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Congenital nystagmus v1.5 AP3D1 Zornitza Stark Classified gene: AP3D1 as Green List (high evidence)
Congenital nystagmus v1.5 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Green List (High Evidence).
Congenital nystagmus v1.4 AP3D1 Zornitza Stark commented on gene: AP3D1: Now four affected individuals from two unrelated families, with a mouse model that recapitulates the human phenotype.
Congenital nystagmus v1.4 AP3D1 Zornitza Stark edited their review of gene: AP3D1: Changed rating: GREEN; Changed publications: 26744459, 9697856, 30472485
Mendeliome v0.11079 AP3D1 Zornitza Stark Classified gene: AP3D1 as Green List (high evidence)
Mendeliome v0.11079 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Green List (High Evidence).
Mendeliome v0.11078 AP3D1 Zornitza Stark edited their review of gene: AP3D1: Added comment: Now four affected individuals from two unrelated families, with a mouse model that recapitulates the human phenotype.; Changed rating: GREEN; Changed publications: 26744459, 9697856, 30472485; Changed phenotypes: Hermansky-Pudlak syndrome 10, MIM# 617050, Oculocutaneous albinism, Severe neutropaenia, Recurrent infections, Seizures, Hearing loss, Neurodevelopmental delay
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
Disorders of immune dysregulation v0.106 AP3D1 Bryony Thompson Publications for gene: AP3D1 were set to 26744459; 9697856
Disorders of immune dysregulation v0.105 AP3D1 Bryony Thompson Classified gene: AP3D1 as Green List (high evidence)
Disorders of immune dysregulation v0.105 AP3D1 Bryony Thompson Gene: ap3d1 has been classified as Green List (High Evidence).
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).
Disorders of immune dysregulation v0.104 AP3D1 Bryony Thompson reviewed gene: AP3D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30472485, 9697856, 26744459; Phenotypes: Hermansky-Pudlak syndrome 10, MIM# 617050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
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).
Mendeliome v0.11078 ADD3 Zornitza Stark edited their review of gene: ADD3: Changed rating: GREEN
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).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.40 TSEN2 Zornitza Stark Marked gene: TSEN2 as ready
Atypical Haemolytic Uraemic Syndrome_MPGN v0.40 TSEN2 Zornitza Stark Gene: tsen2 has been classified as Green List (High 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
Mendeliome v0.11078 ZNFX1 Zornitza Stark Publications for gene: ZNFX1 were set to 33872655; 33876776
Syndromic Retinopathy v0.187 PPP2R3C Zornitza Stark Marked gene: PPP2R3C as ready
Syndromic Retinopathy v0.187 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.187 PPP2R3C Zornitza Stark Classified gene: PPP2R3C as Green List (high evidence)
Syndromic Retinopathy v0.187 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.186 PPP2R3C Zornitza Stark gene: PPP2R3C was added
gene: PPP2R3C was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to 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 v0.4266 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
Mendeliome v0.11077 PPP2R3C Zornitza Stark Marked gene: PPP2R3C as ready
Mendeliome v0.11077 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Mendeliome v0.11077 PPP2R3C Zornitza Stark Classified gene: PPP2R3C as Green List (high evidence)
Mendeliome v0.11077 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
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
Mendeliome v0.11076 PPP2R3C Zornitza Stark gene: PPP2R3C was added
gene: PPP2R3C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to 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 v0.4266 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
Differences of Sex Development v0.242 PPP2R3C Zornitza Stark Marked gene: PPP2R3C as ready
Differences of Sex Development v0.242 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Differences of Sex Development v0.242 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
Mendeliome v0.11075 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
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.104 CDX2 Zornitza Stark Mode of inheritance for gene: CDX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.103 CDX2 Zornitza Stark Publications for gene: CDX2 were set to
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.102 CDX2 Zornitza Stark Phenotypes for gene: CDX2 were changed from to Genetic multiple congenital anomalies/dysmorphic syndrome, MONDO:0043005; Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs
Intellectual disability syndromic and non-syndromic v0.4509 CHKA Zornitza Stark Marked gene: CHKA as ready
Intellectual disability syndromic and non-syndromic v0.4509 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4509 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Intellectual disability syndromic and non-syndromic v0.4508 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4508 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1454 CHKA Zornitza Stark Marked gene: CHKA as ready
Genetic Epilepsy v0.1454 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1454 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Genetic Epilepsy v0.1453 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Genetic Epilepsy v0.1453 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1452 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Genetic Epilepsy v0.1452 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Microcephaly v1.109 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Microcephaly v1.109 CHKA Zornitza Stark Marked gene: CHKA as ready
Microcephaly v1.109 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Microcephaly v1.109 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Microcephaly v1.108 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Microcephaly v1.108 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Mendeliome v0.11074 CHKA Zornitza Stark Marked gene: CHKA as ready
Mendeliome v0.11074 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Mendeliome v0.11074 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Mendeliome v0.11073 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Mendeliome v0.11073 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
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
Atypical Haemolytic Uraemic Syndrome_MPGN v0.40 TSEN2 Chirag Patel Classified gene: TSEN2 as Green List (high evidence)
Atypical Haemolytic Uraemic Syndrome_MPGN v0.40 TSEN2 Chirag Patel Gene: tsen2 has been classified as Green List (High Evidence).
Atypical Haemolytic Uraemic Syndrome_MPGN v0.39 TSEN2 Chirag Patel gene: TSEN2 was added
gene: TSEN2 was added to Atypical Haemolytic Uraemic Syndrome_MPGN. Sources: Literature
Mode of inheritance for gene: TSEN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN2 were set to PMID: 34964109
Phenotypes for gene: TSEN2 were set to TRACK syndrome
Review for gene: TSEN2 was set to GREEN
Added comment: Biallelic variants in TSEN2 cause pontocerebellar hypoplasia. Canpolat et a. (2022) report an intronic recessive founder variant in TSEN2 that results in abnormal splicing of the mRNA of this gene, in 6 individuals from 4 consanguineous families. Individuals were affected with microcephaly, craniofacial malformations, CNS abnormalities, cognitive retardation of variable severity, and all individuals developed atypical hemolytic uremic syndrome (aHUS) with thrombotic microangiopathy, microangiopathic hemolytic anemia, thrombocytopenia, proteinuria, severe hypertension, and end-stage kidney disease (ESKD) early in life. Bulk RNA sequencing of peripheral blood cells of 4 affected individuals revealed abnormal tRNA transcripts, indicating an alteration of the tRNA biogenesis. Morpholino-mediated skipping of exon 10 of tsen2 in zebrafish produced phenotypes similar to human patients. Proposed as TRACK syndrome (TSEN2 Related Atypical hemolytic uremic syndrome, Craniofacial malformations, Kidney failure).
Sources: Literature
Microcephaly v1.107 TSEN2 Chirag Patel Classified gene: TSEN2 as Green List (high evidence)
Microcephaly v1.107 TSEN2 Chirag Patel Gene: tsen2 has been classified as Green List (High Evidence).
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
Microcephaly v1.107 TSEN2 Chirag Patel Classified gene: TSEN2 as Green List (high evidence)
Microcephaly v1.107 TSEN2 Chirag Patel Gene: tsen2 has been classified as Green List (High Evidence).
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
Microcephaly v1.106 TSEN2 Chirag Patel reviewed gene: TSEN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
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
Differences of Sex Development v0.241 PPP2R3C Chirag Patel Classified gene: PPP2R3C as Green List (high evidence)
Differences of Sex Development v0.241 PPP2R3C Chirag Patel Gene: ppp2r3c has been classified as Green List (High Evidence).
Differences of Sex Development v0.240 PPP2R3C Chirag Patel gene: PPP2R3C was added
gene: PPP2R3C was added to Differences of Sex Development. 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
Mendeliome v0.11072 CDX2 Chirag Patel Classified gene: CDX2 as Green List (high evidence)
Mendeliome v0.11072 CDX2 Chirag Patel Gene: cdx2 has been classified as Green List (High Evidence).
Mendeliome v0.11071 CDX2 Chirag Patel edited their review of gene: CDX2: Added comment: 9 families, with heterozygous variants identified with WES, presenting with congenital abnormalities affecting the development of the anus, the renal and urogenital system, the vertebrae and/or the limbs in varying sequences and severity (incl. sirenomelia and persistent cloaca). A recurrent pathogenic missense variant in the HOX domain of the protein p.(Arg237His) was found in 3 unrelated families. In the mouse cdx2 is essential for anteroposterior patterning of embryonal axis and morphogenesis of cloacal structures. Cdx2 heterozygous conditional mutant mice show a variable phenotype (including imperforate anus, sirenomelia, posterior vertebral truncations, and bladder anomalies).; Changed rating: GREEN; Changed publications: PMID: 29177441, 34671974; Changed phenotypes: Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs; Set current diagnostic: yes
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.101 CDX2 Chirag Patel Classified gene: CDX2 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.101 CDX2 Chirag Patel Gene: cdx2 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.100 CDX2 Chirag Patel edited their review of gene: CDX2: Added comment: 9 families, with heterozygous variants identified with WES, presenting with congenital abnormalities affecting the development of the anus, the renal and urogenital system, the vertebrae and/or the limbs in varying sequences and severity (incl. sirenomelia and persistent cloaca). A recurrent pathogenic missense variant in the HOX domain of the protein p.(Arg237His) was found in 3 unrelated families. In the mouse cdx2 is essential for anteroposterior patterning of embryonal axis and morphogenesis of cloacal structures. Cdx2 heterozygous conditional mutant mice show a variable phenotype (including imperforate anus, sirenomelia, posterior vertebral truncations, and bladder anomalies).; Changed rating: GREEN; Changed publications: PMID: 29177441, 34671974; Changed phenotypes: Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.106 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Microcephaly. 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 Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Genetic Epilepsy v0.1451 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Genetic Epilepsy. 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 Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4507 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Intellectual disability syndromic and non-syndromic. 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 Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Mendeliome v0.11071 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Mendeliome. 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 Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
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).
Dilated Cardiomyopathy v1.7 PPCS Michelle Torres reviewed gene: PPCS: Rating: ; Mode of pathogenicity: None; Publications: 29754768; Phenotypes: Cardiomyopathy, dilated, 2C, MIM# 618189; Mode of inheritance: None
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
Anophthalmia_Microphthalmia_Coloboma v1.15 GDF3 Zornitza Stark Classified gene: GDF3 as Red List (low evidence)
Anophthalmia_Microphthalmia_Coloboma v1.15 GDF3 Zornitza Stark Gene: gdf3 has been classified as Red List (Low Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.14 GDF3 Zornitza Stark changed review comment from: Please note 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.
Anophthalmia_Microphthalmia_Coloboma v1.14 GDF3 Zornitza Stark reviewed gene: GDF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Anophthalmia_Microphthalmia_Coloboma v1.14 GDF3 Zornitza Stark Marked gene: GDF3 as ready
Anophthalmia_Microphthalmia_Coloboma v1.14 GDF3 Zornitza Stark Gene: gdf3 has been classified as Green List (High Evidence).
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).
Growth failure v1.38 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange syndrome (no OMIM# yet) to Cornelia de Lange syndrome, MONDO:0016033
Microcephaly v1.106 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange-like syndrome to Cornelia de Lange-like syndrome, MONDO:0016033
Mendeliome v0.11071 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033
Hypertrichosis syndromes v0.36 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033
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).
Mendeliome v0.11070 SOST Zornitza Stark Tag SV/CNV tag was added to gene: SOST.
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.
Osteopetrosis v0.13 RASGRP2 Zornitza Stark Marked gene: RASGRP2 as ready
Osteopetrosis v0.13 RASGRP2 Zornitza Stark Gene: rasgrp2 has been classified as Red List (Low Evidence).
Osteopetrosis v0.13 RASGRP2 Zornitza Stark Phenotypes for gene: RASGRP2 were changed from to Bleeding disorder, platelet-type, 18 - MIM#615888; Osteopetrosis (disease) MONDO:0017198
Osteopetrosis v0.12 RASGRP2 Zornitza Stark Publications for gene: RASGRP2 were set to
Osteopetrosis v0.11 RASGRP2 Zornitza Stark Mode of inheritance for gene: RASGRP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.10 RASGRP2 Zornitza Stark Classified gene: RASGRP2 as Red List (low evidence)
Osteopetrosis v0.10 RASGRP2 Zornitza Stark Gene: rasgrp2 has been classified as Red List (Low Evidence).
Osteopetrosis v0.9 RASGRP2 Zornitza Stark reviewed gene: RASGRP2: Rating: RED; Mode of pathogenicity: None; Publications: 18709451; Phenotypes: Osteopetrosis (disease) MONDO:0017198; Mode of inheritance: None
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.

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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
Anophthalmia_Microphthalmia_Coloboma v1.14 GDF3 Chirag Patel Classified gene: GDF3 as Green List (high evidence)
Anophthalmia_Microphthalmia_Coloboma v1.14 GDF3 Chirag Patel Gene: gdf3 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.13 GDF3 Chirag Patel gene: GDF3 was added
gene: GDF3 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Expert list
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: Expert list
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
Mendeliome v0.11070 SOST Seb Lunke Marked gene: SOST as ready
Mendeliome v0.11070 SOST Seb Lunke Gene: sost has been classified as Green List (High Evidence).
Mendeliome v0.11070 SOST Seb Lunke Phenotypes for gene: SOST were changed from to Sclerosteosis 1, OMIM#269500; Craniodiaphyseal dysplasia, OMIM#122860
Mendeliome v0.11069 SOST Seb Lunke Publications for gene: SOST were set to
Mendeliome v0.11068 SOST Seb Lunke Mode of inheritance for gene: SOST was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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)
Mendeliome v0.11067 SOST Seb Lunke reviewed gene: SOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301406, 35160258, 21221996, 17853455; Phenotypes: Sclerosteosis 1, OMIM#269500, Craniodiaphyseal dysplasia, OMIM#122860; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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
Osteopetrosis v0.9 RASGRP2 Krithika Murali reviewed gene: RASGRP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28637664, 28726538, 28762304, 30046681, 34066320, 33711653, 33376940, 32609603, 30849270, 30046681; Phenotypes: ?Bleeding disorder, platelet-type, 18 - MIM#615888; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.9 RASGRP2 Krithika Murali Deleted their review
Osteopetrosis v0.9 RASGRP2 Krithika Murali reviewed gene: RASGRP2: Rating: RED; Mode of pathogenicity: None; Publications: 28637664, 28726538, 28762304, 30046681, 34066320, 33711653, 33376940, 32609603, 30849270, 30046681; Phenotypes: ?Bleeding disorder, platelet-type, 18 - MIM#615888; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
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
Fetal anomalies v0.3920 PURA Zornitza Stark Gene: pura has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3920 PURA Zornitza Stark Phenotypes for gene: PURA were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 31, MIM# 616158
Fetal anomalies v0.3919 PURA Zornitza Stark Publications for gene: PURA were set to
Fetal anomalies v0.3918 PURA Zornitza Stark Mode of inheritance for gene: PURA was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3917 PURA Zornitza Stark Classified gene: PURA as Amber List (moderate evidence)
Fetal anomalies v0.3917 PURA Zornitza Stark Gene: pura has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3916 PURA Zornitza Stark changed review comment from: Multiple individuals reported with de novo variants in this gene and severe ID, hypotonia, apnoea, seizures.; to: Multiple individuals reported with de novo variants in this gene and severe ID, hypotonia, apnoea, seizures.

Typically presents post-natally, but congenital heart disease reported in some.
Fetal anomalies v0.3916 PURA Zornitza Stark edited their review of gene: PURA: Changed rating: AMBER
Fetal anomalies v0.3916 RASA2 Zornitza Stark Marked gene: RASA2 as ready
Fetal anomalies v0.3916 RASA2 Zornitza Stark Gene: rasa2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3916 RASA2 Zornitza Stark Classified gene: RASA2 as Amber List (moderate evidence)
Fetal anomalies v0.3916 RASA2 Zornitza Stark Gene: rasa2 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.192 MAPK1 Zornitza Stark Marked gene: MAPK1 as ready
Congenital Heart Defect v0.192 MAPK1 Zornitza Stark Gene: mapk1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.192 MAPK1 Zornitza Stark Classified gene: MAPK1 as Green List (high evidence)
Congenital Heart Defect v0.192 MAPK1 Zornitza Stark Gene: mapk1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3915 ALB Krithika Murali gene: ALB was added
gene: ALB was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ALB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALB were set to 23730173; 15300429; 31057599
Phenotypes for gene: ALB were set to Analbuminemia- MIM#616000
Review for gene: ALB was set to GREEN
Added comment: Biallelic variants associated with congenital analbuminaemia. Prenatal features include IUGR and oligohydramnios.

Allelic condition OMIM# 615999
Mono-allelic disease and dysalbuminemic hyperthyroxinemia: gain-of-function mechanism, missense variants of ALB with increased affinity for thyroid hormones. Immunoassay methods may show variably elevated free thyroid hormone levels. Individuals are euthyroid and identification is important to avoid unnecessary medical or surgical treatment.
Sources: Literature
Fetal anomalies v0.3915 MAPK1 Zornitza Stark Marked gene: MAPK1 as ready
Fetal anomalies v0.3915 MAPK1 Zornitza Stark Gene: mapk1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3915 MAPK1 Zornitza Stark Classified gene: MAPK1 as Green List (high evidence)
Fetal anomalies v0.3915 MAPK1 Zornitza Stark Gene: mapk1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3914 PLOD3 Zornitza Stark Marked gene: PLOD3 as ready
Fetal anomalies v0.3914 PLOD3 Zornitza Stark Gene: plod3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3914 PLOD3 Zornitza Stark Phenotypes for gene: PLOD3 were changed from Lysyl hydroxylase 3 deficiency - MIM#612394 to Lysyl hydroxylase 3 deficiency - MIM#612394; Stickler-syndrome like
Fetal anomalies v0.3913 PLOD3 Zornitza Stark Classified gene: PLOD3 as Green List (high evidence)
Fetal anomalies v0.3913 PLOD3 Zornitza Stark Gene: plod3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3912 LOXL3 Zornitza Stark Marked gene: LOXL3 as ready
Fetal anomalies v0.3912 LOXL3 Zornitza Stark Gene: loxl3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3912 LOXL3 Zornitza Stark Classified gene: LOXL3 as Amber List (moderate evidence)
Fetal anomalies v0.3912 LOXL3 Zornitza Stark Gene: loxl3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3911 PDIA6 Zornitza Stark Marked gene: PDIA6 as ready
Fetal anomalies v0.3911 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3911 PDIA6 Zornitza Stark Classified gene: PDIA6 as Amber List (moderate evidence)
Fetal anomalies v0.3911 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Amber List (Moderate Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.6 GRK2 Zornitza Stark Phenotypes for gene: GRK2 were changed from Jeune asphyxiating thoracic dystrophy (ATD) to Jeune asphyxiating thoracic dystrophy (ATD), MONDO:0018770
Mendeliome v0.11067 GRK2 Zornitza Stark Phenotypes for gene: GRK2 were changed from Jeune asphyxiating thoracic dystrophy (ATD) to Jeune asphyxiating thoracic dystrophy (ATD), MONDO:0018770
Ciliopathies v1.23 GRK2 Zornitza Stark Phenotypes for gene: GRK2 were changed from Jeune asphyxiating thoracic dystrophy (ATD) to Jeune asphyxiating thoracic dystrophy (ATD), MONDO:0018770
Fetal anomalies v0.3910 GRK2 Zornitza Stark Marked gene: GRK2 as ready
Fetal anomalies v0.3910 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3910 GRK2 Zornitza Stark Phenotypes for gene: GRK2 were changed from Jeune asphyxiating thoracic dystrophy (ATD) to Jeune asphyxiating thoracic dystrophy (ATD), MONDO:0018770
Fetal anomalies v0.3909 GRK2 Zornitza Stark Classified gene: GRK2 as Amber List (moderate evidence)
Fetal anomalies v0.3909 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3908 RASA2 Krithika Murali gene: RASA2 was added
gene: RASA2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RASA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RASA2 were set to 25049390
Phenotypes for gene: RASA2 were set to Noonan syndrome
Review for gene: RASA2 was set to AMBER
Added comment: No OMIM gene disease association. Borderline red-amber gene. No new publications since last PanelApp review in 2020

--

One previous paper from 2014 described 3 patients with Noonan Syndrome and novel variants in RASA2. No segregation or functional data on the specific variants was provided. One of the three patients had an alternative variant in a different candidate gene.

