or brown discolouration of the teeth. More than 10 families reported.

Cerebellar hypoplasia and ventriculomegaly described.
Fetal anomalies v0.4443 RPGRIP1L Zornitza Stark Marked gene: RPGRIP1L as ready
Fetal anomalies v0.4443 RPGRIP1L Zornitza Stark Gene: rpgrip1l has been classified as Green List (High Evidence).
Fetal anomalies v0.4443 RPGRIP1L Zornitza Stark Phenotypes for gene: RPGRIP1L were changed from MECKEL SYNDROME TYPE 5; COACH SYNDROME; JOUBERT SYNDROME TYPE 7 to Joubert syndrome 7, MIM# 611560; Meckel syndrome 5, MIM# 611561
Fetal anomalies v0.4442 RPGRIP1L Zornitza Stark Publications for gene: RPGRIP1L were set to
Fetal anomalies v0.4441 RPL11 Zornitza Stark Marked gene: RPL11 as ready
Fetal anomalies v0.4441 RPL11 Zornitza Stark Gene: rpl11 has been classified as Green List (High Evidence).
Fetal anomalies v0.4441 RPL11 Zornitza Stark Phenotypes for gene: RPL11 were changed from Diamond-Blackfan anemia with cleft palate and abnormal thumbs; Diamond-Blackfan anemia 7 612562 to Diamond-Blackfan anemia with cleft palate and abnormal thumbs; Diamond-Blackfan anaemia 7, MIM# 612562; MONDO:0012938
Fetal anomalies v0.4440 RPL11 Zornitza Stark Publications for gene: RPL11 were set to
Fetal anomalies v0.4439 RPL11 Zornitza Stark Mode of inheritance for gene: RPL11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4438 RPL5 Zornitza Stark Marked gene: RPL5 as ready
Fetal anomalies v0.4438 RPL5 Zornitza Stark Gene: rpl5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4438 RPL5 Zornitza Stark Phenotypes for gene: RPL5 were changed from Diamond-Blackfan anemia 6 612561 to Diamond-Blackfan anaemia 6, MIM# 612561; MONDO:0012937
Fetal anomalies v0.4437 RPL5 Zornitza Stark Publications for gene: RPL5 were set to
Fetal anomalies v0.4436 RPL5 Zornitza Stark Mode of inheritance for gene: RPL5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4435 RPS10 Zornitza Stark Marked gene: RPS10 as ready
Fetal anomalies v0.4435 RPS10 Zornitza Stark Gene: rps10 has been classified as Green List (High Evidence).
Fetal anomalies v0.4435 RPS10 Zornitza Stark Phenotypes for gene: RPS10 were changed from Diamond-Blackfan anemia 9 613308 to Diamond-Blackfan anaemia 9, MIM# 613308
Fetal anomalies v0.4434 RPS10 Zornitza Stark Publications for gene: RPS10 were set to
Fetal anomalies v0.4433 RPS17 Zornitza Stark Marked gene: RPS17 as ready
Fetal anomalies v0.4433 RPS17 Zornitza Stark Gene: rps17 has been classified as Green List (High Evidence).
Fetal anomalies v0.4433 RPS17 Zornitza Stark Phenotypes for gene: RPS17 were changed from Diamond-Blackfan anemia 4 612527 to Diamond-Blackfan anaemia 4, MIM# 612527
Fetal anomalies v0.4432 RPS17 Zornitza Stark Publications for gene: RPS17 were set to
Fetal anomalies v0.4431 RPS17 Zornitza Stark Mode of inheritance for gene: RPS17 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4430 RPS19 Zornitza Stark Marked gene: RPS19 as ready
Fetal anomalies v0.4430 RPS19 Zornitza Stark Gene: rps19 has been classified as Green List (High Evidence).
Fetal anomalies v0.4430 RPS19 Zornitza Stark Phenotypes for gene: RPS19 were changed from RPS19-RELATED DIAMOND-BLACKFAN ANEMIA to Diamond-Blackfan anaemia 1, MIM# 105650; MONDO:0007110
Fetal anomalies v0.4429 RPS19 Zornitza Stark Publications for gene: RPS19 were set to
Fetal anomalies v0.4428 RPS19 Zornitza Stark Mode of inheritance for gene: RPS19 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4427 RPS26 Zornitza Stark Marked gene: RPS26 as ready
Fetal anomalies v0.4427 RPS26 Zornitza Stark Gene: rps26 has been classified as Green List (High Evidence).
Fetal anomalies v0.4427 RPS26 Zornitza Stark Phenotypes for gene: RPS26 were changed from Diamond-Blackfan anemia 10 613309 to Diamond-Blackfan anemia 10, MIM# 613309; MONDO:0013217
Fetal anomalies v0.4426 RPS26 Zornitza Stark Publications for gene: RPS26 were set to
Fetal anomalies v0.4425 RPS26 Zornitza Stark Mode of inheritance for gene: RPS26 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4424 RTTN Zornitza Stark Marked gene: RTTN as ready
Fetal anomalies v0.4424 RTTN Zornitza Stark Gene: rttn has been classified as Green List (High Evidence).
Fetal anomalies v0.4424 RTTN Zornitza Stark Phenotypes for gene: RTTN were changed from BILATERAL DIFFUSE POLYMICROGYRIA to Microcephaly, short stature, and polymicrogyria with seizures, MIM# 614833; Microcephalic primordial dwarfism due to RTTN deficiency MONDO:0018764
Fetal anomalies v0.4423 RTTN Zornitza Stark Publications for gene: RTTN were set to
Fetal anomalies v0.4422 RTTN Zornitza Stark changed review comment from: More than 10 unrelated families reported, severe microcephaly, ID.; to: More than 10 unrelated families reported, severe microcephaly, PMG.
Fetal anomalies v0.4422 RYR1 Zornitza Stark Marked gene: RYR1 as ready
Fetal anomalies v0.4422 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4422 RYR1 Zornitza Stark Phenotypes for gene: RYR1 were changed from MINICORE MYOPATHY WITH EXTERNAL OPHTHALMOPLEGIA to Fetal akinesia sequence
Fetal anomalies v0.4421 RYR1 Zornitza Stark Publications for gene: RYR1 were set to
Fetal anomalies v0.4420 SALL1 Zornitza Stark Marked gene: SALL1 as ready
Fetal anomalies v0.4420 SALL1 Zornitza Stark Gene: sall1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4420 SALL1 Zornitza Stark Phenotypes for gene: SALL1 were changed from TOWNES-BROCKS SYNDROME to Townes-Brocks syndrome 1, MIM#107480; MONDO:0054581
Fetal anomalies v0.4419 SALL1 Zornitza Stark Mode of inheritance for gene: SALL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4418 SALL1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association, limb and other congenital anomalies.
Fetal anomalies v0.4418 SALL4 Zornitza Stark Marked gene: SALL4 as ready
Fetal anomalies v0.4418 SALL4 Zornitza Stark Gene: sall4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4418 SALL4 Zornitza Stark Phenotypes for gene: SALL4 were changed from ACRO-RENAL-OCULAR SYNDROME; DUANE-RADIAL RAY SYNDROME to Duane-radial ray syndrome, MIM# 607323; MONDO:0011812; IVIC syndrome, MIM# 147750; MONDO:0007836
Fetal anomalies v0.4417 SALL4 Zornitza Stark Mode of inheritance for gene: SALL4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4416 SATB2 Zornitza Stark Marked gene: SATB2 as ready
Fetal anomalies v0.4416 SATB2 Zornitza Stark Gene: satb2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4416 SATB2 Zornitza Stark Phenotypes for gene: SATB2 were changed from NONSPECIFIC SEVERE ID; SYNDROMAL PIERRE ROBIN SEQUENCE; CLEFT PALATE ISOLATED to Glass syndrome, MIM# 612313; MONDO:0100147
Fetal anomalies v0.4415 SATB2 Zornitza Stark Publications for gene: SATB2 were set to
Fetal anomalies v0.4414 SATB2 Zornitza Stark Mode of inheritance for gene: SATB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4413 SBDS Zornitza Stark Marked gene: SBDS as ready
Fetal anomalies v0.4413 SBDS Zornitza Stark Gene: sbds has been classified as Green List (High Evidence).
Fetal anomalies v0.4413 SBDS Zornitza Stark Phenotypes for gene: SBDS were changed from SHWACHMAN-DIAMOND SYNDROME to Shwachman-Diamond syndrome, MIM#260400
Fetal anomalies v0.4412 SBDS Zornitza Stark Publications for gene: SBDS were set to
Fetal anomalies v0.4411 SBDS Zornitza Stark changed review comment from: Some cognitive involvement but ID rare, see reference.; to: Multiple skeletal abnormalities.
Fetal anomalies v0.4411 SBDS Zornitza Stark edited their review of gene: SBDS: Changed rating: GREEN
Fetal anomalies v0.4411 SCARF2 Zornitza Stark Marked gene: SCARF2 as ready
Fetal anomalies v0.4411 SCARF2 Zornitza Stark Gene: scarf2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4411 SCARF2 Zornitza Stark Phenotypes for gene: SCARF2 were changed from VAN DEN ENDE-GUPTA SYNDROME to Van den Ende-Gupta syndrome, MIM# 600920
Fetal anomalies v0.4410 SCARF2 Zornitza Stark Publications for gene: SCARF2 were set to
Fetal anomalies v0.4409 SDCCAG8 Zornitza Stark Marked gene: SDCCAG8 as ready
Fetal anomalies v0.4409 SDCCAG8 Zornitza Stark Gene: sdccag8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4409 SDCCAG8 Zornitza Stark Phenotypes for gene: SDCCAG8 were changed from SENIOR-LOKEN SYNDROME 7 to Bardet-Biedl syndrome 16, MIM# 615993; MONDO:0014444; Senior-Loken syndrome 7, MIM# 613615; MONDO:0013326; Nephronophthisis
Fetal anomalies v0.4408 SDCCAG8 Zornitza Stark Publications for gene: SDCCAG8 were set to
Fetal anomalies v0.4407 SEC23B Zornitza Stark Marked gene: SEC23B as ready
Fetal anomalies v0.4407 SEC23B Zornitza Stark Gene: sec23b has been classified as Green List (High Evidence).
Fetal anomalies v0.4407 SEC23B Zornitza Stark Phenotypes for gene: SEC23B were changed from ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II to Dyserythropoietic anemia, congenital, type II 224100; COPII component SEC23B (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies)
Fetal anomalies v0.4406 SEC23B Zornitza Stark Classified gene: SEC23B as Green List (high evidence)
Fetal anomalies v0.4406 SEC23B Zornitza Stark Gene: sec23b has been classified as Green List (High Evidence).
Fetal anomalies v0.4405 SEC23B Zornitza Stark changed review comment from: Over 20 families reported. Clinical presentation is typically post-natal.; to: Over 20 families reported. Clinical presentation is typically post-natal. However, at least two families reported with fetal hydrops.
Fetal anomalies v0.4405 SEC23B Zornitza Stark edited their review of gene: SEC23B: Changed rating: GREEN; Changed publications: 20381388; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4405 SEC23B Zornitza Stark Classified gene: SEC23B as Red List (low evidence)
Fetal anomalies v0.4405 SEC23B Zornitza Stark Gene: sec23b has been classified as Red List (Low Evidence).
Fetal anomalies v0.4404 SEC23B Zornitza Stark changed review comment from: Over 20 families reported.; to: Over 20 families reported. Clinical presentation is typically post-natal.
Fetal anomalies v0.4404 SEC23B Zornitza Stark edited their review of gene: SEC23B: Changed rating: RED
Fetal anomalies v0.4404 SEMA3A Zornitza Stark Marked gene: SEMA3A as ready
Fetal anomalies v0.4404 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Fetal anomalies v0.4404 TBC1D7 Krithika Murali gene: TBC1D7 was added
gene: TBC1D7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TBC1D7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D7 were set to 23687350; 24515783
Phenotypes for gene: TBC1D7 were set to Macrocephaly/megalencephaly syndrome, autosomal recessive - MIM#248000
Review for gene: TBC1D7 was set to AMBER
Added comment: PMID: 24515783 report 2 siblings with biallelic variants. One noted to be macrosomic at birth and parents reported macrocephaly.

PMID: 23687350 report 2 affected siblings. One was noted to be macrocephalic at birth.
Sources: Literature
Fetal anomalies v0.4404 TAOK1 Krithika Murali gene: TAOK1 was added
gene: TAOK1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TAOK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TAOK1 were set to 35091509; 31230721; 33565190
Phenotypes for gene: TAOK1 were set to Developmental delay with or without intellectual impairment or behavioral abnormalities - MIM#619575
Review for gene: TAOK1 was set to GREEN
Added comment: Heterozygous TAOK1 variants associated with developmental delay

PMID 35091509 - complication of polyhydramnios noted in 2 pregnancies in unrelated families

PMID 33565190:
- 1 patient with ventriculomegaly detected 28 week USS and polyhydramnios with secondary complication of multi-suture craniosynostosis
- 1 infant with low birth weight.
- 1 individual - antenatal history includes polyhydramnios at 5 months gestation

PMID 31230721 - report one individual noted to be macrocephalic at birth with cleft palate
Sources: Literature
Fetal anomalies v0.4404 STT3A Krithika Murali gene: STT3A was added
gene: STT3A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: STT3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: STT3A were set to 34653363; 23842455; 30701557; 28424003
Phenotypes for gene: STT3A were set to Congenital disorder of glycosylation, type Iw, autosomal dominant - MIM#619714; Congenital disorder of glycosylation, type Iw, autosomal recessive - MIM#615596
Review for gene: STT3A was set to GREEN
Added comment: Biallelic variants associated with an earlier onset of symptoms. PMID: 23842455 report IUGR in one infant. PMID: 28424003 - report 5 affected individuals from one family, birth growth parameters of 4/5 individuals suggestive of growth restriction/relative microcephaly.
---
ID/DD reported in all cases (at least 7 individuals from 3 unrelated families, with 2 different homozygous variants in STT3A)

PMID: 34653363 - 16 patients from 9 families with new AD mode of inheritance (both de novo and inherited). All variants were missense within/around acritical active/catalytic sites. Patients aged 3-55yo, with children noted to be "healthy" until reaching young adulthood
Clinical features include dysmorphic features, macrocephaly (6/16), mild-moderate ID/DD (10/16), short stature (8/16), skeletal abnormalities (10/16), muscle cramps (7/16).
Functional studies verifies AR disease is caused by LOF variants, whereas the AD variants cause DN proven by cotransfection in WT yeast resulting in impaired glycosylation (protein levels unchanged).
Sources: Literature
Fetal anomalies v0.4404 RHEB Krithika Murali gene: RHEB was added
gene: RHEB was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RHEB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RHEB were set to 29051493; 31337748
Phenotypes for gene: RHEB were set to Intellectual disability; Macrocephaly; Focal cortical dysplasia
Review for gene: RHEB was set to GREEN
Added comment: No new publications since last PanelApp review. Reviewed PMID: 29051493 supplementary information - three individuals with short stature and macrocephaly. Limited antenatal information provided/birth HC parameters, but one of the affected individuals was noted to have a large head circumference from 20 weeks gestation. PMID 31337748: Somatic variant in this gene found in one individual with focal cortical dysplasia.

---
3 individuals from two families with heterozygous RHEB variants. Two siblings carried the c.110 C > T (p.Pro37Leu) variant, and a sporadic individual carried the c.202 T>C (p.Ser68Pro) allele. All 3 individuals had short stature (−2 to −3 SD) and early brain overgrowth with pronounced macrocephaly during childhood (+2.5/+3 SD). They had severe to profound ID with hypotonia, as well as autism spectrum disorder. 2 of 3 individuals were reported to have epilepsy. In a zebrafish model, overexpression of RHEB produced megalencephaly, supporting a hyperactivating effect. This is supported in mice where loss of RHEB activity does not cause an overt neurological phenotype
Single individual with somatic variants in this gene and focal cortical dysplasia also reported.
Sources: Literature
Fetal anomalies v0.4404 SEPSECS Zornitza Stark Marked gene: SEPSECS as ready
Fetal anomalies v0.4404 SEPSECS Zornitza Stark Gene: sepsecs has been classified as Green List (High Evidence).
Fetal anomalies v0.4404 SEPSECS Zornitza Stark Phenotypes for gene: SEPSECS were changed from Pontocerebellar hypoplasia type 2D to Pontocerebellar hypoplasia type 2D, MIM#613811
Fetal anomalies v0.4403 SEPSECS Zornitza Stark Publications for gene: SEPSECS were set to 26805434; 26888482; 29464431
Fetal anomalies v0.4402 SEPSECS Zornitza Stark Deleted their comment
Fetal anomalies v0.4402 SETD5 Zornitza Stark Marked gene: SETD5 as ready
Fetal anomalies v0.4402 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4402 SETD5 Zornitza Stark Phenotypes for gene: SETD5 were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT 23 to Intellectual disability, autosomal dominant 23 (MIM # 615761)
Fetal anomalies v0.4401 SETD5 Zornitza Stark Publications for gene: SETD5 were set to
Fetal anomalies v0.4400 SHH Zornitza Stark Marked gene: SHH as ready
Fetal anomalies v0.4400 SHH Zornitza Stark Gene: shh has been classified as Green List (High Evidence).
Fetal anomalies v0.4400 SHH Zornitza Stark Phenotypes for gene: SHH were changed from MICROPHTHALMIA ISOLATED WITH COLOBOMA TYPE 5; TRIPHALANGEAL THUMB-POLYSYNDACTYLY SYNDROME; HOLOPROSENCEPHALY TYPE 3; SOLITARY MEDIAN MAXILLARY CENTRAL INCISOR to 1. Holoprosencephaly 3 (MIM#142945), AD; 2. Microphthalmia with coloboma 5 (MIM#611638), AD; 3. Schizencephaly (MIM#269160); 4. Single median maxillary central incisor (MIM#147250) AD
Fetal anomalies v0.4399 SHH Zornitza Stark Publications for gene: SHH were set to
Fetal anomalies v0.4398 SHH Zornitza Stark Mode of inheritance for gene: SHH was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4397 SHOC2 Zornitza Stark Marked gene: SHOC2 as ready
Fetal anomalies v0.4397 SHOC2 Zornitza Stark Gene: shoc2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4397 SHOC2 Zornitza Stark Phenotypes for gene: SHOC2 were changed from NOONAN-LIKE SYNDROME WITH LOOSE ANAGEN HAIR to Noonan syndrome-like with loose anagen hair 1, MIM# 607721
Fetal anomalies v0.4396 SHOC2 Zornitza Stark Publications for gene: SHOC2 were set to
Fetal anomalies v0.4395 SHOC2 Zornitza Stark Mode of pathogenicity for gene: SHOC2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v0.4394 SHOC2 Zornitza Stark Mode of inheritance for gene: SHOC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4393 SHOX Zornitza Stark Marked gene: SHOX as ready
Fetal anomalies v0.4393 SHOX Zornitza Stark Gene: shox has been classified as Green List (High Evidence).
Fetal anomalies v0.4393 SHOX Zornitza Stark Phenotypes for gene: SHOX were changed from LANGER MESOMELIC DYSPLASIA; LERI-WEILL DYSCHONDROSTEOSIS to Leri-Weill dyschondrosteosis, MIM# 127300; Langer mesomelic dysplasia, MIM#249700
Fetal anomalies v0.4392 PPP2R5C Krithika Murali gene: PPP2R5C was added
gene: PPP2R5C was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPP2R5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R5C were set to 25972378
Phenotypes for gene: PPP2R5C were set to macrocephaly; overgrowth
Review for gene: PPP2R5C was set to AMBER
Added comment: x1 case only in the literature with relative macrocephaly noted at birth.

PMID: 25972378 - Loveday et al 2015 undertook trio exome sequencing in children with an overgrowth syndrome phenotype with unaffected parents. One individual with a de novo PPP2R5C c.468_470delAAC p.Thr157del variant identified. The proband had moderate ID, was born at 37 weeks gestation weighing 3100g (0.8SD) with a head circumference of 36cm (2.4SD).
Sources: Literature
Fetal anomalies v0.4392 SHOX Zornitza Stark Tag SV/CNV tag was added to gene: SHOX.
Fetal anomalies v0.4392 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Fetal anomalies v0.4392 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4392 SIL1 Zornitza Stark Publications for gene: SIL1 were set to
Fetal anomalies v0.4391 SIL1 Zornitza Stark reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Marinesco-Sjogren syndrome (MIM#248800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4391 SF3B2 Zornitza Stark Phenotypes for gene: SF3B2 were changed from Craniofacial microsomia to Craniofacial microsomia, MIM#164210
Fetal anomalies v0.4389 SIX3 Zornitza Stark Marked gene: SIX3 as ready
Fetal anomalies v0.4389 SIX3 Zornitza Stark Gene: six3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4389 SIX3 Zornitza Stark Phenotypes for gene: SIX3 were changed from HOLOPROSENCEPHALY to Holoprosencephaly 2, MIM# 157170; Schizencephaly (MIM#269160)
Fetal anomalies v0.4388 SIX3 Zornitza Stark Publications for gene: SIX3 were set to
Fetal anomalies v0.4387 SIX3 Zornitza Stark Mode of inheritance for gene: SIX3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4386 SLC10A7 Zornitza Stark Marked gene: SLC10A7 as ready
Fetal anomalies v0.4386 SLC10A7 Zornitza Stark Gene: slc10a7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4386 SLC10A7 Zornitza Stark Phenotypes for gene: SLC10A7 were changed from Chondrodysplasia with multiple dislocations and amelogenesis imperfecta to Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis, MIM# 618363
Fetal anomalies v0.4385 SLC10A7 Zornitza Stark Publications for gene: SLC10A7 were set to 29878199; 30082715
Fetal anomalies v0.4384 SLC12A1 Zornitza Stark Marked gene: SLC12A1 as ready
Fetal anomalies v0.4384 SLC12A1 Zornitza Stark Gene: slc12a1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4384 SLC12A1 Zornitza Stark Phenotypes for gene: SLC12A1 were changed from Bartter syndrome, type 1 601678 to Bartter syndrome, type 1, MIM#601678
Fetal anomalies v0.4383 SLC12A1 Zornitza Stark Deleted their comment
Fetal anomalies v0.4383 SLC12A1 Zornitza Stark changed review comment from: Polyhydramnios.; to: Polyhydramnios is a presenting feature.
Fetal anomalies v0.4383 SLC12A1 Zornitza Stark edited their review of gene: SLC12A1: Added comment: Polyhydramnios.; Changed rating: GREEN
Fetal anomalies v0.4383 SLC13A5 Zornitza Stark Marked gene: SLC13A5 as ready
Fetal anomalies v0.4383 SLC13A5 Zornitza Stark Gene: slc13a5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4383 SLC13A5 Zornitza Stark Phenotypes for gene: SLC13A5 were changed from EPILEPTIC ENCEPHALOPATHY WITH SEIZURE ONSET IN THE FIRST DAYS OF LIFE to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905; MONDO:0014392
Fetal anomalies v0.4382 SLC13A5 Zornitza Stark Publications for gene: SLC13A5 were set to
Fetal anomalies v0.4381 SLC13A5 Zornitza Stark changed review comment from: At least 7 unrelated families reported.; to: At least 7 unrelated families reported. Microcephaly is a feature.
Fetal anomalies v0.4381 SLC16A2 Zornitza Stark Marked gene: SLC16A2 as ready
Fetal anomalies v0.4381 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4381 SLC16A2 Zornitza Stark Phenotypes for gene: SLC16A2 were changed from MCT8 (SLC16A2)-SPECIFIC THYROID HORMONE CELL TRANSPORTER DEFICIENCY to Allan-Herndon-Dudley syndrome, MIM# 300523
Fetal anomalies v0.4380 SLC16A2 Zornitza Stark Publications for gene: SLC16A2 were set to
Fetal anomalies v0.4379 SLC16A2 Zornitza Stark Classified gene: SLC16A2 as Amber List (moderate evidence)
Fetal anomalies v0.4379 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4378 SLC16A2 Zornitza Stark edited their review of gene: SLC16A2: Added comment: Clinical presentation is typically post-natal, including microcephaly of post-natal onset.; Changed rating: AMBER
Fetal anomalies v0.4378 SLC2A10 Zornitza Stark Marked gene: SLC2A10 as ready
Fetal anomalies v0.4378 SLC2A10 Zornitza Stark Gene: slc2a10 has been classified as Green List (High Evidence).
Fetal anomalies v0.4378 SLC2A10 Zornitza Stark Phenotypes for gene: SLC2A10 were changed from ARTERIAL TORTUOSITY SYNDROME to Arterial tortuosity syndrome, MIM# 208050
Fetal anomalies v0.4377 SLC2A10 Zornitza Stark reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arterial tortuosity syndrome, MIM# 208050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4377 SLC35A2 Zornitza Stark Marked gene: SLC35A2 as ready
Fetal anomalies v0.4377 SLC35A2 Zornitza Stark Gene: slc35a2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4377 SLC35A2 Zornitza Stark Phenotypes for gene: SLC35A2 were changed from CONGENITAL DISORDER OF GLYCOSYLATION to Congenital disorder of glycosylation, type IIm (MIM #300896)
Fetal anomalies v0.4376 SLC35A2 Zornitza Stark Publications for gene: SLC35A2 were set to
Fetal anomalies v0.4375 SLC35A2 Zornitza Stark reviewed gene: SLC35A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IIm (MIM #300896); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.4375 SLC35C1 Zornitza Stark Marked gene: SLC35C1 as ready
Fetal anomalies v0.4375 SLC35C1 Zornitza Stark Gene: slc35c1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4375 SLC35C1 Zornitza Stark Phenotypes for gene: SLC35C1 were changed from CONGENITAL DISORDER OF GLYCOSYLATION TYPE 2C to Congenital disorder of glycosylation, type IIc, MIM# 266265, MONDO:0009953
Fetal anomalies v0.4374 SLC35C1 Zornitza Stark Publications for gene: SLC35C1 were set to
Fetal anomalies v0.4373 SLC35C1 Zornitza Stark Classified gene: SLC35C1 as Amber List (moderate evidence)
Fetal anomalies v0.4373 SLC35C1 Zornitza Stark Gene: slc35c1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4372 SLC35C1 Zornitza Stark changed review comment from: Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe DD/ID, mild dysmorphism, and impaired neutrophil motility. More than 5 unrelated families reported, note immune dysfunction is not always present.

Microcephaly is a feature.; to: Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe DD/ID, mild dysmorphism, and impaired neutrophil motility. More than 5 unrelated families reported, note immune dysfunction is not always present.

Microcephaly is a feature. Variable severity, some present in childhood.
Fetal anomalies v0.4372 SLC35C1 Zornitza Stark changed review comment from: Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe DD/ID, mild dysmorphism, and impaired neutrophil motility. More than 5 unrelated families reported, note immune dysfunction is not always present.; to: Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe DD/ID, mild dysmorphism, and impaired neutrophil motility. More than 5 unrelated families reported, note immune dysfunction is not always present.