A more recent review using ClinGen criteria (2018) only found the disease association to have limited evidence, with no further patients identified since the 2014 paper, and none since.
Sources: Literature
Congenital Heart Defect v0.191 MAPK1 Krithika Murali gene: MAPK1 was added
gene: MAPK1 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK1 were set to 32721402
Phenotypes for gene: MAPK1 were set to Noonan syndrome 13 - MIM#619087
Review for gene: MAPK1 was set to GREEN
Added comment: Associated with Noonan syndrome including congenital heart defects. No new publications since last PanelApp review Aug 2020

--
Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants.

The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once.

MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway.

MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic).

The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome).
Sources: Literature
Fetal anomalies v0.3908 MAPK1 Krithika Murali gene: MAPK1 was added
gene: MAPK1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK1 were set to 32721402
Phenotypes for gene: MAPK1 were set to Noonan syndrome 13 - MIM#619087
Review for gene: MAPK1 was set to GREEN
Added comment: Associated with Noonan syndrome including congenital heart defects. No new publications since last PanelApp review Aug 2020

--
Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants.

The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once.

MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway.

MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic).

The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome).
Sources: Literature
Fetal anomalies v0.3908 PLOD3 Krithika Murali reviewed gene: PLOD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18834968, 30237576, 30463024, 31129566; Phenotypes: Lysyl hydroxylase 3 deficiency - MIM#612394, Stickler-syndrome like; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3908 PLOD3 Krithika Murali Deleted their review
Fetal anomalies v0.3908 PLOD3 Krithika Murali gene: PLOD3 was added
gene: PLOD3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLOD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLOD3 were set to 30237576; 18834968
Phenotypes for gene: PLOD3 were set to Lysyl hydroxylase 3 deficiency - MIM#612394
Review for gene: PLOD3 was set to GREEN
Added comment: 4 unrelated families reported with biallelic PLOD3 variants and Stickler-syndrome like phenotype including antenatal phenotype of IUGR in one family.
--
PMID 30237576 Maddirevula et al 2019 - report homozygous nonsense variant in a proband with dysmorphic facies, microcephaly, ptosis and contractures. No antenatal information provided.

PMID 31129566 Ewans et al 2019 - report 3 affected siblings with a Stickler-syndrome like disorder.
- Patient 1 had congenital nystagmus and presented with hearing loss and myopia. On examination aged 2, noted to have dysmorphic features - prominent eyes, hypertelorism, malar hypoplasia, an upturned nose, low-set ears and microretrognathia.
- Patient 2 noted to have camptodactyly and clinodactyly postnatally. On examination age 5 noted to have DIP joint contractures and mild skin syndactyly.
- Patient 3 - breech delivery. bilateral hand foot camptodactyly, facial dysmorphism.
- No antenatal features reported.

PMID 30463024 Vahidnehzad et al 2019 - report a male proband from a consanguineous Iranian Baloch family referred for assessment age 4.5. Noted to have developmental delay, musculoskeletal manifestations including scoliosis, flexion contractions, cutaneous syndactyly, right diaphragmatic eventration, ocular anomalies, growth failure and skin blisters. No concerns antenatally. Postnatally noted to have cataract and facial dysmorphism (midface hypoplasia). Homozygous PLOD3 missense variant identified, parents unaffected carriers. PLOD3 mRNA levels in the patient’s fibroblasts measured by whole-transcriptome sequencing and confirmed by RT-PCR, were the same as in control cells, however, the expression of type VII collagen was reduced significantly. No antenatal features reported.

PMID: 18834968 Salo et al 2008 - a female proband with significant IUGR, characteristic craniofacial profile, diaphragm eventration, skeletal anomalies (bilateral talipes equinovarus, flexion contractures, scoliosis from age 7), skin anomalies incl blistering and ocular anomalies. One 28 week male stillborn sibling noted to have significant IUGR and skeletal anomalies on post-mortem. Supportive functional evidence. Compound het PLOD3 variants.
Sources: Literature
Fetal anomalies v0.3908 LOXL3 Krithika Murali gene: LOXL3 was added
gene: LOXL3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LOXL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LOXL3 were set to 25663169; 26307084; 26957899; 29802726; 30362103; 34787502
Phenotypes for gene: LOXL3 were set to Stickler syndrome; cleft lip/palate
Review for gene: LOXL3 was set to AMBER
Added comment: Biallelic variants reported in association with Stickler syndrome in 2 unrelated families. Also identified in one individual with non-syndromic Pierre Robin sequence who had a CNV also.

---

PMID 34787502 Sood et al 2021 - proband with non-syndromic Pierre Robin sequence - homozygous missense LOXL3 variant identified. Sibling also had non-syndromic PRS, but genetic testing declined by family. In addition 551 kb chr10q26.2 duplication identified, no parental testing information provided, not previously reported to be associated with CL/P.

PMID 30362103 Chan et al 2019 - report father and son with Stickler syndrome and homozygous LOXL3 missense variants. Predominantly ocular phenotype with no antenatal features reported.

PMID: 29802726 Khan et al 2018 - genotyping of 258 probands with non-syndromic cleft palate (nsCP) and their parents, focusing in particular on common missense variant p.Ile615Phe. Identified four Phe/Phe homozygotes, report significant association between infant’s homozygote Phe/Phe genotype and the risk of nsCP, compared to common Ile/Ile homozygotes

PMID 26957899 Li et al 2016 - A homozygous frameshift mutation (c.39dup; p.L14Afs*21) and a compound heterozygous frameshift mutation (c.39dup; p.L14Afs*21 and c.594delG; p.Q199Kfs*35) in LOXL3 were separately identified in two of 298 probands with early-onset high myopia.

PMID: 26307084 Zhang et al 2015 - Mice lacking LOXL3 exhibited perinatal lethality and were noted to have cleft palate and spinal deformity.

PMID: 25663169 Alzahrani et al 2015 - homozygous variant identified in 2 children with Stickler syndrome from the same family, both children had cleft lip/palate.
Sources: Literature
Fetal anomalies v0.3908 PDIA6 Krithika Murali gene: PDIA6 was added
gene: PDIA6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PDIA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDIA6 were set to 33495992
Phenotypes for gene: PDIA6 were set to Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes
Review for gene: PDIA6 was set to AMBER
Added comment: No new publications since last PanelApp review. Single case upgraded to Amber on the basis of functional data

---

1 case with asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes. Whole exome sequencing revealed a homozygous frameshift variant in the PDIA6 gene. RNA expression was reduced in a gene dosage‐dependent manner, supporting a loss‐of‐function effect of this variant. Phenotypic correlation with the previously reported mouse model recapitulated the growth defect and delay, early lethality, coagulation, diabetes, immunological, and polycystic kidney disease phenotypes. The phenotype of the current patient is consistent with phenotypes associated with the disruption of PDIA6 and the sensors of UPR in mice and humans.
Sources: Literature
Fetal anomalies v0.3908 GRK2 Krithika Murali gene: GRK2 was added
gene: GRK2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GRK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRK2 were set to 33200460
Phenotypes for gene: GRK2 were set to Jeune asphyxiating thoracic dystrophy (ATD)
Review for gene: GRK2 was set to AMBER
Added comment: 2 unrelated families from a single study reported with supportive functional evidence.
Sources: Literature
Fetal anomalies v0.3908 SCN1A Zornitza Stark Marked gene: SCN1A as ready
Fetal anomalies v0.3908 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Fetal anomalies v0.3908 SCN1A Zornitza Stark Publications for gene: SCN1A were set to 29543227; 32928894
Fetal anomalies v0.3907 SCN1A Zornitza Stark Mode of inheritance for gene: SCN1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3906 SCN1A Zornitza Stark changed review comment from: Arthrogryposis reported.; to: Arthrogryposis and malformations of cortical development reported.
Fetal anomalies v0.3906 SCN1A Zornitza Stark edited their review of gene: SCN1A: Changed publications: 35072530, 33820833
Fetal anomalies v0.3906 SCN1A Zornitza Stark Classified gene: SCN1A as Green List (high evidence)
Fetal anomalies v0.3906 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Fetal anomalies v0.3905 SCN1A Zornitza Stark edited their review of gene: SCN1A: Added comment: Arthrogryposis reported.; Changed publications: 33820833
Fetal anomalies v0.3905 RSPH3 Zornitza Stark Marked gene: RSPH3 as ready
Fetal anomalies v0.3905 RSPH3 Zornitza Stark Gene: rsph3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3905 RSPH3 Zornitza Stark Phenotypes for gene: RSPH3 were changed from PRIMARY CILIARY DYSKINESIA WITH CENTRAL-COMPLEX DEFECTS to Ciliary dyskinesia, primary, 32 (MIM#616481)
Fetal anomalies v0.3904 RSPH3 Zornitza Stark Publications for gene: RSPH3 were set to 30166424
Fetal anomalies v0.3903 RSPH1 Zornitza Stark Marked gene: RSPH1 as ready
Fetal anomalies v0.3903 RSPH1 Zornitza Stark Gene: rsph1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3903 RSPH1 Zornitza Stark Phenotypes for gene: RSPH1 were changed from PRIMARY CILIARY DYSKINESIA WITH CENTRAL-COMPLEX AND RADIAL-SPOKE DEFECTS to Ciliary dyskinesia, primary, 24 (MIM#615481)
Fetal anomalies v0.3902 RSPH1 Zornitza Stark Publications for gene: RSPH1 were set to 30166424
Fetal anomalies v0.3901 PTEN Zornitza Stark Marked gene: PTEN as ready
Fetal anomalies v0.3901 PTEN Zornitza Stark Gene: pten has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3901 PTEN Zornitza Stark Phenotypes for gene: PTEN were changed from LHERMITTE-DUCLOS DISEASE; PROTEUS SYNDROME; COWDEN DISEASE; BANNAYAN-ZONANA SYNDROME; VACTERL ASSOCIATION WITH HYDROCEPHALUS; MACROCEPHALY/AUTISM SYNDROME to Macrocephaly/autism syndrome, MIM# 605309
Fetal anomalies v0.3900 PTEN Zornitza Stark Publications for gene: PTEN were set to
Fetal anomalies v0.3899 PTEN Zornitza Stark Mode of inheritance for gene: PTEN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3898 PTEN Zornitza Stark changed review comment from: More than 10 individuals reported with PMG.; to: More than 10 individuals reported with PMG, otherwise clinical presentation is generally post-natal.
Fetal anomalies v0.3898 PTEN Zornitza Stark edited their review of gene: PTEN: Changed rating: AMBER
Fetal anomalies v0.3898 PTEN Zornitza Stark Classified gene: PTEN as Amber List (moderate evidence)
Fetal anomalies v0.3898 PTEN Zornitza Stark Gene: pten has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3897 PYCR1 Zornitza Stark Marked gene: PYCR1 as ready
Fetal anomalies v0.3897 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3897 PYCR1 Zornitza Stark Phenotypes for gene: PYCR1 were changed from CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIB to Cutis laxa, autosomal recessive, type IIB, MIM# 612940
Fetal anomalies v0.3896 PYCR1 Zornitza Stark reviewed gene: PYCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cutis laxa, autosomal recessive, type IIB, MIM# 612940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3896 PTS Zornitza Stark Marked gene: PTS as ready
Fetal anomalies v0.3896 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Fetal anomalies v0.3896 PTS Zornitza Stark Phenotypes for gene: PTS were changed from 6-PYRUVOYLTETRAHYDROPTERIN SYNTHASE DEFICIENCY to Hyperphenylalaninemia, BH4-deficient, A, MIM# 261640
Fetal anomalies v0.3895 PTS Zornitza Stark reviewed gene: PTS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperphenylalaninemia, BH4-deficient, A, MIM# 261640; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3895 PTH1R Zornitza Stark Marked gene: PTH1R as ready
Fetal anomalies v0.3895 PTH1R Zornitza Stark Gene: pth1r has been classified as Green List (High Evidence).
Fetal anomalies v0.3895 PTH1R Zornitza Stark Phenotypes for gene: PTH1R were changed from PRIMARY FAILURE OF TOOTH ERUPTION; EIKEN SKELETAL DYSPLASIA; CHONDRODYSPLASIA BLOMSTRAND TYPE; JANSEN METAPHYSEAL CHONDRODYSPLASIA to Chondrodysplasia, Blomstrand type, MIM# 215045
Fetal anomalies v0.3894 PTH1R Zornitza Stark Publications for gene: PTH1R were set to
Fetal anomalies v0.3893 PTHLH Zornitza Stark Marked gene: PTHLH as ready
Fetal anomalies v0.3893 PTHLH Zornitza Stark Gene: pthlh has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3893 PTHLH Zornitza Stark Classified gene: PTHLH as Amber List (moderate evidence)
Fetal anomalies v0.3893 PTHLH Zornitza Stark Gene: pthlh has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3892 PTHLH Zornitza Stark changed review comment from: Identifiable prenatally.; to: May be identifiable prenatally.
Fetal anomalies v0.3892 PTHLH Zornitza Stark edited their review of gene: PTHLH: Changed rating: AMBER
Fetal anomalies v0.3892 PTHLH Zornitza Stark Phenotypes for gene: PTHLH were changed from BRACHYDACTYLY, TYPE E2; CLUBBING WITH SKELETAL DYSPLASIA INC ACROOSTEOLYSIS to Brachydactyly, type E2, MIM# 613382
Fetal anomalies v0.3891 PTHLH Zornitza Stark reviewed gene: PTHLH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brachydactyly, type E2, MIM# 613382; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3891 PTF1A Zornitza Stark Marked gene: PTF1A as ready
Fetal anomalies v0.3891 PTF1A Zornitza Stark Gene: ptf1a has been classified as Green List (High Evidence).
Fetal anomalies v0.3891 PTF1A Zornitza Stark Phenotypes for gene: PTF1A were changed from PANCREATIC AGENESIS; DIABETES MELLITUS, PERMANENT NEONATAL, WITH CEREBELLAR AGENESIS to Pancreatic and cerebellar agenesis, MIM# 609069
Fetal anomalies v0.3890 PTF1A Zornitza Stark Publications for gene: PTF1A were set to
Fetal anomalies v0.3889 PTF1A Zornitza Stark reviewed gene: PTF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 21749365, 10507728, 15543146, 19650412; Phenotypes: Pancreatic and cerebellar agenesis, MIM# 609069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11066 PTDSS1 Zornitza Stark Marked gene: PTDSS1 as ready
Mendeliome v0.11066 PTDSS1 Zornitza Stark Gene: ptdss1 has been classified as Green List (High Evidence).
Mendeliome v0.11066 PTDSS1 Zornitza Stark Phenotypes for gene: PTDSS1 were changed from to Lenz-Majewski hyperostotic dwarfism MIM#151050
Mendeliome v0.11065 PTDSS1 Zornitza Stark Publications for gene: PTDSS1 were set to
Mendeliome v0.11064 PTDSS1 Zornitza Stark Mode of inheritance for gene: PTDSS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11063 PTDSS1 Zornitza Stark reviewed gene: PTDSS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24241535, 29341480, 31403251; Phenotypes: Lenz-Majewski hyperostotic dwarfism MIM#151050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3889 PTDSS1 Zornitza Stark Marked gene: PTDSS1 as ready
Fetal anomalies v0.3889 PTDSS1 Zornitza Stark Gene: ptdss1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3889 PTDSS1 Zornitza Stark Phenotypes for gene: PTDSS1 were changed from LENZ-MAJEWSKI HYPEROSTOTIC DWARFISM to Lenz-Majewski hyperostotic dwarfism MIM#151050
Fetal anomalies v0.3888 PTDSS1 Zornitza Stark Publications for gene: PTDSS1 were set to
Fetal anomalies v0.3887 PTDSS1 Zornitza Stark Mode of inheritance for gene: PTDSS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3886 PTDSS1 Zornitza Stark reviewed gene: PTDSS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24241535, 29341480, 31403251; Phenotypes: Lenz-Majewski hyperostotic dwarfism MIM#151050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3886 PSPH Zornitza Stark Marked gene: PSPH as ready
Fetal anomalies v0.3886 PSPH Zornitza Stark Gene: psph has been classified as Green List (High Evidence).
Fetal anomalies v0.3886 PSPH Zornitza Stark Phenotypes for gene: PSPH were changed from PHOSPHOSERINE PHOSPHATASE DEFICIENCY; NEU-LAXOVA to Phosphoserine phosphatase deficiency , MIM#614023; Neu-Luxova syndrome
Fetal anomalies v0.3885 PSPH Zornitza Stark Publications for gene: PSPH were set to
Fetal anomalies v0.3884 PSPH Zornitza Stark reviewed gene: PSPH: Rating: GREEN; Mode of pathogenicity: None; Publications: 14673469, 25080166, 27604308, 26888760, 25152457; Phenotypes: Phosphoserine phosphatase deficiency , MIM#614023, Neu-Luxova syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3884 POLR1D Zornitza Stark Marked gene: POLR1D as ready
Fetal anomalies v0.3884 POLR1D Zornitza Stark Gene: polr1d has been classified as Green List (High Evidence).
Fetal anomalies v0.3884 POLR1D Zornitza Stark Phenotypes for gene: POLR1D were changed from TREACHER COLLINS SYNDROME TYPE 2 to Treacher Collins syndrome 2, MIM# 613717
Fetal anomalies v0.3883 POLR1D Zornitza Stark Publications for gene: POLR1D were set to
Fetal anomalies v0.3882 POLR1D Zornitza Stark Mode of inheritance for gene: POLR1D was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3881 POLR1D Zornitza Stark reviewed gene: POLR1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131976, 24603435, 27448281, 25790162; Phenotypes: Treacher Collins syndrome 2, MIM# 613717; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3881 PDGFRB Zornitza Stark Marked gene: PDGFRB as ready
Fetal anomalies v0.3881 PDGFRB Zornitza Stark Gene: pdgfrb has been classified as Green List (High Evidence).
Fetal anomalies v0.3881 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from FAMILIAL INFANTILE MYOFIBROMATOSIS; PREMATURE AGING SYNDROME, PENTTINEN TYPE to Premature aging syndrome, Penttinen type, MIM# 601812
Fetal anomalies v0.3880 PDGFRB Zornitza Stark Mode of inheritance for gene: PDGFRB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3879 PDGFRB Zornitza Stark reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Premature aging syndrome, Penttinen type, MIM# 601812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - adult onset v0.101 ANXA11 Zornitza Stark Marked gene: ANXA11 as ready
Leukodystrophy - adult onset v0.101 ANXA11 Zornitza Stark Gene: anxa11 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.101 ANXA11 Zornitza Stark Phenotypes for gene: ANXA11 were changed from Inclusion body myopathy and brain white matter abnormalities, MIM# 619733; Amyotrophic lateral sclerosis 23, MIM# 617839 to Inclusion body myopathy and brain white matter abnormalities, MIM# 619733
Leukodystrophy - adult onset v0.100 ANXA11 Zornitza Stark Classified gene: ANXA11 as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.100 ANXA11 Zornitza Stark Gene: anxa11 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.99 ANXA11 Zornitza Stark Tag founder tag was added to gene: ANXA11.
Leukodystrophy - adult onset v0.99 ANXA11 Zornitza Stark edited their review of gene: ANXA11: Changed phenotypes: Inclusion body myopathy and brain white matter abnormalities, MIM# 619733
Leukodystrophy - adult onset v0.99 ANXA11 Zornitza Stark gene: ANXA11 was added
gene: ANXA11 was added to Leukodystrophy - adult onset. Sources: Expert Review
Mode of inheritance for gene: ANXA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANXA11 were set to 34048612
Phenotypes for gene: ANXA11 were set to Inclusion body myopathy and brain white matter abnormalities, MIM# 619733; Amyotrophic lateral sclerosis 23, MIM# 617839
Review for gene: ANXA11 was set to AMBER
Added comment: Inclusion body myopathy and brain white matter abnormalities (IBMWMA) is an autosomal dominant adult-onset disorder characterized predominantly by proximal limb girdle muscle weakness affecting the lower and upper limbs and resulting in gait difficulties and scapular winging. Additional features may include dysarthria, dysphagia, low back pain, and hyporeflexia. EMG is consistent with a myopathic process, although neuropathic findings have also been shown. Muscle biopsy shows fiber type variation, internal nuclei, rimmed vacuoles, and cytoplasmic protein aggregates or inclusions. Serum creatine kinase is usually elevated. Cognitive impairment or frontotemporal dementia occurs in some patients. The disorder is slowly progressive; some patients become wheelchair-bound after many years. Rare patients with this mutation develop ALS; some have both myopathy and ALS. Brain imaging shows white matter abnormalities using diffusion tensor imaging. The disorder is classified as multisystem proteinopathy-6 (MSP6) due to the characteristic disease mechanism of protein misfolding and abnormal tissue deposition.