Microcephaly is a feature.
Fetal anomalies v0.4372 SLC35C1 Zornitza Stark edited their review of gene: SLC35C1: Changed rating: AMBER
Fetal anomalies v0.4372 SLC35D1 Zornitza Stark Marked gene: SLC35D1 as ready
Fetal anomalies v0.4372 SLC35D1 Zornitza Stark Gene: slc35d1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4372 SLC35D1 Zornitza Stark Phenotypes for gene: SLC35D1 were changed from SCHNECKENBECKEN DYSPLASIA to Schneckenbecken dysplasia 269250, MONDO:0010013; O-xylosyl/N-acetylgalactosaminylglycan synthesis deficiencies (Disorders of protein O-glycosylation)
Fetal anomalies v0.4371 SLC35D1 Zornitza Stark Publications for gene: SLC35D1 were set to
Fetal anomalies v0.4370 SLC39A8 Zornitza Stark Marked gene: SLC39A8 as ready
Fetal anomalies v0.4370 SLC39A8 Zornitza Stark Gene: slc39a8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4370 SLC39A8 Zornitza Stark Phenotypes for gene: SLC39A8 were changed from Intellectual Disability with Cerebellar Atrophy to Congenital disorder of glycosylation, type IIn , MIM#16721
Fetal anomalies v0.4369 SLC39A8 Zornitza Stark Publications for gene: SLC39A8 were set to
Fetal anomalies v0.4368 SLC39A8 Zornitza Stark changed review comment from: 6 individuals from Hutterite descent and two other unrelated families reported. ID a consistent feature.; to: 6 individuals from Hutterite descent and two other unrelated families reported. Craniosynostosis; brain abnormalities.
Fetal anomalies v0.4368 SLX4 Zornitza Stark commented on gene: SLX4: Multiple congenital anomalies.
Fetal anomalies v0.4368 SLX4 Zornitza Stark Marked gene: SLX4 as ready
Fetal anomalies v0.4368 SLX4 Zornitza Stark Gene: slx4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4368 SLX4 Zornitza Stark Phenotypes for gene: SLX4 were changed from FANCONI ANEMIA COMPLEMENTATION GROUP P to Fanconi anaemia, complementation group P, MIM# 613951; MONDO:0013499
Fetal anomalies v0.4367 SMARCA2 Zornitza Stark Marked gene: SMARCA2 as ready
Fetal anomalies v0.4367 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4367 SMARCA2 Zornitza Stark Phenotypes for gene: SMARCA2 were changed from COFFIN SIRIS; NICOLAIDES-BARAITSER SYNDROME to Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome
Fetal anomalies v0.4366 SMARCA2 Zornitza Stark Publications for gene: SMARCA2 were set to
Fetal anomalies v0.4365 SMARCA2 Zornitza Stark Mode of pathogenicity for gene: SMARCA2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v0.4364 SMARCA2 Zornitza Stark Mode of inheritance for gene: SMARCA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4363 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Fetal anomalies v0.4363 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4363 SMARCA4 Zornitza Stark Phenotypes for gene: SMARCA4 were changed from COFFIN SIRIS; RHABDOID TUMOR PREDISPOSITION SYNDROME 2 to Coffin-Siris syndrome 4, MIM# 614609
Fetal anomalies v0.4362 SMARCA4 Zornitza Stark Publications for gene: SMARCA4 were set to
Fetal anomalies v0.4361 SMARCA4 Zornitza Stark Mode of inheritance for gene: SMARCA4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4360 SMARCA4 Zornitza Stark changed review comment from: Single individual reported as part of a CDH cohort.
Sources: Literature; to: IUGR and multiple congenital anomalies.
Sources: Literature
Fetal anomalies v0.4360 SMARCA4 Zornitza Stark edited their review of gene: SMARCA4: Changed rating: GREEN; Changed phenotypes: Coffin-Siris syndrome 4, MIM# 614609
Fetal anomalies v0.4360 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Fetal anomalies v0.4360 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Fetal anomalies v0.4360 SMC1A Zornitza Stark Phenotypes for gene: SMC1A were changed from Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771; Cornelia de Lange syndrome 2, OMIM:300590; Developmental and epileptic encephalopathy 85, with or without midline brain defects, OMIM:301044; Cornelia de Lange syndrome 2, MONDO:0010370 to Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771; Cornelia de Lange syndrome 2, OMIM:300590; Developmental and epileptic encephalopathy 85, with or without midline brain defects, OMIM:301044; Cornelia de Lange syndrome 2, MONDO:0010370
Fetal anomalies v0.4359 SMC1A Zornitza Stark changed review comment from: CDH is a feature of CdL, but cannot find a report specifically with SMC1A variant.; to: Multiple congenital anomalies syndrome.
Fetal anomalies v0.4359 SMC1A Zornitza Stark edited their review of gene: SMC1A: Changed rating: GREEN
Fetal anomalies v0.4359 SMC3 Zornitza Stark Marked gene: SMC3 as ready
Fetal anomalies v0.4359 SMC3 Zornitza Stark Gene: smc3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4359 SMC3 Zornitza Stark Phenotypes for gene: SMC3 were changed from CORNELIA DE LANGE SYNDROME TYPE 3 to Cornelia de Lange syndrome 3, MIM# 610759
Fetal anomalies v0.4358 SMC3 Zornitza Stark Mode of inheritance for gene: SMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4357 SMC3 Zornitza Stark changed review comment from: CDH is a feature of CdL but cannot find specific reports of SMC3 variants.; to: Multiple congenital anomalies syndrome.
Fetal anomalies v0.4357 SMC3 Zornitza Stark edited their review of gene: SMC3: Changed rating: GREEN
Fetal anomalies v0.4357 SMN1 Zornitza Stark Marked gene: SMN1 as ready
Fetal anomalies v0.4357 SMN1 Zornitza Stark Gene: smn1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4357 SMN1 Zornitza Stark Phenotypes for gene: SMN1 were changed from Spinal muscular atrophy 253400; Spinal muscular atrophy 271150; Spinal muscular atrophy 253550; Spinal muscular atrophy 253300 to Spinal muscular atrophy 253400; Spinal muscular atrophy 271150; Spinal muscular atrophy 253550; Spinal muscular atrophy 253300
Fetal anomalies v0.4356 SMN1 Zornitza Stark Tag SV/CNV tag was added to gene: SMN1.
Fetal anomalies v0.4356 SMO Zornitza Stark Marked gene: SMO as ready
Fetal anomalies v0.4356 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Fetal anomalies v0.4356 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4355 SMO Zornitza Stark Deleted their comment
Fetal anomalies v0.4355 SMO Zornitza Stark edited their review of gene: SMO: Added comment: Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Somatic recurrent missense variant, L412F causes Curry-Jones syndrome.; Changed publications: 32413283, 27236920; Changed phenotypes: Microcephaly, congenital heart disease, polydactyly, aganglionosis, Pallister-Hall-like syndrome, MIM# 241800; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4355 SMO Zornitza Stark Phenotypes for gene: SMO were changed from Curry-Jones Syndrome to Curry-Jones syndrome, somatic mosaic, MIM#601707
Fetal anomalies v0.4354 SMO Zornitza Stark Publications for gene: SMO were set to
Fetal anomalies v0.4353 SMO Zornitza Stark Mode of pathogenicity for gene: SMO was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v0.4352 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Fetal anomalies v0.4351 SMOC1 Zornitza Stark Marked gene: SMOC1 as ready
Fetal anomalies v0.4351 SMOC1 Zornitza Stark Gene: smoc1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4351 SMOC1 Zornitza Stark Phenotypes for gene: SMOC1 were changed from OPHTHALMOACROMELIC SYNDROME to Microphthalmia with limb anomalies, MIM# 206920
Fetal anomalies v0.4350 SMOC1 Zornitza Stark Publications for gene: SMOC1 were set to
Fetal anomalies v0.4349 SMPD1 Zornitza Stark Marked gene: SMPD1 as ready
Fetal anomalies v0.4349 SMPD1 Zornitza Stark Gene: smpd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4349 SMPD1 Zornitza Stark Phenotypes for gene: SMPD1 were changed from NIEMANN-PICK DISEASE TYPE B; NIEMANN-PICK DISEASE TYPE A to Niemann-Pick disease, type A, MIM# 257200; MONDO:0009756
Fetal anomalies v0.4348 SMPD1 Zornitza Stark Publications for gene: SMPD1 were set to
Fetal anomalies v0.4347 ZNHIT3 Zornitza Stark Marked gene: ZNHIT3 as ready
Fetal anomalies v0.4347 ZNHIT3 Zornitza Stark Gene: znhit3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4347 ZNF668 Zornitza Stark Marked gene: ZNF668 as ready
Fetal anomalies v0.4347 ZNF668 Zornitza Stark Gene: znf668 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4347 ZNF668 Zornitza Stark Publications for gene: ZNF668 were set to PMID: 34313816, 26633546
Fetal anomalies v0.4346 PIDD1 Zornitza Stark Marked gene: PIDD1 as ready
Fetal anomalies v0.4346 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4346 PIDD1 Zornitza Stark Classified gene: PIDD1 as Amber List (moderate evidence)
Fetal anomalies v0.4346 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4345 ZNF526 Zornitza Stark Marked gene: ZNF526 as ready
Fetal anomalies v0.4345 ZNF526 Zornitza Stark Gene: znf526 has been classified as Green List (High Evidence).
Fetal anomalies v0.4345 YRDC Zornitza Stark Marked gene: YRDC as ready
Fetal anomalies v0.4345 YRDC Zornitza Stark Gene: yrdc has been classified as Green List (High Evidence).
Fetal anomalies v0.4345 YRDC Zornitza Stark Publications for gene: YRDC were set to PMID: 31481669, 34545459
Fetal anomalies v0.4344 NFIB Zornitza Stark Marked gene: NFIB as ready
Fetal anomalies v0.4344 NFIB Zornitza Stark Gene: nfib has been classified as Green List (High Evidence).
Fetal anomalies v0.4344 NFIB Zornitza Stark Classified gene: NFIB as Green List (high evidence)
Fetal anomalies v0.4344 NFIB Zornitza Stark Gene: nfib has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Fetal anomalies v0.4343 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 YIPF5 Zornitza Stark Marked gene: YIPF5 as ready
Fetal anomalies v0.4343 YIPF5 Zornitza Stark Gene: yipf5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 WDR4 Zornitza Stark Marked gene: WDR4 as ready
Fetal anomalies v0.4343 WDR4 Zornitza Stark Gene: wdr4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 WDR37 Zornitza Stark Marked gene: WDR37 as ready
Fetal anomalies v0.4343 WDR37 Zornitza Stark Gene: wdr37 has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 VPS51 Zornitza Stark Marked gene: VPS51 as ready
Fetal anomalies v0.4343 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4343 VPS50 Zornitza Stark Marked gene: VPS50 as ready
Fetal anomalies v0.4343 VPS50 Zornitza Stark Gene: vps50 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4343 VPS4A Zornitza Stark Marked gene: VPS4A as ready
Fetal anomalies v0.4343 VPS4A Zornitza Stark Gene: vps4a has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 TUBGCP2 Zornitza Stark Marked gene: TUBGCP2 as ready
Fetal anomalies v0.4343 TUBGCP2 Zornitza Stark Gene: tubgcp2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4343 HEXB Zornitza Stark Marked gene: HEXB as ready
Fetal anomalies v0.4343 HEXB Zornitza Stark Gene: hexb has been classified as Red List (Low Evidence).
Fetal anomalies v0.4343 HEXB Zornitza Stark Classified gene: HEXB as Red List (low evidence)
Fetal anomalies v0.4343 HEXB Zornitza Stark Gene: hexb has been classified as Red List (Low Evidence).
Fetal anomalies v0.4342 GTPBP2 Zornitza Stark Marked gene: GTPBP2 as ready
Fetal anomalies v0.4342 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4342 GTPBP2 Zornitza Stark Classified gene: GTPBP2 as Green List (high evidence)
Fetal anomalies v0.4342 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4341 MCF2 Zornitza Stark Marked gene: MCF2 as ready
Fetal anomalies v0.4341 MCF2 Zornitza Stark Gene: mcf2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4341 MCF2 Zornitza Stark Classified gene: MCF2 as Red List (low evidence)
Fetal anomalies v0.4341 MCF2 Zornitza Stark Gene: mcf2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4340 MAN2C1 Zornitza Stark Marked gene: MAN2C1 as ready
Fetal anomalies v0.4340 MAN2C1 Zornitza Stark Gene: man2c1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4340 MAN2C1 Zornitza Stark Classified gene: MAN2C1 as Green List (high evidence)
Fetal anomalies v0.4340 MAN2C1 Zornitza Stark Gene: man2c1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4339 INTS8 Zornitza Stark Marked gene: INTS8 as ready
Fetal anomalies v0.4339 INTS8 Zornitza Stark Gene: ints8 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4339 INTS8 Zornitza Stark Classified gene: INTS8 as Red List (low evidence)
Fetal anomalies v0.4339 INTS8 Zornitza Stark Gene: ints8 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4338 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Fetal anomalies v0.4338 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4338 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Fetal anomalies v0.4338 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4337 ERMARD Zornitza Stark Marked gene: ERMARD as ready
Fetal anomalies v0.4337 ERMARD Zornitza Stark Gene: ermard has been classified as Red List (Low Evidence).
Fetal anomalies v0.4337 ERMARD Zornitza Stark Classified gene: ERMARD as Red List (low evidence)
Fetal anomalies v0.4337 ERMARD Zornitza Stark Gene: ermard has been classified as Red List (Low Evidence).
Fetal anomalies v0.4336 GPT2 Zornitza Stark Marked gene: GPT2 as ready
Fetal anomalies v0.4336 GPT2 Zornitza Stark Gene: gpt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4336 GPT2 Zornitza Stark Classified gene: GPT2 as Red List (low evidence)
Fetal anomalies v0.4336 GPT2 Zornitza Stark Gene: gpt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4335 GON7 Zornitza Stark Marked gene: GON7 as ready
Fetal anomalies v0.4335 GON7 Zornitza Stark Gene: gon7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4335 GON7 Zornitza Stark Classified gene: GON7 as Amber List (moderate evidence)
Fetal anomalies v0.4335 GON7 Zornitza Stark Gene: gon7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4334 GON7 Zornitza Stark reviewed gene: GON7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Galloway-Mowat syndrome 9, MIM# 619603; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4334 EOMES Zornitza Stark Marked gene: EOMES as ready
Fetal anomalies v0.4334 EOMES Zornitza Stark Gene: eomes has been classified as Red List (Low Evidence).
Fetal anomalies v0.4334 EOMES Zornitza Stark Classified gene: EOMES as Red List (low evidence)
Fetal anomalies v0.4334 EOMES Zornitza Stark Gene: eomes has been classified as Red List (Low Evidence).
Fetal anomalies v0.4333 GOLGA2 Zornitza Stark edited their review of gene: GOLGA2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4333 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Fetal anomalies v0.4333 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4333 GOLGA2 Zornitza Stark Phenotypes for gene: GOLGA2 were changed from to neuromuscular disease, GOLGA2-related MONDO#0019056
Fetal anomalies v0.4332 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Amber List (moderate evidence)
Fetal anomalies v0.4332 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4331 GOLGA2 Zornitza Stark reviewed gene: GOLGA2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: neuromuscular disease, GOLGA2-related MONDO#0019056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4331 ENO1 Zornitza Stark Marked gene: ENO1 as ready
Fetal anomalies v0.4331 ENO1 Zornitza Stark Gene: eno1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4331 ENO1 Zornitza Stark Classified gene: ENO1 as Red List (low evidence)
Fetal anomalies v0.4331 ENO1 Zornitza Stark Gene: eno1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4330 CEP85L Zornitza Stark Marked gene: CEP85L as ready
Fetal anomalies v0.4330 CEP85L Zornitza Stark Gene: cep85l has been classified as Green List (High Evidence).
Fetal anomalies v0.4330 CEP85L Zornitza Stark Classified gene: CEP85L as Green List (high evidence)
Fetal anomalies v0.4330 CEP85L Zornitza Stark Gene: cep85l has been classified as Green List (High Evidence).
Fetal anomalies v0.4329 CEP85L Zornitza Stark reviewed gene: CEP85L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 10, posterior predominant (MIM618873); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4329 HEXA Zornitza Stark Marked gene: HEXA as ready
Fetal anomalies v0.4329 HEXA Zornitza Stark Gene: hexa has been classified as Red List (Low Evidence).
Fetal anomalies v0.4329 HEXA Zornitza Stark Classified gene: HEXA as Red List (low evidence)
Fetal anomalies v0.4329 HEXA Zornitza Stark Gene: hexa has been classified as Red List (Low Evidence).
Fetal anomalies v0.4328 FOXR1 Zornitza Stark Marked gene: FOXR1 as ready
Fetal anomalies v0.4328 FOXR1 Zornitza Stark Gene: foxr1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4328 FOXR1 Zornitza Stark Classified gene: FOXR1 as Red List (low evidence)
Fetal anomalies v0.4328 FOXR1 Zornitza Stark Gene: foxr1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4327 FOXR1 Zornitza Stark reviewed gene: FOXR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.4327 HERC1 Zornitza Stark Marked gene: HERC1 as ready
Fetal anomalies v0.4327 HERC1 Zornitza Stark Gene: herc1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4327 HERC1 Zornitza Stark Classified gene: HERC1 as Green List (high evidence)
Fetal anomalies v0.4327 HERC1 Zornitza Stark Gene: herc1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4326 FDXR Zornitza Stark Marked gene: FDXR as ready
Fetal anomalies v0.4326 FDXR Zornitza Stark Gene: fdxr has been classified as Red List (Low Evidence).
Fetal anomalies v0.4326 FDXR Zornitza Stark Classified gene: FDXR as Red List (low evidence)
Fetal anomalies v0.4326 FDXR Zornitza Stark Gene: fdxr has been classified as Red List (Low Evidence).
Fetal anomalies v0.4325 CDK5 Zornitza Stark Marked gene: CDK5 as ready
Fetal anomalies v0.4325 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4325 CDK5 Zornitza Stark Classified gene: CDK5 as Red List (low evidence)
Fetal anomalies v0.4325 CDK5 Zornitza Stark Gene: cdk5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4324 EXOC7 Zornitza Stark Marked gene: EXOC7 as ready
Fetal anomalies v0.4324 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4324 EXOC7 Zornitza Stark Publications for gene: EXOC7 were set to
Fetal anomalies v0.4323 EXOC7 Zornitza Stark Classified gene: EXOC7 as Green List (high evidence)
Fetal anomalies v0.4323 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4322 EXOC7 Zornitza Stark reviewed gene: EXOC7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32103185; Phenotypes: Neurodevelopmental disorder with seizures and brain atrophy MIM#619072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4322 DYNC1I2 Zornitza Stark Marked gene: DYNC1I2 as ready
Fetal anomalies v0.4322 DYNC1I2 Zornitza Stark Gene: dync1i2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4322 DYNC1I2 Zornitza Stark Classified gene: DYNC1I2 as Green List (high evidence)
Fetal anomalies v0.4322 DYNC1I2 Zornitza Stark Gene: dync1i2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4321 FIBP Zornitza Stark Marked gene: FIBP as ready
Fetal anomalies v0.4321 FIBP Zornitza Stark Gene: fibp has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4321 FIBP Zornitza Stark Classified gene: FIBP as Amber List (moderate evidence)
Fetal anomalies v0.4321 FIBP Zornitza Stark Gene: fibp has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4320 B3GNT2 Zornitza Stark Marked gene: B3GNT2 as ready
Fetal anomalies v0.4320 B3GNT2 Zornitza Stark Gene: b3gnt2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4320 B3GNT2 Zornitza Stark Classified gene: B3GNT2 as Amber List (moderate evidence)
Fetal anomalies v0.4320 B3GNT2 Zornitza Stark Gene: b3gnt2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4319 CTNNA2 Zornitza Stark Marked gene: CTNNA2 as ready
Fetal anomalies v0.4319 CTNNA2 Zornitza Stark Gene: ctnna2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4319 CTNNA2 Zornitza Stark Classified gene: CTNNA2 as Green List (high evidence)
Fetal anomalies v0.4319 CTNNA2 Zornitza Stark Gene: ctnna2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4318 TUBGCP2 Chirag Patel Classified gene: TUBGCP2 as Green List (high evidence)
Fetal anomalies v0.4318 TUBGCP2 Chirag Patel Gene: tubgcp2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4317 DICER1 Zornitza Stark Marked gene: DICER1 as ready
Fetal anomalies v0.4317 DICER1 Zornitza Stark Gene: dicer1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4317 TUBGCP2 Chirag Patel gene: TUBGCP2 was added
gene: TUBGCP2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP2 were set to PMID: 31630790
Phenotypes for gene: TUBGCP2 were set to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM # 618737
Review for gene: TUBGCP2 was set to GREEN
Added comment: Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures (PAMDDFS) is an autosomal recessive neurologic disorder characterized by progressive microcephaly associated with abnormal facial features, hypotonia, and variable global developmental delay with impaired intellectual development. Brain imaging shows variable malformation of cortical development on the lissencephaly spectrum, mainly pachygyria and thin corpus callosum.

4 unrelated patients with homozygous or compound heterozygous mutations in the TUBGCP2 gene, found by WES and segregated with the disorder in all families. Functional studies of the variants were not performed, but analysis of patient fibroblasts derived from the patient with a splice site mutation demonstrated the production of several abnormal transcripts that were predicted to result in a loss of function.
Sources: Expert list
Fetal anomalies v0.4316 DICER1 Zornitza Stark Classified gene: DICER1 as Green List (high evidence)
Fetal anomalies v0.4316 DICER1 Zornitza Stark Gene: dicer1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4315 COPB2 Zornitza Stark Marked gene: COPB2 as ready
Fetal anomalies v0.4315 COPB2 Zornitza Stark Gene: copb2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4315 COPB2 Zornitza Stark Classified gene: COPB2 as Red List (low evidence)
Fetal anomalies v0.4315 COPB2 Zornitza Stark Gene: copb2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4314 ARF1 Zornitza Stark Marked gene: ARF1 as ready
Fetal anomalies v0.4314 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4314 ARF1 Zornitza Stark Classified gene: ARF1 as Green List (high evidence)
Fetal anomalies v0.4314 ARF1 Zornitza Stark Gene: arf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4313 ARF1 Zornitza Stark reviewed gene: ARF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Periventricular nodular heterotopia 8 (MIM#618185); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4313 ATXN2L Zornitza Stark Marked gene: ATXN2L as ready
Fetal anomalies v0.4313 ATXN2L Zornitza Stark Gene: atxn2l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4313 ATXN2L Zornitza Stark Classified gene: ATXN2L as Amber List (moderate evidence)
Fetal anomalies v0.4313 ATXN2L Zornitza Stark Gene: atxn2l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4312 VPS4A Chirag Patel Classified gene: VPS4A as Green List (high evidence)
Fetal anomalies v0.4312 VPS4A Chirag Patel Gene: vps4a has been classified as Green List (High Evidence).
Fetal anomalies v0.4311 COPB1 Zornitza Stark Marked gene: COPB1 as ready
Fetal anomalies v0.4311 COPB1 Zornitza Stark Gene: copb1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4311 VPS4A Chirag Patel gene: VPS4A was added
gene: VPS4A was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to PMID: 33186543; 33186545
Phenotypes for gene: VPS4A were set to CIMDAG syndrome MIM# 619273
Review for gene: VPS4A was set to GREEN
Added comment: CIMDAG syndrome is a multisystemic disorder characterized by severely impaired psychomotor development and hematologic abnormalities apparent from early infancy. Affected individuals show poor overall growth with microcephaly, impaired intellectual development, poor or absent speech, poor eye contact, and motor problems, such as inability to walk, hypotonia, and spasticity. Brain imaging typically shows cerebral and cerebellar atrophy, thin corpus callosum, and delayed myelination. The associated hematologic abnormalities are variable, but are mostly consistent with congenital dyserythropoietic anemia. Eight unrelated patients with de novo heterozygous missense mutations in the VPS4A gene.
Sources: Expert list
Fetal anomalies v0.4311 COPB1 Zornitza Stark Classified gene: COPB1 as Red List (low evidence)
Fetal anomalies v0.4311 COPB1 Zornitza Stark Gene: copb1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4310 CHKA Zornitza Stark Marked gene: CHKA as ready
Fetal anomalies v0.4310 CHKA Zornitza Stark Gene: chka has been classified as Red List (Low Evidence).
Fetal anomalies v0.4310 CHKA Zornitza Stark Classified gene: CHKA as Red List (low evidence)
Fetal anomalies v0.4310 CHKA Zornitza Stark Gene: chka has been classified as Red List (Low Evidence).
Fetal anomalies v0.4309 CENPE Zornitza Stark Marked gene: CENPE as ready
Fetal anomalies v0.4309 CENPE Zornitza Stark Gene: cenpe has been classified as Red List (Low Evidence).
Fetal anomalies v0.4309 CENPE Zornitza Stark Classified gene: CENPE as Red List (low evidence)
Fetal anomalies v0.4309 CENPE Zornitza Stark Gene: cenpe has been classified as Red List (Low Evidence).
Fetal anomalies v0.4308 CDK6 Zornitza Stark Marked gene: CDK6 as ready
Fetal anomalies v0.4308 CDK6 Zornitza Stark Gene: cdk6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4308 CDK6 Zornitza Stark Classified gene: CDK6 as Amber List (moderate evidence)
Fetal anomalies v0.4308 CDK6 Zornitza Stark Gene: cdk6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4307 CCDC88A Zornitza Stark Marked gene: CCDC88A as ready
Fetal anomalies v0.4307 CCDC88A Zornitza Stark Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4307 CCDC88A Zornitza Stark Classified gene: CCDC88A as Amber List (moderate evidence)
Fetal anomalies v0.4307 CCDC88A Zornitza Stark Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4306 VPS50 Chirag Patel Classified gene: VPS50 as Amber List (moderate evidence)
Fetal anomalies v0.4306 VPS50 Chirag Patel Gene: vps50 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4305 VPS50 Chirag Patel gene: VPS50 was added
gene: VPS50 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS50 were set to PMID: 34037727
Phenotypes for gene: VPS50 were set to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685
Review for gene: VPS50 was set to AMBER
Added comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants. Common features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. Both individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)). VPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor. As discussed by Schneeberger et al (refs provided in text): - VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development. - Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality. Studies performed by Schneeberger et al included: - Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del). - Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels. - Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts. - Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function. As the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term "GARP and/or EARP deficiency disorders". There is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes.
Sources: Expert list
Fetal anomalies v0.4304 VPS51 Chirag Patel Classified gene: VPS51 as Amber List (moderate evidence)
Fetal anomalies v0.4304 VPS51 Chirag Patel Gene: vps51 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4303 VPS51 Chirag Patel gene: VPS51 was added
gene: VPS51 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to PMID: 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Pontocerebellar hypoplasia type 13 (PCH13) is an autosomal recessive disorder characterized by global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment. Two families reported with bi-allelic variants in this gene.
Sources: Expert list
Fetal anomalies v0.4302 WDR37 Chirag Patel Classified gene: WDR37 as Green List (high evidence)
Fetal anomalies v0.4302 WDR37 Chirag Patel Gene: wdr37 has been classified as Green List (High Evidence).
Fetal anomalies v0.4301 WDR37 Chirag Patel gene: WDR37 was added
gene: WDR37 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: WDR37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR37 were set to PMID: 31327508, 31327510
Phenotypes for gene: WDR37 were set to Neurooculocardiogenitourinary syndrome MIM#618652
Review for gene: WDR37 was set to GREEN
Added comment: Neurooculocardiogenitourinary syndrome (NOCGUS) is a multisystem disorder characterized by poor growth and anomalies of the ocular, craniofacial, neurologic, cardiovascular, genitourinary, skeletal, and gastrointestinal systems. Lethality before 2 years of age has been observed. Nine unrelated patients reported with de novo missense mutations in the WDR37 gene.
Sources: Expert list
Fetal anomalies v0.4300 WDR4 Chirag Patel Classified gene: WDR4 as Green List (high evidence)
Fetal anomalies v0.4300 WDR4 Chirag Patel Gene: wdr4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4299 WDR4 Chirag Patel gene: WDR4 was added
gene: WDR4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR4 were set to PubMed: 26416026; 28617965
Phenotypes for gene: WDR4 were set to Microcephaly, growth deficiency, seizures, and brain malformations, OMIM # 618346
Review for gene: WDR4 was set to GREEN
Added comment: Microcephaly, growth deficiency, seizures, and brain malformations (MIGSB) is a severe autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth deficiency with severe microcephaly, and poor or absent psychomotor development. Additional features include optic atrophy, early-onset seizures, dysmorphic facial features, and brain malformations, such as partial agenesis of the corpus callosum and simplified gyration.

Biallelic variants in the WDR4 gene reported in 4 patients from 3 unrelated families. Studies of patient cells in one family and modeling of the corresponding mutation in yeast showed that the mutation caused a significant reduction in m(7)G46 methylation of specific tRNAs species, particularly at higher temperatures. This was associated with a growth defect in yeast, thus offering a potential mechanism for the growth defects observed in patients with the mutation. The findings suggested that abnormal tRNA modification is a major contributor to disease pathogenesis.
Sources: Literature
Fetal anomalies v0.4298 YIPF5 Chirag Patel Classified gene: YIPF5 as Green List (high evidence)
Fetal anomalies v0.4298 YIPF5 Chirag Patel Gene: yipf5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4297 YIPF5 Chirag Patel gene: YIPF5 was added
gene: YIPF5 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: YIPF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIPF5 were set to PMID: 33164986
Phenotypes for gene: YIPF5 were set to Microcephaly, epilepsy, and diabetes syndrome 2 , MIM#619278
Review for gene: YIPF5 was set to GREEN
Added comment: 6 patients from 5 consanguineous families who had microcephaly, epilepsy, and diabetes syndrome (MEDS). All had severe microcephaly (standard deviation of -6.2); epilepsy diagnosed at ages ranging from 1 to 7 months; and neonatal/early-onset diabetes. All patients had low birth weight consistent with reduced insulin secretion in utero.
Sources: Expert list
Fetal anomalies v0.4296 YIF1B Chirag Patel Classified gene: YIF1B as Green List (high evidence)
Fetal anomalies v0.4296 YIF1B Chirag Patel Gene: yif1b has been classified as Green List (High Evidence).
Fetal anomalies v0.4295 YIF1B Chirag Patel gene: YIF1B was added
gene: YIF1B was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to PMID: 32006098; 26077767
Phenotypes for gene: YIF1B were set to Kaya-Barakat-Masson syndrome, MIM# 619125
Review for gene: YIF1B was set to GREEN
Added comment: Kaya-Barakat-Masson syndrome (KABAMAS) is a severe autosomal recessive neurodevelopmental disorder characterized by profoundly impaired global development, peripheral spasticity, dystonia, impaired intellectual development with absent speech, poor eye contact, and feeding difficulties, resulting in poor overall growth, sometimes with microcephaly. Additional more variable features include early-onset seizures, ocular anomalies, foot deformities, and nonspecific brain imaging findings, such as thin corpus callosum and cerebral, cerebellar, or pontine atrophy. Some patients may die in infancy or early childhood.

6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Expert list
Fetal anomalies v0.4294 NFIB Krithika Murali gene: NFIB was added
gene: NFIB was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NFIB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIB were set to 30388402; 33130023; 32902921
Phenotypes for gene: NFIB were set to Macrocephaly, acquired, with impaired intellectual development - MIM#618286
Review for gene: NFIB was set to GREEN
Added comment: NFIB haploinsufficiency associated with syndromic ID. Macrocephaly and corpus callosum anomalies are recurrent phenotypic features. OMIM notes macrocephaly postnatal in onset, but review of published cases shows some instances of relative macrocephaly at birth. Also corpus callosal anomalies - agenesis and dysgenesis, noted on MRI-B in childhood but possibility of detecting this antenatally in future cases. 2 unrelated individuals reported with minor cardiac anomalies also.

---

OMIM notes macrocephaly postnatal in onset. PMID: 30388402 - 18 individuals reported, of whom 11 had deletions of this gene and the rest had SNVs. Relative macrocephaly noted based on growth parameters in 4 individuals (e.g. x1 male with BW 22nd centile and HC 99th centile in an apparently uncomplicated pregnancy) - macrocephaly became more pronounced with age. In addition, 2 individuals had congenital cardiac anomalies (x1 small VSD and x1 narrow pulmonary artery) and 2 individuals had complete agenesis of the corpus callosum.

33130023 - Report one affected individual. Birth weight was 4.13 kg (Z-score 1.50, 93rd percentile), length was 52 cm (Z-score 1.12, 87th percentile) and his head circumference was 37 cm (Z-score 2.00, 98th percentile). MRI-B at 12 months confirmed agenesis of the corpus callosum

32902921 - report one patient with normal antenatal history, no birth HC provided, macrocephaly noted at 7 months. MRI-B showed mild dysgensis of the corpus callosum age 5. 2nd unrelated patient's birth weight 3.43 kg(57th centile,Zscore 0.17), length 52.8 cm (94th centile, Zscore1.54), and OFC 37.5 cm (99th centile,Zscore 2.39). MRI-B age 5 showed dysgenesis of the corpus callosum.
Sources: Literature
Fetal anomalies v0.4294 YRDC Chirag Patel Classified gene: YRDC as Green List (high evidence)
Fetal anomalies v0.4294 YRDC Chirag Patel Gene: yrdc has been classified as Green List (High Evidence).
Fetal anomalies v0.4293 YRDC Chirag Patel gene: YRDC was added
gene: YRDC was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: YRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YRDC were set to PMID: 31481669, 34545459
Phenotypes for gene: YRDC were set to Galloway-Mowat syndrome 10, OMIM # 619609
Review for gene: YRDC was set to GREEN
Added comment: Galloway-Mowat syndrome-10 (GAMOS10) is a severe autosomal recessive disorder characterized by onset of symptoms soon after birth. Affected individuals have progressive renal dysfunction with proteinuria associated with diffuse mesangial sclerosis (DMS) on renal biopsy. Other features include global developmental delay, microcephaly, hypothyroidism, arachnodactyly, and dysmorphic facial features. Some patients may have seizures or abnormalities on brain imaging. All reported patients have died in infancy.