11 individuals from three unrelated Brazilian families reported, but all had same variant ?founder.
Sources: Expert Review
Incidentalome v0.87 ANXA11 Zornitza Stark Marked gene: ANXA11 as ready
Incidentalome v0.87 ANXA11 Zornitza Stark Gene: anxa11 has been classified as Green List (High Evidence).
Incidentalome v0.87 ANXA11 Zornitza Stark Phenotypes for gene: ANXA11 were changed from Amytrophic lateral sclerosis 23 MIM#617839 to Inclusion body myopathy and brain white matter abnormalities, MIM# 619733; Amyotrophic lateral sclerosis 23, MIM# 617839
Incidentalome v0.86 ANXA11 Zornitza Stark Publications for gene: ANXA11 were set to 28469040; 29845112; 30109997
Incidentalome v0.85 ANXA11 Zornitza Stark reviewed gene: ANXA11: Rating: GREEN; Mode of pathogenicity: None; Publications: 34048612, 28469040; Phenotypes: Inclusion body myopathy and brain white matter abnormalities, MIM# 619733, Amyotrophic lateral sclerosis 23, MIM# 617839; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11063 SLC22A4 Zornitza Stark Marked gene: SLC22A4 as ready
Mendeliome v0.11063 SLC22A4 Zornitza Stark Gene: slc22a4 has been classified as Red List (Low Evidence).
Mendeliome v0.11063 SLC22A4 Zornitza Stark Phenotypes for gene: SLC22A4 were changed from to susceptibility to rheumatoid arthritis MIM#180300
Mendeliome v0.11062 SLC22A4 Zornitza Stark Publications for gene: SLC22A4 were set to
Mendeliome v0.11061 SLC22A4 Zornitza Stark Classified gene: SLC22A4 as Red List (low evidence)
Mendeliome v0.11061 SLC22A4 Zornitza Stark Gene: slc22a4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3879 STAR Zornitza Stark Marked gene: STAR as ready
Fetal anomalies v0.3879 STAR Zornitza Stark Gene: star has been classified as Green List (High Evidence).
Fetal anomalies v0.3879 STAR Zornitza Stark Phenotypes for gene: STAR were changed from CHOLESTEROL DESMOLASE-DEFICIENT CONGENITAL ADRENAL HYPERPLASIA to Lipoid adrenal hyperplasia (MIM#201710)
Fetal anomalies v0.3878 STAR Zornitza Stark Publications for gene: STAR were set to
Fetal anomalies v0.3877 STAR Zornitza Stark reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lipoid adrenal hyperplasia (MIM#201710); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.291 PEX6 Zornitza Stark Publications for gene: PEX6 were set to 32399598
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.290 PEX6 Zornitza Stark Classified gene: PEX6 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.290 PEX6 Zornitza Stark Gene: pex6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11060 HSF2BP Zornitza Stark Publications for gene: HSF2BP were set to 32845237
Mendeliome v0.11059 HSF2BP Zornitza Stark Classified gene: HSF2BP as Green List (high evidence)
Mendeliome v0.11059 HSF2BP Zornitza Stark Gene: hsf2bp has been classified as Green List (High Evidence).
Mendeliome v0.11058 HSF2BP Zornitza Stark edited their review of gene: HSF2BP: Added comment: An additional two patients are described with homozygous missense variants, with supportive in vitro functional assay. PMID: 35174157 Now there are 5 affected patients from three independent families and three different biallelic missense variants associated with the condition.; Changed rating: GREEN; Changed publications: 32845237, 35174157
Mendeliome v0.11058 SLC22A4 Ain Roesley reviewed gene: SLC22A4: Rating: RED; Mode of pathogenicity: None; Publications: 15184985, 24972750; Phenotypes: susceptibility to rheumatoid arthritis MIM#180300; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v0.3877 STAR Daniel Flanagan reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8948562, 16968793; Phenotypes: Lipoid adrenal hyperplasia (MIM#201710); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.289 HSF2BP Zornitza Stark Publications for gene: HSF2BP were set to 32845237
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.288 HSF2BP Zornitza Stark Classified gene: HSF2BP as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.288 HSF2BP Zornitza Stark Gene: hsf2bp has been classified as Green List (High Evidence).
Fetal anomalies v0.3877 SRD5A2 Zornitza Stark Marked gene: SRD5A2 as ready
Fetal anomalies v0.3877 SRD5A2 Zornitza Stark Gene: srd5a2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3877 SRD5A2 Zornitza Stark Publications for gene: SRD5A2 were set to
Fetal anomalies v0.3876 SOX9 Zornitza Stark Marked gene: SOX9 as ready
Fetal anomalies v0.3876 SOX9 Zornitza Stark Gene: sox9 has been classified as Green List (High Evidence).
Fetal anomalies v0.3876 SOX9 Zornitza Stark Phenotypes for gene: SOX9 were changed from CAMPOMELIC DYSPLASIA; PIERRE ROBIN SEQUENCE to Campomelic dysplasia with autosomal sex reversal (MIM#114290); Campomelic dysplasia (MIM#114290); Acampomelic campomelic dysplasia (MIM#114290)
Fetal anomalies v0.3875 SOX9 Zornitza Stark Publications for gene: SOX9 were set to 30712880; 28425981
Fetal anomalies v0.3874 SOX9 Zornitza Stark Mode of inheritance for gene: SOX9 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3873 SOX17 Zornitza Stark Marked gene: SOX17 as ready
Fetal anomalies v0.3873 SOX17 Zornitza Stark Gene: sox17 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3873 SOX17 Zornitza Stark Phenotypes for gene: SOX17 were changed from VESICOURETERAL REFLUX TYPE 3 to Vesicoureteral reflux 3 MIM#613674; Pulmonary arterial hypertension
Fetal anomalies v0.3872 SOX17 Zornitza Stark Publications for gene: SOX17 were set to
Fetal anomalies v0.3871 SOX17 Zornitza Stark Mode of inheritance for gene: SOX17 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3870 SOX17 Zornitza Stark Classified gene: SOX17 as Red List (low evidence)
Fetal anomalies v0.3870 SOX17 Zornitza Stark Gene: sox17 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3869 STAR Belinda Chong reviewed gene: STAR: Rating: RED; Mode of pathogenicity: None; Publications: 7892608, 8948562, 9097960, 11061515, 11297612, 14764819, 16968793, 9326645; Phenotypes: Lipoid adrenal hyperplasia MIM#201710; Mode of inheritance: None
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.287 HSF2BP Elena Hateley Deleted their review
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.287 PEX6 Elena Hateley Deleted their review
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.287 PEX6 Elena Tucker reviewed gene: PEX6: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31555682, PMID: 32399598; Phenotypes: syndromic premature ovarian insufficiency, peroxisomal biogenesis disorders; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.287 PEX6 Elena Hateley reviewed gene: PEX6: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31555682, PMID: 32399598; Phenotypes: premature ovarian insufficiency, peroxisomal biogenesis disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.287 HSF2BP Elena Tucker reviewed gene: HSF2BP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32845237, PMID: 35174157; Phenotypes: premature ovarian insufficiency; Mode of inheritance: None
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.287 HSF2BP Elena Hateley reviewed gene: HSF2BP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35174157, PMID: 32845237; Phenotypes: premature ovarian insufficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3869 SRD5A2 Daniel Flanagan reviewed gene: SRD5A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12843198, 11869378, 18350250, 1944596; Phenotypes: Pseudovaginal perineoscrotal hypospadias (MIM#264600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3869 PRRT2 Zornitza Stark Marked gene: PRRT2 as ready
Fetal anomalies v0.3869 PRRT2 Zornitza Stark Gene: prrt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3869 PRRT2 Zornitza Stark Phenotypes for gene: PRRT2 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; BENIGN FAMILIAL INFANTILE EPILEPSY AND INFANTILE CONVULSIONS WITH CHOREOATHETOSIS SYNDROME to Convulsions, familial infantile, with paroxysmal choreoathetosis, MIM# 602066; Episodic kinesigenic dyskinesia 1, MIM# 128200; Seizures, benign familial infantile, 2, MIM# 605751; intellectual disability, autosomal recessive
Fetal anomalies v0.3868 PRRT2 Zornitza Stark Publications for gene: PRRT2 were set to
Fetal anomalies v0.3867 PRRT2 Zornitza Stark changed review comment from: ID is not part of the phenotype for the mono allelic conditions; two families described with bi-allelic variants and more severe neurological phenotype, including ID.; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.3867 PRRT2 Zornitza Stark edited their review of gene: PRRT2: Changed rating: RED
Fetal anomalies v0.3867 PPM1D Zornitza Stark Marked gene: PPM1D as ready
Fetal anomalies v0.3867 PPM1D Zornitza Stark Gene: ppm1d has been classified as Red List (Low Evidence).
Fetal anomalies v0.3867 PPM1D Zornitza Stark Phenotypes for gene: PPM1D were changed from PPM1D syndrome to Jansen de Vries syndrome (MIM #617450)
Fetal anomalies v0.3866 PPM1D Zornitza Stark Publications for gene: PPM1D were set to
Fetal anomalies v0.3865 PPM1D Zornitza Stark Mode of inheritance for gene: PPM1D was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3864 PPM1D Zornitza Stark reviewed gene: PPM1D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Jansen de Vries syndrome (MIM #617450); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3864 POLG Zornitza Stark Marked gene: POLG as ready
Fetal anomalies v0.3864 POLG Zornitza Stark Gene: polg has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3864 POLG Zornitza Stark Phenotypes for gene: POLG were changed from MITOCHONDRIAL DNA DEPLETION SYNDROME 4A to POLG-related disorders
Fetal anomalies v0.3863 POLG Zornitza Stark Publications for gene: POLG were set to
Fetal anomalies v0.3862 POLG Zornitza Stark Mode of inheritance for gene: POLG was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3861 POLG Zornitza Stark Classified gene: POLG as Amber List (moderate evidence)
Fetal anomalies v0.3861 POLG Zornitza Stark Gene: polg has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3860 POLG Zornitza Stark changed review comment from: Cataracts are described in individuals with bi-allelic and mono-allelic POLG variants.

Fetal presentation with cerebellar abnormalities reported PMID 29574624.; to: Cataracts are described in individuals with bi-allelic and mono-allelic POLG variants, though onset may be later.

Fetal presentation with cerebellar abnormalities reported PMID 29574624.
Fetal anomalies v0.3860 POLG Zornitza Stark edited their review of gene: POLG: Changed rating: AMBER
Fetal anomalies v0.3860 POLG Zornitza Stark changed review comment from: Cataracts are described in individuals with bi-allelic and mono-allelic POLG variants.; to: Cataracts are described in individuals with bi-allelic and mono-allelic POLG variants.

Fetal presentation with cerebellar abnormalities reported PMID 29574624.
Fetal anomalies v0.3860 POLG Zornitza Stark edited their review of gene: POLG: Changed publications: 20301791, 29358615, 22405928, 29574624
Fetal anomalies v0.3860 POLD1 Zornitza Stark Marked gene: POLD1 as ready
Fetal anomalies v0.3860 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3860 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from SUBCUTANEOUS LIPODYSTROPHY, DEAFNESS, MANDIBULAR HYPOPLASIA AND MALE HYPOGONADISM to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome 615381
Fetal anomalies v0.3859 POLD1 Zornitza Stark Publications for gene: POLD1 were set to
Fetal anomalies v0.3858 POLD1 Zornitza Stark Mode of inheritance for gene: POLD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3857 POLD1 Zornitza Stark Classified gene: POLD1 as Green List (high evidence)
Fetal anomalies v0.3857 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3856 POLD1 Zornitza Stark Deleted their comment
Fetal anomalies v0.3856 POLD1 Zornitza Stark edited their review of gene: POLD1: Added comment: Four unrelated individuals with deletion of ser605 residue reported. Mandibular hypoplasia would be identifiable antenatally.; Changed rating: GREEN; Changed publications: 23770608; Changed phenotypes: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome 615381; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3856 SOX9 Daniel Flanagan reviewed gene: SOX9: Rating: GREEN; Mode of pathogenicity: None; Publications: 9002675; Phenotypes: Campomelic dysplasia with autosomal sex reversal (MIM#114290), Campomelic dysplasia (MIM#114290), Acampomelic campomelic dysplasia (MIM#114290); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3856 PDHB Zornitza Stark Marked gene: PDHB as ready
Fetal anomalies v0.3856 PDHB Zornitza Stark Gene: pdhb has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3856 PDHB Zornitza Stark Phenotypes for gene: PDHB were changed from Pyruvate dehydrogenase E1-beta deficiency, 614111 to Pyruvate dehydrogenase E1-beta deficiency, MIM#614111
Fetal anomalies v0.3855 PDHB Zornitza Stark Publications for gene: PDHB were set to 26865159
Fetal anomalies v0.3854 PDHB Zornitza Stark Classified gene: PDHB as Amber List (moderate evidence)
Fetal anomalies v0.3854 PDHB Zornitza Stark Gene: pdhb has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3853 PDHB Zornitza Stark Deleted their comment
Fetal anomalies v0.3853 PDHB Zornitza Stark edited their review of gene: PDHB: Changed rating: AMBER
Fetal anomalies v0.3853 PDHB Zornitza Stark edited their review of gene: PDHB: Added comment: Fetal presentation at 22 weeks reported with intrauterine growth retardation, short corpus callosum, ventricular dilation, and cerebellar hypoplasia, PMID 26865159.; Changed publications: 15138885, 26014431, 26865159
Fetal anomalies v0.3853 NT5C2 Zornitza Stark Marked gene: NT5C2 as ready
Fetal anomalies v0.3853 NT5C2 Zornitza Stark Gene: nt5c2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3853 NT5C2 Zornitza Stark Phenotypes for gene: NT5C2 were changed from Spastic paraplegia 45, autosomal recessive 613162 to Spastic paraplegia 45, autosomal recessive, MIM# 613162; MONDO:0013165
Fetal anomalies v0.3852 NT5C2 Zornitza Stark Publications for gene: NT5C2 were set to
Fetal anomalies v0.3851 NT5C2 Zornitza Stark Classified gene: NT5C2 as Amber List (moderate evidence)
Fetal anomalies v0.3851 NT5C2 Zornitza Stark Gene: nt5c2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3850 NT5C2 Zornitza Stark changed review comment from: ID and CC abnormalities are associated variable features. Nine unrelated families reported, ID reported in >3.; to: ID and CC abnormalities are associated variable features. Nine unrelated families reported.
Fetal anomalies v0.3850 NT5C2 Zornitza Stark edited their review of gene: NT5C2: Changed rating: AMBER
Fetal anomalies v0.3850 NR2F1 Zornitza Stark Marked gene: NR2F1 as ready
Fetal anomalies v0.3850 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3850 NR2F1 Zornitza Stark Phenotypes for gene: NR2F1 were changed from BOSCH-BOONSTRA OPTIC ATROPHY SYNDROME to Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM# 615722
Fetal anomalies v0.3849 NR2F1 Zornitza Stark Publications for gene: NR2F1 were set to
Fetal anomalies v0.3848 NR2F1 Zornitza Stark Mode of inheritance for gene: NR2F1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3847 NR2F1 Zornitza Stark changed review comment from: Recent review of 54 affected individuals with Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS): 22 individuals with point mutations or in-frame deletions in the DNA-binding domain (DBD), and 32 individuals with other types of variants including whole-gene deletions, nonsense and frameshift variants, and point mutations outside the DBD. A more severe phenotype appears to be associated with DBD variants.

Clinical characteristics include developmental delay, intellectual disability, autism spectrum disorder diagnoses/features thereof, cognitive/behavioral anomalies, hypotonia, feeding difficulties, abnormal brain MRI findings, and seizures. Vision phenotype includes optic nerve hypoplasia, optic atrophy, and cortical visual impairment; rarely, alacrima and latent nystagmus (fusional maldevelopment). The behavioural phenotypic spectrum includes a love of music, an unusually good long-term memory, sleep difficulties, a high pain tolerance, and touch sensitivity.; to: Recent review of 54 affected individuals with Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS): 22 individuals with point mutations or in-frame deletions in the DNA-binding domain (DBD), and 32 individuals with other types of variants including whole-gene deletions, nonsense and frameshift variants, and point mutations outside the DBD. A more severe phenotype appears to be associated with DBD variants.