4 individuals from 3 unrelated families with typical features of Galloway-Mowat syndrome including proteinuria, microcephaly, developmental delay and brain malformations. Supportive functional data.
Sources: Expert list
Fetal anomalies v0.4292 ZNF526 Chirag Patel Classified gene: ZNF526 as Green List (high evidence)
Fetal anomalies v0.4292 ZNF526 Chirag Patel Gene: znf526 has been classified as Green List (High Evidence).
Fetal anomalies v0.4291 ZNF526 Chirag Patel gene: ZNF526 was added
gene: ZNF526 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ZNF526 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF526 were set to PMID: 33397746, 21937992, 25558065,
Phenotypes for gene: ZNF526 were set to Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia
Review for gene: ZNF526 was set to GREEN
Added comment: - PMID: 21937992 (2011) - Two unrelated families (with 4 affected individuals in each) with non-syndromic ID (mild or moderate, respectively) identified harbouring different biallelic missense variants in the ZNF526 gene.

- PMID: 25558065 (2015) - One family with ID, Noonan-like facies, pulmonary stenosis and a homozygous missense variant in this gene. No further details provided.

- PMID: 33397746 (2021) - Five individuals from four unrelated families with homozygous ZNF526 variants. Four harboured truncating variants, and were all affected by profound DD and severe ID, severe pre/postnatal microcephaly (ranging from -4 SD to -8 SD), bilateral progressive cataracts, hypertonic-dystonic movements, epilepsy and brain MRI anomalies. The fifth patient had a homozygous missense variant and a slightly less severe disorder, with postnatal microcephaly (-2 SD), progressive bilateral cataracts, severe ID, and normal brain MRI. Zebrafish model demonstrated brain and eye malformations resembling findings seen in the human holoprosencephaly spectrum
Sources: Expert list
Fetal anomalies v0.4290 PIDD1 Daniel Flanagan gene: PIDD1 was added
gene: PIDD1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIDD1 were set to 28397838; 29302074; 33414379; 34163010
Phenotypes for gene: PIDD1 were set to Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum
Review for gene: PIDD1 was set to AMBER
Added comment: Doesn't appear to have an antenatal onset. Clinical findings in supplementary table for PMID: 34163010 doesn't mention any prenatal findings. For family M278, two affected siblings were "born at term after uneventful pregnancies, neonatal periods and normal development." Mean age of cohort was 13.2 years.

Biallelic PIDD1 pathogenic variants have been reported in 26 individuals (11 families) with DD (all), variable degrees of ID (mild to severe), behavioral (eg. aggression/self-mutilation in several, ADHD) and/or psychiatric abnormalities (ASD, psychosis in 5 belonging to 3 families), well-controlled epilepsy is some (9 subjects from 6 families) and MRI abnormalities notably abnormal gyration pattern (pachygyria with predominant anterior gradient) as well as corpus callosum anomalies (commonly thinning) in several. Dysmorphic features have been reported in almost all, although there has been no specific feature suggested.

The first reports on the phenotype associated with biallelic PIDD1 mutations were made by Harripaul et al (2018 - PMID: 28397838) and Hu et al (2019 - PMID: 29302074) [both studies investigating large cohorts of individuals with ID from consanguineous families].

Sheikh et al (2021 - PMID: 33414379) provided details on the phenotype of 15 individuals from 5 families including those from the previous 2 reports and studied provided evidence on the role of PIDD1 and the effect of variants.

Zaki et al (2021 - PMID: 34163010) reported 11 additional individuals from 6 consanguineous families, summarize the features of all subjects published in the literature and review the neuroradiological features of the disorder.

PIDD1 encodes p53-induced death domain protein 1. The protein is part of the PIDDosome, a multiprotein complex also composed of the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 and induces apoptosis in response to DNA damage.

There are 5 potential PIDD1 mRNA transcript variants with NM_145886.4 corresponding to the longest. Similar to the protein encoded by CRADD, PIDD1 contains a death domain (DD - aa 774-893). Constitutive post-translational processing gives PIDD1-N, PIDD1-C the latter further processed into PIDD1-CC (by auto-cleavage). Serine residues at pos. 446 and 588 are involved in this autoprocessing generating PIDD1-C (aa 446-910) and PIDD1-CC (aa 774-893). The latter is needed for caspase-2 activation.

Most (if not all) individuals belonged to consanguineous families of different origins and harbored pLoF or missense variants.

Variants reported so far include : c.2587C>T; p.Gln863* / c.1909C>T ; p.Arg637* / c.2443C>T / p.Arg815Trp / c.2275-1G>A which upon trap assay was shown to lead to skipping of ex15 with direct splicing form exon14 to the terminal exon 16 (resulting to p.Arg759Glyfs*1 with exlcusion of the entire DD) / c.2584C>T; p.Arg862Trp / c.1340G>A; p.Trp447* / c.2116_2120del; p.Val706His*, c.1564_1565del; p.Gly602fs*26

Evidence so far provided includes:
- Biallelic CRADD variants cause a NDD disorder and a highly similar gyration pattern.
- Confirmation of splicing effect (eg. for c.2275-1G>A premature stop in position 760) or poor expression (NM_145886.3:c.2587C>T; p.Gln863*). Arg815Trp did not affect autoprocessing or protein stability.
- Abnormal localization pattern, loss of interaction with CRADD and failure to activate caspase-2 (MDM2 cleavage assay) [p.Gln863* and Arg815Trp]
- Available expression data from GTEx (PIDD1 having broad expression in multiple tissues, but higher in brain cerebellum) as well as BrainSpan and PsychEncode studies suggesting high coexpression of PIDD1, CRADD and CASP2 in many regions in the developing human brain.
- Variants in other genes encoding proteins interacting with PIDD1 (MADD, FADD, DNAJ, etc) are associated with NDD.

Pidd-1 ko mice (ex3-15 removal) lack however CNS-related phenotypes. These show decreased anxiety but no motor anomalies. This has also been the case with Cradd-/- mice displaying no significant CNS phenotypes without lamination defects.
Sources: Expert list
Fetal anomalies v0.4290 ZNF668 Chirag Patel Classified gene: ZNF668 as Amber List (moderate evidence)
Fetal anomalies v0.4290 ZNF668 Chirag Patel Gene: znf668 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4289 ZNF668 Chirag Patel gene: ZNF668 was added
gene: ZNF668 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ZNF668 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF668 were set to PMID: 34313816, 26633546
Phenotypes for gene: ZNF668 were set to DNA damage repair defect; microcephaly; growth deficiency; severe global developmental delay; brain malformation; facial dysmorphism
Review for gene: ZNF668 was set to AMBER
Added comment: 2 consanguineous families reported with different biallelic truncating (not NMD) variants in ZNF668. Phenotypes included microcephaly, growth deficiency, severe global developmental delay, brain malformation, and distinct facial dysmorphism. Immunofluorescence indicated ZNF668 deficiency. An increased DNA damage phenotype was demonstrated in patient fibroblasts.
Sources: Expert list
Fetal anomalies v0.4288 ZNHIT3 Chirag Patel Classified gene: ZNHIT3 as Green List (high evidence)
Fetal anomalies v0.4288 ZNHIT3 Chirag Patel Gene: znhit3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4287 ZNHIT3 Chirag Patel gene: ZNHIT3 was added
gene: ZNHIT3 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ZNHIT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNHIT3 were set to PMID: 28335020; 28335020; 31048081
Phenotypes for gene: ZNHIT3 were set to PEHO syndrome, MIM# 260565
Review for gene: ZNHIT3 was set to GREEN
Added comment: PEHO is a severe autosomal recessive neurodevelopmental disorder characterized by extreme cerebellar atrophy due to almost total loss of granule neurons. Affected individuals present in early infancy with hypotonia, profoundly delayed psychomotor development, optic atrophy, progressive atrophy of the cerebellum and brainstem, and dysmyelination. Most patients also develop infantile seizures that are often associated with hypsarrhythmia on EEG, and many have peripheral oedema. More than 20 affected individuals reported of Finnish origin, p.Ser31Leu is a founder variant. One compound het reported and supportive animal model.
Sources: Expert list
Fetal anomalies v0.4286 GON7 Ain Roesley edited their review of gene: GON7: Changed rating: GREEN
Fetal anomalies v0.4286 APC2 Zornitza Stark Marked gene: APC2 as ready
Fetal anomalies v0.4286 APC2 Zornitza Stark Gene: apc2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4286 APC2 Zornitza Stark Classified gene: APC2 as Green List (high evidence)
Fetal anomalies v0.4286 APC2 Zornitza Stark Gene: apc2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4285 APC2 Zornitza Stark reviewed gene: APC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 10, MIM#618677; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4285 C7orf43 Zornitza Stark Marked gene: C7orf43 as ready
Fetal anomalies v0.4285 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4285 C7orf43 Zornitza Stark Tag new gene name tag was added to gene: C7orf43.
Fetal anomalies v0.4285 C7orf43 Zornitza Stark Classified gene: C7orf43 as Amber List (moderate evidence)
Fetal anomalies v0.4285 C7orf43 Zornitza Stark Gene: c7orf43 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4284 ATRIP Zornitza Stark Marked gene: ATRIP as ready
Fetal anomalies v0.4284 ATRIP Zornitza Stark Gene: atrip has been classified as Red List (Low Evidence).
Fetal anomalies v0.4284 ATRIP Zornitza Stark Classified gene: ATRIP as Red List (low evidence)
Fetal anomalies v0.4284 ATRIP Zornitza Stark Gene: atrip has been classified as Red List (Low Evidence).
Fetal anomalies v0.4283 ATP9A Zornitza Stark Marked gene: ATP9A as ready
Fetal anomalies v0.4283 ATP9A Zornitza Stark Gene: atp9a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4283 ATP9A Zornitza Stark Classified gene: ATP9A as Amber List (moderate evidence)
Fetal anomalies v0.4283 ATP9A Zornitza Stark Gene: atp9a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4282 ARPC4 Zornitza Stark Marked gene: ARPC4 as ready
Fetal anomalies v0.4282 ARPC4 Zornitza Stark Gene: arpc4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4282 ARPC4 Zornitza Stark Classified gene: ARPC4 as Red List (low evidence)
Fetal anomalies v0.4282 ARPC4 Zornitza Stark Gene: arpc4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4281 ANKLE2 Zornitza Stark Marked gene: ANKLE2 as ready
Fetal anomalies v0.4281 ANKLE2 Zornitza Stark Gene: ankle2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4281 ANKLE2 Zornitza Stark Classified gene: ANKLE2 as Green List (high evidence)
Fetal anomalies v0.4281 ANKLE2 Zornitza Stark Gene: ankle2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4280 AGMO Zornitza Stark Marked gene: AGMO as ready
Fetal anomalies v0.4280 AGMO Zornitza Stark Gene: agmo has been classified as Red List (Low Evidence).
Fetal anomalies v0.4280 AGMO Zornitza Stark Classified gene: AGMO as Red List (low evidence)
Fetal anomalies v0.4280 AGMO Zornitza Stark Gene: agmo has been classified as Red List (Low Evidence).
Fetal anomalies v0.4279 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Fetal anomalies v0.4279 ADD3 Zornitza Stark Gene: add3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4279 ADD3 Zornitza Stark Classified gene: ADD3 as Red List (low evidence)
Fetal anomalies v0.4279 ADD3 Zornitza Stark Gene: add3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4278 ADARB1 Zornitza Stark Marked gene: ADARB1 as ready
Fetal anomalies v0.4278 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4278 ADARB1 Zornitza Stark Classified gene: ADARB1 as Amber List (moderate evidence)
Fetal anomalies v0.4278 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4277 D2HGDH Zornitza Stark Marked gene: D2HGDH as ready
Fetal anomalies v0.4277 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Fetal anomalies v0.4277 D2HGDH Zornitza Stark Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria, MIM# 600721
Fetal anomalies v0.4276 D2HGDH Zornitza Stark Classified gene: D2HGDH as Green List (high evidence)
Fetal anomalies v0.4276 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Fetal anomalies v0.4275 D2HGDH Zornitza Stark reviewed gene: D2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: D-2-hydroxyglutaric aciduria, MIM# 600721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4275 HEXB Krithika Murali gene: HEXB was added
gene: HEXB was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HEXB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEXB were set to 23046579; 24613245; 33407268; 27697305; 11869411; 33363784
Phenotypes for gene: HEXB were set to Sandhoff disease, infantile, juvenile, and adult forms-MIM#268800
Review for gene: HEXB was set to RED
Added comment: Biallelic variants associated with Sandhoff disease which includes a severe, infantile onset form. Authors of reported cases note normal antenatal and immediate postnatal course with onset of phenotypic features generally from 2 months of age onwards. Note subset with cardiomyopathy and secondary valvular incompetence, not congenital heart defects.
Sources: Literature
Fetal anomalies v0.4273 GTPBP2 Ain Roesley gene: GTPBP2 was added
gene: GTPBP2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GTPBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP2 were set to 26675814; 29449720; 30790272
Phenotypes for gene: GTPBP2 were set to Jaberi-Elahi syndrome MIM#617988
Review for gene: GTPBP2 was set to GREEN
gene: GTPBP2 was marked as current diagnostic
Added comment: Nine individuals from six unrelated families

microcephaly noted but measurements at birth not provided.
1x weight 5th percentile and OFC 25-50 percentile

scoliosis consistently reported
Other features include clenched hands, talipes, abnormal brain imaging, pectus excavatum
Sources: Literature
Fetal anomalies v0.4273 MCF2 Daniel Flanagan gene: MCF2 was added
gene: MCF2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MCF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MCF2 were set to 31846234
Phenotypes for gene: MCF2 were set to Perisylvian polymicrogyria
Review for gene: MCF2 was set to RED
Added comment: Single individual reported, inherited missense variant from unaffected mother, some support from mouse model.
Sources: Expert list
Fetal anomalies v0.4273 MAN2C1 Daniel Flanagan gene: MAN2C1 was added
gene: MAN2C1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MAN2C1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2C1 were set to 35045343
Phenotypes for gene: MAN2C1 were set to MAN2C1-related neurodevelopmental disorder MONDO:0700092
Review for gene: MAN2C1 was set to GREEN
Added comment: Six individuals from four different families, including two fetuses, exhibiting dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Variants include PTC and missense.
*3 unrelated individuals presented polymicrogyria
Sources: Expert list
Fetal anomalies v0.4273 B3GNT2 Belinda Chong commented on gene: B3GNT2
Fetal anomalies v0.4273 INTS8 Daniel Flanagan gene: INTS8 was added
gene: INTS8 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: INTS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS8 were set to 28542170
Phenotypes for gene: INTS8 were set to Neurodevelopmental disorder with cerebellar hypoplasia and spasticity (MIM#618572)
Review for gene: INTS8 was set to RED
Added comment: Single family with three affected sibs with compound het INTS8 variants, Microcephaly, Cerebellar hypoplasia, Nodular heterotopia. Some functional evidence.
Sources: Expert list
Fetal anomalies v0.4273 GRM7 Ain Roesley gene: GRM7 was added
gene: GRM7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities MIM#618922
Review for gene: GRM7 was set to GREEN
gene: GRM7 was marked as current diagnostic
Added comment: progressive/post-natal microcephaly consistently reported

6 families with 11 affecteds
5 of the pregnancies were complicated by polyhydramnios/decreased fetal movements
Sources: Literature
Fetal anomalies v0.4273 ERMARD Daniel Flanagan gene: ERMARD was added
gene: ERMARD was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ERMARD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERMARD were set to 27087860; 24056535
Phenotypes for gene: ERMARD were set to Periventricular nodular heterotopia 6 (MIM#615544)
Review for gene: ERMARD was set to RED
Added comment: Single individual described with heterozygous ERMARD missense and periventricular nodular heterotopia, developmental delay and epilepsy.

PMID: 27087860. Fetus was diagnosed by prenatal ultrasound with symmetric bilateral ventriculomegaly. The fetus carried a 0.78-Mb deletion of chromosomal region 6q27 (ERMARD included).
Sources: Expert list
Fetal anomalies v0.4273 GPT2 Ain Roesley gene: GPT2 was added
gene: GPT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPT2 were set to 25758935; 27601654; 28130718; 29226631; 29882329; 31471722
Phenotypes for gene: GPT2 were set to Neurodevelopmental disorder with microcephaly and spastic paraplegia MIM#616281
Review for gene: GPT2 was set to RED
gene: GPT2 was marked as current diagnostic
Added comment: post-natal microcephaly

of note;
1x family where fisting was observed in a 4 yr old
1x adducted thumbs and scoliosis
a handful had reduced white matter volume and/or thin corpus callosum
Sources: Literature
Fetal anomalies v0.4273 GON7 Ain Roesley edited their review of gene: GON7: Changed rating: AMBER
Fetal anomalies v0.4273 GON7 Ain Roesley gene: GON7 was added
gene: GON7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GON7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GON7 were set to 31481669
Phenotypes for gene: GON7 were set to Galloway-Mowat syndrome 9, MIM# 619603
Review for gene: GON7 was set to GREEN
gene: GON7 was marked as current diagnostic
Added comment: 11 individuals from 5 families. Four of the families had the same homozygous variant, shared haplotype suggestive of founder effect.

post-natal microcephaly and brain malformations such as cerebellar atrophy, atrophic/thin corpus callosum. Cranial imaging done as young as 6 months.

Maybe detectable antenatally
Sources: Literature
Fetal anomalies v0.4273 EOMES Daniel Flanagan gene: EOMES was added
gene: EOMES was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: EOMES was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EOMES were set to 17353897
Phenotypes for gene: EOMES were set to microcephaly; polymicrogyria; corpus callosum agenesis
Review for gene: EOMES was set to RED
Added comment: Single family with homozygous balanced translocation between chromosomes 3p and 10q affecting EOMES.
Sources: Expert list
Fetal anomalies v0.4273 GOLGA2 Ain Roesley edited their review of gene: GOLGA2: Changed phenotypes: neuromuscular disease, GOLGA2-related MONDO#0019056
Fetal anomalies v0.4273 GOLGA2 Ain Roesley gene: GOLGA2 was added
gene: GOLGA2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to 34424553; 26742501; 30237576
Review for gene: GOLGA2 was set to GREEN
gene: GOLGA2 was marked as current diagnostic
Added comment: 3x unrelated families

1x noted with a smaller head at birth head circumference 32.5 cm (7th percentile). weight 3.22 kg (37th percentile), length 49.5 cm (53rd percentile)

Nonspecific cerebral volume loss / cortical atrophy with delayed myelination and thin corpus callosum reported in all post-natally. Maybe detectable antenatally
Sources: Literature
Fetal anomalies v0.4273 APC2 Belinda Chong commented on gene: APC2: Youngest affected was 3 months however, 31585108 indicated All affected children were born full term without any complications during pregnancy and delivery.
Fetal anomalies v0.4273 ENO1 Daniel Flanagan gene: ENO1 was added
gene: ENO1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ENO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ENO1 were set to 32488097
Phenotypes for gene: ENO1 were set to Polymicrogyria; microcephaly
Review for gene: ENO1 was set to RED
Added comment: ENO1 identified as a polymicrogyria candidate gene from the smallest case of 1p36 duplication reported to date, in a 35yo F (onset at 8mo) presenting intellectual disability, microcephaly, epilepsy and perisylvian polymicrogyria. The duplication only encompassed 2 genes, ENO1 and RERE, and gene expression analysis performed using the patient cells revealed reduced expression, mimicking haploinsufficiency. Eno1 inactivation in rats was shown to cause a brain development defect. According to OMIM, ENO1 is deleted in glioblastoma, which is tolerated by the expression of ENO2.
Sources: Expert list
Fetal anomalies v0.4273 CEP85L Daniel Flanagan gene: CEP85L was added
gene: CEP85L was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CEP85L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CEP85L were set to 32097630
Phenotypes for gene: CEP85L were set to Lissencephaly 10, posterior predominant (MIM618873)
Review for gene: CEP85L was set to RED
Added comment: Thirteen individuals reported with mono allelic variants in this gene, inherited in two of the families. Mouse model had neuronal migration defects. Earliest symptom onset 5 months, most develop seizures after several years.
Sources: Expert list
Fetal anomalies v0.4273 HEXA Krithika Murali gene: HEXA was added
gene: HEXA was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HEXA were set to Tay-Sachs disease - MIM#272800
Review for gene: HEXA was set to RED
Added comment: Associated features not reported prenatally or at birth.
Sources: Literature
Fetal anomalies v0.4273 FOXR1 Ain Roesley gene: FOXR1 was added
gene: FOXR1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FOXR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXR1 were set to 34723967
Phenotypes for gene: FOXR1 were set to Postnatal microcephaly, progressive brain atrophy and global developmental delay
Review for gene: FOXR1 was set to AMBER
gene: FOXR1 was marked as current diagnostic
Added comment: 1 individual with functional studies done for the specific variant

post-natal microcephaly with progressive brain atrophy from 1 yr onwards
Sources: Literature
Fetal anomalies v0.4273 HERC1 Krithika Murali gene: HERC1 was added
gene: HERC1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HERC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HERC1 were set to 28323226; 27108999; 26153217; 26138117
Phenotypes for gene: HERC1 were set to Macrocephaly, dysmorphic facies, and psychomotor retardation - MIM#617011
Review for gene: HERC1 was set to GREEN
Added comment: Multiple individuals reported with macrosomia and macrocephaly detected at birth.
Sources: Literature
Fetal anomalies v0.4273 FDXR Ain Roesley gene: FDXR was added
gene: FDXR was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDXR were set to 30250212; 28965846
Phenotypes for gene: FDXR were set to Auditory neuropathy and optic atrophy, MIM# 617717
Review for gene: FDXR was set to RED
gene: FDXR was marked as current diagnostic
Added comment: Bi-allelic variants in FDXR cause an autosomal recessive neurologic disorder characterised by onset of visual and hearing impairment in the first or second decades. Two individuals described with a more severe phenotype, including one with microcephaly.
Sources: Literature
Fetal anomalies v0.4273 CDK5 Daniel Flanagan gene: CDK5 was added
gene: CDK5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CDK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5 were set to 25560765
Phenotypes for gene: CDK5 were set to Lissencephaly 7 with cerebellar hypoplasia (MIM#616342)
Review for gene: CDK5 was set to RED
Added comment: Single consanguineous family with multiple affected individuals reported, lissencephaly prominent. Head circumference at the low-normal range (5th–25th percentile).
Sources: Literature
Fetal anomalies v0.4273 EXOC7 Ain Roesley edited their review of gene: EXOC7: Changed publications: 32103185; Changed phenotypes: Neurodevelopmental disorder with seizures and brain atrophy MIM#619072
Fetal anomalies v0.4273 EXOC7 Ain Roesley gene: EXOC7 was added
gene: EXOC7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EXOC7 were set to Neurodevelopmental disorder with seizures and brain atrophy MIM#619072
Review for gene: EXOC7 was set to GREEN
gene: EXOC7 was marked as current diagnostic
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families.
Sources: Literature
Fetal anomalies v0.4273 DYNC1I2 Ain Roesley gene: DYNC1I2 was added
gene: DYNC1I2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DYNC1I2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DYNC1I2 were set to 31079899
Phenotypes for gene: DYNC1I2 were set to Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492
Review for gene: DYNC1I2 was set to GREEN
gene: DYNC1I2 was marked as current diagnostic
Added comment: 5 affecteds from 3 families

1x microcephaly at birth and head ultrasound at 2 months detected absent corpus callosum. Furthermore, abrain MRI revealed the absence of the rostrum and genu ofthe corpus callosum and partial absence of the splenium,as well as absence of the septum pellucidum and megacisterna magna.

1x microcephaly at birth (-2 SD). Brain MRI at 3 months of age re-vealed a hypoplastic corpus callosum, prominent ventri-cles, reduced white matter volume, and simplified gyralpattern
Sources: Literature
Fetal anomalies v0.4273 FIBP Krithika Murali gene: FIBP was added
gene: FIBP was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FIBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FIBP were set to 27183861; 26660953
Phenotypes for gene: FIBP were set to Thauvin-Robinet-Faivre syndrome - MIM#617107
Review for gene: FIBP was set to AMBER
Added comment: Thauvin-Robinet-Faivre syndrome is an autosomal recessive disorder characterized by generalized overgrowth, mainly of height, and mildly delayed psychomotor development with mild or severe learning difficulties. More variable features may include congenital heart defects, kidney abnormalities, and skeletal defects. Patients may have an increased risk for Wilms tumor.

2 unrelated families reported.

27183861 - report one family with 3 affected children. Prenatally relevant phenotypic features include:
- congenital heart disease in one child
- preterm delivery and bilateral talipes equinovarus 2nd child
- cystic kidney disease, nephromegaly and polyhydramnios 3rd child

26660953 - report one child with ventricular septal defect, mitral valve prolapse, renal malrotation with left bifid ureter, macrocephaly and macrosomia noted at birth.
Sources: Literature
Fetal anomalies v0.4273 B3GNT2 Daniel Flanagan gene: B3GNT2 was added
gene: B3GNT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: B3GNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GNT2 were set to 23359570; 23877401
Phenotypes for gene: B3GNT2 were set to Walker-Warburg syndrome
Review for gene: B3GNT2 was set to AMBER
Added comment: Only 2 families reported

PMID: 23877401. Homozygous frameshift in B3GNT1 identified in a proband born with occipital encephalocele, anencephaly, cloudy cornea, proptotic eyes, spastic posture and micropenis.

PMID: 23359570. Family with two homozygous B3GNT1 missense in affected. 4 pregnancies with abnormalities identified by ultrasound, including: hydrocephalus with the lateral ventricles, severe cerebral ventriculomegaly, cystic dysplastic kidney
Sources: Literature
Fetal anomalies v0.4273 CTNNA2 Ain Roesley gene: CTNNA2 was added
gene: CTNNA2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CTNNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNNA2 were set to 30013181
Phenotypes for gene: CTNNA2 were set to Cortical dysplasia, complex, with other brain malformations 9, MIM#618174
Review for gene: CTNNA2 was set to GREEN
gene: CTNNA2 was marked as current diagnostic
Added comment: acquired microcephaly. Pachygyria is also a feature, which can be detectable in a prenatal MRI, though none of the reports thus far were diagnosed antenatally

3 families with 7 affecteds
Sources: Literature
Fetal anomalies v0.4273 DICER1 Krithika Murali gene: DICER1 was added
gene: DICER1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DICER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DICER1 were set to 27960159; 29343557; 26227654; 33208384; 35114704; 31232238; 24676357
Phenotypes for gene: DICER1 were set to GLOW syndrome, somatic mosaic - MIM#618272; Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors - MIM#138800; Pleuropulmonary blastoma - MIM#601200
Review for gene: DICER1 was set to GREEN
Added comment: Heterozygous pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic somatic missense DICER1 variants in the RNase IIIb domain are linked to GLOW syndrome (global developmental delay, lung cysts, overgrowth, and Wilms’ tumor) syndrome. While the DICER1 syndrome is classically caused by frameshift, nonsense or other mutations that ablate DICER1 function in a true heterozygous state, GLOW-syndrome mutations occur at specific residues within the RNase IIIb domain that only affect the function of this domain.

Both syndromes have been reported to have features that can be detected prenatally.

PMID 33208384 - report a patient with heterozygous germline DICER1 variant. The patient was born at gestational week 39 after a difficult delivery due to macrocephaly. Clinical findings at birth included two blood vessels in the umbilical cord, undescended testis, inguinal hernia, postaxial polydactyly, ear pits and rocker bottom feet.

PMID: 34331184 - report 4 unrelated families with germline DICER1 variants. In family 1 - one child was born with Pierre Robin sequence, shortening of the left arm and leg and bilateral
hip dysplasia. In Family 2 a child had macrosomia and macrocephaly at birth. Family 4 - born at 33 weeks, dysmorphic facies including hypertelorism and macroglossia.

PMID 24676357 - report 2 unrelated children with GLOW syndrome. Patient 1 was noted to have enlarged kidneys on 24 week ultrasound. At birth was found to have renal and pulmonary cysts. Patient 2 - macrocephaly was noted at birth.

DICER1 implicated in ~60% of PPB - reports of PPB detecteed antenatally, although no reports in the context of confirmed DICER1 syndrome.
Sources: Literature
Fetal anomalies v0.4273 COLGALT1 Zornitza Stark Marked gene: COLGALT1 as ready
Fetal anomalies v0.4273 COLGALT1 Zornitza Stark Gene: colgalt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4273 COLGALT1 Zornitza Stark Phenotypes for gene: COLGALT1 were changed from to Brain small vessel disease 3, MIM# 618360
Fetal anomalies v0.4272 COLGALT1 Zornitza Stark Publications for gene: COLGALT1 were set to
Fetal anomalies v0.4271 COLGALT1 Zornitza Stark edited their review of gene: COLGALT1: Changed publications: 30412317, 33709034, 31759980
Fetal anomalies v0.4271 COLGALT1 Zornitza Stark commented on gene: COLGALT1: 3 unrelated cases with biallelic variants, and supporting functional assays. The main features of the cases were porencephalic cysts, leukoencephalopathy, lacunar infarcts, cerebral microbleeds/haemorrhages and calcifications. A null mouse model was embryonic lethal, but had defects in the vascular networks of the embryos.
Fetal anomalies v0.4271 COLGALT1 Zornitza Stark Classified gene: COLGALT1 as Green List (high evidence)
Fetal anomalies v0.4271 COLGALT1 Zornitza Stark Gene: colgalt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4270 COLGALT1 Zornitza Stark reviewed gene: COLGALT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain small vessel disease 3, MIM# 618360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4270 C2orf69 Zornitza Stark Marked gene: C2orf69 as ready
Fetal anomalies v0.4270 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Fetal anomalies v0.4270 C2orf69 Zornitza Stark Phenotypes for gene: C2orf69 were changed from to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Fetal anomalies v0.4269 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Fetal anomalies v0.4269 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Fetal anomalies v0.4268 C2orf69 Zornitza Stark reviewed gene: C2orf69: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4268 ABHD16A Zornitza Stark Marked gene: ABHD16A as ready
Fetal anomalies v0.4268 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Green List (High Evidence).
Fetal anomalies v0.4268 ABHD16A Zornitza Stark Phenotypes for gene: ABHD16A were changed from to Spastic paraplegia 86, autosomal recessive, MIM# 619735
Fetal anomalies v0.4267 ABHD16A Zornitza Stark Classified gene: ABHD16A as Green List (high evidence)
Fetal anomalies v0.4267 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Green List (High Evidence).
Fetal anomalies v0.4266 ABHD16A Zornitza Stark reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 86, autosomal recessive, MIM# 619735; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4266 COPB2 Ain Roesley gene: COPB2 was added
gene: COPB2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COPB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COPB2 were set to 29036432; 34450031
Phenotypes for gene: COPB2 were set to Microcephaly 19, primary, autosomal recessive, MIM# 617800
Review for gene: COPB2 was set to RED
gene: COPB2 was marked as current diagnostic
Added comment: IUGR or small at birth (including microcephaly) not noted for any of the probands. Fractures and osteopenia were not detected antenatally.
Sources: Literature
Fetal anomalies v0.4266 ARF1 Daniel Flanagan gene: ARF1 was added
gene: ARF1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARF1 were set to 28868155; 34353862
Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8 (MIM#618185)
Review for gene: ARF1 was set to RED
Added comment: Three unrelated individuals reported with de novo missense in this gene. PMID: 34353862: Additional report of affected parent and child.

1 patient had microcephaly in teens but normal head circumference at first examination.
Sources: Literature
Fetal anomalies v0.4266 ATXN2L Krithika Murali gene: ATXN2L was added
gene: ATXN2L was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ATXN2L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATXN2L were set to 33283965; 33057194
Phenotypes for gene: ATXN2L were set to macrocephaly; intellectual disability
Review for gene: ATXN2L was set to AMBER
Added comment: Combined data from three large exome groups identified several de novo variants, including frameshift and missense, in ATXN2L in patients with developmental delay (Kaplanis et al., 2020). pLI=1.0

33283965 - Single case report of a novel de novo missense variant in a child with macrocephaly and developmental delay. No functional work. Macrocephaly was detected prenatally. This together with breech presentation resulted in elective C-section at 36 weeks.
Sources: Literature
Fetal anomalies v0.4266 COPB1 Ain Roesley gene: COPB1 was added
gene: COPB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COPB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COPB1 were set to Baralle-Macken syndrome, MIM# 619255; Severe intellectual disability; variable microcephaly; cataracts
Review for gene: COPB1 was set to RED
gene: COPB1 was marked as current diagnostic
Added comment: Two unrelated families, some supportive functional data. Microcephaly is not a consistent feature in the families reported to date.

Cataracts were also post-natal
Sources: Literature
Fetal anomalies v0.4266 CHKA Ain Roesley gene: CHKA was added
gene: CHKA was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to neurodevelopmental disorder, CHKA-related MONDO#0700092
Review for gene: CHKA was set to RED
gene: CHKA was marked as current diagnostic
Added comment: post-natal microcephaly and short stature.
Symptoms which were present within the first few months post birth include developmental delay and seizures
Sources: Literature
Fetal anomalies v0.4266 CENPE Ain Roesley gene: CENPE was added
gene: CENPE was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CENPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPE were set to 24748105; 30086807
Phenotypes for gene: CENPE were set to Microcephaly 13, primary, autosomal recessive (MIM#616051)
Review for gene: CENPE was set to RED
gene: CENPE was marked as current diagnostic
Added comment: PMID: 24748105;
- 2 siblings from non-consanguineous family of European descent
- patient A: at birth, OFC of -5SD which progressed to -9SD at 5 years of age
- patient B: no measurement at birth but OFC was -7SD at 3 years of age
- cHet for 2 missense

*no new reports since. A review of AR primary microcephaly in 2018 still states just 1 family (PMID: 30086807)
Sources: Literature
Fetal anomalies v0.4266 CDK6 Ain Roesley changed review comment from: 1x 8-generational family with 10 affecteds

unclear of microcephaly was present at birth or acquired
Sources: Literature; to: 1x 8-generational family with 10 affecteds

unclear if microcephaly was present at birth or acquired
Sources: Literature
Fetal anomalies v0.4266 CDK6 Ain Roesley gene: CDK6 was added
gene: CDK6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CDK6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK6 were set to 23918663
Phenotypes for gene: CDK6 were set to Microcephaly 12, primary, autosomal recessive, MIM#616080
Review for gene: CDK6 was set to AMBER
gene: CDK6 was marked as current diagnostic
Added comment: 1x 8-generational family with 10 affecteds

unclear of microcephaly was present at birth or acquired
Sources: Literature
Fetal anomalies v0.4266 CCDC88A Ain Roesley gene: CCDC88A was added
gene: CCDC88A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CCDC88A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC88A were set to 30392057; 26917597
Phenotypes for gene: CCDC88A were set to PEHO syndrome-like (MIM#617507)
Review for gene: CCDC88A was set to AMBER
gene: CCDC88A was marked as current diagnostic
Added comment: PMID: 26917597;
1x family with 3 affecteds microcephaly (birth OFC -3 - -4 SD)

total of 2 consanguineous families with 5 affecteds and functional studies of KO mice
Sources: Literature
Fetal anomalies v0.4266 PPP2R3C Zornitza Stark Marked gene: PPP2R3C as ready
Fetal anomalies v0.4266 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Fetal anomalies v0.4266 APC2 Belinda Chong gene: APC2 was added
gene: APC2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: APC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APC2 were set to 31585108
Phenotypes for gene: APC2 were set to Cortical dysplasia, complex, with other brain malformations 10, MIM#618677
Review for gene: APC2 was set to RED
gene: APC2 was marked as current diagnostic
Added comment: Onset in infancy

12 individuals from 8 unrelated families; intellectual disability, seizures, cortical dysplasia including posterior to anterior predominant pattern of lissencephaly, heterotopias, paucity of white matter, thin corpus callosum.
Sources: Literature
Fetal anomalies v0.4266 PPP2R3C Zornitza Stark Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818
Fetal anomalies v0.4265 CDX2 Zornitza Stark Phenotypes for gene: CDX2 were changed from Persistent cloaca to Genetic multiple congenital anomalies/dysmorphic syndrome, MONDO:0043005; Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs
Fetal anomalies v0.4264 C7orf43 Ain Roesley gene: C7orf43 was added
gene: C7orf43 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: C7orf43 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C7orf43 were set to 30715179
Phenotypes for gene: C7orf43 were set to Microcephaly 25, primary, autosomal recessive, MIM# 618351
Penetrance for gene: C7orf43 were set to Complete
Review for gene: C7orf43 was set to AMBER
gene: C7orf43 was marked as current diagnostic
Added comment: HGNC approved name TRAPPC14

Single family reported: three affected siblings with homozygous truncating variant. Supportive zebrafish model.

Occipital-frontal circumferences were below2 SD at birth, with microcephaly progressing later in life
Sources: Literature
Fetal anomalies v0.4264 ATRIP Ain Roesley gene: ATRIP was added
gene: ATRIP was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ATRIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATRIP were set to 23144622
Phenotypes for gene: ATRIP were set to Seckel Syndrome
Review for gene: ATRIP was set to RED
gene: ATRIP was marked as current diagnostic
Added comment: Red in Mendeliome - only 1 report of post-natal progressive microcephaly
Sources: Literature
Fetal anomalies v0.4264 ATP9A Ain Roesley gene: ATP9A was added
gene: ATP9A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ATP9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP9A were set to 34764295; 34379057
Phenotypes for gene: ATP9A were set to neurodevelopmental disorder, ATP9A-related MONDO#0700092
Penetrance for gene: ATP9A were set to Complete
Review for gene: ATP9A was set to AMBER
gene: ATP9A was marked as current diagnostic
Added comment: post-natal microcephaly, 4 unrelated families

1x polyhydramnios noted and born small, weight of 3570g (−0.41 SD), a length of 50cm (−1.37 SD) and an OFC of 34cm (−1.47 SD).
Sources: Literature
Fetal anomalies v0.4264 ARPC4 Ain Roesley gene: ARPC4 was added
gene: ARPC4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ARPC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPC4 were set to 35047857
Phenotypes for gene: ARPC4 were set to neurodevelopmental disorder, ARPC4-related MONDO#0700092
Penetrance for gene: ARPC4 were set to Complete
Review for gene: ARPC4 was set to RED
gene: ARPC4 was marked as current diagnostic
Added comment: post natal microcephaly except for 1 noted as 4% at birth

7 affected individuals from 6 families (gonadal mosaicism was confirmed in the mother of the 2 affected siblings) with a recurrent missense variant (NM_005718.4:c.472C>T; p.R158C).

Core features in affected individuals include microcephaly, mild motor delays, and significant speech impairment
Sources: Literature
Fetal anomalies v0.4264 ANKLE2 Ain Roesley gene: ANKLE2 was added
gene: ANKLE2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ANKLE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANKLE2 were set to 25259927; 30214071; 31735666
Phenotypes for gene: ANKLE2 were set to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Review for gene: ANKLE2 was set to GREEN
gene: ANKLE2 was marked as current diagnostic
Added comment: total of 4 unrelated born with microcephaly
Sources: Literature
Fetal anomalies v0.4264 AGMO Ain Roesley gene: AGMO was added
gene: AGMO was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AGMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGMO were set to 31555905; 27000257
Phenotypes for gene: AGMO were set to neurodevelopmental disorder, AGMO-related MONDO#0700092
Penetrance for gene: AGMO were set to Complete
Review for gene: AGMO was set to RED
gene: AGMO was marked as current diagnostic
Added comment: syndromic neurodevelopmental disorder with ID, microcephaly and epilesy reported

1x oligo-hydramnios, maternal hypothyroidism, and decreased fetal movement
birth weight was 2892 g (23%) and length was 49.5 cm (50%). Head circumference was not known but noted to be 5–10%

1x uneventful pregnancy
birth weight was 2977 g (55%) and length was 53.3 cm (98%)

1x siblings with post natal microcephaly
Sources: Literature
Fetal anomalies v0.4264 ADD3 Ain Roesley gene: ADD3 was added
gene: ADD3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to 23836506; 29768408
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3 MIM#617008
Penetrance for gene: ADD3 were set to Complete
Review for gene: ADD3 was set to RED
gene: ADD3 was marked as current diagnostic
Added comment: post natal borderline microcephaly and cataract
Sources: Literature
Fetal anomalies v0.4264 ADARB1 Ain Roesley gene: ADARB1 was added
gene: ADARB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ADARB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADARB1 were set to 32220291; 32719099
Phenotypes for gene: ADARB1 were set to Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, MIM#618862
Penetrance for gene: ADARB1 were set to Complete
Review for gene: ADARB1 was set to AMBER
gene: ADARB1 was marked as current diagnostic
Added comment: 6 unrelated families

1 microcephalic at birth (-2.2 SD) + 1 birth length at -4.3 SD
Sources: Literature
Fetal anomalies v0.4264 UNC13A Zornitza Stark Marked gene: UNC13A as ready
Fetal anomalies v0.4264 UNC13A Zornitza Stark Gene: unc13a has been classified as Red List (Low Evidence).
Fetal anomalies v0.4264 UNC13A Zornitza Stark Classified gene: UNC13A as Red List (low evidence)
Fetal anomalies v0.4264 UNC13A Zornitza Stark Gene: unc13a has been classified as Red List (Low Evidence).
Fetal anomalies v0.4263 SYT2 Zornitza Stark Marked gene: SYT2 as ready
Fetal anomalies v0.4263 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4263 SYT2 Zornitza Stark Classified gene: SYT2 as Green List (high evidence)
Fetal anomalies v0.4263 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4262 SLC25A1 Zornitza Stark Marked gene: SLC25A1 as ready
Fetal anomalies v0.4262 SLC25A1 Zornitza Stark Gene: slc25a1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4262 SLC25A1 Zornitza Stark Phenotypes for gene: SLC25A1 were changed from ?Myasthenic syndrome, congenital, 23, presynaptic MIM#618197; Combined D-2- and L-2-hydroxyglutaric aciduria MIM#615182 to Myasthenic syndrome, congenital, 23, presynaptic MIM#618197; Combined D-2- and L-2-hydroxyglutaric aciduria MIM#615182
Fetal anomalies v0.4261 SLC25A1 Zornitza Stark Classified gene: SLC25A1 as Red List (low evidence)
Fetal anomalies v0.4261 SLC25A1 Zornitza Stark Gene: slc25a1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4260 NHS Zornitza Stark Publications for gene: NHS were set to
Fetal anomalies v0.4259 RPH3A Zornitza Stark Marked gene: RPH3A as ready
Fetal anomalies v0.4259 RPH3A Zornitza Stark Gene: rph3a has been classified as Red List (Low Evidence).
Fetal anomalies v0.4259 RPH3A Zornitza Stark Classified gene: RPH3A as Red List (low evidence)
Fetal anomalies v0.4259 RPH3A Zornitza Stark Gene: rph3a has been classified as Red List (Low Evidence).
Fetal anomalies v0.4258 NHEJ1 Zornitza Stark changed review comment from: Clinical presentation is with SCID, short stature and microcephaly. ID was part of the phenotype in only one individual in the original paper describing this condition.; to: Clinical presentation is with SCID, short stature and microcephaly.
Fetal anomalies v0.4258 NHEJ1 Zornitza Stark edited their review of gene: NHEJ1: Changed rating: GREEN
Fetal anomalies v0.4258 PLEC Zornitza Stark Marked gene: PLEC as ready
Fetal anomalies v0.4258 PLEC Zornitza Stark Gene: plec has been classified as Green List (High Evidence).
Fetal anomalies v0.4258 PLEC Zornitza Stark Classified gene: PLEC as Green List (high evidence)
Fetal anomalies v0.4258 PLEC Zornitza Stark Gene: plec has been classified as Green List (High Evidence).
Fetal anomalies v0.4257 NDUFAF5 Zornitza Stark edited their review of gene: NDUFAF5: Changed rating: GREEN
Fetal anomalies v0.4257 NDUFAF5 Zornitza Stark Deleted their comment
Fetal anomalies v0.4257 LAMA5 Zornitza Stark Marked gene: LAMA5 as ready
Fetal anomalies v0.4257 LAMA5 Zornitza Stark Gene: lama5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4257 LAMA5 Zornitza Stark Classified gene: LAMA5 as Red List (low evidence)
Fetal anomalies v0.4257 LAMA5 Zornitza Stark Gene: lama5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4256 NBN Zornitza Stark Deleted their comment
Fetal anomalies v0.4256 NBN Zornitza Stark edited their review of gene: NBN: Changed rating: GREEN
Fetal anomalies v0.4256 NACC1 Zornitza Stark Deleted their comment
Fetal anomalies v0.4256 NACC1 Zornitza Stark edited their review of gene: NACC1: Changed rating: GREEN
Fetal anomalies v0.4256 D2HGDH Chloe Stutterd gene: D2HGDH was added
gene: D2HGDH was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: D2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: D2HGDH was set to GREEN
Added comment: Antenatal features: macrocephaly, enlarged cerebral ventricles, micrognathia
Sources: Literature
Fetal anomalies v0.4256 COLGALT1 Chloe Stutterd gene: COLGALT1 was added
gene: COLGALT1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Antenatal features: porencephalic cyst, calcifications
Sources: Literature
Fetal anomalies v0.4256 C2orf69 Chloe Stutterd gene: C2orf69 was added
gene: C2orf69 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: C2orf69 was set to GREEN
Added comment: Antenatal features: microcephaly, thin CC, Dandy-Walker malformation
Sources: Literature
Fetal anomalies v0.4256 ABHD16A Chloe Stutterd gene: ABHD16A was added
gene: ABHD16A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Antenatal features: thin CC, joint contractures/foot deformity
Sources: Literature
Fetal anomalies v0.4256 PPP2R3C Chirag Patel Classified gene: PPP2R3C as Green List (high evidence)
Fetal anomalies v0.4256 PPP2R3C Chirag Patel Gene: ppp2r3c has been classified as Green List (High Evidence).
Fetal anomalies v0.4255 PPP2R3C Chirag Patel gene: PPP2R3C was added
gene: PPP2R3C was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818
Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419
Review for gene: PPP2R3C was set to GREEN
Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility.
Sources: Literature
Fetal anomalies v0.4254 CDX2 Chirag Patel Classified gene: CDX2 as Green List (high evidence)
Fetal anomalies v0.4254 CDX2 Chirag Patel Gene: cdx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4254 CDX2 Chirag Patel Classified gene: CDX2 as Green List (high evidence)
Fetal anomalies v0.4254 CDX2 Chirag Patel Gene: cdx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4253 CDX2 Chirag Patel reviewed gene: CDX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29177441, 34671974; Phenotypes: Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4253 UNC13A Belinda Chong gene: UNC13A was added
gene: UNC13A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: UNC13A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UNC13A were set to 27648472; 28192369
Phenotypes for gene: UNC13A were set to Congenital myasthenia; dyskinesia; autism; developmental delay
Review for gene: UNC13A was set to RED
Added comment: One individual described with biallelic variants in this gene and a myasthenic syndrome; another individual reported with de novo variant in this gene and a different neurological phenotype (abnormal movements, developmental delay and autism).
Sources: Literature
Fetal anomalies v0.4253 SYT2 Belinda Chong gene: SYT2 was added
gene: SYT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SYT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SYT2 were set to 25192047; 32776697; 32250532; 30533528
Phenotypes for gene: SYT2 were set to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Review for gene: SYT2 was set to GREEN
gene: SYT2 was marked as current diagnostic
Added comment: Myasthenic syndrome bi-allelic #619461- Decreased fetal movements

Mono-allelic disease, PMID 25192047 and 30533528: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in three families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.

Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.
Sources: Literature
Fetal anomalies v0.4253 SLC25A1 Belinda Chong gene: SLC25A1 was added
gene: SLC25A1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SLC25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A1 were set to 26870663; 31527857; 29226520
Phenotypes for gene: SLC25A1 were set to ?Myasthenic syndrome, congenital, 23, presynaptic MIM#618197; Combined D-2- and L-2-hydroxyglutaric aciduria MIM#615182
Review for gene: SLC25A1 was set to RED
gene: SLC25A1 was marked as current diagnostic
Added comment: Neonatal onset.

Green for MIM#618197
Four unrelated families. mild congenital myasthenic syndrome.

Red for MIM#615182
Five infants of two consanguineous Bedouin families of the same tribe homozygous for the same variant with EEG compatible with white matter disorder. Death usually occurs in childhood.
Sources: Literature
Fetal anomalies v0.4253 NHS Alison Yeung Marked gene: NHS as ready
Fetal anomalies v0.4253 NHS Alison Yeung Gene: nhs has been classified as Green List (High Evidence).
Fetal anomalies v0.4253 NHS Alison Yeung Phenotypes for gene: NHS were changed from CATARACT CONGENITAL X-LINKED; NANCE-HORAN SYNDROME to Nance-Horan syndrome, MIM# 302350
Fetal anomalies v0.4252 NHS Alison Yeung Mode of inheritance for gene: NHS was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v0.4251 RPH3A Belinda Chong gene: RPH3A was added
gene: RPH3A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RPH3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPH3A were set to 29441694
Phenotypes for gene: RPH3A were set to Congenital myasthenic syndrome
Review for gene: RPH3A was set to RED
gene: RPH3A was marked as current diagnostic
Added comment: Only one patient with a complex phenotype that included myasthenia, with compound het missense variants, of which only one variant had plausible functional expression data.
Sources: Literature
Fetal anomalies v0.4251 NHEJ1 Alison Yeung Marked gene: NHEJ1 as ready
Fetal anomalies v0.4251 NHEJ1 Alison Yeung Gene: nhej1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4251 NHEJ1 Alison Yeung Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 611291 to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Cernunnos-XLF deficiency MONDO:0012650
Fetal anomalies v0.4250 NHEJ1 Alison Yeung Publications for gene: NHEJ1 were set to
Fetal anomalies v0.4249 NHEJ1 Alison Yeung reviewed gene: NHEJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30898087, 30666249, 28741180, 25288157, 24511403, 21721379, 21535335; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291, Cernunnos-XLF deficiency MONDO:0012650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4249 NF1 Alison Yeung Marked gene: NF1 as ready
Fetal anomalies v0.4249 NF1 Alison Yeung Gene: nf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4249 NF1 Alison Yeung reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurofibromatosis, type 1, MIM# 162200, Neurofibromatosis-Noonan syndrome, MIM# 601321; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4249 NF1 Alison Yeung Phenotypes for gene: NF1 were changed from FAMILIAL SPINAL NEUROFIBROMATOSIS; NEUROFIBROMATOSIS-NOONAN SYNDROME; WATSON SYNDROME; NEUROFIBROMATOSIS TYPE 1 to Neurofibromatosis, type 1, MIM# 162200; Neurofibromatosis-Noonan syndrome, MIM# 601321
Fetal anomalies v0.4248 NF1 Alison Yeung Mode of inheritance for gene: NF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4247 PLEC Belinda Chong gene: PLEC was added
gene: PLEC was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLEC was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PLEC were set to 22144912; 31509265; 21263134; 20624679; 20624679; 21109228; 28824526
Phenotypes for gene: PLEC were set to Epidermolysis bullosa simplex 5C, with pyloric atresia MIM#612138; Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex 5A, Ogna type MIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17 (MIM#613723)
Review for gene: PLEC was set to GREEN
gene: PLEC was marked as current diagnostic
Added comment: Multiple variations of EB and also associated with limb-girdle muscular dystrophy. Neonatal to Early childhood onset. However, Epidermolysis bullosa simplex 5C, with pyloric atresia MIM#612138 has prenatal manifestation of Polyhydramnios.
Sources: Literature
Fetal anomalies v0.4247 NEK1 Alison Yeung Marked gene: NEK1 as ready
Fetal anomalies v0.4247 NEK1 Alison Yeung Gene: nek1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4247 NEK1 Alison Yeung Phenotypes for gene: NEK1 were changed from SHORT RIB-POLYDACTYLY SYNDROME, TYPE II; Short-rib thoracic dysplasia 6 with or without polydactyly, 263520; SHORT RIB-POLYDACTYLY SYNDORME, TYPE II to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520
Fetal anomalies v0.4246 NEK1 Alison Yeung Publications for gene: NEK1 were set to
Fetal anomalies v0.4245 NEB Alison Yeung Marked gene: NEB as ready
Fetal anomalies v0.4245 NEB Alison Yeung Gene: neb has been classified as Green List (High Evidence).
Fetal anomalies v0.4245 NEB Alison Yeung Phenotypes for gene: NEB were changed from AUTOSOMAL RECESSIVE TYPICAL NEMALINE MYOPATHY to Arthrogryposis multiplex congenita 6, MIM# 619334
Fetal anomalies v0.4244 NEB Alison Yeung Publications for gene: NEB were set to
Fetal anomalies v0.4243 NDUFAF5 Alison Yeung Marked gene: NDUFAF5 as ready
Fetal anomalies v0.4243 NDUFAF5 Alison Yeung Gene: ndufaf5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4243 NDUFAF5 Alison Yeung Phenotypes for gene: NDUFAF5 were changed from Mitochondrial complex I deficiency, nuclear type 16, 618238 to Mitochondrial complex I deficiency, nuclear type 16, MIM# 618238
Fetal anomalies v0.4242 NDUFAF5 Alison Yeung Publications for gene: NDUFAF5 were set to 30266093; 18940309; 21620786
Fetal anomalies v0.4241 NDUFAF5 Alison Yeung reviewed gene: NDUFAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 16, MIM# 618238; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4241 NDP Alison Yeung Marked gene: NDP as ready
Fetal anomalies v0.4241 NDP Alison Yeung Gene: ndp has been classified as Green List (High Evidence).
Fetal anomalies v0.4241 NDP Alison Yeung reviewed gene: NDP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Norrie disease, MIM# 310600; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.4241 NDP Alison Yeung Phenotypes for gene: NDP were changed from NORRIE DISEASE to Norrie disease, MIM# 310600
Fetal anomalies v0.4240 NDE1 Alison Yeung Marked gene: NDE1 as ready
Fetal anomalies v0.4240 NDE1 Alison Yeung Gene: nde1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4240 NDE1 Alison Yeung Phenotypes for gene: NDE1 were changed from LISSENCEPHALY 4 to Lissencephaly 4 (with microcephaly), MIM# 614019; MONDO:0013527; Microhydranencephaly, MIM# 605013; MONDO:0011504
Fetal anomalies v0.4239 NDE1 Alison Yeung Publications for gene: NDE1 were set to
Fetal anomalies v0.4238 NBN Alison Yeung Publications for gene: NBN were set to
Fetal anomalies v0.4237 LAMA5 Belinda Chong gene: LAMA5 was added
gene: LAMA5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LAMA5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LAMA5 were set to 33242826; 29534211; 16790509; 30589377; 28735299; 30631761
Phenotypes for gene: LAMA5 were set to bent bone dysplasia; nephrotic syndrome; Presynaptic congenital myasthenic syndrome; multisystem syndrome; developmental delay
Review for gene: LAMA5 was set to RED
Added comment: Currently amber gene and appears postnatal onset (not enough information)