Clinical characteristics include developmental delay, intellectual disability, autism spectrum disorder diagnoses/features thereof, cognitive/behavioral anomalies, hypotonia, feeding difficulties, abnormal brain MRI findings, and seizures. Vision phenotype includes optic nerve hypoplasia, optic atrophy, and cortical visual impairment; rarely, alacrima and latent nystagmus (fusional maldevelopment). The behavioural phenotypic spectrum includes a love of music, an unusually good long-term memory, sleep difficulties, a high pain tolerance, and touch sensitivity.

Clinical presentation is typically post-natal.
Fetal anomalies v0.3847 NR2F1 Zornitza Stark edited their review of gene: NR2F1: Changed rating: RED
Fetal anomalies v0.3847 NGLY1 Zornitza Stark Marked gene: NGLY1 as ready
Fetal anomalies v0.3847 NGLY1 Zornitza Stark Gene: ngly1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3847 NGLY1 Zornitza Stark Phenotypes for gene: NGLY1 were changed from CONGENITAL DISORDER OF DEGLYCOSYLATION to Congenital disorder of deglycosylation, MIM# 615273
Fetal anomalies v0.3846 NGLY1 Zornitza Stark Publications for gene: NGLY1 were set to
Fetal anomalies v0.3845 NGLY1 Zornitza Stark changed review comment from: Over 20 affected individuals reported with bi-allelic variants in this gene. Rat model.; to: Over 20 affected individuals reported with bi-allelic variants in this gene. Rat model.

Clinical presentation is typically post-natal with predominantly neurological features.
Fetal anomalies v0.3845 NGLY1 Zornitza Stark edited their review of gene: NGLY1: Changed rating: RED
Fetal anomalies v0.3845 NFU1 Zornitza Stark Marked gene: NFU1 as ready
Fetal anomalies v0.3845 NFU1 Zornitza Stark Gene: nfu1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3845 NFU1 Zornitza Stark Phenotypes for gene: NFU1 were changed from MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 1 to Multiple mitochondrial dysfunctions syndrome 1, MIM# 605711
Fetal anomalies v0.3844 NFU1 Zornitza Stark Publications for gene: NFU1 were set to
Fetal anomalies v0.3843 NFU1 Zornitza Stark changed review comment from: Bi-allelic variants in this gene cause multiple mitochondrial dysfunctions syndrome, a severe autosomal recessive disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, and early death. Cavitating leukodystrophy and other white matter changes described in multiple affected individuals.; to: Bi-allelic variants in this gene cause multiple mitochondrial dysfunctions syndrome, a severe autosomal recessive disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, and early death. Cavitating leukodystrophy and other white matter changes described in multiple affected individuals.

Clinical presentation is typically post-natal.
Fetal anomalies v0.3843 NFU1 Zornitza Stark edited their review of gene: NFU1: Changed rating: RED
Fetal anomalies v0.3843 SOX17 Daniel Flanagan reviewed gene: SOX17: Rating: RED; Mode of pathogenicity: None; Publications: 29650961, 31406341; Phenotypes: Vesicoureteral reflux 3 MIM#613674, Pulmonary arterial hypertension; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3843 NDUFS7 Zornitza Stark Marked gene: NDUFS7 as ready
Fetal anomalies v0.3843 NDUFS7 Zornitza Stark Gene: ndufs7 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3843 NDUFS7 Zornitza Stark Phenotypes for gene: NDUFS7 were changed from MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 3, MIM#618224
Fetal anomalies v0.3842 NDUFS7 Zornitza Stark Publications for gene: NDUFS7 were set to
Fetal anomalies v0.3841 NDUFS4 Zornitza Stark Marked gene: NDUFS4 as ready
Fetal anomalies v0.3841 NDUFS4 Zornitza Stark Gene: ndufs4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3841 NDUFS4 Zornitza Stark Phenotypes for gene: NDUFS4 were changed from MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY; LEIGH SYNDROME; LEIGH SYNDROME DUP to Mitochondrial complex I deficiency, nuclear type 1, 252010; Leigh syndrome, MIM#252010
Fetal anomalies v0.3840 NDUFS4 Zornitza Stark Publications for gene: NDUFS4 were set to
Fetal anomalies v0.3839 NDUFS4 Zornitza Stark changed review comment from: Well established gene-disease association. See PMID:27079373 for a literature review of 22 published cases.; to: Well established gene-disease association. See PMID:27079373 for a literature review of 22 published cases.

Typically presents post-natally.
Fetal anomalies v0.3839 NDUFS4 Zornitza Stark edited their review of gene: NDUFS4: Changed rating: RED
Fetal anomalies v0.3839 NDUFS1 Zornitza Stark Marked gene: NDUFS1 as ready
Fetal anomalies v0.3839 NDUFS1 Zornitza Stark Gene: ndufs1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3839 NDUFS1 Zornitza Stark Phenotypes for gene: NDUFS1 were changed from MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY; LEIGH SYNDROME to Mitochondrial complex I deficiency, nuclear type 5, MIM# 618226
Fetal anomalies v0.3838 NDUFS1 Zornitza Stark Publications for gene: NDUFS1 were set to
Fetal anomalies v0.3837 NDUFS1 Zornitza Stark changed review comment from: Neurologic disability is a prominent feature.; to: Progressive disorder, typically presents post-natally.
Fetal anomalies v0.3837 NDUFS1 Zornitza Stark edited their review of gene: NDUFS1: Changed rating: RED
Fetal anomalies v0.3837 MYT1L Zornitza Stark Marked gene: MYT1L as ready
Fetal anomalies v0.3837 MYT1L Zornitza Stark Gene: myt1l has been classified as Red List (Low Evidence).
Fetal anomalies v0.3837 MYT1L Zornitza Stark Phenotypes for gene: MYT1L were changed from MYT1L syndrome to Mental retardation, autosomal dominant 39, MIM# 616521
Fetal anomalies v0.3836 MYT1L Zornitza Stark Publications for gene: MYT1L were set to
Fetal anomalies v0.3835 MYT1L Zornitza Stark Mode of inheritance for gene: MYT1L was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3834 MYT1L Zornitza Stark changed review comment from: Over 50 individuals reported with deletions and SNVs affecting MYT1L, and variable phenotype comprising intellectual disability, obesity, and behavioral problems.; to: Over 50 individuals reported with deletions and SNVs affecting MYT1L, and variable phenotype comprising intellectual disability, obesity, and behavioral problems. Clinical presentation is typically post-natal.
Fetal anomalies v0.3834 MYT1L Zornitza Stark edited their review of gene: MYT1L: Changed rating: RED
Fetal anomalies v0.3834 MYBPC2 Zornitza Stark Marked gene: MYBPC2 as ready
Fetal anomalies v0.3834 MYBPC2 Zornitza Stark Gene: mybpc2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3834 MPZ Zornitza Stark Marked gene: MPZ as ready
Fetal anomalies v0.3834 MPZ Zornitza Stark Gene: mpz has been classified as Green List (High Evidence).
Fetal anomalies v0.3834 MPZ Zornitza Stark Phenotypes for gene: MPZ were changed from Roussy-Levy syndrome 180800; Charcot-Marie-Tooth disease, type 2I 607677; Charcot-Marie-Tooth disease, type 1B 118200; Dejerine-Sottas disease 145900; Charcot-Marie-Tooth disease, type 2J 607736; Charcot-Marie-Tooth disease, dominant intermediate D 607791; Neuropathy, congenital hypomyelinating 605253 to Hypomyelinating neuropathy, congenital, 2, MIM# 618184
Fetal anomalies v0.3833 MPZ Zornitza Stark Mode of inheritance for gene: MPZ was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3832 MPZ Zornitza Stark Classified gene: MPZ as Green List (high evidence)
Fetal anomalies v0.3832 MPZ Zornitza Stark Gene: mpz has been classified as Green List (High Evidence).
Fetal anomalies v0.3831 MPZ Zornitza Stark Deleted their comment
Fetal anomalies v0.3831 MPZ Zornitza Stark edited their review of gene: MPZ: Added comment: Variants in this gene are associated with various types of neuropathy, most with post-natal onset.

However, at the severe end of the spectrum can present antenatally with decreased fetal movements and arthrogryposis.; Changed rating: GREEN; Changed phenotypes: Hypomyelinating neuropathy, congenital, 2, MIM# 618184; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3831 MPZ Zornitza Stark reviewed gene: MPZ: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v0.3831 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Fetal anomalies v0.3831 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Fetal anomalies v0.3831 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from KALLMANN SYNDROME WITH DEAFNESS; PERIPHERAL DEMYELINATING NEUROPATHY, CENTRAL DYSMYELINATING LEUKODYSTROPHY, WAARDENBURG SYNDROME, AND HIRSCHSPRUNG DISEASE; WAARDENBURG SYNDROME TYPE 4C; WAARDENBURG SYNDROME TYPE 2E; YEMENITE DEAF-BLIND HYPOPIGMENTATION SYNDROME to PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)
Fetal anomalies v0.3830 SOX10 Zornitza Stark Mode of inheritance for gene: SOX10 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3829 SOX10 Zornitza Stark reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PCWH syndrome (MIM#609136), Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584), Waardenburg syndrome, type 4C (MIM#613266); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3829 SNX14 Zornitza Stark Marked gene: SNX14 as ready
Fetal anomalies v0.3829 SNX14 Zornitza Stark Gene: snx14 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3829 SNX14 Zornitza Stark Phenotypes for gene: SNX14 were changed from ID, MACROCEPHALY AND CEREBELLAR HYPOPLASIA to Spinocerebellar ataxia, autosomal recessive 20 (MIM#616354)
Fetal anomalies v0.3828 SNX14 Zornitza Stark Publications for gene: SNX14 were set to
Fetal anomalies v0.3827 SNX14 Zornitza Stark Classified gene: SNX14 as Amber List (moderate evidence)
Fetal anomalies v0.3827 SNX14 Zornitza Stark Gene: snx14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11058 AGO1 Zornitza Stark Phenotypes for gene: AGO1 were changed from Intellectual disability; autism to Neurodevelopmental disorder MONDO:0700092, AGO1-related; non-syndromic ID and seizures
Mendeliome v0.11057 AGO1 Zornitza Stark Publications for gene: AGO1 were set to 30213762; 22495306; 23020937; 25363768; 25356899; 27620904; 29346770; 28135719
Genetic Epilepsy v0.1451 AGO1 Zornitza Stark Marked gene: AGO1 as ready
Genetic Epilepsy v0.1451 AGO1 Zornitza Stark Gene: ago1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1451 AGO1 Zornitza Stark Phenotypes for gene: AGO1 were changed from focal epilepsy; intellectual disability; global developmental delay to Neurodevelopmental disorder MONDO:0700092, AGO1-related; non-syndromic ID and seizures
Genetic Epilepsy v0.1450 AGO1 Zornitza Stark Classified gene: AGO1 as Green List (high evidence)
Genetic Epilepsy v0.1450 AGO1 Zornitza Stark Gene: ago1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1449 AGO1 Zornitza Stark reviewed gene: AGO1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder MONDO:0700092, AGO1-related, non-syndromic ID and seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v1.33 TSHR Zornitza Stark Marked gene: TSHR as ready
Craniosynostosis v1.33 TSHR Zornitza Stark Gene: tshr has been classified as Green List (High Evidence).
Craniosynostosis v1.33 TSHR Zornitza Stark Classified gene: TSHR as Green List (high evidence)
Craniosynostosis v1.33 TSHR Zornitza Stark Gene: tshr has been classified as Green List (High Evidence).
Fetal anomalies v0.3826 TSHR Zornitza Stark Marked gene: TSHR as ready
Fetal anomalies v0.3826 TSHR Zornitza Stark Gene: tshr has been classified as Green List (High Evidence).
Fetal anomalies v0.3826 TSHR Zornitza Stark Classified gene: TSHR as Green List (high evidence)
Fetal anomalies v0.3826 TSHR Zornitza Stark Gene: tshr has been classified as Green List (High Evidence).
Fetal anomalies v0.3825 SOX10 Daniel Flanagan reviewed gene: SOX10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: PCWH syndrome (MIM#609136), Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584), Waardenburg syndrome, type 4C (MIM#613266); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3825 SNX14 Daniel Flanagan reviewed gene: SNX14: Rating: AMBER; Mode of pathogenicity: None; Publications: 25848753, 25439728; Phenotypes: Spinocerebellar ataxia, autosomal recessive 20 (MIM#616354); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11056 AGO1 Krithika Murali reviewed gene: AGO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35060114, 30213762, 25356899; Phenotypes: focal epilepsy, intellectual disability, global developmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1449 AGO1 Krithika Murali changed review comment from: PMID 35060114 Niu et al 2022 - 4 additional individuals reported with ID/GDD associated with heterozygous de novo AGO1 variants. Authors provide a review of 14 individuals reported in the literature. 5 out of 14 from 3 different studies noted to have epilepsy, predominantly focal seizures.
Sources: Literature; to: PMID 35060114 Niu et al 2022 - 4 additional individuals reported with ID/GDD associated with heterozygous de novo AGO1 variants. Authors provide a review of the 18 individuals reported in the literature. 5 out of 18 from 3 different studies noted to have epilepsy, predominantly focal seizures.
Sources: Literature
Genetic Epilepsy v0.1449 AGO1 Krithika Murali gene: AGO1 was added
gene: AGO1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: AGO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGO1 were set to 35060114; 30213762; 25356899
Phenotypes for gene: AGO1 were set to focal epilepsy; intellectual disability; global developmental delay
Review for gene: AGO1 was set to GREEN
Added comment: PMID 35060114 Niu et al 2022 - 4 additional individuals reported with ID/GDD associated with heterozygous de novo AGO1 variants. Authors provide a review of 14 individuals reported in the literature. 5 out of 14 from 3 different studies noted to have epilepsy, predominantly focal seizures.
Sources: Literature
Fetal anomalies v0.3825 TSHR Krithika Murali changed review comment from: Heterozygous variants associated with hyperthyroidism. De novo GoF variants in particular associated with more severe, non-autoimmune congenital hyperthyroidism. Biallelic LoF variants associated with congenital hypothyroidism.

Premature delivery, IUGR and fetal tachycardia are reported antenatal phenotypes. Goitre also noted at birth in some cases. Craniosynostosis also a feature, but diagnosed postnatally in the context of rapidly advancing bone age.

---
PMID: 9360555 Holzapfel 1997 - report IUGR and antenatal fetal tachycardia

PMID: 7800007 Kopp et al 1995 - proband born prematurely at 32 weeks gestation with BW of 1660g. Fetal tachycardia and diffuse goitre noted postnatally.

PMID: 18655531 Chester et al 2008 - proband born at 34 weeks. Antenatal ultrasound had shown thickened nuchal fold.

PMID: 15163335 Vaidya et al 2004 - report two siblings born premature with IUGR, heterozygous variant inherited from affected father.
Sources: Literature; to: Heterozygous variants associated with hyperthyroidism. De novo GoF variants in particular associated with more severe, non-autoimmune congenital hyperthyroidism. Biallelic LoF variants associated with congenital hypothyroidism.

Premature delivery, IUGR and fetal tachycardia are reported antenatal phenotypes. Goitre also noted at birth in some cases. Craniosynostosis also a feature, but diagnosed postnatally in the context of rapidly advancing bone age.

---
PMID: 9360555 Holzapfel 1997 - report IUGR and antenatal fetal tachycardia

PMID: 7800007 Kopp et al 1995 - proband born prematurely at 32 weeks gestation with BW of 1660g. Fetal tachycardia and diffuse goitre noted postnatally.

PMID: 18655531 Chester et al 2008 - proband born at 34 weeks. Antenatal ultrasound had shown thickened nuchal fold.

PMID: 15163335 Vaidya et al 2004 - report two siblings born premature with IUGR, heterozygous variant inherited from affected father.

PMID: 11081252 M Tonacchera et al 2000 - report SGA

PMID: 16960398 Nishihara et al 2006 - proband born 32 weeks with 1860g birthweight, postnatal goitre and craniosynostosis





Sources: Literature
Craniosynostosis v1.32 TSHR Krithika Murali changed review comment from: Monoallelic variants associated with hyperthyroidism - de novo GoF variants in particular associated with more severe phenotype including congenital hyperthyroidism.

Multiple case reports of postnatal diagnosis of craniosynostosis in the context of advancing bone age. Review summarising phenotypic features - PMID 20138963. CS reported in PMID 30599487; 9589634; 18655531; 16260895; 16960398 ; 11081252; 18528812
Sources: Literature; to: Monoallelic variants associated with hyperthyroidism - de novo GoF variants in particular associated with more severe phenotype including congenital hyperthyroidism.

Multiple case reports of postnatal diagnosis of craniosynostosis in the context of advancing bone age. Review summarising phenotypic features - PMID 20138963. CS reported in PMID 30599487; 9589634; 18655531; 16260895; 16960398 ; 11081252; 18528812

Biallelic LoF variants associated with congenital hypothyroidism, CS not a feature.
Sources: Literature
Craniosynostosis v1.32 TSHR Krithika Murali gene: TSHR was added
gene: TSHR was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: TSHR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TSHR were set to 9589634; 18655531; 10095169; 8981019; 16260895; 16960398; 11081252; 18528812; 30599487; 20138963
Phenotypes for gene: TSHR were set to Hyperthyroidism, nonautoimmune - MIM#609152; Hyperthyroidism, familial gestational - MIM#603373; Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200
Review for gene: TSHR was set to GREEN
Added comment: Monoallelic variants associated with hyperthyroidism - de novo GoF variants in particular associated with more severe phenotype including congenital hyperthyroidism.

Multiple case reports of postnatal diagnosis of craniosynostosis in the context of advancing bone age. Review summarising phenotypic features - PMID 20138963. CS reported in PMID 30599487; 9589634; 18655531; 16260895; 16960398 ; 11081252; 18528812
Sources: Literature
Fetal anomalies v0.3825 TSHR Krithika Murali gene: TSHR was added
gene: TSHR was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TSHR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TSHR were set to 23295291; 9360555; 7800007; 18655531; 15163335
Phenotypes for gene: TSHR were set to Hyperthyroidism, nonautoimmune - MIM#609152; Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200
Review for gene: TSHR was set to GREEN
Added comment: Heterozygous variants associated with hyperthyroidism. De novo GoF variants in particular associated with more severe, non-autoimmune congenital hyperthyroidism. Biallelic LoF variants associated with congenital hypothyroidism.

Premature delivery, IUGR and fetal tachycardia are reported antenatal phenotypes. Goitre also noted at birth in some cases. Craniosynostosis also a feature, but diagnosed postnatally in the context of rapidly advancing bone age.

---
PMID: 9360555 Holzapfel 1997 - report IUGR and antenatal fetal tachycardia

PMID: 7800007 Kopp et al 1995 - proband born prematurely at 32 weeks gestation with BW of 1660g. Fetal tachycardia and diffuse goitre noted postnatally.

PMID: 18655531 Chester et al 2008 - proband born at 34 weeks. Antenatal ultrasound had shown thickened nuchal fold.