PMID: 29534211 - Three consanguineous families with homozygous missense variants (VUS) identified in two affected siblings with paediatric nephrotic syndrome within each family. No functional studies conducted on the missense variants.
PMID: 16790509 - A hypomorphic Lama5 homozygous mouse model demonstrated proteinuria, cystic kidney disease and death from progressive renal failure at 3–4 weeks of age.
PMID: 24130771 - a single case focal segmental glomerulosclerosis (proteinuria) with biallelic missense variants (VUS - S1469A & V2440I). Also reports p.Gly3685Arg in 2 other cases, which has 11 homozygotes in gnomAD v2.1
PMID: 29764427, 30808327 - Four families with haematuria and proteinuria reported with digenic inheritance of a LAMA5 missense variant with a COL4A4/5 variant. One of those variants (p.His1717Tyr) has 892 homozygotes in gnomAD v2.1
PMID: 28735299, 30589377 - A single large multigenerational family with a multisystem syndrome (including ophthalmic fetures), segregating a heterozygous missense p.V3140M, and supporting knock-in mouse model that recapitulates the phenotype.
PMID: 33242826 - A single family with a bent bone dysplasia in 3 affected siblings with biallelic variants, and some supporting in vitro functional assays.
PMID: 28544784, 29377152 - Single family with congenital myasthenic syndrome with a homozygous missense reported twice.
PMID: 30631761 - a single case with a de novo splice site variant with developmental delay, epilepsy, and hypotonia
Sources: Literature
Fetal anomalies v0.4237 NBN Alison Yeung Marked gene: NBN as ready
Fetal anomalies v0.4237 NBN Alison Yeung Gene: nbn has been classified as Green List (High Evidence).
Fetal anomalies v0.4237 NBN Alison Yeung Phenotypes for gene: NBN were changed from NIJMEGEN BREAKAGE SYNDROME to Nijmegen breakage syndrome, MIM# 251260
Fetal anomalies v0.4236 NBN Alison Yeung reviewed gene: NBN: Rating: GREEN; Mode of pathogenicity: None; Publications: 7545870, 2421804, 8914736, 3802554; Phenotypes: Nijmegen breakage syndrome, MIM#251260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4236 NBN Alison Yeung Classified gene: NBN as Green List (high evidence)
Fetal anomalies v0.4236 NBN Alison Yeung Gene: nbn has been classified as Green List (High Evidence).
Fetal anomalies v0.4235 NACC1 Alison Yeung Marked gene: NACC1 as ready
Fetal anomalies v0.4235 NACC1 Alison Yeung Gene: nacc1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4235 NACC1 Alison Yeung Added comment: Comment on phenotypes: Fetal anomalies reported include cataracts (5/7 patients) and microcephaly (5/7) patients
Fetal anomalies v0.4235 NACC1 Alison Yeung Phenotypes for gene: NACC1 were changed from Infantile Epilepsy, Cataracts, and Profound Developmental Delay to Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination delayed brain myelination, MIM# 617393)
Fetal anomalies v0.4234 NACC1 Alison Yeung Publications for gene: NACC1 were set to
Fetal anomalies v0.4233 NACC1 Alison Yeung Mode of inheritance for gene: NACC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4232 MYT1 Alison Yeung Marked gene: MYT1 as ready
Fetal anomalies v0.4232 MYT1 Alison Yeung Gene: myt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4232 MYT1 Alison Yeung Phenotypes for gene: MYT1 were changed from Oculo-auriculo-vertebral spectrum (OAVS); OAVS/Goldenhar syndrome to Hemifacial microsomia, MONDO:0015398
Fetal anomalies v0.4231 MYT1 Alison Yeung Publications for gene: MYT1 were set to 28612832; 27358179
Fetal anomalies v0.4230 MYT1 Alison Yeung Mode of inheritance for gene: MYT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4229 MYT1 Alison Yeung changed review comment from: Associated with OAV spectrum / hemifacial microsomia; to: Reported in patients with OAV spectrum / hemifacial microsomia
Fetal anomalies v0.4229 MYT1 Alison Yeung reviewed gene: MYT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28612832, 32871052, 27358179; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4229 MYRF Alison Yeung Marked gene: MYRF as ready
Fetal anomalies v0.4229 MYRF Alison Yeung Gene: myrf has been classified as Green List (High Evidence).
Fetal anomalies v0.4229 MYRF Alison Yeung Phenotypes for gene: MYRF were changed from Congenital diaphragmatic hernia (CDH); Cardiac-urogenital syndrome, 618280; Disorders of sex development (DSD) to Cardiac-urogenital syndrome, MIM# 618280
Fetal anomalies v0.4228 MYRF Alison Yeung Mode of inheritance for gene: MYRF was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4227 SNRPB Zornitza Stark Marked gene: SNRPB as ready
Fetal anomalies v0.4227 SNRPB Zornitza Stark Gene: snrpb has been classified as Green List (High Evidence).
Fetal anomalies v0.4227 SNRPB Zornitza Stark Phenotypes for gene: SNRPB were changed from CEREBRO-COSTO-MANDIBULAR SYNDROME to Cerebrocostomandibular syndrome, MIM# 117650
Fetal anomalies v0.4226 SNRPB Zornitza Stark Publications for gene: SNRPB were set to
Fetal anomalies v0.4225 SNRPB Zornitza Stark Mode of inheritance for gene: SNRPB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4224 SON Zornitza Stark Marked gene: SON as ready
Fetal anomalies v0.4224 SON Zornitza Stark Gene: son has been classified as Green List (High Evidence).
Fetal anomalies v0.4224 SON Zornitza Stark Phenotypes for gene: SON were changed from Intellectual Disability, Congenital Malformations, and Failure to Thrive to ZTTK syndrome, MIM# 617140
Fetal anomalies v0.4223 SON Zornitza Stark Publications for gene: SON were set to
Fetal anomalies v0.4222 SON Zornitza Stark Mode of inheritance for gene: SON was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4221 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Fetal anomalies v0.4221 SOS1 Zornitza Stark Gene: sos1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4221 SOS1 Zornitza Stark Phenotypes for gene: SOS1 were changed from NOONAN SYNDROME 4 to Noonan syndrome 4, MIM# 610733
Fetal anomalies v0.4220 SOS1 Zornitza Stark Publications for gene: SOS1 were set to
Fetal anomalies v0.4219 SOS1 Zornitza Stark Mode of pathogenicity for gene: SOS1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v0.4218 SOS1 Zornitza Stark Mode of inheritance for gene: SOS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4217 SOS2 Zornitza Stark Marked gene: SOS2 as ready
Fetal anomalies v0.4217 SOS2 Zornitza Stark Gene: sos2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4216 ATN1 Zornitza Stark Marked gene: ATN1 as ready
Fetal anomalies v0.4216 ATN1 Zornitza Stark Gene: atn1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4216 ATN1 Zornitza Stark Classified gene: ATN1 as Green List (high evidence)
Fetal anomalies v0.4216 ATN1 Zornitza Stark Gene: atn1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4215 NFIA Zornitza Stark Marked gene: NFIA as ready
Fetal anomalies v0.4215 NFIA Zornitza Stark Gene: nfia has been classified as Green List (High Evidence).
Fetal anomalies v0.4215 NFIA Zornitza Stark Classified gene: NFIA as Green List (high evidence)
Fetal anomalies v0.4215 NFIA Zornitza Stark Gene: nfia has been classified as Green List (High Evidence).
Fetal anomalies v0.4214 PACS2 Zornitza Stark Marked gene: PACS2 as ready
Fetal anomalies v0.4214 PACS2 Zornitza Stark Gene: pacs2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4214 PACS2 Zornitza Stark Classified gene: PACS2 as Green List (high evidence)
Fetal anomalies v0.4214 PACS2 Zornitza Stark Gene: pacs2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4213 PPP2CA Zornitza Stark Marked gene: PPP2CA as ready
Fetal anomalies v0.4213 PPP2CA Zornitza Stark Gene: ppp2ca has been classified as Green List (High Evidence).
Fetal anomalies v0.4213 PPP2CA Zornitza Stark Classified gene: PPP2CA as Green List (high evidence)
Fetal anomalies v0.4213 PPP2CA Zornitza Stark Gene: ppp2ca has been classified as Green List (High Evidence).
Fetal anomalies v0.4212 ZMIZ1 Zornitza Stark Marked gene: ZMIZ1 as ready
Fetal anomalies v0.4212 ZMIZ1 Zornitza Stark Gene: zmiz1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4212 ZMIZ1 Zornitza Stark Classified gene: ZMIZ1 as Green List (high evidence)
Fetal anomalies v0.4212 ZMIZ1 Zornitza Stark Gene: zmiz1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4211 SEMA3E Zornitza Stark Marked gene: SEMA3E as ready
Fetal anomalies v0.4211 SEMA3E Zornitza Stark Gene: sema3e has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4211 SEMA3E Zornitza Stark Phenotypes for gene: SEMA3E were changed from ?CHARGE syndrome - MIM#214800 to CHARGE syndrome - MIM#214800
Fetal anomalies v0.4210 SEMA3E Zornitza Stark Classified gene: SEMA3E as Amber List (moderate evidence)
Fetal anomalies v0.4210 SEMA3E Zornitza Stark Gene: sema3e has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4209 TMEM53 Zornitza Stark Marked gene: TMEM53 as ready
Fetal anomalies v0.4209 TMEM53 Zornitza Stark Gene: tmem53 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4209 TMEM53 Zornitza Stark Classified gene: TMEM53 as Red List (low evidence)
Fetal anomalies v0.4209 TMEM53 Zornitza Stark Gene: tmem53 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4208 SGMS2 Zornitza Stark Marked gene: SGMS2 as ready
Fetal anomalies v0.4208 SGMS2 Zornitza Stark Gene: sgms2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4208 SGMS2 Zornitza Stark Classified gene: SGMS2 as Red List (low evidence)
Fetal anomalies v0.4208 SGMS2 Zornitza Stark Gene: sgms2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4207 ZMIZ1 Krithika Murali gene: ZMIZ1 was added
gene: ZMIZ1 was added to Fetal anomalies. Sources: Literature,Expert list
Mode of inheritance for gene: ZMIZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMIZ1 were set to 30639322; 31879022
Phenotypes for gene: ZMIZ1 were set to Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies - MIM#618659
Review for gene: ZMIZ1 was set to GREEN
Added comment: Syndromic ID associated with multiple congenital malformations
Sources: Literature, Expert list
Fetal anomalies v0.4207 UBA2 Zornitza Stark Marked gene: UBA2 as ready
Fetal anomalies v0.4207 UBA2 Zornitza Stark Gene: uba2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4207 SCNN1B Zornitza Stark Marked gene: SCNN1B as ready
Fetal anomalies v0.4207 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Fetal anomalies v0.4207 SCNN1A Zornitza Stark Marked gene: SCNN1A as ready
Fetal anomalies v0.4207 SCNN1A Zornitza Stark Gene: scnn1a has been classified as Green List (High Evidence).
Fetal anomalies v0.4207 PAM16 Zornitza Stark Marked gene: PAM16 as ready
Fetal anomalies v0.4207 PAM16 Zornitza Stark Gene: pam16 has been classified as Green List (High Evidence).
Fetal anomalies v0.4207 NME8 Zornitza Stark Marked gene: NME8 as ready
Fetal anomalies v0.4207 NME8 Zornitza Stark Gene: nme8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4207 NME8 Zornitza Stark Publications for gene: NME8 were set to PubMed: 12032915, 12483741, 12928894
Fetal anomalies v0.4206 MIA3 Zornitza Stark Marked gene: MIA3 as ready
Fetal anomalies v0.4206 MIA3 Zornitza Stark Gene: mia3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4206 MIA3 Zornitza Stark Publications for gene: MIA3 were set to PMID: 32101163, 33778321
Fetal anomalies v0.4205 MBTPS1 Zornitza Stark Marked gene: MBTPS1 as ready
Fetal anomalies v0.4205 MBTPS1 Zornitza Stark Gene: mbtps1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4205 PPP2CA Krithika Murali gene: PPP2CA was added
gene: PPP2CA was added to Fetal anomalies. Sources: Literature,Expert list
Mode of inheritance for gene: PPP2CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2CA were set to 30595372
Phenotypes for gene: PPP2CA were set to Neurodevelopmental disorder and language delay with or without structural brain abnormalities - MIM#618354
Review for gene: PPP2CA was set to GREEN
Added comment: Syndromic ID associated with congenital brain and heart anomalies.
Sources: Literature, Expert list
Fetal anomalies v0.4205 HOXA11 Zornitza Stark Marked gene: HOXA11 as ready
Fetal anomalies v0.4205 HOXA11 Zornitza Stark Gene: hoxa11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4205 PACS2 Krithika Murali gene: PACS2 was added
gene: PACS2 was added to Fetal anomalies. Sources: Literature,Expert list
Mode of inheritance for gene: PACS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PACS2 were set to 34894068; 34859793
Phenotypes for gene: PACS2 were set to Developmental and epileptic encephalopathy 66 - MIM#618067
Review for gene: PACS2 was set to GREEN
Added comment: Associated with syndromic ID/infantile onset epileptic encephalopathy. Phenotypic features include brain and cardiac malformations.
Sources: Literature, Expert list
Fetal anomalies v0.4205 GDF3 Zornitza Stark changed review comment from: The variants originally reported are present at a high frequency in gnomad which is not consistent with a rare Mendelian disorder.; to: The variants originally reported are present at a high frequency in gnomad which is not consistent with a rare Mendelian disorder. Some individuals had skeletal features.

More recent publication PMID 29260090: variant inherited from phenotypically normal parent, leading authors to speculate about reduced penetrance.
Fetal anomalies v0.4205 GDF3 Zornitza Stark edited their review of gene: GDF3: Changed publications: 29260090; Changed phenotypes: Klippel-Feil syndrome 3, autosomal dominant 613702
Fetal anomalies v0.4205 NFIA Krithika Murali gene: NFIA was added
gene: NFIA was added to Fetal anomalies. Sources: Literature,Expert list
Mode of inheritance for gene: NFIA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIA were set to 35018717; 33973697; 32926563
Phenotypes for gene: NFIA were set to Brain malformations with or without urinary tract defects - MIM#613735
Review for gene: NFIA was set to GREEN
Added comment: Haploinsufficiency of the NFIA gene causes NFIA-related disorder, which includes brain abnormalities and intellectual disability, with or without urinary tract defects.
Sources: Literature, Expert list
Fetal anomalies v0.4205 GDF3 Zornitza Stark Classified gene: GDF3 as Red List (low evidence)
Fetal anomalies v0.4205 GDF3 Zornitza Stark Gene: gdf3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4204 GDF3 Zornitza Stark reviewed gene: GDF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.4204 GDF3 Zornitza Stark Marked gene: GDF3 as ready
Fetal anomalies v0.4204 GDF3 Zornitza Stark Gene: gdf3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4204 COL27A1 Zornitza Stark Marked gene: COL27A1 as ready
Fetal anomalies v0.4204 COL27A1 Zornitza Stark Gene: col27a1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4204 CHST11 Zornitza Stark Marked gene: CHST11 as ready
Fetal anomalies v0.4204 CHST11 Zornitza Stark Gene: chst11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4204 PRDM15 Zornitza Stark Marked gene: PRDM15 as ready
Fetal anomalies v0.4204 PRDM15 Zornitza Stark Gene: prdm15 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4204 NODAL Zornitza Stark Marked gene: NODAL as ready
Fetal anomalies v0.4204 NODAL Zornitza Stark Gene: nodal has been classified as Red List (Low Evidence).
Fetal anomalies v0.4204 NODAL Zornitza Stark Phenotypes for gene: NODAL were changed from HETEROTAXY SYNDROME to Heterotaxy, visceral, 5 (MIM#270100)
Fetal anomalies v0.4203 NODAL Zornitza Stark Publications for gene: NODAL were set to
Fetal anomalies v0.4202 NODAL Zornitza Stark Mode of inheritance for gene: NODAL was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4201 RNF113A Zornitza Stark Marked gene: RNF113A as ready
Fetal anomalies v0.4201 RNF113A Zornitza Stark Gene: rnf113a has been classified as Green List (High Evidence).
Fetal anomalies v0.4201 RAP1B Zornitza Stark Marked gene: RAP1B as ready
Fetal anomalies v0.4201 RAP1B Zornitza Stark Gene: rap1b has been classified as Green List (High Evidence).
Fetal anomalies v0.4201 RAD50 Zornitza Stark Marked gene: RAD50 as ready
Fetal anomalies v0.4201 RAD50 Zornitza Stark Gene: rad50 has been classified as Green List (High Evidence).
Fetal anomalies v0.4201 FRA10AC1 Zornitza Stark Marked gene: FRA10AC1 as ready
Fetal anomalies v0.4201 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4200 ATN1 Krithika Murali gene: ATN1 was added
gene: ATN1 was added to Fetal anomalies. Sources: Literature,Expert list
Mode of inheritance for gene: ATN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATN1 were set to 34212383; 30827498
Phenotypes for gene: ATN1 were set to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies - MIM#618494
Review for gene: ATN1 was set to GREEN
Added comment: Monoallelic variants associated with syndromic ID. Phenotypic features include arthrogryposis, epilepsy and congenital malformations of the brain, heart, and genitourinary systems.
Sources: Literature, Expert list
Fetal anomalies v0.4200 DNA2 Zornitza Stark Marked gene: DNA2 as ready
Fetal anomalies v0.4200 DNA2 Zornitza Stark Gene: dna2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4200 BRD4 Zornitza Stark Marked gene: BRD4 as ready
Fetal anomalies v0.4200 BRD4 Zornitza Stark Gene: brd4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4200 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange syndrome (no OMIM# yet) to Cornelia de Lange syndrome, MONDO:0016033
Fetal anomalies v0.4199 BRD4 Zornitza Stark Publications for gene: BRD4 were set to PMID: 29379197, 30302754, 11997514, 34035299
Fetal anomalies v0.4198 PPP1R12A Zornitza Stark Marked gene: PPP1R12A as ready
Fetal anomalies v0.4198 PPP1R12A Zornitza Stark Gene: ppp1r12a has been classified as Green List (High Evidence).
Fetal anomalies v0.4198 MNS1 Zornitza Stark Marked gene: MNS1 as ready
Fetal anomalies v0.4198 MNS1 Zornitza Stark Gene: mns1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4198 CFAP52 Zornitza Stark Marked gene: CFAP52 as ready
Fetal anomalies v0.4198 CFAP52 Zornitza Stark Gene: cfap52 has been classified as Green List (High Evidence).
Fetal anomalies v0.4198 CFAP45 Zornitza Stark Marked gene: CFAP45 as ready
Fetal anomalies v0.4198 CFAP45 Zornitza Stark Gene: cfap45 has been classified as Green List (High Evidence).
Fetal anomalies v0.4198 EDN3 Zornitza Stark Marked gene: EDN3 as ready
Fetal anomalies v0.4198 EDN3 Zornitza Stark Gene: edn3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4198 SOST Zornitza Stark Tag SV/CNV tag was added to gene: SOST.
Fetal anomalies v0.4198 SOX3 Zornitza Stark Tag SV/CNV tag was added to gene: SOX3.
Fetal anomalies v0.4198 RASGRP2 Zornitza Stark Marked gene: RASGRP2 as ready
Fetal anomalies v0.4198 RASGRP2 Zornitza Stark Gene: rasgrp2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4198 RASGRP2 Zornitza Stark Phenotypes for gene: RASGRP2 were changed from ?Bleeding disorder, platelet-type, 18 - MIM#615888 to Bleeding disorder, platelet-type, 18 - MIM#615888
Fetal anomalies v0.4197 RASGRP2 Zornitza Stark Classified gene: RASGRP2 as Red List (low evidence)
Fetal anomalies v0.4197 RASGRP2 Zornitza Stark Gene: rasgrp2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4196 ALG14 Zornitza Stark Marked gene: ALG14 as ready
Fetal anomalies v0.4196 ALG14 Zornitza Stark Gene: alg14 has been classified as Green List (High Evidence).
Fetal anomalies v0.4196 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036
Fetal anomalies v0.4195 ALG14 Zornitza Stark Classified gene: ALG14 as Green List (high evidence)
Fetal anomalies v0.4195 ALG14 Zornitza Stark Gene: alg14 has been classified as Green List (High Evidence).
Fetal anomalies v0.4194 ALG14 Zornitza Stark reviewed gene: ALG14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myasthenic syndrome, congenital, 15, without tubular aggregates 616227, Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4194 PLEKHM1 Zornitza Stark Marked gene: PLEKHM1 as ready
Fetal anomalies v0.4194 PLEKHM1 Zornitza Stark Gene: plekhm1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4194 PLEKHM1 Zornitza Stark Phenotypes for gene: PLEKHM1 were changed from ?Osteopetrosis, autosomal recessive 6 - MIM#611497; Osteopetrosis, autosomal dominant 3 - MIM#618107 to Osteopetrosis, autosomal recessive 6 - MIM#611497; Osteopetrosis, autosomal dominant 3 - MIM#618107
Fetal anomalies v0.4193 PLEKHM1 Zornitza Stark Classified gene: PLEKHM1 as Red List (low evidence)
Fetal anomalies v0.4193 PLEKHM1 Zornitza Stark Gene: plekhm1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4192 SEMA3E Krithika Murali gene: SEMA3E was added
gene: SEMA3E was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SEMA3E was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA3E were set to 31691538; 31464029; 15235037
Phenotypes for gene: SEMA3E were set to ?CHARGE syndrome - MIM#214800
Review for gene: SEMA3E was set to AMBER
Added comment: Heterozygous variant identified in a fetus given a clinical diagnosis of CHARGE syndrome.
One individual with a translocation and one individual with a missense variant reported in 2004; some functional data.
Sources: Literature
Fetal anomalies v0.4192 TMEM53 Krithika Murali gene: TMEM53 was added
gene: TMEM53 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TMEM53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM53 were set to 33824347
Phenotypes for gene: TMEM53 were set to Craniotubular dysplasia, Ikegawa type - MIM#619727
Review for gene: TMEM53 was set to RED
Added comment: 33824347 Guo et al 2021 report 5 individuals from 4 unrelated Indian families with a sclerosing bone disorder. Authors report normal prenatal and early postnatal development.
Sources: Literature
Fetal anomalies v0.4192 SGMS2 Krithika Murali gene: SGMS2 was added
gene: SGMS2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 34236445; 32028018; 30779713; 34761145; 34504906
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia - MIM#126550
Review for gene: SGMS2 was set to RED
Added comment: Heterozygous variants in SGMS2 associated with childhood-onset osteoporosis and skeletal
dysplasia. Evidence suggests that some heterozygous missense variants have a dominant negative effect and lead to severe bone fragility and spondylometaphyseal dysplasia, while one recurrent nonsense variant (c.148C > T, p.Arg50*) has been associated with milder bone fragility with or without cranial sclerosis (cranial doughnut lesions). No antenatal features reported in published cases including growth parameters.

---


PMID 32028018 Robinson et al 2020 - provide phenotypic information for 2 unrelated individuals with c.148C > T, p.Arg50* variant. No antenatal history reported.

PMID: 30779713 Pekkinen et al 2019 - identified heterozygous SGMS2 variants in 13 individuals from 6 unrelated families with early-onset osteoporosis and skeletal dysplasia. Identified recurrent nonsense variant in 4 families ( p.Arg50*) presented with childhood-onset osteoporosis with or without cranial sclerosis. 2 families had p.Ile62Ser or p.Met64Arg and. more severe phenotype including with neonatal fracture (clavicular fracture at birth), severe short stature, and spondylometaphyseal dysplasia. No antenatal phenotype/birth growth parameters provided.

PMID: 34761145 Makitie et al 2021 - further examination of bone changes in two individuals already reported in Pekkinen et al 2019 paper with recurrent nonsense variant.

PMID: 34504906 Basalom et al 2021 - no antenatal features reported
Sources: Literature
Fetal anomalies v0.4192 UBA2 Chirag Patel Classified gene: UBA2 as Green List (high evidence)
Fetal anomalies v0.4192 UBA2 Chirag Patel Gene: uba2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4191 UBA2 Chirag Patel gene: UBA2 was added
gene: UBA2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBA2 were set to PMID: 31332306; 31587267
Phenotypes for gene: UBA2 were set to Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Review for gene: UBA2 was set to GREEN
Added comment: 2x unrelated probands with isolated split hand malformation. fs variants - 1x de novo and 1x inherited from apparent unaffected mother (no radiographs of her hand available.

1x proband with unilateral split-hand malformation (missense). Her daughter and grandson reported to have ectrofactyly but were unavailable for testing

PMID: 31332306 - a single individual with a de novo PTC and split hand/foot malformation (SHFM). Additional two multigenic CNVs including this gene in individuals with SHFM and ectrodactyly. Authors mention an additional de novo missense but the patient didnt have SHFM, argue low penetrance PMID: 31587267 - a mother and son with aplasia cutis congenita (ACC), with a heterozygous PTC. Son also has ectrodactyly. Authors note an additional de novo missense in a patient with ACC.
Sources: Expert list
Fetal anomalies v0.4190 SCNN1B Chirag Patel Classified gene: SCNN1B as Green List (high evidence)
Fetal anomalies v0.4190 SCNN1B Chirag Patel Gene: scnn1b has been classified as Green List (High Evidence).
Fetal anomalies v0.4189 SCNN1B Chirag Patel gene: SCNN1B was added
gene: SCNN1B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SCNN1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SCNN1B were set to PubMed: 8589714
Phenotypes for gene: SCNN1B were set to Pseudohypoaldosteronism, type I - MIM#264350
Review for gene: SCNN1B was set to GREEN
Added comment: Autosomal recessive pseudohypoaldosteronism type I caused by homozygous or compound heterozygous mutation in SCNN1B is characterized by renal salt wasting and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially threatening in the neonatal period. Multiple patients reported.
Sources: Literature
Fetal anomalies v0.4188 SCNN1A Chirag Patel Classified gene: SCNN1A as Green List (high evidence)
Fetal anomalies v0.4188 SCNN1A Chirag Patel Gene: scnn1a has been classified as Green List (High Evidence).
Fetal anomalies v0.4187 SCNN1A Chirag Patel gene: SCNN1A was added
gene: SCNN1A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SCNN1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SCNN1A were set to PubMed: 8589714, 31301676
Phenotypes for gene: SCNN1A were set to Pseudohypoaldosteronism, type I - MIM#264350
Review for gene: SCNN1A was set to GREEN
Added comment: Autosomal recessive pseudohypoaldosteronism type I caused by homozygous or compound heterozygous mutation in SCNN1A is characterized by renal salt wasting and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially threatening in the neonatal period. Multiple patients reported.
Sources: Literature
Fetal anomalies v0.4186 SCNN1G Chirag Patel Classified gene: SCNN1G as Green List (high evidence)
Fetal anomalies v0.4186 SCNN1G Chirag Patel Gene: scnn1g has been classified as Green List (High Evidence).
Fetal anomalies v0.4185 PAM16 Chirag Patel Classified gene: PAM16 as Green List (high evidence)
Fetal anomalies v0.4185 PAM16 Chirag Patel Gene: pam16 has been classified as Green List (High Evidence).
Fetal anomalies v0.4184 PAM16 Chirag Patel gene: PAM16 was added
gene: PAM16 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PAM16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAM16 were set to PubMed: 24786642, 27354339
Phenotypes for gene: PAM16 were set to Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, OMIM # 613320
Review for gene: PAM16 was set to GREEN
Added comment: Megarbane-Dagher-Melki type of spondylometaphyseal dysplasia (SMDMDM) has chondrodysplasia, developmental delay, severe pre- and postnatal short stature, dysmorphic facial appearance, narrow chest, prominent abdomen, and short limbs. 5 patients from 3 unrelated families with homozygous missense mutations which segregate with disease.
Sources: Expert list
Fetal anomalies v0.4183 NME8 Chirag Patel Classified gene: NME8 as Green List (high evidence)
Fetal anomalies v0.4183 NME8 Chirag Patel Gene: nme8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4182 NME8 Chirag Patel gene: NME8 was added
gene: NME8 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NME8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NME8 were set to PubMed: 12032915, 12483741, 12928894
Phenotypes for gene: NME8 were set to CINCA syndrome, OMIM # 607115
Review for gene: NME8 was set to GREEN
Added comment: Chronic infantile neurologic cutaneous and articular (CINCA) syndrome also known as 'neonatal onset multisystem inflammatory disease,' or NOMID, is a rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation. 14 families with heterozygous missense mutations in exon 3. Presenting perinatally so suitable for fetal anomalies panel.
Sources: Literature
Fetal anomalies v0.4181 MIA3 Chirag Patel Classified gene: MIA3 as Amber List (moderate evidence)
Fetal anomalies v0.4181 MIA3 Chirag Patel Gene: mia3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4180 MIA3 Chirag Patel gene: MIA3 was added
gene: MIA3 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIA3 were set to PMID: 32101163, 33778321
Phenotypes for gene: MIA3 were set to Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269
Review for gene: MIA3 was set to AMBER
Added comment: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Four affected siblings reported, homozygous variant affecting splicing. Mouse model has absence of bone mineralization. Can present with IUGR antenatally. Suitable for fetal anomalies panel.
Sources: Expert list
Fetal anomalies v0.4179 MBTPS1 Chirag Patel Classified gene: MBTPS1 as Green List (high evidence)
Fetal anomalies v0.4179 MBTPS1 Chirag Patel Gene: mbtps1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4178 MBTPS1 Chirag Patel gene: MBTPS1 was added
gene: MBTPS1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MBTPS1 were set to PMID: 32857899; 32420688; 30046013
Phenotypes for gene: MBTPS1 were set to Skeletal dysplasia, no OMIM #
Review for gene: MBTPS1 was set to GREEN
Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature.
Sources: Expert list
Fetal anomalies v0.4177 HOXA11 Chirag Patel Classified gene: HOXA11 as Amber List (moderate evidence)
Fetal anomalies v0.4177 HOXA11 Chirag Patel Gene: hoxa11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4176 HOXA11 Chirag Patel gene: HOXA11 was added
gene: HOXA11 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HOXA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HOXA11 were set to PubMed: 11101832
Phenotypes for gene: HOXA11 were set to Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 , OMIM #605432
Review for gene: HOXA11 was set to AMBER
Added comment: Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is characterized by thrombocytopenia that progresses to pancytopenia, in association with congenital proximal fusion of the radius and ulna that results in extremely limited pronation and supination of the forearm. A heterozygous mutation in the HOXA11 gene was found in affected members of 2 families segregating radioulnar synostosis and amegakaryocytic thrombocytopenia.
Sources: Literature
Fetal anomalies v0.4175 GDF3 Chirag Patel Classified gene: GDF3 as Green List (high evidence)
Fetal anomalies v0.4175 GDF3 Chirag Patel Gene: gdf3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4174 GDF3 Chirag Patel gene: GDF3 was added
gene: GDF3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GDF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GDF3 were set to PubMed: 19864492
Phenotypes for gene: GDF3 were set to Microphthalmia with coloboma 6, OMIM #613703; Microphthalmia, isolated 7, OMIM # 613704
Review for gene: GDF3 was set to GREEN
Added comment: Ye et al. (2010) identified heterozygous missense mutations in the GDF3 gene in 3 probands with bilateral colobomatous microphthalmia.
Sources: Literature
Fetal anomalies v0.4173 COL27A1 Chirag Patel Classified gene: COL27A1 as Green List (high evidence)
Fetal anomalies v0.4173 COL27A1 Chirag Patel Gene: col27a1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4172 COL27A1 Chirag Patel gene: COL27A1 was added
gene: COL27A1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COL27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL27A1 were set to PubMed: 24986830, 28276056, 28322503
Phenotypes for gene: COL27A1 were set to Steel syndrome, OMIM #615155
Review for gene: COL27A1 was set to GREEN
Added comment: Steel syndrome is characterized by characteristic facies, congenital dislocated hips and radial heads, carpal coalition (fusion of carpal bones), short stature, scoliosis, and cervical spine anomalies. The dislocated hips are resistant to surgical intervention. 3 families with biallelic variants reported.
Sources: Literature
Fetal anomalies v0.4171 CHST11 Chirag Patel reviewed gene: CHST11: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.4171 CHST11 Chirag Patel Deleted their review
Fetal anomalies v0.4171 CHST11 Chirag Patel Classified gene: CHST11 as Amber List (moderate evidence)
Fetal anomalies v0.4171 CHST11 Chirag Patel Gene: chst11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4170 CHST11 Chirag Patel gene: CHST11 was added
gene: CHST11 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CHST11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST11 were set to PMID: 26436107; 29514872
Phenotypes for gene: CHST11 were set to Osteochondrodysplasia, brachydactyly, and overlapping malformed digits, MIM# 618167
Review for gene: CHST11 was set to GREEN
Added comment: Osteochondrodysplasia, brachydactyly, and overlapping malformed digits (OCBMD) is characterized by bilateral symmetric skeletal defects that primarily affect the limbs. Affected individuals have mild short stature due to shortening of the lower leg bones, as well as hand and foot malformations, predominantly brachydactyly and overlapping digits. Other skeletal defects include scoliosis, dislocated patellae and fibulae, and pectus excavatum. Two unrelated families reported, note one had a homozygous deletion.
Sources: Expert list
Fetal anomalies v0.4169 PRDM15 Chirag Patel Classified gene: PRDM15 as Amber List (moderate evidence)
Fetal anomalies v0.4169 PRDM15 Chirag Patel Gene: prdm15 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4168 PRDM15 Chirag Patel gene: PRDM15 was added
gene: PRDM15 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PRDM15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM15 were set to PMID: 31950080
Phenotypes for gene: PRDM15 were set to Holoprosenephaly; Steroid resistant nephrotic syndrome; Multiple congenital anomalies
Review for gene: PRDM15 was set to AMBER
Added comment: Four consanguineous families reported with same homozygous variant, C844Y, shown to be LoF. Syndromic HPE including SRNS, brain malformations, polydactyly, congenital heart disease. Mouse model, extensive functional data. Two additional homozygous missense identified with isolated SRNS.
Sources: Expert list
Fetal anomalies v0.4167 NODAL Chirag Patel Classified gene: NODAL as Red List (low evidence)
Fetal anomalies v0.4167 NODAL Chirag Patel Gene: nodal has been classified as Red List (Low Evidence).
Fetal anomalies v0.4166 FERMT3 Zornitza Stark Marked gene: FERMT3 as ready
Fetal anomalies v0.4166 FERMT3 Zornitza Stark Gene: fermt3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4166 RNF113A Chirag Patel Classified gene: RNF113A as Green List (high evidence)
Fetal anomalies v0.4166 RNF113A Chirag Patel Gene: rnf113a has been classified as Green List (High Evidence).
Fetal anomalies v0.4165 RNF113A Chirag Patel gene: RNF113A was added
gene: RNF113A was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: RNF113A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RNF113A were set to PMID: 25612912; 31793730; 31880405
Phenotypes for gene: RNF113A were set to Trichothiodystrophy 5, nonphotosensitive; OMIM #300953
Review for gene: RNF113A was set to GREEN
Added comment: Four families reported, two with same variant. Clinical features include ID, microcephaly, IUGR/growth failure, hypogonadism, and sparse/brittle hair. One of the families had antenatal presentation.
Sources: Expert list
Fetal anomalies v0.4164 RAP1B Chirag Patel Classified gene: RAP1B as Green List (high evidence)
Fetal anomalies v0.4164 RAP1B Chirag Patel Gene: rap1b has been classified as Green List (High Evidence).
Fetal anomalies v0.4163 RAP1B Chirag Patel gene: RAP1B was added
gene: RAP1B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAP1B were set to PMID: 32627184; 26280580
Phenotypes for gene: RAP1B were set to Syndromic intellectual disability; short stature
Review for gene: RAP1B was set to GREEN
Added comment: Three unrelated individuals reported, Kabuki-like disorder (multiple malformations, microcephaly, learning difficulties, dysmorphism and other features).
Sources: Literature
Fetal anomalies v0.4162 RAD50 Chirag Patel Classified gene: RAD50 as Green List (high evidence)
Fetal anomalies v0.4162 RAD50 Chirag Patel Gene: rad50 has been classified as Green List (High Evidence).
Fetal anomalies v0.4161 RAD50 Chirag Patel gene: RAD50 was added
gene: RAD50 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: RAD50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAD50 were set to PMID: 19409520; 32212377; 33378670
Phenotypes for gene: RAD50 were set to Nijmegen breakage syndrome-like disorder, MIM# 613078; MONDO:0013118
Review for gene: RAD50 was set to GREEN
Added comment: Nijmegen breakage syndrome-like disorder (NBSLD) is an autosomal recessive disorder characterized by severe prenatal growth retardation and persistent postnatal growth restriction, congenital microcephaly, borderline to mildly impaired intellectual development, normal sexual development, and radioresistant DNA synthesis with no immunodeficiency, myelodysplasia, or early neurodegeneration. Three unrelated families reported.
Sources: Expert list
Fetal anomalies v0.4160 PROP1 Chirag Patel Classified gene: PROP1 as Red List (low evidence)
Fetal anomalies v0.4160 PROP1 Chirag Patel Gene: prop1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4159 LHX4 Chirag Patel Classified gene: LHX4 as Red List (low evidence)
Fetal anomalies v0.4159 LHX4 Chirag Patel Gene: lhx4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4158 LHX4 Chirag Patel reviewed gene: LHX4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.4158 FRA10AC1 Chirag Patel Classified gene: FRA10AC1 as Green List (high evidence)
Fetal anomalies v0.4158 FRA10AC1 Chirag Patel Gene: fra10ac1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4157 FRA10AC1 Chirag Patel gene: FRA10AC1 was added
gene: FRA10AC1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: FRA10AC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRA10AC1 were set to PMID: 34694367
Phenotypes for gene: FRA10AC1 were set to Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related
Review for gene: FRA10AC1 was set to GREEN
Added comment: 5 individuals from 3 unrelated families reported. Variable ID, possibly related to variant type with LoF variants associated with more severe ID. All individuals had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.
Sources: Expert list
Fetal anomalies v0.4156 DNA2 Chirag Patel Classified gene: DNA2 as Green List (high evidence)
Fetal anomalies v0.4156 DNA2 Chirag Patel Gene: dna2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4155 DNA2 Chirag Patel gene: DNA2 was added
gene: DNA2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNA2 were set to PMID: 24389050; 31045292
Phenotypes for gene: DNA2 were set to Seckel syndrome 8, MIM#615807
Review for gene: DNA2 was set to GREEN
Added comment: Three families described with bi-allelic variants in this gene and a primordial dwarfism/Seckel syndrome phenotype (intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance). Note this gene is associated with multiple phenotypes.
Sources: Expert list
Fetal anomalies v0.4154 BRD4 Chirag Patel Classified gene: BRD4 as Green List (high evidence)
Fetal anomalies v0.4154 BRD4 Chirag Patel Gene: brd4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4153 BRD4 Chirag Patel gene: BRD4 was added
gene: BRD4 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: BRD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRD4 were set to PMID: 29379197, 30302754, 11997514, 34035299
Phenotypes for gene: BRD4 were set to Cornelia de Lange syndrome (no OMIM# yet)
Review for gene: BRD4 was set to GREEN
Added comment: Cornelia de Lange syndrome is a clinically heterogeneous developmental disorder characterized by malformations affecting multiple systems. Affected individuals have dysmorphic facial features, cleft palate, distal limb defects, prenatal onset growth retardation, and developmental delay. About 1% of patients have mutations in the BRD4 gene. % patients reported with functional evidence.
Sources: Expert list
Fetal anomalies v0.4152 PPP1R12A Chirag Patel Classified gene: PPP1R12A as Green List (high evidence)
Fetal anomalies v0.4152 PPP1R12A Chirag Patel Gene: ppp1r12a has been classified as Green List (High Evidence).
Fetal anomalies v0.4151 PPP1R12A Chirag Patel gene: PPP1R12A was added
gene: PPP1R12A was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PPP1R12A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP1R12A were set to PMID: 31883643
Phenotypes for gene: PPP1R12A were set to Intellectual disability; holoprosencephaly; disorder of sex development
Review for gene: PPP1R12A was set to GREEN
Added comment: 12 unrelated individuals now published.
Sources: Expert list
Fetal anomalies v0.4150 MNS1 Chirag Patel Classified gene: MNS1 as Green List (high evidence)
Fetal anomalies v0.4150 MNS1 Chirag Patel Gene: mns1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4149 MNS1 Chirag Patel gene: MNS1 was added
gene: MNS1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MNS1 were set to PMID: 31534215; 30148830
Phenotypes for gene: MNS1 were set to Heterotaxy; male infertility; Heterotaxy, visceral, 9, autosomal, with male infertility 618948
Review for gene: MNS1 was set to GREEN
Added comment: Eight families reported altogether. However, four are Amish and share same homozygous founder variant, and some of the other reported families are consanguineous and share another founder. A reported female with a third variant, also had a homozygous variant in DNAH5 with a blended phenotype postulated.
Sources: Expert list
Fetal anomalies v0.4148 CFAP52 Chirag Patel Classified gene: CFAP52 as Green List (high evidence)
Fetal anomalies v0.4148 CFAP52 Chirag Patel Gene: cfap52 has been classified as Green List (High Evidence).
Fetal anomalies v0.4147 CFAP52 Chirag Patel gene: CFAP52 was added
gene: CFAP52 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CFAP52 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP52 were set to PMID: 25469542; 33139725
Phenotypes for gene: CFAP52 were set to Heterotaxy, visceral, 10, autosomal, with male infertility, MIM#619607
Review for gene: CFAP52 was set to GREEN
Added comment: Five unrelated families and functional data.
Sources: Expert list
Fetal anomalies v0.4146 CFAP45 Chirag Patel Classified gene: CFAP45 as Green List (high evidence)
Fetal anomalies v0.4146 CFAP45 Chirag Patel Gene: cfap45 has been classified as Green List (High Evidence).
Fetal anomalies v0.4145 CFAP45 Chirag Patel gene: CFAP45 was added
gene: CFAP45 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CFAP45 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP45 were set to PMID: 33139725
Phenotypes for gene: CFAP45 were set to Heterotaxy, visceral, 11, autosomal, with male infertility, MIM#619608
Review for gene: CFAP45 was set to GREEN
Added comment: Three unrelated individuals reported with bi-alleic LOF variants, mouse model recapitulated phenotype.
Sources: Expert list
Fetal anomalies v0.4144 EDN3 Chirag Patel Classified gene: EDN3 as Green List (high evidence)
Fetal anomalies v0.4144 EDN3 Chirag Patel Gene: edn3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4143 EDN3 Chirag Patel gene: EDN3 was added
gene: EDN3 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: EDN3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EDN3 were set to PMID: 8630502; 11303518; 9359047; 10231870; 30171849; 27370713
Phenotypes for gene: EDN3 were set to Central hypoventilation syndrome, congenital, MIM# 209880; Waardenburg syndrome, type 4B, MIM# 613265; {Hirschsprung disease, susceptibility to, 4}, MIM# 613712
Review for gene: EDN3 was set to GREEN
Added comment: Variants in this gene have been reported in both isolated HD and syndromic HD, variable penetrance. However, the variants reported in PMID 9359047 with isolated HD are present at high frequencies in gnomad: p.Ala17Thr >800 hets in gnomad, p.Ala224Thr >100 hets. Association with syndromic neural crest disorders is more definitive, and HD is reported in a proportion of individuals.
Sources: Expert list
Fetal anomalies v0.4142 SOST Seb Lunke Marked gene: SOST as ready
Fetal anomalies v0.4142 SOST Seb Lunke Gene: sost has been classified as Green List (High Evidence).
Fetal anomalies v0.4142 SOST Seb Lunke changed review comment from: Well established association with recessive Sclerosteosis 1 (OMIM#122860) characterised by overgrowth and multiple facial and skeletal abnormalities