PMID: 15163335 Vaidya et al 2004 - report two siblings born premature with IUGR, heterozygous variant inherited from affected father.
Sources: Literature
Fetal anomalies v0.3825 MPV17 Zornitza Stark Marked gene: MPV17 as ready
Fetal anomalies v0.3825 MPV17 Zornitza Stark Gene: mpv17 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3825 MPV17 Zornitza Stark Phenotypes for gene: MPV17 were changed from MITOCHONDRIAL DNA DEPLETION SYNDROME 6 to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), OMIM #256810
Fetal anomalies v0.3824 MPV17 Zornitza Stark Publications for gene: MPV17 were set to
Fetal anomalies v0.3823 MPV17 Zornitza Stark reviewed gene: MPV17: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), OMIM #256810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3823 MPI Zornitza Stark Marked gene: MPI as ready
Fetal anomalies v0.3823 MPI Zornitza Stark Gene: mpi has been classified as Red List (Low Evidence).
Fetal anomalies v0.3823 MPI Zornitza Stark Publications for gene: MPI were set to
Fetal anomalies v0.3822 MGAT2 Zornitza Stark Marked gene: MGAT2 as ready
Fetal anomalies v0.3822 MGAT2 Zornitza Stark Gene: mgat2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3822 MGAT2 Zornitza Stark Phenotypes for gene: MGAT2 were changed from CONGENITAL DISORDER OF GLYCOSYLATION TYPE 2A to Congenital disorder of glycosylation, type IIa, MIM# 212066; MGAT2-CDG, MONDO:0008908
Fetal anomalies v0.3821 MGAT2 Zornitza Stark Publications for gene: MGAT2 were set to
Fetal anomalies v0.3820 MGAT2 Zornitza Stark Classified gene: MGAT2 as Amber List (moderate evidence)
Fetal anomalies v0.3820 MGAT2 Zornitza Stark Gene: mgat2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3819 MGAT2 Zornitza Stark edited their review of gene: MGAT2: Changed rating: AMBER
Fetal anomalies v0.3819 MECP2 Zornitza Stark Marked gene: MECP2 as ready
Fetal anomalies v0.3819 MECP2 Zornitza Stark Gene: mecp2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3819 MECP2 Zornitza Stark Phenotypes for gene: MECP2 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 13; MENTAL RETARDATION SYNDROMIC X-LINKED LUBS TYPE; CHROMOSOME XQ28 DUPLICATION SYNDROME; ENCEPHALOPATHY NEONATAL SEVERE DUE TO MECP2 MUTATIONS; RETT SYNDROME (RTT)[ to Rett syndrome, MIM# 312750; Encephalopathy, neonatal severe 300673
Fetal anomalies v0.3818 MECP2 Zornitza Stark changed review comment from: Well established gene-disease association, microcephaly is a key phenotypic feature both in Rett syndrome and in males affected by severe neonatal encephalopathy.; to: Well established gene-disease association, typically presents post-natally.
Fetal anomalies v0.3818 MECP2 Zornitza Stark edited their review of gene: MECP2: Changed rating: RED
Fetal anomalies v0.3818 MAOA Zornitza Stark Marked gene: MAOA as ready
Fetal anomalies v0.3818 MAOA Zornitza Stark Gene: maoa has been classified as Red List (Low Evidence).
Fetal anomalies v0.3818 MAOA Zornitza Stark Phenotypes for gene: MAOA were changed from BRUNNER SYNDROME to Brunner syndrome, MIM# 300615
Fetal anomalies v0.3817 MAOA Zornitza Stark Publications for gene: MAOA were set to
Fetal anomalies v0.3816 MAOA Zornitza Stark changed review comment from: Increased serotonin. ID, autonomic dysfunction, essential tremor, behavioural abnormalities.; to: Increased serotonin. ID, autonomic dysfunction, essential tremor, behavioural abnormalities. Typically presents post-natally.
Fetal anomalies v0.3816 MAOA Zornitza Stark edited their review of gene: MAOA: Changed rating: RED
Fetal anomalies v0.3816 MAN2B1 Zornitza Stark Marked gene: MAN2B1 as ready
Fetal anomalies v0.3816 MAN2B1 Zornitza Stark Gene: man2b1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3816 MAN2B1 Zornitza Stark Phenotypes for gene: MAN2B1 were changed from LYSOSOMAL ALPHA-MANNOSIDOSIS to Mannosidosis, alpha-, types I and II, MIM# 248500; MONDO:0009561
Fetal anomalies v0.3815 MAN2B1 Zornitza Stark edited their review of gene: MAN2B1: Changed rating: RED
Fetal anomalies v0.3815 TPO Zornitza Stark Marked gene: TPO as ready
Fetal anomalies v0.3815 TPO Zornitza Stark Gene: tpo has been classified as Green List (High Evidence).
Fetal anomalies v0.3815 TPO Zornitza Stark Classified gene: TPO as Green List (high evidence)
Fetal anomalies v0.3815 TPO Zornitza Stark Gene: tpo has been classified as Green List (High Evidence).
Fetal anomalies v0.3814 PRMT7 Zornitza Stark Marked gene: PRMT7 as ready
Fetal anomalies v0.3814 PRMT7 Zornitza Stark Gene: prmt7 has been classified as Green List (High Evidence).
Fetal anomalies v0.3814 PRMT7 Zornitza Stark Phenotypes for gene: PRMT7 were changed from Pseudohypoparathyroidism-like disorder to Short stature, brachydactyly, intellectual developmental disability, and seizures, OMIM #617157
Fetal anomalies v0.3813 PRMT7 Zornitza Stark Publications for gene: PRMT7 were set to
Fetal anomalies v0.3812 TBC1D24 Zornitza Stark Marked gene: TBC1D24 as ready
Fetal anomalies v0.3812 TBC1D24 Zornitza Stark Gene: tbc1d24 has been classified as Green List (High Evidence).
Fetal anomalies v0.3812 TBC1D24 Zornitza Stark Phenotypes for gene: TBC1D24 were changed from NON SYNDROMAL HEARING LOSS; DOORS SYNDROME; MYOCLONIC EPILEPSY, INFANTILE, FAMILIAL to DOORS syndrome MIM#220500
Fetal anomalies v0.3811 TBC1D24 Zornitza Stark Publications for gene: TBC1D24 were set to
Fetal anomalies v0.3810 PHOX2B Zornitza Stark Marked gene: PHOX2B as ready
Fetal anomalies v0.3810 PHOX2B Zornitza Stark Gene: phox2b has been classified as Green List (High Evidence).
Fetal anomalies v0.3810 PHOX2B Zornitza Stark Phenotypes for gene: PHOX2B were changed from CENTRAL HYPOVENTILATION SYNDROME, CONGENITAL, WITH OR WITHOUT HIRSCHSPRUNG DISEASE; NEUROBLASTOMA WITH HIRSCHSPRUNG DISEASE to Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, OMIM #209880
Fetal anomalies v0.3809 PHOX2B Zornitza Stark Publications for gene: PHOX2B were set to
Fetal anomalies v0.3808 PHOX2B Zornitza Stark Mode of inheritance for gene: PHOX2B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3807 PRG4 Zornitza Stark Marked gene: PRG4 as ready
Fetal anomalies v0.3807 PRG4 Zornitza Stark Gene: prg4 has been classified as Green List (High Evidence).
Fetal anomalies v0.3807 PRG4 Zornitza Stark Publications for gene: PRG4 were set to
Fetal anomalies v0.3806 PIEZO1 Zornitza Stark Marked gene: PIEZO1 as ready
Fetal anomalies v0.3806 PIEZO1 Zornitza Stark Gene: piezo1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3806 PIEZO1 Zornitza Stark Phenotypes for gene: PIEZO1 were changed from Congenital lymphatic dysplasia with hydrops and/or lymphoedema; hydrops fetalis gene 616843 to Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM #194380; Lymphatic malformation 6, OMIM #616843
Fetal anomalies v0.3805 PIEZO1 Zornitza Stark Publications for gene: PIEZO1 were set to 23695678; 30712880; 26333996; 28425981
Mendeliome v0.11056 TBC1D24 Zornitza Stark Marked gene: TBC1D24 as ready
Mendeliome v0.11056 TBC1D24 Zornitza Stark Gene: tbc1d24 has been classified as Green List (High Evidence).
Mendeliome v0.11056 TBC1D24 Zornitza Stark Phenotypes for gene: TBC1D24 were changed from to Deafness, autosomal dominant 65 MIM#616044; Deafness, autosomal recessive 86 MIM#614617; Developmental and epileptic encephalopathy 16 MIM#615338; DOORS syndrome MIM#220500; Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp MIM#608105; Myoclonic epilepsy, infantile, familial MIM#605021
Mendeliome v0.11055 TBC1D24 Zornitza Stark Publications for gene: TBC1D24 were set to
Mendeliome v0.11054 TBC1D24 Zornitza Stark Mode of inheritance for gene: TBC1D24 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3804 PLOD2 Zornitza Stark Marked gene: PLOD2 as ready
Fetal anomalies v0.3804 PLOD2 Zornitza Stark Gene: plod2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3804 PLOD2 Zornitza Stark Phenotypes for gene: PLOD2 were changed from BRUCK SYNDROME TYPE 2 to Bruck syndrome 2 , OMIM #609220
Fetal anomalies v0.3803 PLOD2 Zornitza Stark Publications for gene: PLOD2 were set to
Fetal anomalies v0.3802 PLOD1 Zornitza Stark Marked gene: PLOD1 as ready
Fetal anomalies v0.3802 PLOD1 Zornitza Stark Gene: plod1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3802 PLOD1 Zornitza Stark Phenotypes for gene: PLOD1 were changed from EHLERS-DANLOS SYNDROME, KYPHOSCOLIOTIC FORM to Ehlers-Danlos syndrome, kyphoscoliotic type, 1, OMIM #225400
Fetal anomalies v0.3801 PLOD1 Zornitza Stark Publications for gene: PLOD1 were set to
Fetal anomalies v0.3800 THRB Zornitza Stark Marked gene: THRB as ready
Fetal anomalies v0.3800 THRB Zornitza Stark Gene: thrb has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3800 THRB Zornitza Stark Classified gene: THRB as Amber List (moderate evidence)
Fetal anomalies v0.3800 THRB Zornitza Stark Gene: thrb has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3799 THRB Zornitza Stark reviewed gene: THRB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3799 PHF6 Zornitza Stark Marked gene: PHF6 as ready
Fetal anomalies v0.3799 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3799 PHF6 Zornitza Stark Phenotypes for gene: PHF6 were changed from BOERJESON-FORSSMAN-LEHMANN SYNDROME to Borjeson-Forssman-Lehmann syndrome, OMIM # 301900
Fetal anomalies v0.3798 PEPD Zornitza Stark Marked gene: PEPD as ready
Fetal anomalies v0.3798 PEPD Zornitza Stark Gene: pepd has been classified as Red List (Low Evidence).
Fetal anomalies v0.3798 PEPD Zornitza Stark Phenotypes for gene: PEPD were changed from PROLIDASE DEFICIENCY to Prolidase deficiency, OMIM #170100
Fetal anomalies v0.3797 TBC1D23 Zornitza Stark Marked gene: TBC1D23 as ready
Fetal anomalies v0.3797 TBC1D23 Zornitza Stark Gene: tbc1d23 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3797 TBC1D23 Zornitza Stark Phenotypes for gene: TBC1D23 were changed from Non-degenerative Pontocerebellar Hypoplasia to Pontocerebellar hypoplasia, type 11, MIM# 617695
Fetal anomalies v0.3796 TBC1D23 Zornitza Stark Publications for gene: TBC1D23 were set to
Fetal anomalies v0.3795 TBC1D23 Zornitza Stark Classified gene: TBC1D23 as Amber List (moderate evidence)
Fetal anomalies v0.3795 TBC1D23 Zornitza Stark Gene: tbc1d23 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3794 PITX2 Zornitza Stark Marked gene: PITX2 as ready
Fetal anomalies v0.3794 PITX2 Zornitza Stark Gene: pitx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3794 PITX2 Zornitza Stark Phenotypes for gene: PITX2 were changed from AXENFELD-RIEGER SYNDROME TYPE 1; PETERS ANOMALY; RING DERMOID OF CORNEA; IRIDOGONIODYSGENESIS TYPE 2 to Anterior segment dysgenesis 4, OMIM #137600; Axenfeld-Rieger syndrome, type 1, OMIM #180500
Fetal anomalies v0.3793 PITX2 Zornitza Stark Publications for gene: PITX2 were set to
Fetal anomalies v0.3792 PITX2 Zornitza Stark Mode of inheritance for gene: PITX2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3791 TAPT1 Zornitza Stark Marked gene: TAPT1 as ready
Fetal anomalies v0.3791 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3791 TAPT1 Zornitza Stark Phenotypes for gene: TAPT1 were changed from COMPLEX LETHAL OSTEOCHONDRODYSPLASIA to Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897)
Fetal anomalies v0.3790 TAPT1 Zornitza Stark Classified gene: TAPT1 as Amber List (moderate evidence)
Fetal anomalies v0.3790 TAPT1 Zornitza Stark Gene: tapt1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3789 TAPT1 Zornitza Stark reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.701 TFAM Zornitza Stark Publications for gene: TFAM were set to 27448789; 29021295; 9500544; 32399598; 34647195; 34647195
Fetal anomalies v0.3789 PKD2 Zornitza Stark Marked gene: PKD2 as ready
Fetal anomalies v0.3789 PKD2 Zornitza Stark Gene: pkd2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3789 PKD2 Zornitza Stark Phenotypes for gene: PKD2 were changed from Polycystic kidney disease 613095 to Polycystic kidney disease 2, OMIM #613095
Fetal anomalies v0.3788 PKD2 Zornitza Stark Publications for gene: PKD2 were set to
Fetal anomalies v0.3787 PKD2 Zornitza Stark Mode of inheritance for gene: PKD2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v0.3786 PKD1 Zornitza Stark Marked gene: PKD1 as ready
Fetal anomalies v0.3786 PKD1 Zornitza Stark Gene: pkd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3786 PKD1 Zornitza Stark Phenotypes for gene: PKD1 were changed from Autosomal dominant polycystic kidney disease (ADPKD); Polycystic kidney disease, 173900 to Polycystic kidney disease 1, OMIM #173900
Fetal anomalies v0.3785 PKD1 Zornitza Stark Publications for gene: PKD1 were set to 23624871; 20558538
Fetal anomalies v0.3784 TBL1X Zornitza Stark Marked gene: TBL1X as ready
Fetal anomalies v0.3784 TBL1X Zornitza Stark Gene: tbl1x has been classified as Red List (Low Evidence).
Fetal anomalies v0.3784 TBL1X Zornitza Stark Classified gene: TBL1X as Red List (low evidence)
Fetal anomalies v0.3784 TBL1X Zornitza Stark Gene: tbl1x has been classified as Red List (Low Evidence).
Fetal anomalies v0.3783 TBL1X Zornitza Stark reviewed gene: TBL1X: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3783 SMARCB1 Zornitza Stark Marked gene: SMARCB1 as ready
Fetal anomalies v0.3783 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3783 SMARCB1 Zornitza Stark Phenotypes for gene: SMARCB1 were changed from RHABDOID PREDISPOSITION SYNDROME 1; ?COFFIN-SIRIS SYNDROME to Coffin-Siris syndrome 3, OMIM #614608
Fetal anomalies v0.3782 SMARCB1 Zornitza Stark Publications for gene: SMARCB1 were set to
Fetal anomalies v0.3781 SMARCB1 Zornitza Stark Mode of inheritance for gene: SMARCB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3780 TALDO1 Zornitza Stark Marked gene: TALDO1 as ready
Fetal anomalies v0.3780 TALDO1 Zornitza Stark Gene: taldo1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3780 TALDO1 Zornitza Stark Publications for gene: TALDO1 were set to
Fetal anomalies v0.3779 PLK4 Zornitza Stark Marked gene: PLK4 as ready
Fetal anomalies v0.3779 PLK4 Zornitza Stark Gene: plk4 has been classified as Green List (High Evidence).
Fetal anomalies v0.3779 PLK4 Zornitza Stark Phenotypes for gene: PLK4 were changed from MICROCEPHALY, GROWTH FAILURE AND RETINOPATHY to Microcephaly and chorioretinopathy, autosomal recessive, 2, OMIM #616171
Fetal anomalies v0.3778 PLK4 Zornitza Stark Publications for gene: PLK4 were set to
Fetal anomalies v0.3777 SUCLG1 Zornitza Stark Marked gene: SUCLG1 as ready
Fetal anomalies v0.3777 SUCLG1 Zornitza Stark Gene: suclg1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3777 SUCLG1 Zornitza Stark Phenotypes for gene: SUCLG1 were changed from FATAL INFANTILE LACTIC ACIDOSIS to Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400
Fetal anomalies v0.3776 SUCLG1 Zornitza Stark Publications for gene: SUCLG1 were set to 21093335
Fetal anomalies v0.3775 SRY Zornitza Stark Marked gene: SRY as ready
Fetal anomalies v0.3775 SRY Zornitza Stark Gene: sry has been classified as Green List (High Evidence).
Fetal anomalies v0.3775 SRY Zornitza Stark Phenotypes for gene: SRY were changed from 46XY SEX REVERSAL 1 to 46XY sex reversal 1, OMIM #400044; 46XX sex reversal 1, OMIM #400045
Fetal anomalies v0.3774 SRY Zornitza Stark Publications for gene: SRY were set to
Fetal anomalies v0.3773 TG Zornitza Stark Marked gene: TG as ready
Fetal anomalies v0.3773 TG Zornitza Stark Gene: tg has been classified as Green List (High Evidence).
Fetal anomalies v0.3773 TG Zornitza Stark Classified gene: TG as Green List (high evidence)
Fetal anomalies v0.3773 TG Zornitza Stark Gene: tg has been classified as Green List (High Evidence).
Fetal anomalies v0.3772 SLC5A5 Zornitza Stark Marked gene: SLC5A5 as ready
Fetal anomalies v0.3772 SLC5A5 Zornitza Stark Gene: slc5a5 has been classified as Green List (High Evidence).
Fetal anomalies v0.3772 SLC5A5 Zornitza Stark Classified gene: SLC5A5 as Green List (high evidence)
Fetal anomalies v0.3772 SLC5A5 Zornitza Stark Gene: slc5a5 has been classified as Green List (High Evidence).
Fetal anomalies v0.3771 TRPS1 Zornitza Stark Marked gene: TRPS1 as ready
Fetal anomalies v0.3771 TRPS1 Zornitza Stark Gene: trps1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3771 TRPS1 Zornitza Stark Phenotypes for gene: TRPS1 were changed from TRICHO-RHINO-PHALANGEAL SYNDROME TYPE 1 to Trichorhinophalangeal syndrome, type I, OMIM #190350; Trichorhinophalangeal syndrome, type III, OMIM #190351
Fetal anomalies v0.3770 TRPS1 Zornitza Stark Publications for gene: TRPS1 were set to
Fetal anomalies v0.3769 TRPS1 Zornitza Stark Mode of inheritance for gene: TRPS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11053 SUCLG1 Zornitza Stark Marked gene: SUCLG1 as ready
Mendeliome v0.11053 SUCLG1 Zornitza Stark Gene: suclg1 has been classified as Green List (High Evidence).
Mendeliome v0.11053 SUCLG1 Zornitza Stark Phenotypes for gene: SUCLG1 were changed from to Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400
Mendeliome v0.11052 SUCLG1 Zornitza Stark Publications for gene: SUCLG1 were set to
Mendeliome v0.11051 SUCLG1 Zornitza Stark Mode of inheritance for gene: SUCLG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3768 TBCE Zornitza Stark Marked gene: TBCE as ready
Fetal anomalies v0.3768 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Fetal anomalies v0.3768 TBCE Zornitza Stark Phenotypes for gene: TBCE were changed from HYPOPARATHYROIDISM-RETARDATION-DYSMORPHISM SYNDROME; Early-Onset Progressive Encephalopathy with Distal Spinal Muscular Atrophy; KENNY-CAFFEY SYNDROME TYPE 1 to Hypoparathyroidism-retardation-dysmorphism syndrome, OMIM #241410; Kenny-Caffey syndrome, type 1, OMIM #244460; Encephalopathy, progressive, with amyotrophy and optic atrophy OMIM #617207
Fetal anomalies v0.3767 TBCE Zornitza Stark Publications for gene: TBCE were set to
Fetal anomalies v0.3766 SLC26A7 Zornitza Stark Marked gene: SLC26A7 as ready
Fetal anomalies v0.3766 SLC26A7 Zornitza Stark Gene: slc26a7 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3766 SLC26A7 Zornitza Stark Classified gene: SLC26A7 as Red List (low evidence)
Fetal anomalies v0.3766 SLC26A7 Zornitza Stark Gene: slc26a7 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3765 SLC26A7 Zornitza Stark reviewed gene: SLC26A7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.11050 RUNX2 Zornitza Stark Marked gene: RUNX2 as ready
Mendeliome v0.11050 RUNX2 Zornitza Stark Gene: runx2 has been classified as Green List (High Evidence).
Mendeliome v0.11050 RUNX2 Zornitza Stark Phenotypes for gene: RUNX2 were changed from to Cleidocranial dysplasia MIM#119600; Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600; Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600; Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510
Mendeliome v0.11049 RUNX2 Zornitza Stark Publications for gene: RUNX2 were set to
Mendeliome v0.11048 RUNX2 Zornitza Stark Mode of inheritance for gene: RUNX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3765 PEX7 Zornitza Stark Marked gene: PEX7 as ready
Fetal anomalies v0.3765 PEX7 Zornitza Stark Gene: pex7 has been classified as Green List (High Evidence).
Fetal anomalies v0.3765 PEX7 Zornitza Stark Phenotypes for gene: PEX7 were changed from RHIZOMELIC CHONDRODYSPLASIA PUNCTATA TYPE 1; REFSUM DISEASE; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 11 to Peroxisome biogenesis disorder 9B, OMIM# 614879; Rhizomelic chondrodysplasia punctata, type 1, OMIM# 215100
Fetal anomalies v0.3764 PEX7 Zornitza Stark Publications for gene: PEX7 were set to
Fetal anomalies v0.3763 RUNX2 Zornitza Stark Marked gene: RUNX2 as ready
Fetal anomalies v0.3763 RUNX2 Zornitza Stark Gene: runx2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3763 RUNX2 Zornitza Stark Phenotypes for gene: RUNX2 were changed from CLEIDOCRANIAL DYSPLASIA to Cleidocranial dysplasia MIM#119600; Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600
Fetal anomalies v0.3762 RUNX2 Zornitza Stark Publications for gene: RUNX2 were set to
Fetal anomalies v0.3761 RUNX2 Zornitza Stark Mode of inheritance for gene: RUNX2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3760 SLC26A4 Zornitza Stark Marked gene: SLC26A4 as ready
Fetal anomalies v0.3760 SLC26A4 Zornitza Stark Gene: slc26a4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3760 SLC26A4 Zornitza Stark Classified gene: SLC26A4 as Red List (low evidence)
Fetal anomalies v0.3760 SLC26A4 Zornitza Stark Gene: slc26a4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3759 SLC26A4 Zornitza Stark reviewed gene: SLC26A4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3759 RTEL1 Zornitza Stark Marked gene: RTEL1 as ready
Fetal anomalies v0.3759 RTEL1 Zornitza Stark Gene: rtel1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3759 RTEL1 Zornitza Stark Phenotypes for gene: RTEL1 were changed from DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 5; DYSKERATOSIS CONGENITA, AUTOSOMAL DOMINANT 4 to Dyskeratosis congenita, autosomal recessive 5 MIM#615190; Hoyeraal-Hreidarsson syndrome
Fetal anomalies v0.3758 RTEL1 Zornitza Stark Publications for gene: RTEL1 were set to
Fetal anomalies v0.3757 PROP1 Zornitza Stark Marked gene: PROP1 as ready
Fetal anomalies v0.3757 PROP1 Zornitza Stark Gene: prop1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3757 PROP1 Zornitza Stark Classified gene: PROP1 as Amber List (moderate evidence)
Fetal anomalies v0.3757 PROP1 Zornitza Stark Gene: prop1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3756 TPO Krithika Murali gene: TPO was added
gene: TPO was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TPO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPO were set to 34220711; 30662777
Phenotypes for gene: TPO were set to Thyroid dyshormonogenesis 2A - MIM#274500
Review for gene: TPO was set to GREEN
Added comment: Well-established association with thyroid dyshormonogenesis. 3 affected individuals from 2 unrelated families reported with fetal goitre.