Dominant association with Craniodiaphyseal dysplasia (OMIM#122860) has been described in two indipendent patients only, with different missense variants at the same residue (V21M, V21L)

NOTE: Common 52-kb deletion downstream of SOST (van Buchem disease, MIM#239100); to: Well established association with recessive Sclerosteosis 1 (OMIM#269500) characterised by overgrowth and multiple facial and skeletal abnormalities

Dominant association with Craniodiaphyseal dysplasia (OMIM#122860) has been described in two indipendent patients only, with different missense variants at the same residue (V21M, V21L)

NOTE: Common 52-kb deletion downstream of SOST (van Buchem disease, MIM#239100)
Fetal anomalies v0.4142 SOST Seb Lunke Phenotypes for gene: SOST were changed from Craniodiaphyseal dysplasia, autosomal dominant, 122860; Sclerosteosis 1, 269500; SOST-Related Sclerosing Bone Dysplasias 122860 to Sclerosteosis 1, OMIM#269500; Craniodiaphyseal dysplasia, OMIM#122860
Fetal anomalies v0.4141 SOST Seb Lunke reviewed gene: SOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301406, 35160258, 21221996, 17853455; Phenotypes: Sclerosteosis 1, OMIM#122860, Craniodiaphyseal dysplasia, OMIM#122860; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4141 SOX2 Seb Lunke Marked gene: SOX2 as ready
Fetal anomalies v0.4141 SOX2 Seb Lunke Gene: sox2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4141 SOX2 Seb Lunke Phenotypes for gene: SOX2 were changed from AEG SYNDROME; MICROPHTHALMIA SYNDROMIC TYPE 3 to Microphthalmia, syndromic 3, MIM# 206900; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900
Fetal anomalies v0.4140 SOX2 Seb Lunke Publications for gene: SOX2 were set to
Fetal anomalies v0.4139 SOX2 Seb Lunke Mode of inheritance for gene: SOX2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4138 SOX3 Seb Lunke Marked gene: SOX3 as ready
Fetal anomalies v0.4138 SOX3 Seb Lunke Gene: sox3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4138 SOX3 Seb Lunke Publications for gene: SOX3 were set to
Fetal anomalies v0.4137 SOX3 Seb Lunke Added comment: Comment on mode of pathogenicity: Mouse model demonstrates that mechanism of disease is polyAlanine tract leading to a loss of function of the protein
Fetal anomalies v0.4137 SOX3 Seb Lunke Mode of pathogenicity for gene: SOX3 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v0.4136 SOX3 Seb Lunke Classified gene: SOX3 as Amber List (moderate evidence)
Fetal anomalies v0.4136 SOX3 Seb Lunke Added comment: Comment on list classification: Ala Repeat expansion linked to growth hormone deficiency, but not much evidence so far, onset appears post-natal, and described brain MRI findings appear subtle.
Fetal anomalies v0.4136 SOX3 Seb Lunke Gene: sox3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4135 FERMT3 Zornitza Stark Classified gene: FERMT3 as Red List (low evidence)
Fetal anomalies v0.4135 FERMT3 Zornitza Stark Gene: fermt3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4134 SPAG1 Seb Lunke Marked gene: SPAG1 as ready
Fetal anomalies v0.4134 SPAG1 Seb Lunke Added comment: Comment when marking as ready: Situs inversus in 50% of patients
Fetal anomalies v0.4134 SPAG1 Seb Lunke Gene: spag1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4134 SPAG1 Seb Lunke Phenotypes for gene: SPAG1 were changed from PRIMARY CILIARY DYSKINESIA ASSOCIATED WITH DEFECTIVE OUTER AND INNER DYNEIN ARMS. to Ciliary dyskinesia, primary, 28 (MIM#615505)
Fetal anomalies v0.4133 SPAG1 Seb Lunke Added comment: Comment on publications: 32622824 Withdrawn
Fetal anomalies v0.4133 SPAG1 Seb Lunke Publications for gene: SPAG1 were set to
Fetal anomalies v0.4132 RASGRP2 Krithika Murali gene: RASGRP2 was added
gene: RASGRP2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RASGRP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RASGRP2 were set to 28637664; 28726538; 28762304; 30046681; 34066320; 33711653; 33376940; 32609603; 30849270; 30046681
Phenotypes for gene: RASGRP2 were set to ?Bleeding disorder, platelet-type, 18 - MIM#615888
Review for gene: RASGRP2 was set to RED
Added comment: Postnatal presentation only with no antenatal features reported.
Sources: Literature
Fetal anomalies v0.4132 ALG14 Belinda Chong gene: ALG14 was added
gene: ALG14 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ALG14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG14 were set to 23404334; 28733338; 30221345; 23404334; 28733338
Phenotypes for gene: ALG14 were set to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation
Review for gene: ALG14 was set to GREEN
gene: ALG14 was marked as current diagnostic
Added comment: Three OMIM disorders however, only Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036 with prenatal manifestations.

5 individuals from unrelated families described in the literature: one with myasthenic syndrome, no report of ID; second with predominantly ID phenotype; and three more with a neurodegenerative phenotype. ALG14 is part of the UDP-GlcNAc transferase, which catalyzes a key step in endoplasmic reticulum N-linked glycosylation. The three OMIM disorders may represent a spectrum of severity for CDG.
Sources: Literature
Fetal anomalies v0.4132 PLEKHM1 Krithika Murali gene: PLEKHM1 was added
gene: PLEKHM1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLEKHM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PLEKHM1 were set to 17404618; 17997709; 27291868; 27777970; 28290981
Phenotypes for gene: PLEKHM1 were set to ?Osteopetrosis, autosomal recessive 6 - MIM#611497; Osteopetrosis, autosomal dominant 3 - MIM#618107
Review for gene: PLEKHM1 was set to RED
Added comment: No antenatal features reported.

--
PMID: 17997709 Del Fattore et al 2008 - female proband with monoallelic variant, no antenatal features reported.

PMID: 27291868 Bo et al 2016 - male proband with osteopetrosis and heterozygous de novo variant. No antenatal features reported.

PMID: 28290981 Moore et al 2017 - compound het variants, osteopetrosis diagnosis in a 19 year old. No antenatal features reported.

PMID: 21054159 Almarzooqi et al 2010 - heterozygous variant, infantile osteopetrosis and xanthogranuloma, uncomplicated pregnancy.
Sources: Literature
Fetal anomalies v0.4132 FERMT3 Krithika Murali gene: FERMT3 was added
gene: FERMT3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FERMT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FERMT3 were set to 31068971; 34485203; 33391282; 31724816; 30412664; 25854317; 28095295; 26359933; 25072369; 22134107; 20216991; 19234463; 19234460; 18779414
Phenotypes for gene: FERMT3 were set to Leukocyte adhesion deficiency, type III - MIM#612840
Review for gene: FERMT3 was set to RED
Added comment: Biallelic variants associated with LAD3 syndrome (primary immunodeficiency and platelet function defects). Symptom onset reported from birth, no antenatal features reported.

---

PMID: 34485203 Yahya et al 2021 - no antenatal issues reported

PMID: 33391282 Kambli et al 2020 - no antenatal features reported for 5 individuals with LAD3

PMID 31068971 Shahid et al 2019 - no antenatal features

PMID: 31724816 Manukjan et al 2019 - no antenatal issues reported in 1 affected individual

PMID: 28095295 Palagano et al 2017 - report female proband with infantile-onset osteopetrosis and symptomatic haematological anomalies at birth requiring bone marrow transplant. Authors postulate in utero onset but no antenatal features reported.

PMID: 26359933 Suratannon et al 2016 - report a female Thai proband with a milder/atypical phenotype, no antenatal features reported

PMID: 25854317 Crazzolara et al 2015 - presented D7 of life with infection, bleeeding issues and noted radiologically to have dense bones. No antenatal features.

PMID: 25072369 Stepensky et al 2015 - report 3 individuals with bleeding tendency from birth and onset of recurrent infections as an infant, normal antenatal history.

PMID: 20357244 McDowall et al 2010 - symptom onset from birth, no antenatal features

PMID: 20216991 Jurk et al 2010 - 2 affected siblings, no antenatal features reported.

PMID: 19234463 Svensson et al 2009 - no antenatal features reported

PMID: 19234460 Malinin et al 2009 - no antenatal features reported

PMID: 19064721 Kuijpers et al 2009 - 9 individuals from 7 unrelated families, no antenatal features reported.
Sources: Literature
Fetal anomalies v0.4132 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Fetal anomalies v0.4132 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4132 SPATA5 Zornitza Stark Phenotypes for gene: SPATA5 were changed from EPILEPSY, HEARING LOSS, AND MENTAL RETARDATION SYNDROME to Epilepsy, hearing loss, and mental retardation syndrome MIM#616577
Fetal anomalies v0.4131 SPATA5 Zornitza Stark Publications for gene: SPATA5 were set to
Fetal anomalies v0.4130 SPEG Zornitza Stark Marked gene: SPEG as ready
Fetal anomalies v0.4130 SPEG Zornitza Stark Gene: speg has been classified as Green List (High Evidence).
Fetal anomalies v0.4130 SPEG Zornitza Stark Phenotypes for gene: SPEG were changed from CENTRONUCLEAR MYOPATHY WITH DILATED CARDIOMYOPATHY to Centronuclear myopathy 5, MIM# 615959
Fetal anomalies v0.4129 SPEG Zornitza Stark reviewed gene: SPEG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Centronuclear myopathy 5, MIM# 615959; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4129 SPG11 Zornitza Stark Marked gene: SPG11 as ready
Fetal anomalies v0.4129 SPG11 Zornitza Stark Gene: spg11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4129 SPG11 Zornitza Stark Phenotypes for gene: SPG11 were changed from SPASTIC PARAPLEGIA-11 to Spastic paraplegia 11, autosomal recessive, MIM# 604360
Fetal anomalies v0.4128 SPG11 Zornitza Stark Publications for gene: SPG11 were set to
Fetal anomalies v0.4127 SPG11 Zornitza Stark Classified gene: SPG11 as Amber List (moderate evidence)
Fetal anomalies v0.4127 SPG11 Zornitza Stark Gene: spg11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4126 SPG11 Zornitza Stark edited their review of gene: SPG11: Changed rating: AMBER
Fetal anomalies v0.4126 SPG11 Zornitza Stark changed review comment from: Bi-alllelic variants in this gene also cause spastic paraplegia-11 (OMIM# 604360) but also juvenile amyotrophic lateral sclerosis-5 (OMIM# 602099), and CMT2X. Same variants have been reported in association with different phenotypes, poor genotype-phenotype correlation.

Recent review of >300 individuals with SPG11-related disease. Mean age at onset was 13.10 ± 3.65 years, with initial symptoms like gait disturbance (107/195, 54.87%) and intellectual disability (47/195, 24.10%). Cognitive decline (228/270, 84.44%) was the most common complex manifestation stepped by dysarthria (134/195, 68.72%), neuropathy (112/177, 63.28%), amyatrophy, sphincter disturbance (60/130, 46.15%) and ataxia (90/194, 46.39%).; to: Bi-alllelic variants in this gene also cause spastic paraplegia-11 (OMIM# 604360) but also juvenile amyotrophic lateral sclerosis-5 (OMIM# 602099), and CMT2X. Same variants have been reported in association with different phenotypes, poor genotype-phenotype correlation.

Recent review of >300 individuals with SPG11-related disease. Mean age at onset was 13.10 ± 3.65 years, with initial symptoms like gait disturbance (107/195, 54.87%) and intellectual disability (47/195, 24.10%). Cognitive decline (228/270, 84.44%) was the most common complex manifestation stepped by dysarthria (134/195, 68.72%), neuropathy (112/177, 63.28%), amyatrophy, sphincter disturbance (60/130, 46.15%) and ataxia (90/194, 46.39%).

Although onset of clinical features is typically in childhood or later, absent CC/CC abnormalities reported.
Fetal anomalies v0.4126 SPRED1 Zornitza Stark Marked gene: SPRED1 as ready
Fetal anomalies v0.4126 SPRED1 Zornitza Stark Gene: spred1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4126 SPRED1 Zornitza Stark Phenotypes for gene: SPRED1 were changed from LEGIUS SYNDROME to Legius syndrome, MIM# 611431
Fetal anomalies v0.4125 SPRED1 Zornitza Stark Publications for gene: SPRED1 were set to
Fetal anomalies v0.4124 SPRED1 Zornitza Stark Mode of inheritance for gene: SPRED1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4123 SPRED1 Zornitza Stark Classified gene: SPRED1 as Red List (low evidence)
Fetal anomalies v0.4123 SPRED1 Zornitza Stark Gene: spred1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4122 SPRED1 Zornitza Stark changed review comment from: Multiple affected individuals reported, deletions account for ~10% of causative variants. Legius syndrome is characterised by multiple cafe-au-lait spots, sometimes associated with skin fold freckling, variable dysmorphic features such as hypertelorism or macrocephaly, lipomas, and mild learning disabilities or attention problems. It is not associated with neurofibromas, optic gliomas, Lisch nodules, or tumor predisposition. The SPRED1 gene encodes a negative regulator of the RAS-MAPK pathway, similar to neurofibromin.; to: Multiple affected individuals reported, deletions account for ~10% of causative variants. Legius syndrome is characterised by multiple cafe-au-lait spots, sometimes associated with skin fold freckling, variable dysmorphic features such as hypertelorism or macrocephaly, lipomas, and mild learning disabilities or attention problems. It is not associated with neurofibromas, optic gliomas, Lisch nodules, or tumor predisposition. The SPRED1 gene encodes a negative regulator of the RAS-MAPK pathway, similar to neurofibromin.

Clinical presentation is typically post-natal.
Fetal anomalies v0.4122 SPRED1 Zornitza Stark edited their review of gene: SPRED1: Changed rating: RED
Fetal anomalies v0.4122 SRCAP Zornitza Stark Marked gene: SRCAP as ready
Fetal anomalies v0.4122 SRCAP Zornitza Stark Gene: srcap has been classified as Green List (High Evidence).
Fetal anomalies v0.4122 SRCAP Zornitza Stark Phenotypes for gene: SRCAP were changed from FLOATING-HARBOR SYNDROME to Floating-Harbor syndrome, MIM# 136140
Fetal anomalies v0.4121 SRCAP Zornitza Stark Publications for gene: SRCAP were set to
Fetal anomalies v0.4120 SRCAP Zornitza Stark Mode of inheritance for gene: SRCAP was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4119 SRCAP Zornitza Stark edited their review of gene: SRCAP: Added comment: IUGR and multiple congenital anomalies.; Changed phenotypes: Floating-Harbor syndrome, MIM# 136140
Fetal anomalies v0.4119 SRD5A3 Zornitza Stark Marked gene: SRD5A3 as ready
Fetal anomalies v0.4119 SRD5A3 Zornitza Stark Gene: srd5a3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4119 SRD5A3 Zornitza Stark Phenotypes for gene: SRD5A3 were changed from CONGENITAL DISORDERS OF GLYCOSYLATION to Congenital disorder of glycosylation, type Iq, MIM# 612379; Kahrizi syndrome, MIM# 612713
Fetal anomalies v0.4118 SRD5A3 Zornitza Stark Publications for gene: SRD5A3 were set to
Fetal anomalies v0.4117 STAG2 Zornitza Stark Marked gene: STAG2 as ready
Fetal anomalies v0.4117 STAG2 Zornitza Stark Gene: stag2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4117 STAG2 Zornitza Stark Phenotypes for gene: STAG2 were changed from STAG2-related developmental delay with microcephaly and congenital anomalies to Mullegama-Klein-Martinez syndrome, MIM# 301022; Holoprosencephaly 13, X-linked, MIM# 301043
Fetal anomalies v0.4116 STAG2 Zornitza Stark Publications for gene: STAG2 were set to 29263825; 28296084; 30158690
Fetal anomalies v0.4115 STAMBP Zornitza Stark Marked gene: STAMBP as ready
Fetal anomalies v0.4115 STAMBP Zornitza Stark Gene: stambp has been classified as Green List (High Evidence).
Fetal anomalies v0.4115 STAMBP Zornitza Stark Phenotypes for gene: STAMBP were changed from MICROCEPHALY CAPILLARY MALFORMATION (MIC-CAP) SYNDROME to Microcephaly-capillary malformation syndrome, MIM# 614261; MONDO:0013659
Fetal anomalies v0.4114 STAMBP Zornitza Stark Publications for gene: STAMBP were set to
Fetal anomalies v0.4113 STRA6 Zornitza Stark Marked gene: STRA6 as ready
Fetal anomalies v0.4113 STRA6 Zornitza Stark Gene: stra6 has been classified as Green List (High Evidence).
Fetal anomalies v0.4113 STRA6 Zornitza Stark Phenotypes for gene: STRA6 were changed from MICROPHTHALMIA SYNDROMIC TYPE 9 to Microphthalmia, syndromic 9, MIM# 601186
Fetal anomalies v0.4112 STRA6 Zornitza Stark Publications for gene: STRA6 were set to
Fetal anomalies v0.4111 SUMF1 Zornitza Stark Marked gene: SUMF1 as ready
Fetal anomalies v0.4111 SUMF1 Zornitza Stark Gene: sumf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4111 SUMF1 Zornitza Stark Phenotypes for gene: SUMF1 were changed from SULFATIDOSIS, JUVENILE, AUSTIN TYPE to Multiple sulfatase deficiency, MIM# 272200
Fetal anomalies v0.4110 SUMF1 Zornitza Stark Publications for gene: SUMF1 were set to
Fetal anomalies v0.4109 SUMF1 Zornitza Stark changed review comment from: Single case report found of hydrops in this metabolic condition.
Sources: Expert list; to: Single case report found of hydrops in this metabolic condition. Hydrocephalus and structural brain abnormalities reported.