34220711 Rodrigues et al 2021 - report 2 siblings who were diagnosed with fetal goitre on antenatal ultrasound at 26 and 32 weeks gestation. Pathogenic compound het TPO variants identified inherited from unaffected carrier parents.

30662777 - report a proband diagnosed with fetal goitre at 29 weeks gestation. Compound heterozygous TPO variants identified.
Sources: Literature
Mendeliome v0.11047 RRM2B Zornitza Stark Marked gene: RRM2B as ready
Mendeliome v0.11047 RRM2B Zornitza Stark Gene: rrm2b has been classified as Green List (High Evidence).
Mendeliome v0.11047 RRM2B Zornitza Stark Phenotypes for gene: RRM2B were changed from to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) MIM#612075; Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075
Mendeliome v0.11046 RRM2B Zornitza Stark Publications for gene: RRM2B were set to
Mendeliome v0.11045 RRM2B Zornitza Stark Mode of inheritance for gene: RRM2B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3756 RRM2B Zornitza Stark Marked gene: RRM2B as ready
Fetal anomalies v0.3756 RRM2B Zornitza Stark Gene: rrm2b has been classified as Red List (Low Evidence).
Fetal anomalies v0.3756 RRM2B Zornitza Stark Phenotypes for gene: RRM2B were changed from Mitochondrial depletion syndrome to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) MIM#612075; Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075
Fetal anomalies v0.3755 RRM2B Zornitza Stark Publications for gene: RRM2B were set to
Fetal anomalies v0.3754 RRM2B Zornitza Stark Classified gene: RRM2B as Red List (low evidence)
Fetal anomalies v0.3754 RRM2B Zornitza Stark Gene: rrm2b has been classified as Red List (Low Evidence).
Fetal anomalies v0.3753 RPS6KA3 Zornitza Stark Marked gene: RPS6KA3 as ready
Fetal anomalies v0.3753 RPS6KA3 Zornitza Stark Gene: rps6ka3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3753 RPS6KA3 Zornitza Stark Phenotypes for gene: RPS6KA3 were changed from COFFIN-LOWRY SYNDROME to Coffin-Lowry syndrome MIM#303600; Intellectual developmental disorder, X-linked 19 MIM#300844
Fetal anomalies v0.3752 RPS6KA3 Zornitza Stark Publications for gene: RPS6KA3 were set to
Fetal anomalies v0.3751 ROR2 Zornitza Stark Marked gene: ROR2 as ready
Fetal anomalies v0.3751 ROR2 Zornitza Stark Gene: ror2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3751 ROR2 Zornitza Stark Phenotypes for gene: ROR2 were changed from BRACHYDACTYLY, TYPE B1; ROBINOW SYNDROME, AUTOSOMAL DOMINANT; ROR2-RELATED DISORDERS AR to Brachydactyly, type B1 MIM#113000; Robinow syndrome, autosomal recessive MIM#268310
Fetal anomalies v0.3750 ROR2 Zornitza Stark Publications for gene: ROR2 were set to
Fetal anomalies v0.3749 ROR2 Zornitza Stark Mode of inheritance for gene: ROR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v0.3748 RNASET2 Zornitza Stark Marked gene: RNASET2 as ready
Fetal anomalies v0.3748 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3748 RNASET2 Zornitza Stark Phenotypes for gene: RNASET2 were changed from LEUKOENCEPHALOPATHY, CYSTIC, WITHOUT MEGALENCEPHALY to Leukoencephalopathy, cystic, without megalencephaly MIM#612951
Fetal anomalies v0.3747 RNASET2 Zornitza Stark Publications for gene: RNASET2 were set to
Fetal anomalies v0.3746 RNASET2 Zornitza Stark Classified gene: RNASET2 as Amber List (moderate evidence)
Fetal anomalies v0.3746 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11044 RNASET2 Zornitza Stark Marked gene: RNASET2 as ready
Mendeliome v0.11044 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Green List (High Evidence).
Mendeliome v0.11044 RNASET2 Zornitza Stark Phenotypes for gene: RNASET2 were changed from to Leukoencephalopathy, cystic, without megalencephaly MIM#612951
Mendeliome v0.11043 RNASET2 Zornitza Stark Publications for gene: RNASET2 were set to
Mendeliome v0.11042 RNASET2 Zornitza Stark Mode of inheritance for gene: RNASET2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11041 C17orf53 Zornitza Stark Marked gene: C17orf53 as ready
Mendeliome v0.11041 C17orf53 Zornitza Stark Gene: c17orf53 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11041 C17orf53 Zornitza Stark Classified gene: C17orf53 as Amber List (moderate evidence)
Mendeliome v0.11041 C17orf53 Zornitza Stark Gene: c17orf53 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11040 C17orf53 Zornitza Stark gene: C17orf53 was added
gene: C17orf53 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: C17orf53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf53 were set to 34707299; 31467087
Phenotypes for gene: C17orf53 were set to Primary ovarian insufficiency
Review for gene: C17orf53 was set to AMBER
Added comment: PMID: 34707299. Homozygous LOF variant in individual with primary ovarian insufficiency PMID: 31467087. Mice with targeted mutations in Hrob are infertile due to depletion of germ cells.
Sources: Expert Review
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.287 C17orf53 Zornitza Stark Marked gene: C17orf53 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.287 C17orf53 Zornitza Stark Gene: c17orf53 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.287 C17orf53 Zornitza Stark Classified gene: C17orf53 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.287 C17orf53 Zornitza Stark Gene: c17orf53 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3745 RNASEH2C Zornitza Stark Marked gene: RNASEH2C as ready
Fetal anomalies v0.3745 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Fetal anomalies v0.3745 RNASEH2C Zornitza Stark Phenotypes for gene: RNASEH2C were changed from AICARDI-GOUTIERES SYNDROME 3 to Aicardi-Goutieres syndrome 3 (MIM# 610329), AR
Fetal anomalies v0.3744 RNASEH2C Zornitza Stark Publications for gene: RNASEH2C were set to
Mitochondrial disease v0.700 TFAM Zornitza Stark Publications for gene: TFAM were set to 27448789; 29021295; 9500544
Mitochondrial disease v0.699 TFAM Zornitza Stark Classified gene: TFAM as Green List (high evidence)
Mitochondrial disease v0.699 TFAM Zornitza Stark Gene: tfam has been classified as Green List (High Evidence).
Mendeliome v0.11039 TFAM Zornitza Stark Phenotypes for gene: TFAM were changed from Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156 to Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156; Perrault syndrome
Mitochondrial disease v0.699 TFAM Zornitza Stark Classified gene: TFAM as Green List (high evidence)
Mitochondrial disease v0.699 TFAM Zornitza Stark Gene: tfam has been classified as Green List (High Evidence).
Mendeliome v0.11038 TFAM Zornitza Stark Publications for gene: TFAM were set to 27448789; 29021295; 9500544
Mendeliome v0.11037 TFAM Zornitza Stark Classified gene: TFAM as Green List (high evidence)
Mendeliome v0.11037 TFAM Zornitza Stark Gene: tfam has been classified as Green List (High Evidence).
Mendeliome v0.11036 TFAM Zornitza Stark edited their review of gene: TFAM: Added comment: PMID: 32399598. Homozygous missense variant predicted pathogenic in patient presenting with Perrault syndrome and intellectual disability

PMID: 34647195. Same homozygous missense variant in two sisters with premature ovarian insufficiency +/- seizures and their brother with seizures + intellectual disability. Patient fibroblasts have mtDNA depletion

PMID: 34647195. Zebrafish model with in-frame deletion has ovarian dysgenesis and mtDNA depletion; Changed rating: GREEN; Changed publications: 27448789, 29021295, 9500544, 32399598, 34647195, 34647195; Changed phenotypes: Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156, Perrault syndrome
Mitochondrial disease v0.698 TFAM Zornitza Stark reviewed gene: TFAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 32399598, 34647195, 34647195; Phenotypes: Perrault syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.286 TFAM Zornitza Stark Marked gene: TFAM as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.286 TFAM Zornitza Stark Gene: tfam has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.286 TFAM Zornitza Stark Phenotypes for gene: TFAM were changed from to Perrault syndrome; primary ovarian insufficiency +/- seizures/intellectual disability/hearing loss
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.285 TFAM Zornitza Stark Publications for gene: TFAM were set to PMID: 34647195
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.284 TFAM Zornitza Stark Classified gene: TFAM as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.284 TFAM Zornitza Stark Gene: tfam has been classified as Green List (High Evidence).
Fetal anomalies v0.3743 NKX2-1 Zornitza Stark Marked gene: NKX2-1 as ready
Fetal anomalies v0.3743 NKX2-1 Zornitza Stark Gene: nkx2-1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3743 NKX2-1 Zornitza Stark Classified gene: NKX2-1 as Amber List (moderate evidence)
Fetal anomalies v0.3743 NKX2-1 Zornitza Stark Gene: nkx2-1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3742 NKX2-1 Zornitza Stark edited their review of gene: NKX2-1: Changed rating: AMBER
Fetal anomalies v0.3742 NKX2-1 Zornitza Stark reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3742 IYD Zornitza Stark Marked gene: IYD as ready
Fetal anomalies v0.3742 IYD Zornitza Stark Gene: iyd has been classified as Red List (Low Evidence).
Fetal anomalies v0.3742 IYD Zornitza Stark Classified gene: IYD as Red List (low evidence)
Fetal anomalies v0.3742 IYD Zornitza Stark Gene: iyd has been classified as Red List (Low Evidence).
Fetal anomalies v0.3741 IYD Zornitza Stark reviewed gene: IYD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3741 IRS4 Zornitza Stark Marked gene: IRS4 as ready
Fetal anomalies v0.3741 IRS4 Zornitza Stark Gene: irs4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3741 IRS4 Zornitza Stark Classified gene: IRS4 as Red List (low evidence)
Fetal anomalies v0.3741 IRS4 Zornitza Stark Gene: irs4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3740 IRS4 Zornitza Stark edited their review of gene: IRS4: Changed rating: RED
Fetal anomalies v0.3740 IRS4 Zornitza Stark reviewed gene: IRS4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3740 DUOXA2 Zornitza Stark Marked gene: DUOXA2 as ready
Fetal anomalies v0.3740 DUOXA2 Zornitza Stark Gene: duoxa2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3740 DUOXA2 Zornitza Stark Classified gene: DUOXA2 as Red List (low evidence)
Fetal anomalies v0.3740 DUOXA2 Zornitza Stark Gene: duoxa2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3739 DUOXA2 Zornitza Stark reviewed gene: DUOXA2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3739 DUOXA1 Zornitza Stark Marked gene: DUOXA1 as ready
Fetal anomalies v0.3739 DUOXA1 Zornitza Stark Gene: duoxa1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3739 DUOXA1 Zornitza Stark Classified gene: DUOXA1 as Red List (low evidence)
Fetal anomalies v0.3739 DUOXA1 Zornitza Stark Gene: duoxa1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3738 DUOXA1 Zornitza Stark reviewed gene: DUOXA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3738 DUOX2 Zornitza Stark Marked gene: DUOX2 as ready
Fetal anomalies v0.3738 DUOX2 Zornitza Stark Gene: duox2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3738 DUOX2 Zornitza Stark Classified gene: DUOX2 as Red List (low evidence)
Fetal anomalies v0.3738 DUOX2 Zornitza Stark Gene: duox2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3737 DUOX2 Zornitza Stark reviewed gene: DUOX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3737 DUOX1 Zornitza Stark Marked gene: DUOX1 as ready
Fetal anomalies v0.3737 DUOX1 Zornitza Stark Gene: duox1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3737 DUOX1 Zornitza Stark Classified gene: DUOX1 as Red List (low evidence)
Fetal anomalies v0.3737 DUOX1 Zornitza Stark Gene: duox1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3736 DUOX1 Zornitza Stark reviewed gene: DUOX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3736 RNASEH2B Zornitza Stark Marked gene: RNASEH2B as ready
Fetal anomalies v0.3736 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Fetal anomalies v0.3736 RNASEH2B Zornitza Stark Phenotypes for gene: RNASEH2B were changed from AICARDI-GOUTIERES SYNDROME 2 to Aicardi-Goutieres syndrome 2, MIM# 610181
Fetal anomalies v0.3735 RNASEH2B Zornitza Stark Publications for gene: RNASEH2B were set to
Fetal anomalies v0.3734 RNASEH2A Zornitza Stark Marked gene: RNASEH2A as ready
Fetal anomalies v0.3734 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Fetal anomalies v0.3734 RNASEH2A Zornitza Stark Phenotypes for gene: RNASEH2A were changed from AICARDI-GOUTIERES SYNDROME 4 to Aicardi-Goutieres syndrome 4 MIM#610333
Fetal anomalies v0.3733 RNASEH2A Zornitza Stark Publications for gene: RNASEH2A were set to
Fetal anomalies v0.3732 CDCA8 Zornitza Stark Marked gene: CDCA8 as ready
Fetal anomalies v0.3732 CDCA8 Zornitza Stark Gene: cdca8 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3732 CDCA8 Zornitza Stark Classified gene: CDCA8 as Red List (low evidence)
Fetal anomalies v0.3732 CDCA8 Zornitza Stark Gene: cdca8 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3731 CDCA8 Zornitza Stark reviewed gene: CDCA8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital hypothyroidism, thyroid dysgenesis, no OMIM #; Mode of inheritance: None
Fetal anomalies v0.3731 NPRL3 Zornitza Stark Marked gene: NPRL3 as ready
Fetal anomalies v0.3731 NPRL3 Zornitza Stark Gene: nprl3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3731 NPRL3 Zornitza Stark Classified gene: NPRL3 as Green List (high evidence)
Fetal anomalies v0.3731 NPRL3 Zornitza Stark Gene: nprl3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3730 NPRL2 Zornitza Stark Marked gene: NPRL2 as ready
Fetal anomalies v0.3730 NPRL2 Zornitza Stark Gene: nprl2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3730 NPRL2 Zornitza Stark Classified gene: NPRL2 as Green List (high evidence)
Fetal anomalies v0.3730 NPRL2 Zornitza Stark Gene: nprl2 has been classified as Green List (High Evidence).
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.46 NPRL2 Zornitza Stark Phenotypes for gene: NPRL2 were changed from Focal epilepsy; Focal cortical dysplasia to Epilepsy, familial focal, with variable foci 2- MIM#617116
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.45 NPRL2 Zornitza Stark Publications for gene: NPRL2 were set to 29281825; 27173016; 31625153
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.44 NPRL2 Zornitza Stark Classified gene: NPRL2 as Green List (high evidence)
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.44 NPRL2 Zornitza Stark Gene: nprl2 has been classified as Green List (High Evidence).
Mendeliome v0.11036 SPATA16 Zornitza Stark Marked gene: SPATA16 as ready
Mendeliome v0.11036 SPATA16 Zornitza Stark Gene: spata16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11036 SPATA16 Zornitza Stark Phenotypes for gene: SPATA16 were changed from to Spermatogenic failure 6 MIM#102530; Spermatogenic failure 6 MONDO:0007060
Mendeliome v0.11035 SPATA16 Zornitza Stark Publications for gene: SPATA16 were set to
Mendeliome v0.11034 SPATA16 Zornitza Stark Mode of inheritance for gene: SPATA16 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11033 SPATA16 Zornitza Stark Classified gene: SPATA16 as Amber List (moderate evidence)
Mendeliome v0.11033 SPATA16 Zornitza Stark Gene: spata16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11032 TNFRSF10B Zornitza Stark Marked gene: TNFRSF10B as ready
Mendeliome v0.11032 TNFRSF10B Zornitza Stark Gene: tnfrsf10b has been classified as Red List (Low Evidence).
Mendeliome v0.11032 TNFRSF10B Zornitza Stark Phenotypes for gene: TNFRSF10B were changed from to Squamous cell carcinoma, head and neck MIM#275355
Mendeliome v0.11031 TNFRSF10B Zornitza Stark Publications for gene: TNFRSF10B were set to
Mendeliome v0.11030 TNFRSF10B Zornitza Stark Mode of inheritance for gene: TNFRSF10B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11029 TNFRSF10B Zornitza Stark Classified gene: TNFRSF10B as Red List (low evidence)
Mendeliome v0.11029 TNFRSF10B Zornitza Stark Gene: tnfrsf10b has been classified as Red List (Low Evidence).
Mendeliome v0.11028 MAPK8IP1 Zornitza Stark Marked gene: MAPK8IP1 as ready
Mendeliome v0.11028 MAPK8IP1 Zornitza Stark Gene: mapk8ip1 has been classified as Red List (Low Evidence).
Mendeliome v0.11028 MAPK8IP1 Zornitza Stark Phenotypes for gene: MAPK8IP1 were changed from to Susceptibility to diabetes mellitus, noninsulin-dependent MIM#125853
Mendeliome v0.11027 MAPK8IP1 Zornitza Stark Publications for gene: MAPK8IP1 were set to
Mendeliome v0.11026 MAPK8IP1 Zornitza Stark Mode of inheritance for gene: MAPK8IP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11025 MAPK8IP1 Zornitza Stark Classified gene: MAPK8IP1 as Red List (low evidence)
Mendeliome v0.11025 MAPK8IP1 Zornitza Stark Gene: mapk8ip1 has been classified as Red List (Low Evidence).
Mendeliome v0.11024 SMIM1 Zornitza Stark Marked gene: SMIM1 as ready
Mendeliome v0.11024 SMIM1 Zornitza Stark Gene: smim1 has been classified as Red List (Low Evidence).
Mendeliome v0.11024 SMIM1 Zornitza Stark Phenotypes for gene: SMIM1 were changed from to Blood group, Vel system MIM#615264
Mendeliome v0.11023 SMIM1 Zornitza Stark Classified gene: SMIM1 as Red List (low evidence)
Mendeliome v0.11023 SMIM1 Zornitza Stark Gene: smim1 has been classified as Red List (Low Evidence).
Mendeliome v0.11022 ACKR1 Zornitza Stark Marked gene: ACKR1 as ready
Mendeliome v0.11022 ACKR1 Zornitza Stark Gene: ackr1 has been classified as Red List (Low Evidence).
Mendeliome v0.11022 ACKR1 Zornitza Stark Phenotypes for gene: ACKR1 were changed from to Blood group, Duffy system MIM#110700
Mendeliome v0.11021 ACKR1 Zornitza Stark Classified gene: ACKR1 as Red List (low evidence)
Mendeliome v0.11021 ACKR1 Zornitza Stark Gene: ackr1 has been classified as Red List (Low Evidence).
Mendeliome v0.11020 OGG1 Zornitza Stark Marked gene: OGG1 as ready
Mendeliome v0.11020 OGG1 Zornitza Stark Gene: ogg1 has been classified as Red List (Low Evidence).
Mendeliome v0.11020 OGG1 Zornitza Stark Phenotypes for gene: OGG1 were changed from to Renal cell carcinoma, clear cell, somatic MIM#144700
Mendeliome v0.11019 OGG1 Zornitza Stark Publications for gene: OGG1 were set to
Mendeliome v0.11018 OGG1 Zornitza Stark Mode of inheritance for gene: OGG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11017 OGG1 Zornitza Stark Classified gene: OGG1 as Red List (low evidence)
Mendeliome v0.11017 OGG1 Zornitza Stark Gene: ogg1 has been classified as Red List (Low Evidence).
Mendeliome v0.11016 B3GALNT1 Zornitza Stark Marked gene: B3GALNT1 as ready
Mendeliome v0.11016 B3GALNT1 Zornitza Stark Gene: b3galnt1 has been classified as Red List (Low Evidence).
Mendeliome v0.11016 B3GALNT1 Zornitza Stark Phenotypes for gene: B3GALNT1 were changed from to Blood group, globoside system MIM#615021
Mendeliome v0.11015 B3GALNT1 Zornitza Stark Classified gene: B3GALNT1 as Red List (low evidence)
Mendeliome v0.11015 B3GALNT1 Zornitza Stark Gene: b3galnt1 has been classified as Red List (Low Evidence).
Mendeliome v0.11014 SERPINA7 Zornitza Stark Marked gene: SERPINA7 as ready
Mendeliome v0.11014 SERPINA7 Zornitza Stark Gene: serpina7 has been classified as Green List (High Evidence).
Mendeliome v0.11014 SERPINA7 Zornitza Stark Phenotypes for gene: SERPINA7 were changed from to Thyroxine-binding globulin QTL MIM#300932; Thyroxine-binding globulin deficiency
Mendeliome v0.11013 SERPINA7 Zornitza Stark Publications for gene: SERPINA7 were set to
Mendeliome v0.11012 SERPINA7 Zornitza Stark Mode of inheritance for gene: SERPINA7 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v0.3729 PRMT7 Chirag Patel reviewed gene: PRMT7: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 26437029, 27718516, 30513135; Phenotypes: Short stature, brachydactyly, intellectual developmental disability, and seizures, OMIM #617157; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3729 TBC1D24 Ain Roesley edited their review of gene: TBC1D24: Changed publications: 25719194
Fetal anomalies v0.3729 TBC1D24 Ain Roesley edited their review of gene: TBC1D24: Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3729 TBC1D24 Ain Roesley reviewed gene: TBC1D24: Rating: ; Mode of pathogenicity: None; Publications: Polyhydramnios is often noted when a fetus has DOORS syndrome [James et al 2007]. A subsequent affected pregnancy in one family with DOORS syndrome was terminated due to an elevated nuchal translucency of 5.1 mm at 12 weeks' estimated gestational age; Phenotypes: Developmental and epileptic encephalopathy 16 MIM#615338, DOORS syndrome MIM#220500, Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp MIM#608105, Myoclonic epilepsy, infantile, familial MIM#605021; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v0.3729 PKD2 Chirag Patel Classified gene: PKD2 as Green List (high evidence)
Fetal anomalies v0.3729 PKD2 Chirag Patel Gene: pkd2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3728 PKD2 Chirag Patel reviewed gene: PKD2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26139440; Phenotypes: Polycystic kidney disease 2, OMIM #613095; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3728 PKD2 Chirag Patel Deleted their review
Fetal anomalies v0.3728 PKD1 Chirag Patel changed review comment from: Rare cases of ADPKD diagnosed antenatally, usually with biallelic variants. Suitable for fetal anomalies panel.; to: Rare cases of ADPKD diagnosed antenatally, usually with biallelic variants. Suitable for fetal anomalies panel.
Fetal anomalies v0.3728 PKD1 Chirag Patel Deleted their comment
Fetal anomalies v0.3728 PKD1 Chirag Patel edited their review of gene: PKD1: Added comment: Rare cases of ADPKD diagnosed antenatally, usually with biallelic variants. Suitable for fetal anomalies panel.; Changed rating: GREEN; Changed publications: PMID: 30631912, 26139440; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3728 PKD1 Chirag Patel Classified gene: PKD1 as Green List (high evidence)
Fetal anomalies v0.3728 PKD1 Chirag Patel Gene: pkd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3727 PKD1 Chirag Patel Phenotypes for gene: PKD1 were changed from Autosomal recessive polycystic kidney disease (ARPKD); Autosomal dominant polycystic kidney disease (ADPKD); Polycystic kidney disease, 173900 to Autosomal dominant polycystic kidney disease (ADPKD); Polycystic kidney disease, 173900
Fetal anomalies v0.3726 PHOX2B Chirag Patel reviewed gene: PHOX2B: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 14608649, 15657873, 15121777, 26063465; Phenotypes: Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, OMIM #209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3726 PRG4 Chirag Patel reviewed gene: PRG4: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 10545950, 29397575; Phenotypes: Camptodactyly-arthropathy-coxa vara-pericarditis syndrome, OMIM #208250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3726 PIEZO1 Chirag Patel reviewed gene: PIEZO1: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 26333996, 23479567, 23695678; Phenotypes: Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM #194380, Lymphatic malformation 6, OMIM #616843; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11011 TBC1D24 Ain Roesley reviewed gene: TBC1D24: Rating: GREEN; Mode of pathogenicity: None; Publications: 25719194; Phenotypes: Deafness, autosomal dominant 65 MIM#616044, Deafness, autosomal recessive 86 MIM#614617, Developmental and epileptic encephalopathy 16 MIM#615338, DOORS syndrome MIM#220500, Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp MIM#608105, Myoclonic epilepsy, infantile, familial MIM#605021; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3726 PLOD2 Chirag Patel reviewed gene: PLOD2: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 22689593, 12881513, 33664768, 33778323, 29178448; Phenotypes: Bruck syndrome 2 , OMIM #609220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3726 PLOD1 Chirag Patel reviewed gene: PLOD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 15666309, 20301635, 28757364; Phenotypes: Ehlers-Danlos syndrome, kyphoscoliotic type, 1, OMIM #225400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3726 THRB Krithika Murali gene: THRB was added
gene: THRB was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: THRB was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: THRB were set to 35130567; 30430796; 30074255; 28938413; 4163616
Phenotypes for gene: THRB were set to Thyroid hormone resistance, autosomal recessive - MIM#274300; Thyroid hormone resistance - MIM#188570; Thyroid hormone resistance, selective pituitary - MIM#145650
Review for gene: THRB was set to GREEN
Added comment: Biallelic variants associated with thyroid hormone resistance. PMID 4163616 first reported this condition in a consanguineous Mexican family with congenital deafness, goitre and stippled epiphyses. Diagnosis was made incidentally at a later age but possibility of goitre being detected antenatally. SGA also reported but this is generally in the context of having a mother also affected by thyroid hormone resistance secondary to biallelic or monoallelic variants.
Sources: Literature
Fetal anomalies v0.3726 PHF6 Chirag Patel Classified gene: PHF6 as Red List (low evidence)
Fetal anomalies v0.3726 PHF6 Chirag Patel Gene: phf6 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3725 PHF6 Chirag Patel reviewed gene: PHF6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Borjeson-Forssman-Lehmann syndrome, OMIM # 301900; 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 v0.3725 PEPD Chirag Patel Classified gene: PEPD as Red List (low evidence)
Fetal anomalies v0.3725 PEPD Chirag Patel Gene: pepd has been classified as Red List (Low Evidence).
Fetal anomalies v0.3725 PEPD Chirag Patel Classified gene: PEPD as Red List (low evidence)
Fetal anomalies v0.3725 PEPD Chirag Patel Gene: pepd has been classified as Red List (Low Evidence).
Fetal anomalies v0.3724 PEPD Chirag Patel reviewed gene: PEPD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Prolidase deficiency, OMIM #170100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3724 TBC1D23 Ain Roesley reviewed gene: TBC1D23: Rating: AMBER; Mode of pathogenicity: None; Publications: 28823707, 28823706; Phenotypes: Pontocerebellar hypoplasia, type 11, MIM# 617695; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3724 PITX2 Chirag Patel reviewed gene: PITX2: Rating: GREEN; Mode of pathogenicity: None; Publications: [PubMed: 12015277; Phenotypes: Anterior segment dysgenesis 4, OMIM #137600, Axenfeld-Rieger syndrome, type 1, OMIM #180500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3724 TAPT1 Ain Roesley reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3724 PKD2 Chirag Patel Classified gene: PKD2 as Red List (low evidence)
Fetal anomalies v0.3724 PKD2 Chirag Patel Gene: pkd2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3723 PKD2 Chirag Patel reviewed gene: PKD2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 2, OMIM #613095; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3723 PKD1 Chirag Patel Classified gene: PKD1 as Red List (low evidence)
Fetal anomalies v0.3723 PKD1 Chirag Patel Gene: pkd1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3722 PKD1 Chirag Patel reviewed gene: PKD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 1, OMIM #173900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3722 TBL1X Krithika Murali gene: TBL1X was added
gene: TBL1X was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TBL1X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: TBL1X were set to 30591955; 27603907
Phenotypes for gene: TBL1X were set to Hypothyroidism, congenital, nongoitrous, 8 - MIM#301033
Review for gene: TBL1X was set to AMBER
Added comment: Associated with central congenital hypothyroidism. Antenatal phenotype not reported. Thyroid hypoplasia has been noted in affected individuals. Generally diagnosed after newborn screening or later in childhood.
Sources: Literature
Fetal anomalies v0.3722 SMARCB1 Chirag Patel reviewed gene: SMARCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 22426308, 22726846, 23929686; Phenotypes: Coffin-Siris syndrome 3, OMIM #614608; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3722 SUCLG1 Ain Roesley reviewed gene: SUCLG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33230783, 28358460; Phenotypes: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3722 TALDO1 Chirag Patel reviewed gene: TALDO1: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 25388407, 23315216, 29923087, 26238251, 11283793; Phenotypes: Transaldolase deficiency, OMIM #606003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3722 PLK4 Chirag Patel reviewed gene: PLK4: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 25344692, 25320347, 33756487, 27650967; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 2, OMIM #616171; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3722 SUCLG1 Chirag Patel reviewed gene: SUCLG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 17668387, 19526370, 20693550, 30470562; Phenotypes: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) , OMIM #245400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3722 SRY Chirag Patel reviewed gene: SRY: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 1570829, 1734522, 9143916, 12764225; Phenotypes: 46XY sex reversal 1, OMIM #400044, 46XX sex reversal 1, OMIM #400045; Mode of inheritance: Other
Fetal anomalies v0.3722 TG Krithika Murali gene: TG was added
gene: TG was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TG were set to 33832185; 19169491; 28620499; 18631008; 12915634
Phenotypes for gene: TG were set to Thyroid dyshormonogenesis 3 - MIM#274700
Review for gene: TG was set to GREEN
Added comment: Well-established gene-disease association with congenital hypothyroidism and fetal goitre.
Sources: Literature
Fetal anomalies v0.3722 SLC5A5 Krithika Murali gene: SLC5A5 was added
gene: SLC5A5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SLC5A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A5 were set to 34806438; 34726525; 33815280; 32805706; 31115276
Phenotypes for gene: SLC5A5 were set to Thyroid dyshormonogenesis 1 - MIM#274400
Review for gene: SLC5A5 was set to GREEN
Added comment: Biallelic variants associated with congenital hypothyroidism. PMID 32805706 Stoupa et al 2020 report an affected male with antenatal goitre diagnosed at 25 weeks gestation and treated with intraamniotic levothyroxine injections.
Sources: Literature
Fetal anomalies v0.3722 TRPS1 Chirag Patel Classified gene: TRPS1 as Red List (low evidence)
Fetal anomalies v0.3722 TRPS1 Chirag Patel Gene: trps1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3721 TRPS1 Chirag Patel reviewed gene: TRPS1: Rating: RED; Mode of pathogenicity: None; Publications: PubMed: 10615131, 11950061, 11112658; Phenotypes: Trichorhinophalangeal syndrome, type I, OMIM #190350, Trichorhinophalangeal syndrome, type III, OMIM #190351; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11011 SUCLG1 Ain Roesley reviewed gene: SUCLG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33230783, 28358460; Phenotypes: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3721 TBCE Chirag Patel reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12389028, 27666369; Phenotypes: Hypoparathyroidism-retardation-dysmorphism syndrome, OMIM #241410, Kenny-Caffey syndrome, type 1, OMIM #244460, Encephalopathy, progressive, with amyotrophy and optic atrophy OMIM #617207; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3721 SLC26A7 Krithika Murali gene: SLC26A7 was added
gene: SLC26A7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SLC26A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC26A7 were set to 34780050; 32486989; 31372509; 30333321; 29546359
Phenotypes for gene: SLC26A7 were set to Thyroid dyshormogenesis - no OMIM gene disease association
Review for gene: SLC26A7 was set to GREEN
Added comment: Biallelic variants associated with congenital hypothyroidism secondary to thyroid dyshormogenesis. PMID 32486989 report an affected female diagnosed with goitre D4 of life.
Sources: Literature
Mendeliome v0.11011 RUNX2 Ain Roesley reviewed gene: RUNX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301686; Phenotypes: Cleidocranial dysplasia MIM#119600, Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600, Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600, Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3721 PEX7 Chirag Patel reviewed gene: PEX7: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 11781871, 12325024,,; Phenotypes: Peroxisome biogenesis disorder 9B, OMIM# 614879, Rhizomelic chondrodysplasia punctata, type 1, OMIM# 215100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3721 RUNX2 Ain Roesley reviewed gene: RUNX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301686; Phenotypes: Cleidocranial dysplasia MIM#119600, Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3721 SLC26A4 Krithika Murali gene: SLC26A4 was added
gene: SLC26A4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SLC26A4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC26A4 were set to Pendred syndrome - MIM#274600
Review for gene: SLC26A4 was set to AMBER
Added comment: Known association with congenital hypothyroidism and bilateral sensorineural hearing loss. If goitre present, manifests later in childhood. No antenatal phenotype reported.
Sources: Literature
Fetal anomalies v0.3721 RTEL1 Ain Roesley reviewed gene: RTEL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23329068, 20301779, 29296694; Phenotypes: Dyskeratosis congenita, autosomal recessive 5 MIM#615190; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3721 PROP1 Krithika Murali gene: PROP1 was added
gene: PROP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PROP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PROP1 were set to 15941866; 11549703; 20301521; 32415500
Phenotypes for gene: PROP1 were set to Pituitary hormone deficiency, combined, 2- #262600
Review for gene: PROP1 was set to AMBER
Added comment: Biallelic variants associated with panhypopituitarism. Features include central congenital hypothyroidism and hypogonadotrophic hypogonadism including micropenis. Diagnosed postnatally in infancy or early childhood due to growth failure and failure to thrive. Antenatal diagnosis not reported, although severe micropenis due to other disorders has been detected antenatally.
Sources: Literature
Mendeliome v0.11011 RRM2B Ain Roesley reviewed gene: RRM2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 24741716; Phenotypes: Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) MIM#612075, Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3721 RRM2B Ain Roesley reviewed gene: RRM2B: Rating: RED; Mode of pathogenicity: None; Publications: 24741716; Phenotypes: Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) MIM#612075, Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3721 RPS6KA3 Ain Roesley reviewed gene: RPS6KA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301520; Phenotypes: Coffin-Lowry syndrome MIM#303600, Intellectual developmental disorder, X-linked 19 MIM#300844; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Fetal anomalies v0.3721 ROR2 Ain Roesley reviewed gene: ROR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10932186, 10932187, 10986040, 19461659, 20301418; Phenotypes: Brachydactyly, type B1 MIM#113000, Robinow syndrome, autosomal recessive MIM#268310; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3721 RNASET2 Ain Roesley reviewed gene: RNASET2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31349848, 19525954, 27091087, 29336640, 18545798, 15851732; Phenotypes: Leukoencephalopathy, cystic, without megalencephaly MIM#612951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11011 RNASET2 Ain Roesley reviewed gene: RNASET2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31349848, 19525954, 27091087, 29336640, 18545798, 15851732; Phenotypes: Leukoencephalopathy, cystic, without megalencephaly MIM#612951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.283 C17orf53 Elena Tucker gene: C17orf53 was added
gene: C17orf53 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: C17orf53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf53 were set to PMID: 34707299; PMID: 31467087
Phenotypes for gene: C17orf53 were set to Primary ovarian insufficiency
Penetrance for gene: C17orf53 were set to Complete
Review for gene: C17orf53 was set to AMBER
Added comment: PMID: 34707299. Homozygous LOF variant in individual with primary ovarian insufficiency
PMID: 31467087. Mice with targeted mutations in Hrob are infertile due to depletion of germ cells.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.283 TFAM Elena Tucker reviewed gene: TFAM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34647195, 32399598; Phenotypes: Perrault syndrome, primary ovarian insufficiency +/- seizures/intellectual disability/hearing loss; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3721 RNASEH2C Ain Roesley reviewed gene: RNASEH2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 24183309, 23322642; Phenotypes: Aicardi-Goutieres syndrome 3 (MIM# 610329), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.283 TFAM Elena Tucker gene: TFAM was added
gene: TFAM was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: TFAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TFAM were set to PMID: 34647195
Penetrance for gene: TFAM were set to Complete
Fetal anomalies v0.3721 KMT2E Zornitza Stark Marked gene: KMT2E as ready
Fetal anomalies v0.3721 KMT2E Zornitza Stark Gene: kmt2e has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3721 KMT2E Zornitza Stark Phenotypes for gene: KMT2E were changed from INTELLECTUAL DISABILITY; O'Donnell-Luria-Rodan syndrome, 618512 to O'Donnell-Luria-Rodan syndrome MIM#618512
Fetal anomalies v0.3720 KMT2E Zornitza Stark Publications for gene: KMT2E were set to
Fetal anomalies v0.3719 KMT2E Zornitza Stark Classified gene: KMT2E as Amber List (moderate evidence)
Fetal anomalies v0.3719 KMT2E Zornitza Stark Gene: kmt2e has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3718 KMT2E Zornitza Stark changed review comment from: 38 individuals from 36 families reported. Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. Additional common features include autism, macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. The four individuals with missense variants presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E postulated to explain this divergence in phenotype.; to: Micro/macrocephaly reported, see below, age of onset uncertain. Non-specific brain abnormalities also.