Sources: Expert list
Fetal anomalies v0.4109 SUMF1 Zornitza Stark edited their review of gene: SUMF1: Changed rating: GREEN; Changed phenotypes: Multiple sulfatase deficiency, MIM# 272200
Fetal anomalies v0.4109 SUZ12 Zornitza Stark Marked gene: SUZ12 as ready
Fetal anomalies v0.4109 SUZ12 Zornitza Stark Gene: suz12 has been classified as Green List (High Evidence).
Fetal anomalies v0.4109 SUZ12 Zornitza Stark Phenotypes for gene: SUZ12 were changed from Weaver-like overgrowth syndrome; Imagawa-Matsumoto syndrome #618786 to Imagawa-Matsumoto syndrome #618786
Fetal anomalies v0.4108 SUZ12 Zornitza Stark Publications for gene: SUZ12 were set to 30019515; 28229514
Fetal anomalies v0.4107 SUZ12 Zornitza Stark Mode of inheritance for gene: SUZ12 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4106 SUZ12 Zornitza Stark changed review comment from: Thirteen individuals from 12 families.; to: Thirteen individuals from 12 families. Overgrowth of prenatal onset, brain abnormalities reported in some.
Fetal anomalies v0.4106 TAF1 Zornitza Stark Marked gene: TAF1 as ready
Fetal anomalies v0.4106 TAF1 Zornitza Stark Gene: taf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4106 TAF1 Zornitza Stark Phenotypes for gene: TAF1 were changed from Dysmorphic Features, Intellectual Disability, and Neurological Manifestations to Mental retardation, X-linked, syndromic 33, MIM# 300966
Fetal anomalies v0.4105 TAF1 Zornitza Stark Publications for gene: TAF1 were set to
Fetal anomalies v0.4104 TAZ Zornitza Stark Marked gene: TAZ as ready
Fetal anomalies v0.4104 TAZ Zornitza Stark Gene: taz has been classified as Green List (High Evidence).
Fetal anomalies v0.4104 TAZ Zornitza Stark Phenotypes for gene: TAZ were changed from BARTH SYNDROME to Barth syndrome, MIM#302060
Fetal anomalies v0.4103 TAZ Zornitza Stark Publications for gene: TAZ were set to
Fetal anomalies v0.4102 TBC1D20 Zornitza Stark Marked gene: TBC1D20 as ready
Fetal anomalies v0.4102 TBC1D20 Zornitza Stark Gene: tbc1d20 has been classified as Green List (High Evidence).
Fetal anomalies v0.4102 TBC1D20 Zornitza Stark Phenotypes for gene: TBC1D20 were changed from Warburg micro syndrome 4; Warburg micro syndrome 4 615663 to Warburg micro syndrome 4, MIM# 615663
Fetal anomalies v0.4101 TBCD Zornitza Stark Marked gene: TBCD as ready
Fetal anomalies v0.4101 TBCD Zornitza Stark Gene: tbcd has been classified as Green List (High Evidence).
Fetal anomalies v0.4101 TBCD Zornitza Stark Publications for gene: TBCD were set to
Fetal anomalies v0.4100 TBCD Zornitza Stark changed review comment from: CC abnormalities.; to: CC abnormalities, arthrogryposis are relevant to fetal panel.
Fetal anomalies v0.4100 TBCD Zornitza Stark commented on gene: TBCD: CC abnormalities.
Fetal anomalies v0.4100 TBX1 Zornitza Stark Marked gene: TBX1 as ready
Fetal anomalies v0.4100 TBX1 Zornitza Stark Gene: tbx1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4100 TBX1 Zornitza Stark Phenotypes for gene: TBX1 were changed from 22Q11.2 DELETION SYNDROME to DiGeorge syndrome, MIM# 188400
Fetal anomalies v0.4099 TBX1 Zornitza Stark Publications for gene: TBX1 were set to
Fetal anomalies v0.4098 TBX1 Zornitza Stark Mode of pathogenicity for gene: TBX1 was changed from to None
Fetal anomalies v0.4097 TBX1 Zornitza Stark Mode of inheritance for gene: TBX1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4096 TBX3 Zornitza Stark Marked gene: TBX3 as ready
Fetal anomalies v0.4096 TBX3 Zornitza Stark Gene: tbx3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4096 TBX3 Zornitza Stark Phenotypes for gene: TBX3 were changed from ULNAR-MAMMARY SYNDROME to Ulnar-mammary syndrome, MIM# 181450; MONDO:0008411
Fetal anomalies v0.4095 TBX3 Zornitza Stark Publications for gene: TBX3 were set to
Fetal anomalies v0.4094 TBX3 Zornitza Stark Mode of inheritance for gene: TBX3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4093 TBX5 Zornitza Stark Marked gene: TBX5 as ready
Fetal anomalies v0.4093 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4093 TBX5 Zornitza Stark Phenotypes for gene: TBX5 were changed from HOLT-ORAM SYNDROME to Holt-Oram syndrome, MIM# 142900
Fetal anomalies v0.4092 TBX5 Zornitza Stark Publications for gene: TBX5 were set to
Fetal anomalies v0.4091 TBX5 Zornitza Stark Mode of inheritance for gene: TBX5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4090 TCF4 Zornitza Stark Marked gene: TCF4 as ready
Fetal anomalies v0.4090 TCF4 Zornitza Stark Gene: tcf4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4090 TCF4 Zornitza Stark Phenotypes for gene: TCF4 were changed from PITT-HOPKINS SYNDROME to Pitt-Hopkins syndrome, MIM# 610954
Fetal anomalies v0.4089 TCF4 Zornitza Stark Publications for gene: TCF4 were set to
Fetal anomalies v0.4088 TCF4 Zornitza Stark Mode of inheritance for gene: TCF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4087 TCIRG1 Zornitza Stark Marked gene: TCIRG1 as ready
Fetal anomalies v0.4087 TCIRG1 Zornitza Stark Gene: tcirg1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4087 TCTN1 Zornitza Stark Marked gene: TCTN1 as ready
Fetal anomalies v0.4087 TCTN1 Zornitza Stark Gene: tctn1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4087 TCTN1 Zornitza Stark Phenotypes for gene: TCTN1 were changed from Joubert syndrome 13 614173; JOUBERT SYNDROME AND RELATED DISORDERS to Joubert syndrome 13, MIM# 614173
Fetal anomalies v0.4086 TCTN1 Zornitza Stark Publications for gene: TCTN1 were set to
Fetal anomalies v0.4085 TCTN2 Zornitza Stark Marked gene: TCTN2 as ready
Fetal anomalies v0.4085 TCTN2 Zornitza Stark Gene: tctn2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4085 TCTN2 Zornitza Stark Phenotypes for gene: TCTN2 were changed from JOUBERT SYNDROME AND RELATED DISORDERS to Joubert syndrome 24, MIM# 616654; MONDO:0014724; Meckel syndrome 8, MIM# 613885; MONDO:0013482
Fetal anomalies v0.4084 TCTN2 Zornitza Stark Publications for gene: TCTN2 were set to 30712880
Fetal anomalies v0.4083 TCTN3 Zornitza Stark Marked gene: TCTN3 as ready
Fetal anomalies v0.4083 TCTN3 Zornitza Stark Gene: tctn3 has been classified as Green List (High Evidence).
Fetal anomalies v0.4083 TCTN3 Zornitza Stark Phenotypes for gene: TCTN3 were changed from MOHR-MAJEWSKI SYNDROME to Joubert syndrome 18, OMIM #614815; Orofaciodigital syndrome IV, OMIM #258860
Fetal anomalies v0.4082 TCTN3 Zornitza Stark Publications for gene: TCTN3 were set to
Fetal anomalies v0.4081 TFAP2A Zornitza Stark Marked gene: TFAP2A as ready
Fetal anomalies v0.4081 TFAP2A Zornitza Stark Gene: tfap2a has been classified as Green List (High Evidence).
Fetal anomalies v0.4081 TFAP2A Zornitza Stark Phenotypes for gene: TFAP2A were changed from BRANCHIOOCULOFACIAL SYNDROME to Branchiooculofacial syndrome, MIM# 113620
Fetal anomalies v0.4080 TFAP2A Zornitza Stark Publications for gene: TFAP2A were set to
Fetal anomalies v0.4079 TFAP2A Zornitza Stark Mode of inheritance for gene: TFAP2A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4078 TFAP2B Zornitza Stark Marked gene: TFAP2B as ready
Fetal anomalies v0.4078 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Green List (High Evidence).
Fetal anomalies v0.4078 TFAP2B Zornitza Stark Phenotypes for gene: TFAP2B were changed from CHAR SYNDROME to Char syndrome, MIM# 169100; Syndromic craniosynostosis
Fetal anomalies v0.4077 TFAP2B Zornitza Stark Publications for gene: TFAP2B were set to
Fetal anomalies v0.4076 TFAP2B Zornitza Stark Mode of inheritance for gene: TFAP2B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4075 TFAP2B Zornitza Stark Classified gene: TFAP2B as Green List (high evidence)
Fetal anomalies v0.4075 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Green List (High Evidence).
Fetal anomalies v0.4074 TFAP2B Zornitza Stark changed review comment from: PDA, facial dysmorphism and clinodactyly unlikely to be detectable antenatally.; to: Char syndrome: PDA, facial dysmorphism and clinodactyly unlikely to be detectable antenatally.

Craniosynostosis: Four individuals reported in PMID: 31292255 (Correction in PMID: 31405973) as part of a craniosynostosis cohort: 2 de novo and 2 inherited. There is evidence for reduced penetrance as in one case the variant was inherited from an unaffected parent (affected parent for the other inherited variant).
Fetal anomalies v0.4074 TFAP2B Zornitza Stark edited their review of gene: TFAP2B: Changed rating: GREEN; Changed publications: 31292255; Changed phenotypes: Char syndrome, MIM# 169100, Syndromic craniosynostosis
Fetal anomalies v0.4074 TFAP2B Zornitza Stark Classified gene: TFAP2B as Red List (low evidence)
Fetal anomalies v0.4074 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Red List (Low Evidence).
Fetal anomalies v0.4073 TFAP2B Zornitza Stark reviewed gene: TFAP2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Char syndrome, MIM# 169100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4073 TGFBR1 Zornitza Stark Marked gene: TGFBR1 as ready
Fetal anomalies v0.4073 TGFBR1 Zornitza Stark Gene: tgfbr1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4073 TGFBR1 Zornitza Stark Phenotypes for gene: TGFBR1 were changed from LOEYS-DIETZ SYNDROME TYPE 2A; AORTIC ANEURYSM FAMILIAL THORACIC TYPE 5; LOEYS-DIETZ SYNDROME TYPE 1A to Loeys-Dietz syndrome 1, MIM# 609192
Fetal anomalies v0.4072 TGFBR1 Zornitza Stark Mode of inheritance for gene: TGFBR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4071 TGFBR1 Zornitza Stark reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 1, MIM# 609192; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4071 TGFBR2 Zornitza Stark Marked gene: TGFBR2 as ready
Fetal anomalies v0.4071 TGFBR2 Zornitza Stark Gene: tgfbr2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4071 TGFBR2 Zornitza Stark Phenotypes for gene: TGFBR2 were changed from LOEYS-DIETZ SYNDROME; TGFBR2-RELATED LOEYS-DIETZ SYNDROME to Loeys-Dietz syndrome 2, MIM# 610168
Fetal anomalies v0.4070 TGFBR2 Zornitza Stark Mode of inheritance for gene: TGFBR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4069 TGFBR2 Zornitza Stark reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 2 610168; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4069 TGIF1 Zornitza Stark Marked gene: TGIF1 as ready
Fetal anomalies v0.4069 TGIF1 Zornitza Stark Gene: tgif1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4069 TGIF1 Zornitza Stark Phenotypes for gene: TGIF1 were changed from HOLOPROSENCEPHALY; Holoprosencephaly 4 142946 to Holoprosencephaly 4, MIM# 142946; MONDO:0007734
Fetal anomalies v0.4068 TGIF1 Zornitza Stark Publications for gene: TGIF1 were set to
Fetal anomalies v0.4067 TGIF1 Zornitza Stark Mode of inheritance for gene: TGIF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4066 TINF2 Zornitza Stark Marked gene: TINF2 as ready
Fetal anomalies v0.4066 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4066 TINF2 Zornitza Stark Phenotypes for gene: TINF2 were changed from EXUDATIVE RETINOPATHY WITH BONE MARROW FAILURE to Revesz syndrome, MIM# 268130
Fetal anomalies v0.4065 TINF2 Zornitza Stark Publications for gene: TINF2 were set to
Fetal anomalies v0.4064 TINF2 Zornitza Stark Mode of inheritance for gene: TINF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4063 TINF2 Zornitza Stark changed review comment from: Bone marrow failure is the main presenting feature. DD is part of the phenotype, neurological involvement progressive.; to: IUGR.
Fetal anomalies v0.4063 TMEM138 Zornitza Stark Marked gene: TMEM138 as ready
Fetal anomalies v0.4063 TMEM138 Zornitza Stark Gene: tmem138 has been classified as Green List (High Evidence).
Fetal anomalies v0.4063 TMEM138 Zornitza Stark Phenotypes for gene: TMEM138 were changed from Joubert syndrome 16 614465 to Joubert syndrome 16, MIM# 614465; MONDO:0013764
Fetal anomalies v0.4062 TMEM138 Zornitza Stark Publications for gene: TMEM138 were set to
Fetal anomalies v0.4061 TMEM165 Zornitza Stark Marked gene: TMEM165 as ready
Fetal anomalies v0.4061 TMEM165 Zornitza Stark Gene: tmem165 has been classified as Green List (High Evidence).
Fetal anomalies v0.4061 TMEM165 Zornitza Stark Phenotypes for gene: TMEM165 were changed from CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIK to Congenital disorder of glycosylation, type IIk, MIM# 614727; TMEM165-CDG, MONDO:0013870
Fetal anomalies v0.4060 TMEM165 Zornitza Stark Publications for gene: TMEM165 were set to
Fetal anomalies v0.4059 TMEM231 Zornitza Stark Marked gene: TMEM231 as ready
Fetal anomalies v0.4059 TMEM231 Zornitza Stark Gene: tmem231 has been classified as Green List (High Evidence).
Fetal anomalies v0.4059 TMEM231 Zornitza Stark Phenotypes for gene: TMEM231 were changed from Joubert syndrome 20 614970; Meckel syndrome 11 615397 to Joubert syndrome 20, MIM# 614970; MONDO:0013994; Meckel syndrome 11, MIM# 615397; MONDO:0014164
Fetal anomalies v0.4058 TMEM231 Zornitza Stark Publications for gene: TMEM231 were set to
Fetal anomalies v0.4057 TMEM237 Zornitza Stark Marked gene: TMEM237 as ready
Fetal anomalies v0.4057 TMEM237 Zornitza Stark Gene: tmem237 has been classified as Green List (High Evidence).
Fetal anomalies v0.4057 TMEM237 Zornitza Stark Phenotypes for gene: TMEM237 were changed from JOUBERT SYNDROME 14 to Joubert syndrome 14, MIM# 614424
Fetal anomalies v0.4056 TMEM237 Zornitza Stark Publications for gene: TMEM237 were set to
Fetal anomalies v0.4055 TMEM5 Zornitza Stark Marked gene: TMEM5 as ready
Fetal anomalies v0.4055 TMEM5 Zornitza Stark Gene: tmem5 has been classified as Green List (High Evidence).
Fetal anomalies v0.4055 TMEM5 Zornitza Stark Phenotypes for gene: TMEM5 were changed from SEVERE COBBLESTONE LISSENCEPHALY to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10, MIM# 615041, MONDO:0014022
Fetal anomalies v0.4054 TMEM5 Zornitza Stark Publications for gene: TMEM5 were set to
Fetal anomalies v0.4053 TMEM67 Zornitza Stark Marked gene: TMEM67 as ready
Fetal anomalies v0.4053 TMEM67 Zornitza Stark Gene: tmem67 has been classified as Green List (High Evidence).
Fetal anomalies v0.4053 TMEM67 Zornitza Stark Phenotypes for gene: TMEM67 were changed from COACH SYNDROM; JOUBERT SYNDROME TYPE 6; MECKEL SYNDROME TYPE 3; NEPHRONOPHTHISIS TYPE 11 to Joubert syndrome 6, MIM# 610688; Meckel syndrome 3, MIM# 607361
Fetal anomalies v0.4052 TMEM67 Zornitza Stark Publications for gene: TMEM67 were set to
Fetal anomalies v0.4051 TMEM94 Zornitza Stark Marked gene: TMEM94 as ready
Fetal anomalies v0.4051 TMEM94 Zornitza Stark Gene: tmem94 has been classified as Green List (High Evidence).
Fetal anomalies v0.4051 TOP3A Zornitza Stark Marked gene: TOP3A as ready
Fetal anomalies v0.4051 TOP3A Zornitza Stark Gene: top3a has been classified as Green List (High Evidence).
Fetal anomalies v0.4051 TOP3A Zornitza Stark Phenotypes for gene: TOP3A were changed from Bloom Syndrome like Disorder to Microcephaly, growth restriction, and increased sister chromatid exchange 2, MIM# 618097
Fetal anomalies v0.4050 TOP3A Zornitza Stark Publications for gene: TOP3A were set to 30193137
Fetal anomalies v0.4049 TP63 Zornitza Stark Marked gene: TP63 as ready
Fetal anomalies v0.4049 TP63 Zornitza Stark Gene: tp63 has been classified as Green List (High Evidence).
Fetal anomalies v0.4049 TP63 Zornitza Stark Phenotypes for gene: TP63 were changed from ANKYLOBLEPHARON-ECTODERMAL DEFECTS-CLEFT LIP/PALATE; ACRO-DERMATO-UNGUAL-LACRIMAL-TOOTH SYNDROME; ECTRODACTYLY-ECTODERMAL DYSPLASIA-CLEFT LIP/PALATE SYNDROME TYPE 3; SPLIT-HAND/FOOT MALFORMATION TYPE 4; ECTODERMAL DYSPLASIA RAPP-HODGKIN TYPE; NON-SYNDROMIC OROFACIAL CLEFT TYPE 8; LIMB-MAMMARY SYNDROME to ADULT syndrome, OMIM #103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292; Hay-Wells syndrome, OMIM #106260; Limb-mammary syndrome, OMIM #603543; Orofacial cleft 8, OMIM #618149; Rapp-Hodgkin syndrome, OMIM #129400; Split-hand/foot malformation 4, OMIM #605289
Fetal anomalies v0.4048 TP63 Zornitza Stark Mode of inheritance for gene: TP63 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4047 TP63 Zornitza Stark reviewed gene: TP63: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ADULT syndrome, OMIM #103285, Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292, Hay-Wells syndrome, OMIM #106260, Limb-mammary syndrome, OMIM #603543, Orofacial cleft 8, OMIM #618149, Rapp-Hodgkin syndrome, OMIM #129400, Split-hand/foot malformation 4, OMIM #605289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4047 TPM2 Zornitza Stark Marked gene: TPM2 as ready
Fetal anomalies v0.4047 TPM2 Zornitza Stark Gene: tpm2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4047 TPM2 Zornitza Stark Phenotypes for gene: TPM2 were changed from Arthrogryposis multiplex congenita, distal, type 1, 108120; Arthrogryposis, distal, type 2B, 601680; ARTHROGRYPOSIS, DISTAL, TYPE 1 to Arthrogryposis multiplex congenita, distal, type 1, 108120; Arthrogryposis, distal, type 2B, 601680; Multiple pterygium syndrome
Fetal anomalies v0.4046 TPM2 Zornitza Stark Publications for gene: TPM2 were set to 12592607; 17339586
Fetal anomalies v0.4045 TPM2 Zornitza Stark Mode of inheritance for gene: TPM2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.4044 TRAF7 Zornitza Stark Marked gene: TRAF7 as ready
Fetal anomalies v0.4044 TRAF7 Zornitza Stark Gene: traf7 has been classified as Green List (High Evidence).
Fetal anomalies v0.4044 TRAF7 Zornitza Stark Phenotypes for gene: TRAF7 were changed from Developmental Delay, Congenital Anomalies, and Dysmorphic Features; Cardiac, facial, and digital anomalies with developmental delay, 618164 to Cardiac, facial, and digital anomalies with developmental delay, MIM# 618164
Fetal anomalies v0.4043 TRAF7 Zornitza Stark Publications for gene: TRAF7 were set to 29961569
Fetal anomalies v0.4042 TRAF7 Zornitza Stark Mode of inheritance for gene: TRAF7 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4041 TRAPPC9 Zornitza Stark Marked gene: TRAPPC9 as ready
Fetal anomalies v0.4041 TRAPPC9 Zornitza Stark Gene: trappc9 has been classified as Green List (High Evidence).
Fetal anomalies v0.4041 TRAPPC9 Zornitza Stark Phenotypes for gene: TRAPPC9 were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 13 to Intellectual disability, autosomal recessive 13 (MIM# 613192)
Fetal anomalies v0.4040 TRAPPC9 Zornitza Stark Publications for gene: TRAPPC9 were set to
Fetal anomalies v0.4039 TRAPPC9 Zornitza Stark changed review comment from: Note multiple intragenic CNVs reported for this gene.; to: Note multiple intragenic CNVs reported for this gene. Cleft lip and brain abnormalities reported.
Fetal anomalies v0.4039 TRIM37 Zornitza Stark Marked gene: TRIM37 as ready
Fetal anomalies v0.4039 TRIM37 Zornitza Stark Gene: trim37 has been classified as Green List (High Evidence).
Fetal anomalies v0.4039 TRIM37 Zornitza Stark Phenotypes for gene: TRIM37 were changed from MULIBREY NANISM to Mulibrey nanism, OMIM #253250
Fetal anomalies v0.4038 TRIM37 Zornitza Stark reviewed gene: TRIM37: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mulibrey nanism, OMIM #253250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4038 TRIP11 Zornitza Stark Marked gene: TRIP11 as ready
Fetal anomalies v0.4038 TRIP11 Zornitza Stark Gene: trip11 has been classified as Green List (High Evidence).
Fetal anomalies v0.4038 TRIP11 Zornitza Stark Phenotypes for gene: TRIP11 were changed from ACHONDROGENESIS TYPE 1A to Achondrogenesis, type IA, MIM# 200600
Fetal anomalies v0.4037 TRIP11 Zornitza Stark Publications for gene: TRIP11 were set to
Fetal anomalies v0.4036 TRIP12 Zornitza Stark Marked gene: TRIP12 as ready
Fetal anomalies v0.4036 TRIP12 Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4036 TRIP12 Zornitza Stark Phenotypes for gene: TRIP12 were changed from TRIP12-related intellectual disability with/without autism spectrum disorder to Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752
Fetal anomalies v0.4035 TRIP12 Zornitza Stark Publications for gene: TRIP12 were set to
Fetal anomalies v0.4034 TRIP12 Zornitza Stark Mode of inheritance for gene: TRIP12 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4033 TRIP12 Zornitza Stark Classified gene: TRIP12 as Red List (low evidence)
Fetal anomalies v0.4033 TRIP12 Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence).
Fetal anomalies v0.4032 TRIP12 Zornitza Stark reviewed gene: TRIP12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4032 TRIP4 Zornitza Stark Marked gene: TRIP4 as ready
Fetal anomalies v0.4032 TRIP4 Zornitza Stark Gene: trip4 has been classified as Green List (High Evidence).
Fetal anomalies v0.4032 TRIP4 Zornitza Stark Phenotypes for gene: TRIP4 were changed from Prenatal-onset spinal muscular atrophy with congenital bone fractures, MONDO:0000209; Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, MONDO:0014896; ?Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066; Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866; Spinal muscular atrophy with congenital bone fractures 1, MONDO:0014806 to Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866; Spinal muscular atrophy with congenital bone fractures 1, MONDO:0014806
Fetal anomalies v0.4031 TSEN54 Zornitza Stark Marked gene: TSEN54 as ready
Fetal anomalies v0.4031 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Green List (High Evidence).
Fetal anomalies v0.4031 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from ?Pontocerebellar hypoplasia type 5, OMIM:610204; Pontocerebellar hypoplasia type 4, OMIM:225753; Pontocerebellar hypoplasia type 2A, OMIM:277470 to Pontocerebellar hypoplasia type 5, OMIM:610204; Pontocerebellar hypoplasia type 4, OMIM:225753; Pontocerebellar hypoplasia type 2A, OMIM:277470
Fetal anomalies v0.4030 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to 16470708; 20952379; 20956791
Fetal anomalies v0.4029 TTC21B Zornitza Stark Marked gene: TTC21B as ready
Fetal anomalies v0.4029 TTC21B Zornitza Stark Gene: ttc21b has been classified as Green List (High Evidence).
Fetal anomalies v0.4029 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from Short-rib thoracic dysplasia 4 with or without polydactyly 613819 to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819
Fetal anomalies v0.4028 TTC21B Zornitza Stark Publications for gene: TTC21B were set to
Fetal anomalies v0.4027 TTC8 Zornitza Stark Marked gene: TTC8 as ready
Fetal anomalies v0.4027 TTC8 Zornitza Stark Gene: ttc8 has been classified as Green List (High Evidence).
Fetal anomalies v0.4027 TTC8 Zornitza Stark Phenotypes for gene: TTC8 were changed from RETINITIS PIGMENTOSA TYPE 51; BARDET-BIEDL SYNDROME TYPE 8 to Bardet-Biedl syndrome 8, MIM# 615985
Fetal anomalies v0.4026 TTC8 Zornitza Stark Publications for gene: TTC8 were set to
Fetal anomalies v0.4025 TTN Zornitza Stark Marked gene: TTN as ready
Fetal anomalies v0.4025 TTN Zornitza Stark Gene: ttn has been classified as Green List (High Evidence).
Fetal anomalies v0.4025 TTN Zornitza Stark Phenotypes for gene: TTN were changed from congenital titinopathy with arthrogryposis to Salih myopathy; Muscular dystrophy, limb-girdle, autosomal recessive 10
Fetal anomalies v0.4024 TTN Zornitza Stark Publications for gene: TTN were set to 29575618; 28040389; 29691892
Fetal anomalies v0.4023 TUBB Zornitza Stark Marked gene: TUBB as ready
Fetal anomalies v0.4023 TUBB Zornitza Stark Gene: tubb has been classified as Green List (High Evidence).
Fetal anomalies v0.4023 TUBB Zornitza Stark Phenotypes for gene: TUBB were changed from CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 6; Circumferential Skin Creases Kunze Type to Cortical dysplasia, complex, with other brain malformations 6, MIM#615771
Fetal anomalies v0.4022 TUBB Zornitza Stark Publications for gene: TUBB were set to
Fetal anomalies v0.4021 TUBB Zornitza Stark Mode of inheritance for gene: TUBB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4020 TUBB2A Zornitza Stark Marked gene: TUBB2A as ready
Fetal anomalies v0.4020 TUBB2A Zornitza Stark Gene: tubb2a has been classified as Green List (High Evidence).
Fetal anomalies v0.4020 TUBB2A Zornitza Stark Publications for gene: TUBB2A were set to 28840640; 30016746; 25326637; 27770045; 24702957
Fetal anomalies v0.4019 TUBB2A Zornitza Stark Mode of inheritance for gene: TUBB2A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4018 TUBB2B Zornitza Stark Marked gene: TUBB2B as ready
Fetal anomalies v0.4018 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Green List (High Evidence).
Fetal anomalies v0.4018 TUBB2B Zornitza Stark Phenotypes for gene: TUBB2B were changed from POLYMICROGYRIA ASYMMETRIC to Cortical dysplasia, complex, with other brain malformations 7 MIM#610031
Fetal anomalies v0.4017 TUBB2B Zornitza Stark Publications for gene: TUBB2B were set to
Fetal anomalies v0.4016 TUBGCP6 Zornitza Stark Marked gene: TUBGCP6 as ready
Fetal anomalies v0.4016 TUBGCP6 Zornitza Stark Gene: tubgcp6 has been classified as Green List (High Evidence).
Fetal anomalies v0.4016 TUBGCP6 Zornitza Stark Phenotypes for gene: TUBGCP6 were changed from MICROCEPHALY AND CHORIORETINOPATHY WITH OR WITHOUT MENTAL RETARDATION to Microcephaly and chorioretinopathy, autosomal recessive, 1, MIM#251270
Fetal anomalies v0.4015 TUBGCP6 Zornitza Stark Publications for gene: TUBGCP6 were set to
Fetal anomalies v0.4014 UBA1 Zornitza Stark Marked gene: UBA1 as ready
Fetal anomalies v0.4014 UBA1 Zornitza Stark Gene: uba1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4014 UBA1 Zornitza Stark Phenotypes for gene: UBA1 were changed from Spinal muscular atrophy, X-linked 2, infantile 301830 to Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830
Fetal anomalies v0.4013 UBA1 Zornitza Stark Publications for gene: UBA1 were set to
Fetal anomalies v0.4012 UBE3B Zornitza Stark Marked gene: UBE3B as ready
Fetal anomalies v0.4012 UBE3B Zornitza Stark Gene: ube3b has been classified as Green List (High Evidence).
Fetal anomalies v0.4012 UBE3B Zornitza Stark Phenotypes for gene: UBE3B were changed from BLEPHAROPHIMOSIS-MENTAL RETARDATION to Kaufman oculocerebrofacial syndrome, MIM# 244450; MONDO:0009485
Fetal anomalies v0.4011 UBE3B Zornitza Stark Publications for gene: UBE3B were set to
Fetal anomalies v0.4010 UBE3B Zornitza Stark changed review comment from: Intellectual disability, microcephaly, dysmorphic features, including blepharophimosis and ptosis. Over 20 families reported.; to: Intellectual disability, microcephaly, dysmorphic features, including blepharophimosis and ptosis. Congenital heart disease. Over 20 families reported.
Fetal anomalies v0.4010 UBR1 Zornitza Stark Marked gene: UBR1 as ready
Fetal anomalies v0.4010 UBR1 Zornitza Stark Gene: ubr1 has been classified as Green List (High Evidence).
Fetal anomalies v0.4010 UBR1 Zornitza Stark Phenotypes for gene: UBR1 were changed from JOHANSON-BLIZZARD SYNDROME to Johanson-Blizzard syndrome (MIM#243800)
Fetal anomalies v0.4009 UBR1 Zornitza Stark Publications for gene: UBR1 were set to
Fetal anomalies v0.4008 UMPS Zornitza Stark Marked gene: UMPS as ready
Fetal anomalies v0.4008 UMPS Zornitza Stark Gene: umps has been classified as Green List (High Evidence).
Fetal anomalies v0.4008 UMPS Zornitza Stark Phenotypes for gene: UMPS were changed from OROTIC ACIDURIA TYPE 1 to Orotic aciduria MIM# 258900
Fetal anomalies v0.4007 UMPS Zornitza Stark Publications for gene: UMPS were set to
Fetal anomalies v0.4006 VIPAS39 Zornitza Stark Marked gene: VIPAS39 as ready
Fetal anomalies v0.4006 VIPAS39 Zornitza Stark Gene: vipas39 has been classified as Green List (High Evidence).
Fetal anomalies v0.4006 VIPAS39 Zornitza Stark Phenotypes for gene: VIPAS39 were changed from ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2 to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM #613404
Fetal anomalies v0.4005 VIPAS39 Zornitza Stark Publications for gene: VIPAS39 were set to
Fetal anomalies v0.4004 VIPAS39 Zornitza Stark reviewed gene: VIPAS39: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM #613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4004 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Fetal anomalies v0.4004 VPS13B Zornitza Stark Gene: vps13b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4004 VPS13B Zornitza Stark Phenotypes for gene: VPS13B were changed from COHEN SYNDROME to Cohen syndrome (MIM# 216550)
Fetal anomalies v0.4003 VPS13B Zornitza Stark Classified gene: VPS13B as Amber List (moderate evidence)
Fetal anomalies v0.4003 VPS13B Zornitza Stark Gene: vps13b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.4002 VPS13B Zornitza Stark reviewed gene: VPS13B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cohen syndrome (MIM# 216550); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4002 VPS33B Zornitza Stark Marked gene: VPS33B as ready
Fetal anomalies v0.4002 VPS33B Zornitza Stark Gene: vps33b has been classified as Green List (High Evidence).
Fetal anomalies v0.4002 VPS33B Zornitza Stark Phenotypes for gene: VPS33B were changed from ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1 to Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085)
Fetal anomalies v0.4001 VPS33B Zornitza Stark Publications for gene: VPS33B were set to
Fetal anomalies v0.4000 VSX2 Zornitza Stark Marked gene: VSX2 as ready
Fetal anomalies v0.4000 VSX2 Zornitza Stark Gene: vsx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.4000 VSX2 Zornitza Stark Phenotypes for gene: VSX2 were changed from MICROPHTHALMIA ISOLATED TYPE 2; MICROPHTHALMIA WITH CATARACTS AND IRIS ABNORMALITIES; MICROPHTHALMIA ISOLATED WITH COLOBOMA TYPE 3 to Microphthalmia with coloboma 3, MIM# 610092; Microphthalmia, isolated 2, MIM# 610093
Fetal anomalies v0.3999 VSX2 Zornitza Stark Publications for gene: VSX2 were set to
Fetal anomalies v0.3998 WDPCP Zornitza Stark Marked gene: WDPCP as ready
Fetal anomalies v0.3998 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Fetal anomalies v0.3998 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from BARDET-BIEDL SYNDROME TYPE 15 to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Fetal anomalies v0.3997 WDPCP Zornitza Stark Publications for gene: WDPCP were set to
Fetal anomalies v0.3996 WDR19 Zornitza Stark Marked gene: WDR19 as ready
Fetal anomalies v0.3996 WDR19 Zornitza Stark Gene: wdr19 has been classified as Green List (High Evidence).
Fetal anomalies v0.3996 WDR19 Zornitza Stark Phenotypes for gene: WDR19 were changed from CRANIOECTODERMAL DYSPLASIA 4; ASPHYXIATING THORACIC DYSTROPHY 5 to Nephronophthisis 13, MIM# 614377; Senior-Loken syndrome 8, MIM# 616307; Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376; Cranioectodermal dysplasia 4, MIM# 614378
Fetal anomalies v0.3995 WDR19 Zornitza Stark Publications for gene: WDR19 were set to
Fetal anomalies v0.3994 WDR19 Zornitza Stark changed review comment from: Variants in this gene are associated with a range of ciliopathies. Two families reported with a predominantly skeletal phenotype.; to: Variants in this gene are associated with a range of ciliopathies.
Fetal anomalies v0.3994 WDR19 Zornitza Stark edited their review of gene: WDR19: Changed rating: GREEN; Changed publications: 33946315, 33875766, 33606107, 22019273, 23559409, 23683095, 32055034; Changed phenotypes: Nephronophthisis 13, MIM# 614377, Senior-Loken syndrome 8, MIM# 616307, Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376, Cranioectodermal dysplasia 4, MIM# 614378
Fetal anomalies v0.3994 TBC1D1 Zornitza Stark Marked gene: TBC1D1 as ready
Fetal anomalies v0.3994 TBC1D1 Zornitza Stark Gene: tbc1d1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3994 TBC1D1 Zornitza Stark Classified gene: TBC1D1 as Green List (high evidence)
Fetal anomalies v0.3994 TBC1D1 Zornitza Stark Gene: tbc1d1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3993 SRGAP1 Zornitza Stark Marked gene: SRGAP1 as ready
Fetal anomalies v0.3993 SRGAP1 Zornitza Stark Gene: srgap1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3993 SRGAP1 Zornitza Stark Classified gene: SRGAP1 as Amber List (moderate evidence)
Fetal anomalies v0.3993 SRGAP1 Zornitza Stark Gene: srgap1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3992 SLIT2 Zornitza Stark Marked gene: SLIT2 as ready
Fetal anomalies v0.3992 SLIT2 Zornitza Stark Gene: slit2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3992 SLIT2 Zornitza Stark Classified gene: SLIT2 as Amber List (moderate evidence)
Fetal anomalies v0.3992 SLIT2 Zornitza Stark Gene: slit2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3991 ANKRD17 Zornitza Stark Marked gene: ANKRD17 as ready
Fetal anomalies v0.3991 ANKRD17 Zornitza Stark Gene: ankrd17 has been classified as Green List (High Evidence).
Fetal anomalies v0.3991 ANKRD17 Zornitza Stark Classified gene: ANKRD17 as Green List (high evidence)
Fetal anomalies v0.3991 ANKRD17 Zornitza Stark Gene: ankrd17 has been classified as Green List (High Evidence).
Fetal anomalies v0.3990 ALB Zornitza Stark Marked gene: ALB as ready
Fetal anomalies v0.3990 ALB Zornitza Stark Gene: alb has been classified as Green List (High Evidence).
Fetal anomalies v0.3990 ALB Zornitza Stark Classified gene: ALB as Green List (high evidence)
Fetal anomalies v0.3990 ALB Zornitza Stark Gene: alb has been classified as Green List (High Evidence).
Fetal anomalies v0.3989 ACBD5 Zornitza Stark Marked gene: ACBD5 as ready
Fetal anomalies v0.3989 ACBD5 Zornitza Stark Gene: acbd5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3989 ACBD5 Zornitza Stark Classified gene: ACBD5 as Red List (low evidence)
Fetal anomalies v0.3989 ACBD5 Zornitza Stark Gene: acbd5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3988 ZNF711 Zornitza Stark Marked gene: ZNF711 as ready
Fetal anomalies v0.3988 ZNF711 Zornitza Stark Gene: znf711 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3988 ZNF711 Zornitza Stark Phenotypes for gene: ZNF711 were changed from MENTAL RETARDATION X-LINKED ZNF711-RELATED to Mental retardation, X-linked 97, OMIM #300803
Fetal anomalies v0.3987 ZNF711 Zornitza Stark Publications for gene: ZNF711 were set to
Fetal anomalies v0.3986 ZNF711 Zornitza Stark reviewed gene: ZNF711: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked 97, OMIM #300803; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3986 ZNF3 Zornitza Stark Marked gene: ZNF3 as ready
Fetal anomalies v0.3986 ZNF3 Zornitza Stark Gene: znf3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3986 XPA Zornitza Stark Marked gene: XPA as ready
Fetal anomalies v0.3986 XPA Zornitza Stark Gene: xpa has been classified as Red List (Low Evidence).
Fetal anomalies v0.3986 XPA Zornitza Stark Phenotypes for gene: XPA were changed from XERODERMA PIGMENTOSUM, GROUP A to Xeroderma pigmentosum, group A, OMIM# 278700
Fetal anomalies v0.3985 XPA Zornitza Stark Publications for gene: XPA were set to
Fetal anomalies v0.3984 XPA Zornitza Stark changed review comment from: Multiple families reported where ID is part of the phenotype, though some share haplotype and are likely distantly related.; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.3984 XPA Zornitza Stark edited their review of gene: XPA: Changed rating: RED
Fetal anomalies v0.3984 WDR91 Zornitza Stark Marked gene: WDR91 as ready
Fetal anomalies v0.3984 WDR91 Zornitza Stark Gene: wdr91 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3984 WDR91 Zornitza Stark Classified gene: WDR91 as Amber List (moderate evidence)
Fetal anomalies v0.3984 WDR91 Zornitza Stark Gene: wdr91 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3983 WDR11 Zornitza Stark Marked gene: WDR11 as ready
Fetal anomalies v0.3983 WDR11 Zornitza Stark Gene: wdr11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3983 WDR11 Zornitza Stark Phenotypes for gene: WDR11 were changed from KALLMANN SYNDROME to Intellectual disability; Microcephaly; Short stature
Fetal anomalies v0.3982 WDR11 Zornitza Stark Publications for gene: WDR11 were set to
Fetal anomalies v0.3981 WDR11 Zornitza Stark Mode of inheritance for gene: WDR11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3980 WDR11 Zornitza Stark Classified gene: WDR11 as Amber List (moderate evidence)
Fetal anomalies v0.3980 WDR11 Zornitza Stark Gene: wdr11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3979 WDR11 Zornitza Stark edited their review of gene: WDR11: Changed rating: AMBER
Fetal anomalies v0.3979 WASHC5 Zornitza Stark Marked gene: WASHC5 as ready
Fetal anomalies v0.3979 WASHC5 Zornitza Stark Gene: washc5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3979 WASHC5 Zornitza Stark Phenotypes for gene: WASHC5 were changed from Ritscher-Schinzel syndrome 1 220210; Spastic paraplegia 8, autosomal dominant 603563 to Ritscher-Schinzel syndrome 1, MIM# 220210
Fetal anomalies v0.3978 WASHC5 Zornitza Stark Publications for gene: WASHC5 were set to
Fetal anomalies v0.3977 WASHC5 Zornitza Stark Tag founder tag was added to gene: WASHC5.
Fetal anomalies v0.3977 WASHC5 Zornitza Stark reviewed gene: WASHC5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ritscher-Schinzel syndrome 1, MIM# 220210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3977 WAC Zornitza Stark Marked gene: WAC as ready
Fetal anomalies v0.3977 WAC Zornitza Stark Gene: wac has been classified as Red List (Low Evidence).
Fetal anomalies v0.3977 WAC Zornitza Stark Phenotypes for gene: WAC were changed from INTELLECTUAL DISABILITY; WAC syndrome to Desanto-Shinawi syndrome, MIM# 616708
Fetal anomalies v0.3976 WAC Zornitza Stark Publications for gene: WAC were set to
Fetal anomalies v0.3975 WAC Zornitza Stark Mode of inheritance for gene: WAC was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3974 WAC Zornitza Stark reviewed gene: WAC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Desanto-Shinawi syndrome, MIM# 616708; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3974 UROC1 Zornitza Stark Marked gene: UROC1 as ready
Fetal anomalies v0.3974 UROC1 Zornitza Stark Gene: uroc1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3974 UROC1 Zornitza Stark Phenotypes for gene: UROC1 were changed from UROCANASE DEFICIENCY to Urocanase deficiency, MIM#276880
Fetal anomalies v0.3973 UROC1 Zornitza Stark Publications for gene: UROC1 were set to
Fetal anomalies v0.3972 UPF3B Zornitza Stark Marked gene: UPF3B as ready
Fetal anomalies v0.3972 UPF3B Zornitza Stark Gene: upf3b has been classified as Red List (Low Evidence).
Fetal anomalies v0.3972 UPF3B Zornitza Stark Phenotypes for gene: UPF3B were changed from MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 14 to Mental retardation, X-linked, syndromic 14, MIM# 300676
Fetal anomalies v0.3971 UPF3B Zornitza Stark Publications for gene: UPF3B were set to
Fetal anomalies v0.3970 UPF3B Zornitza Stark changed review comment from: Well established gene-disease association, more than 7 families reported, mouse model and other functional data.; to: Well established gene-disease association, more than 7 families reported, mouse model and other functional data. Clinical presentation is typically post-natal.
Fetal anomalies v0.3970 UPF3B Zornitza Stark edited their review of gene: UPF3B: Changed rating: RED
Fetal anomalies v0.3970 UNC80 Zornitza Stark Marked gene: UNC80 as ready
Fetal anomalies v0.3970 UNC80 Zornitza Stark Gene: unc80 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3970 UNC80 Zornitza Stark Publications for gene: UNC80 were set to
Fetal anomalies v0.3969 UNC80 Zornitza Stark edited their review of gene: UNC80: Changed rating: RED
Fetal anomalies v0.3969 UFM1 Zornitza Stark Marked gene: UFM1 as ready
Fetal anomalies v0.3969 UFM1 Zornitza Stark Gene: ufm1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3969 UFM1 Zornitza Stark Phenotypes for gene: UFM1 were changed from Severe early-onset encephalopathy with progressive microcephaly, to Leukodystrophy, hypomyelinating, 14 MIM#617899
Fetal anomalies v0.3968 UFM1 Zornitza Stark Publications for gene: UFM1 were set to 29868776
Fetal anomalies v0.3967 UFM1 Zornitza Stark edited their review of gene: UFM1: Added comment: Clinical presentation is typically post-natal.; Changed rating: RED; Changed phenotypes: Leukodystrophy, hypomyelinating, 14 MIM#617899; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3967 UFC1 Zornitza Stark Marked gene: UFC1 as ready
Fetal anomalies v0.3967 UFC1 Zornitza Stark Gene: ufc1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3967 UFC1 Zornitza Stark Phenotypes for gene: UFC1 were changed from Severe early-onset encephalopathy with progressive microcephaly to Neurodevelopmental disorder with spasticity and poor growth (MIM#618076)
Fetal anomalies v0.3966 UFC1 Zornitza Stark Publications for gene: UFC1 were set to
Fetal anomalies v0.3965 UFC1 Zornitza Stark reviewed gene: UFC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with spasticity and poor growth (MIM#618076); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3965 UBE3A Zornitza Stark Marked gene: UBE3A as ready
Fetal anomalies v0.3965 UBE3A Zornitza Stark Gene: ube3a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3965 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from ANGELMAN SYNDROME to Angelman syndrome MIM#105830
Fetal anomalies v0.3964 UBE3A Zornitza Stark commented on gene: UBE3A: Clinical presentation is typically post-natal.
Fetal anomalies v0.3964 UBE3A Zornitza Stark edited their review of gene: UBE3A: Changed rating: RED
Fetal anomalies v0.3964 UBE2A Zornitza Stark Marked gene: UBE2A as ready
Fetal anomalies v0.3964 UBE2A Zornitza Stark Gene: ube2a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3964 UBE2A Zornitza Stark Phenotypes for gene: UBE2A were changed from UBE2A-RELATED X-LINKED SYNDROMIC MENTAL RETARDATION to Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860)
Fetal anomalies v0.3963 UBE2A Zornitza Stark Publications for gene: UBE2A were set to
Fetal anomalies v0.3962 UBE2A Zornitza Stark reviewed gene: UBE2A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3962 UBA5 Zornitza Stark Marked gene: UBA5 as ready
Fetal anomalies v0.3962 UBA5 Zornitza Stark Gene: uba5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3962 UBA5 Zornitza Stark Phenotypes for gene: UBA5 were changed from Severe Infantile-Onset Encephalopathy to Epileptic encephalopathy, early infantile, 44 (MIM#617132)
Fetal anomalies v0.3961 UBA5 Zornitza Stark Publications for gene: UBA5 were set to
Fetal anomalies v0.3960 UBA5 Zornitza Stark reviewed gene: UBA5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 44 (MIM#617132); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3960 TUSC3 Zornitza Stark Marked gene: TUSC3 as ready
Fetal anomalies v0.3960 TUSC3 Zornitza Stark Gene: tusc3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3960 TUSC3 Zornitza Stark Phenotypes for gene: TUSC3 were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 7 to Mental retardation, autosomal recessive 7, MIM# 611093, MONDO:0012615; TUSC3-CDG (Disorders of protein N-glycosylation)
Fetal anomalies v0.3959 TUSC3 Zornitza Stark Publications for gene: TUSC3 were set to
Fetal anomalies v0.3958 TUSC3 Zornitza Stark changed review comment from: More than 5 unrelated families reported, note homozygous deletions in at least two.; to: More than 5 unrelated families reported, note homozygous deletions in at least two. Clinical presentation is typically post-natal.
Fetal anomalies v0.3958 TUSC3 Zornitza Stark edited their review of gene: TUSC3: Changed rating: RED
Fetal anomalies v0.3958 TMEM70 Zornitza Stark Marked gene: TMEM70 as ready
Fetal anomalies v0.3958 TMEM70 Zornitza Stark Gene: tmem70 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3958 TMEM70 Zornitza Stark Phenotypes for gene: TMEM70 were changed from MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2 to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 MIM#614052
Fetal anomalies v0.3957 TMEM70 Zornitza Stark Publications for gene: TMEM70 were set to
Fetal anomalies v0.3956 TMEM70 Zornitza Stark Classified gene: TMEM70 as Amber List (moderate evidence)
Fetal anomalies v0.3956 TMEM70 Zornitza Stark Gene: tmem70 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3955 TIMM8A Zornitza Stark Marked gene: TIMM8A as ready
Fetal anomalies v0.3955 TIMM8A Zornitza Stark Gene: timm8a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3955 TIMM8A Zornitza Stark Phenotypes for gene: TIMM8A were changed from JENSEN SYNDROME; MOHR-TRANEBJAERG SYNDROME to Mohr-Tranebjaerg syndrome, MIM# 304700
Fetal anomalies v0.3954 TIMM8A Zornitza Stark reviewed gene: TIMM8A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mohr-Tranebjaerg syndrome, MIM# 304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3954 TGFB1 Zornitza Stark Marked gene: TGFB1 as ready
Fetal anomalies v0.3954 TGFB1 Zornitza Stark Gene: tgfb1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3954 TGFB1 Zornitza Stark Phenotypes for gene: TGFB1 were changed from CAMURATI-ENGELMANN DISEASE to Inflammatory bowel disease, immunodeficiency, and encephalopathy, MIM# 618213
Fetal anomalies v0.3953 TGFB1 Zornitza Stark Publications for gene: TGFB1 were set to
Fetal anomalies v0.3952 TGFB1 Zornitza Stark Mode of inheritance for gene: TGFB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3951 TGFB1 Zornitza Stark changed review comment from: Three individuals from two unrelated families reported. DD/ID and seizures in addition to IBD/immunodeficiency.
Sources: Expert list; to: Three individuals from two unrelated families reported. DD/ID and seizures in addition to IBD/immunodeficiency, clinical presentation is typically post-natal.
Fetal anomalies v0.3951 TGFB1 Zornitza Stark edited their review of gene: TGFB1: Changed rating: RED
Fetal anomalies v0.3951 TERT Zornitza Stark Marked gene: TERT as ready
Fetal anomalies v0.3951 TERT Zornitza Stark Gene: tert has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3951 TERT Zornitza Stark Phenotypes for gene: TERT were changed from Dyskeratosis congenita, autosomal recessive 4 to Dyskeratosis congenita, autosomal recessive 4, OMIM #613989; Hoyeraal-Hreidarsson syndrome
Fetal anomalies v0.3950 TERT Zornitza Stark Publications for gene: TERT were set to
Fetal anomalies v0.3949 TERT Zornitza Stark Classified gene: TERT as Amber List (moderate evidence)
Fetal anomalies v0.3949 TERT Zornitza Stark Gene: tert has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3948 TERT Zornitza Stark commented on gene: TERT: IUGR is a feature of HHS, the most severe end of the spectrum for this condition.
Fetal anomalies v0.3948 TERT Zornitza Stark edited their review of gene: TERT: Changed rating: AMBER
Fetal anomalies v0.3948 TCN2 Zornitza Stark Marked gene: TCN2 as ready
Fetal anomalies v0.3948 TCN2 Zornitza Stark Gene: tcn2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3948 TCN2 Zornitza Stark Phenotypes for gene: TCN2 were changed from Transcobalamin II deficiency to Transcobalamin II deficiency, 275350
Fetal anomalies v0.3947 TCN2 Zornitza Stark Publications for gene: TCN2 were set to
Fetal anomalies v0.3946 TCN2 Zornitza Stark edited their review of gene: TCN2: Changed rating: RED
Fetal anomalies v0.3946 SYNGAP1 Zornitza Stark Marked gene: SYNGAP1 as ready
Fetal anomalies v0.3946 SYNGAP1 Zornitza Stark Gene: syngap1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3946 SYNGAP1 Zornitza Stark Phenotypes for gene: SYNGAP1 were changed from MENTAL RETARDATION AUTOSOMAL DOMINANT TYPE 5; EPILEPTIC ENCEPHALOPATHY to Intellectual disability, autosomal dominant 5 (MIM # 612621)
Fetal anomalies v0.3945 SYNGAP1 Zornitza Stark Publications for gene: SYNGAP1 were set to
Fetal anomalies v0.3944 SYNGAP1 Zornitza Stark Mode of inheritance for gene: SYNGAP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3943 SYNGAP1 Zornitza Stark reviewed gene: SYNGAP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, autosomal dominant 5 (MIM # 612621); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3943 STAG1 Zornitza Stark Marked gene: STAG1 as ready
Fetal anomalies v0.3943 STAG1 Zornitza Stark Gene: stag1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3943 STAG1 Zornitza Stark Phenotypes for gene: STAG1 were changed from STAG1 syndromic intellectual disability to Mental retardation, autosomal dominant 47, MIM# 617635
Fetal anomalies v0.3942 STAG1 Zornitza Stark Publications for gene: STAG1 were set to
Fetal anomalies v0.3941 STAG1 Zornitza Stark Mode of inheritance for gene: STAG1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3940 STAG1 Zornitza Stark changed review comment from: Microcephaly is mild and inconsistent feature of this condition.; to: Microcephaly is mild and inconsistent feature of this condition, clinical presentation is typically post-natal.
Fetal anomalies v0.3940 STAG1 Zornitza Stark edited their review of gene: STAG1: Changed rating: RED
Fetal anomalies v0.3940 SLC9A6 Zornitza Stark Marked gene: SLC9A6 as ready
Fetal anomalies v0.3940 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3940 SLC9A6 Zornitza Stark Phenotypes for gene: SLC9A6 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED CHRISTIANSON TYPE to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; MONDO:0010278
Fetal anomalies v0.3939 SLC9A6 Zornitza Stark Publications for gene: SLC9A6 were set to
Fetal anomalies v0.3938 SLC9A6 Zornitza Stark changed review comment from: Angelman-like disorder. ID, seizures, microcephaly. More than 20 unrelated families reported, functional data including mouse model.; to: Angelman-like disorder. ID, seizures, microcephaly. More than 20 unrelated families reported, functional data including mouse model. Clinical presentation is typically post-natal.
Fetal anomalies v0.3938 SLC9A6 Zornitza Stark edited their review of gene: SLC9A6: Changed rating: RED
Fetal anomalies v0.3938 SLC46A1 Zornitza Stark Marked gene: SLC46A1 as ready
Fetal anomalies v0.3938 SLC46A1 Zornitza Stark Gene: slc46a1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3938 SLC46A1 Zornitza Stark Phenotypes for gene: SLC46A1 were changed from HEREDITARY FOLATE MALABSORPTION to Folate malabsorption, hereditary, MIM# 229050
Fetal anomalies v0.3937 SLC46A1 Zornitza Stark Publications for gene: SLC46A1 were set to
Fetal anomalies v0.3936 SLC46A1 Zornitza Stark edited their review of gene: SLC46A1: Changed rating: RED
Fetal anomalies v0.3936 SLC37A4 Zornitza Stark Marked gene: SLC37A4 as ready
Fetal anomalies v0.3936 SLC37A4 Zornitza Stark Gene: slc37a4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3936 SLC37A4 Zornitza Stark Phenotypes for gene: SLC37A4 were changed from Glycogen storage disease Ib 232220 to Glycogen storage disease Ib 232220; Congenital disorder of glycosylation, type IIw 619525
Fetal anomalies v0.3935 SLC37A4 Zornitza Stark Publications for gene: SLC37A4 were set to
Fetal anomalies v0.3934 SLC37A4 Zornitza Stark changed review comment from: Bi-allelic LOF variants in this gene cause glycogen storage disorder.

Single individual reported with heterozygous de novo variant in this gene. Clinical features included dysmorphic features (low set ears, a broad nose, mandibular micrognathia and facial asymmetry) and hepatopathy. The variant abolishes the ER retention signal of the transporter and generates a weak Golgi retention signal. Intracellular mislocalization of the transporter is postulated to lead to a congenital disorder of glycosylation instead of glycogen storage disease.
Sources: Literature; to: Bi-allelic LOF variants in this gene cause glycogen storage disorder. Clinical presentation is typically post-natal.

Single individual reported with heterozygous de novo variant in this gene. Clinical features included dysmorphic features (low set ears, a broad nose, mandibular micrognathia and facial asymmetry) and hepatopathy. The variant abolishes the ER retention signal of the transporter and generates a weak Golgi retention signal. Intracellular mislocalization of the transporter is postulated to lead to a congenital disorder of glycosylation instead of glycogen storage disease.
Sources: Literature
Fetal anomalies v0.3934 SLC37A4 Zornitza Stark edited their review of gene: SLC37A4: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3934 SLC2A2 Zornitza Stark Marked gene: SLC2A2 as ready
Fetal anomalies v0.3934 SLC2A2 Zornitza Stark Gene: slc2a2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3934 SLC2A2 Zornitza Stark Phenotypes for gene: SLC2A2 were changed from FANCONI-BICKEL SYNDROME to Fanconi-Bickel syndrome, MIM# 227810
Fetal anomalies v0.3933 SLC2A2 Zornitza Stark edited their review of gene: SLC2A2: Changed rating: RED
Fetal anomalies v0.3933 SLC2A2 Zornitza Stark changed review comment from: Presentation is typically with liver and renal dysfunction, ID is not a consistent/prominent feature.; to: Presentation is typically with liver and renal dysfunction post-natally.
Fetal anomalies v0.3933 SLC22A5 Zornitza Stark Marked gene: SLC22A5 as ready
Fetal anomalies v0.3933 SLC22A5 Zornitza Stark Gene: slc22a5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3933 SLC22A5 Zornitza Stark Phenotypes for gene: SLC22A5 were changed from SYSTEMIC PRIMARY CARNITINE DEFICIENCY to Carnitine deficiency, systemic primary, MIM#212140
Fetal anomalies v0.3932 SLC22A5 Zornitza Stark changed review comment from: Encephalopathy due to episodes of hypoglycaemia, ID is not part of the phenotype.; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.3932 SLC2A1 Zornitza Stark Marked gene: SLC2A1 as ready
Fetal anomalies v0.3932 SLC2A1 Zornitza Stark Gene: slc2a1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3932 SLC2A1 Zornitza Stark Phenotypes for gene: SLC2A1 were changed from GLUT1 DEFICIENCY SYNDROME TYPE 2; GLUT1 DEFICIENCY SYNDROME TYPE 1 to GLUT1 deficiency syndrome 1, infantile onset, severe, MIM# 606777
Fetal anomalies v0.3931 SLC2A1 Zornitza Stark Mode of inheritance for gene: SLC2A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3930 SLC2A1 Zornitza Stark changed review comment from: Progressive microcephaly is a feature.; to: Typically presents post-natally.
Fetal anomalies v0.3930 SLC2A1 Zornitza Stark edited their review of gene: SLC2A1: Changed rating: RED
Fetal anomalies v0.3930 SKIV2L Zornitza Stark Marked gene: SKIV2L as ready
Fetal anomalies v0.3930 SKIV2L Zornitza Stark Gene: skiv2l has been classified as Green List (High Evidence).
Fetal anomalies v0.3930 SKIV2L Zornitza Stark Phenotypes for gene: SKIV2L were changed from TRICHOHEPATOENTERIC SYNDROME 2 to Trichohepatoenteric syndrome 2, MIM#614602
Fetal anomalies v0.3929 SKIV2L Zornitza Stark Classified gene: SKIV2L as Green List (high evidence)
Fetal anomalies v0.3929 SKIV2L Zornitza Stark Gene: skiv2l has been classified as Green List (High Evidence).
Fetal anomalies v0.3928 SKIV2L Zornitza Stark reviewed gene: SKIV2L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichohepatoenteric syndrome 2, MIM#614602; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3928 SHROOM4 Zornitza Stark Marked gene: SHROOM4 as ready
Fetal anomalies v0.3928 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3928 SHROOM4 Zornitza Stark edited their review of gene: SHROOM4: Changed rating: RED
Fetal anomalies v0.3928 SHROOM4 Zornitza Stark Classified gene: SHROOM4 as Red List (low evidence)
Fetal anomalies v0.3928 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3927 SHROOM4 Zornitza Stark edited their review of gene: SHROOM4: Changed rating: AMBER
Fetal anomalies v0.3927 SHROOM4 Zornitza Stark changed review comment from: Two families only, clinical presentation is typically post-natal.; to: Two families only, clinical presentation is typically post-natal; there are only two P/LP variants in this gene in ClinVar. Fetus identified as part of an ACC cohort with LoF variant in SHROOM4, PMID 32565546.
Fetal anomalies v0.3927 SHROOM4 Zornitza Stark edited their review of gene: SHROOM4: Changed publications: 16249884, 26740508, 32565546
Fetal anomalies v0.3927 SHROOM4 Zornitza Stark Publications for gene: SHROOM4 were set to 32565546
Fetal anomalies v0.3926 SHROOM4 Zornitza Stark changed review comment from: Two families only.; to: Two families only, clinical presentation is typically post-natal.
Fetal anomalies v0.3926 SHROOM4 Zornitza Stark edited their review of gene: SHROOM4: Changed rating: RED
Fetal anomalies v0.3926 SGCA Zornitza Stark Marked gene: SGCA as ready
Fetal anomalies v0.3926 SGCA Zornitza Stark Gene: sgca has been classified as Red List (Low Evidence).
Fetal anomalies v0.3926 SGCA Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.3926 SELENON Zornitza Stark Marked gene: SELENON as ready
Fetal anomalies v0.3926 SELENON Zornitza Stark Gene: selenon has been classified as Red List (Low Evidence).
Fetal anomalies v0.3926 SELENON Zornitza Stark Mode of inheritance for gene: SELENON was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3925 SELENON Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.3925 SDHAF1 Zornitza Stark Marked gene: SDHAF1 as ready
Fetal anomalies v0.3925 SDHAF1 Zornitza Stark Gene: sdhaf1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3925 SDHAF1 Zornitza Stark Phenotypes for gene: SDHAF1 were changed from MITOCHONDRIAL COMPLEX II DEFICIENCY to Mitochondrial complex II deficiency, nuclear type 2, MIM# 619166
Fetal anomalies v0.3924 SDHAF1 Zornitza Stark Publications for gene: SDHAF1 were set to
Fetal anomalies v0.3923 SDHAF1 Zornitza Stark changed review comment from: More than 5 families reported, functional data. Presentation is typically with leukoencephalopathy.; to: More than 5 families reported, functional data. Presentation is typically post-natal.
Fetal anomalies v0.3923 SDHAF1 Zornitza Stark edited their review of gene: SDHAF1: Changed rating: RED
Fetal anomalies v0.3923 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Fetal anomalies v0.3923 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3923 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Fetal anomalies v0.3922 SCN7A Zornitza Stark Marked gene: SCN7A as ready
Fetal anomalies v0.3922 SCN7A Zornitza Stark Gene: scn7a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3922 SCN1B Zornitza Stark Marked gene: SCN1B as ready
Fetal anomalies v0.3922 SCN1B Zornitza Stark Gene: scn1b has been classified as Red List (Low Evidence).
Fetal anomalies v0.3922 SCN1B Zornitza Stark Phenotypes for gene: SCN1B were changed from EPILEPSY, GENERALIZED, WITH FEBRILE SEIZURES PLUS, TYPE 1; BRUGADA SYNDROME 5 to Epileptic encephalopathy, early infantile, 52, MIM#617350; Atrial fibrillation, familial, 13, MIM# 615377
Fetal anomalies v0.3921 SCN1B Zornitza Stark Mode of inheritance for gene: SCN1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3920 SCN1B Zornitza Stark changed review comment from: Note heterozygous variants linked to cardiac phenotypes and to GEFS+. Bi-allelic variants cause EE/ID.; to: Note heterozygous variants linked to cardiac phenotypes and to GEFS+. Bi-allelic variants cause EE/ID.

Clinical presentation is typically post-natal.
Fetal anomalies v0.3920 SCN1B Zornitza Stark edited their review of gene: SCN1B: Changed phenotypes: Epileptic encephalopathy, early infantile, 52, MIM#617350, Atrial fibrillation, familial, 13, MIM# 615377
Fetal anomalies v0.3920 SCN1B Zornitza Stark edited their review of gene: SCN1B: Changed rating: RED; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3920 PURA Zornitza Stark Marked gene: PURA as ready