38 individuals from 36 families reported. Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. Additional common features include autism, macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. The four individuals with missense variants presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E postulated to explain this divergence in phenotype.
Fetal anomalies v0.3718 KMT2E Zornitza Stark edited their review of gene: KMT2E: Changed rating: AMBER
Fetal anomalies v0.3718 KCNQ3 Zornitza Stark Marked gene: KCNQ3 as ready
Fetal anomalies v0.3718 KCNQ3 Zornitza Stark Gene: kcnq3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3718 KCNQ3 Zornitza Stark Phenotypes for gene: KCNQ3 were changed from KCNQ3 syndrome to Seizures, benign neonatal, 2, MIM# 121201
Fetal anomalies v0.3717 KCNQ3 Zornitza Stark Publications for gene: KCNQ3 were set to
Fetal anomalies v0.3716 KCNQ3 Zornitza Stark Mode of inheritance for gene: KCNQ3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3715 KCNQ3 Zornitza Stark changed review comment from: Intellectual disability has been reported as a feature.; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.3715 KCNQ3 Zornitza Stark edited their review of gene: KCNQ3: Changed rating: RED
Fetal anomalies v0.3715 KCNQ1 Zornitza Stark Marked gene: KCNQ1 as ready
Fetal anomalies v0.3715 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3715 KCNQ1 Zornitza Stark Phenotypes for gene: KCNQ1 were changed from JERVELL AND LANGE-NIELSEN SYNDROME TYPE 1 to Long QT syndrome 1, 192500
Fetal anomalies v0.3714 KCNQ1 Zornitza Stark Publications for gene: KCNQ1 were set to
Fetal anomalies v0.3713 KCNQ1 Zornitza Stark Mode of inheritance for gene: KCNQ1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3712 KCNQ1 Zornitza Stark Classified gene: KCNQ1 as Green List (high evidence)
Fetal anomalies v0.3712 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3711 KCNQ1 Zornitza Stark changed review comment from: Can present antenatally with bradycardia, but no specific mention of hydrops.
Sources: Expert Review; to: Can present antenatally with bradycardia.
Sources: Expert Review
Fetal anomalies v0.3711 KCNQ1 Zornitza Stark edited their review of gene: KCNQ1: Changed rating: GREEN
Fetal anomalies v0.3711 KARS Zornitza Stark Marked gene: KARS as ready
Fetal anomalies v0.3711 KARS Zornitza Stark Gene: kars has been classified as Red List (Low Evidence).
Fetal anomalies v0.3711 KARS Zornitza Stark Phenotypes for gene: KARS were changed from DEAFNESS, AUTOSOMAL RECESSIVE 89; CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE INTERMEDIATE, B to Leukoencephalopathy with or without deafness (LEPID), MIM#619147
Fetal anomalies v0.3710 KARS Zornitza Stark Publications for gene: KARS were set to
Fetal anomalies v0.3709 KARS Zornitza Stark changed review comment from: Sources: Expert list; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.3709 KARS Zornitza Stark edited their review of gene: KARS: Changed rating: RED; Changed phenotypes: Leukoencephalopathy with or without deafness (LEPID), MIM#619147
Fetal anomalies v0.3709 NKX2-1 Krithika Murali gene: NKX2-1 was added
gene: NKX2-1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NKX2-1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NKX2-1 were set to 23911641; 11854319; 24714694
Phenotypes for gene: NKX2-1 were set to Choreoathetosis, hypothyroidism, and neonatal respiratory distress - MIM#610978
Review for gene: NKX2-1 was set to GREEN
Added comment: Heterozygous variants associated with congenital hypothyroidism, choreathetosis with or without pulmonary dysfunction. Allelic disorder to benign hereditary chorea (118700), which is less severe. Hypoplasia of the thyroid reported in some individuals. OMIM also reports septal heart defects noted in some patients.
Sources: Literature
Fetal anomalies v0.3709 IYD Krithika Murali gene: IYD was added
gene: IYD was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: IYD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IYD were set to 18434651; 18765512; 838849; 14169503
Phenotypes for gene: IYD were set to Thyroid dyshormonogenesis 4 - MIM#274800
Review for gene: IYD was set to GREEN
Added comment: Known association with congenital hypothyroidism secondary to thyroid dyshormonogenesis. Although antenatal diagnosis not reported, goitre known phenotypic feature.
Sources: Literature
Fetal anomalies v0.3709 IRS4 Krithika Murali edited their review of gene: IRS4: Added comment: Associated with isolated central congenital hypothyroidism (insufficient pituitary TSH production). Postnatal diagnosis with no prenatal features reported. Small thyroid gland is a late postnatal phenotypic feature.; Changed rating: AMBER
Fetal anomalies v0.3709 IRS4 Krithika Murali gene: IRS4 was added
gene: IRS4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: IRS4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IRS4 were set to 34566885; 34225927; 34093435; 33107432; 30061370
Phenotypes for gene: IRS4 were set to Hypothyroidism, congenital, nongoitrous, 9- MIM#301035
Review for gene: IRS4 was set to RED
Added comment: Associated with isolated central congenital hypothyroidism (insufficient pituitary TSH production). Postnatal diagnosis with no prenatal features reported.
Sources: Literature
Fetal anomalies v0.3709 DUOXA2 Krithika Murali gene: DUOXA2 was added
gene: DUOXA2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DUOXA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DUOXA2 were set to Thyroid dyshormonogenesis 5, MIM# 274900
Review for gene: DUOXA2 was set to GREEN
Added comment: Well-established gene disease association with congenital hypothyroidism
Sources: Literature
Fetal anomalies v0.3709 DUOXA1 Krithika Murali gene: DUOXA1 was added
gene: DUOXA1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DUOXA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DUOXA1 were set to 31428054; 29650690
Phenotypes for gene: DUOXA1 were set to congenital hypothyroidism, No OMIM #
Review for gene: DUOXA1 was set to AMBER
Added comment: No new publications since last PanelApp review Feb 2021

--

12 cases, but digenic model with variants in other genes
Sources: Literature
Mendeliome v0.11011 DLC1 Bryony Thompson Marked gene: DLC1 as ready
Mendeliome v0.11011 DLC1 Bryony Thompson Gene: dlc1 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.152 ATP13A2 Bryony Thompson Marked gene: ATP13A2 as ready
Ataxia - adult onset v0.152 ATP13A2 Bryony Thompson Gene: atp13a2 has been classified as Green List (High Evidence).
Mendeliome v0.11011 DLC1 Bryony Thompson Classified gene: DLC1 as Green List (high evidence)
Mendeliome v0.11011 DLC1 Bryony Thompson Gene: dlc1 has been classified as Green List (High Evidence).
Mendeliome v0.11010 DLC1 Bryony Thompson gene: DLC1 was added
gene: DLC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DLC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLC1 were set to 29773874
Phenotypes for gene: DLC1 were set to Nephrotic syndrome MONDO:0005377
Review for gene: DLC1 was set to GREEN
Added comment: Biallelic variants in 4 families, and knockdown of DLC1 in cultured podocytes reduces migration rate and treatment with dexamethasone abolishes RhoA activation.
Sources: Expert list
Fetal anomalies v0.3709 DUOX2 Krithika Murali gene: DUOX2 was added
gene: DUOX2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DUOX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DUOX2 were set to 33692749; 34019632; 34341225; 16134168
Phenotypes for gene: DUOX2 were set to Thyroid dyshormonogenesis 6 - MIM#607200
Review for gene: DUOX2 was set to GREEN
Added comment: Well-established gene disease association with congenital hypothyroidism.
Sources: Literature
Fetal anomalies v0.3709 DUOX1 Krithika Murali gene: DUOX1 was added
gene: DUOX1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DUOX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DUOX1 were set to 29650690; 34019632
Phenotypes for gene: DUOX1 were set to congenital hypothyroidism, No OMIM #
Review for gene: DUOX1 was set to AMBER
Added comment: Gene reviewed for PanelApp in Feb 2021 - "11 cases, but digenic model, with variants in other genes". No further case reports published since. PMID 34019632 provide evidence of recapitulation of congenital hypothyroidism phenotype in duox mutant zebrafish.
Sources: Literature
Ataxia - adult onset v0.152 ATP13A2 Bryony Thompson Classified gene: ATP13A2 as Green List (high evidence)
Ataxia - adult onset v0.152 ATP13A2 Bryony Thompson Gene: atp13a2 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.151 ATP13A2 Bryony Thompson gene: ATP13A2 was added
gene: ATP13A2 was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: ATP13A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP13A2 were set to 21362476; 21696388; 31588715; 32559632; 33033738; 33091395; 34405108
Phenotypes for gene: ATP13A2 were set to Kufor-Rakeb syndrome MIM#606693
Review for gene: ATP13A2 was set to GREEN
Added comment: At least 3 families with ataxia as a feature of the condition. Mainly adult-onset ataxia. Also, a Tibetan terrier with a homozygous frameshift variant had cerebellar ataxia.
Sources: Literature
Fetal anomalies v0.3709 RNASEH2B Ain Roesley reviewed gene: RNASEH2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 16845400, 33307271, 29239743; Phenotypes: Aicardi-Goutieres syndrome 2, MIM# 610181; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11009 RNASEH2A Ain Roesley reviewed gene: RNASEH2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 15870678, 25604658, 23592335, 20301648; Phenotypes: Aicardi-Goutieres syndrome 4 MIM#610333; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3709 RNASEH2A Ain Roesley reviewed gene: RNASEH2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 15870678, 25604658, 23592335; Phenotypes: Aicardi-Goutieres syndrome 4 MIM#610333; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3709 CDCA8 Krithika Murali gene: CDCA8 was added
gene: CDCA8 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CDCA8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDCA8 were set to 28025328; 29546359
Phenotypes for gene: CDCA8 were set to Congenital hypothyroidism, thyroid dysgenesis, no OMIM #
Review for gene: CDCA8 was set to GREEN
Added comment: Gene associated with congenital hypothyroidism secondary to thyroid dysgenesis. No new publications since last PanelApp review Feb 2021

---

4 families (1 with bilallelic variants [parent affected as HTZ], 3 with monoallelic variants) with functional evidence of variants. GREEN for mono allelic, RED for biallelic.
Sources: Literature
Fetal anomalies v0.3709 NPRL3 Krithika Murali gene: NPRL3 was added
gene: NPRL3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NPRL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPRL3 were set to 27173016; 26285051; 33461085
Phenotypes for gene: NPRL3 were set to Epilepsy, familial focal, with variable foci 3- MIM#617118
Review for gene: NPRL3 was set to GREEN
Added comment: Known association with focal epilepsy (variable penetrance) with focal cortical dysplasia being a reported feature. FCD has the potential to be detected prenatally.
Sources: Literature
Fetal anomalies v0.3709 NPRL2 Krithika Murali gene: NPRL2 was added
gene: NPRL2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NPRL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPRL2 were set to 29281825; 27173016; 31625153; 33461085; 22268191
Phenotypes for gene: NPRL2 were set to Epilepsy, familial focal, with variable foci 2 - MIM#617116
Review for gene: NPRL2 was set to GREEN
Added comment: Heterozygous NPRL2 variants associated with focal epilepsy of variable severity. Incomplete penetrance also a known feature. Probands from 3 unrelated families noted to have focal cortical dysplasia which has the potential to be detected prenatally.
Sources: Literature
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.43 NPRL2 Krithika Murali reviewed gene: NPRL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33461085; Phenotypes: Epilepsy, familial focal, with variable foci 2- MIM#617116; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v1.13 IL6ST Zornitza Stark Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant
Combined Immunodeficiency v1.12 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed phenotypes: Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523, Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant
Mendeliome v0.11009 IL6ST Zornitza Stark Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant
Mendeliome v0.11008 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed phenotypes: Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523, Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant
Ataxia - paediatric v0.325 WARS2 Zornitza Stark Marked gene: WARS2 as ready
Ataxia - paediatric v0.325 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.325 WARS2 Zornitza Stark Classified gene: WARS2 as Green List (high evidence)
Ataxia - paediatric v0.325 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.324 WARS2 Zornitza Stark gene: WARS2 was added
gene: WARS2 was added to Ataxia - paediatric. Sources: Expert Review
Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS2 were set to 29120065; 31970218; 34890876; 28236339; 28650581; 28905505; 30920170
Phenotypes for gene: WARS2 were set to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710
Review for gene: WARS2 was set to GREEN
Added comment: Childhood-onset parkinsonism-dystonia-3 (PKDYS3) is an autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. 8 individuals from 4 families reported.

NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding. 12 individuals from 8 unrelated families reported.

It is unclear whether these are two distinct disorders or whether they represent a spectrum of severity for a single condition.
Sources: Expert Review
Dystonia - complex v0.208 WARS2 Zornitza Stark Marked gene: WARS2 as ready
Dystonia - complex v0.208 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Dystonia - complex v0.208 WARS2 Zornitza Stark Classified gene: WARS2 as Green List (high evidence)
Dystonia - complex v0.208 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Dystonia - complex v0.207 WARS2 Zornitza Stark gene: WARS2 was added
gene: WARS2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS2 were set to 29120065; 31970218; 34890876; 28236339; 28650581; 28905505; 30920170
Phenotypes for gene: WARS2 were set to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710
Review for gene: WARS2 was set to GREEN
Added comment: Childhood-onset parkinsonism-dystonia-3 (PKDYS3) is an autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. 8 individuals from 4 families reported.

NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding. 12 individuals from 8 unrelated families reported.

It is unclear whether these are two distinct disorders or whether they represent a spectrum of severity for a single condition.
Sources: Literature
Mendeliome v0.11008 WARS2 Zornitza Stark Marked gene: WARS2 as ready
Mendeliome v0.11008 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Mendeliome v0.11008 WARS2 Zornitza Stark Phenotypes for gene: WARS2 were changed from to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710
Mendeliome v0.11007 WARS2 Zornitza Stark Publications for gene: WARS2 were set to
Mendeliome v0.11006 WARS2 Zornitza Stark Mode of inheritance for gene: WARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11005 WARS2 Zornitza Stark reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29120065, 31970218, 34890876, 28236339, 28650581, 28905505, 30920170; Phenotypes: Parkinsonism-dystonia 3, childhood-onset, MIM# 619738, Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11005 NHLH2 Zornitza Stark Marked gene: NHLH2 as ready
Mendeliome v0.11005 NHLH2 Zornitza Stark Gene: nhlh2 has been classified as Red List (Low Evidence).
Mendeliome v0.11005 NHLH2 Zornitza Stark gene: NHLH2 was added
gene: NHLH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NHLH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLH2 were set to 35066646
Phenotypes for gene: NHLH2 were set to Hypogonadotropic hypogonadism 27 without anosmia , MIM# 619755
Review for gene: NHLH2 was set to RED
Added comment: Single individual reported homozygous for a missense variant in this gene. Two other individuals heterozygous for missense variants identified as part of this cohort; however, had alternative diagnoses.
Sources: Literature
Differences of Sex Development v0.239 NHLH2 Zornitza Stark Marked gene: NHLH2 as ready
Differences of Sex Development v0.239 NHLH2 Zornitza Stark Gene: nhlh2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.239 NHLH2 Zornitza Stark gene: NHLH2 was added
gene: NHLH2 was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: NHLH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLH2 were set to 35066646
Phenotypes for gene: NHLH2 were set to Hypogonadotropic hypogonadism 27 without anosmia , MIM# 619755
Review for gene: NHLH2 was set to RED
Added comment: Single individual reported homozygous for a missense variant in this gene. Two other individuals heterozygous for missense variants identified as part of this cohort; however, had alternative diagnoses.
Sources: Expert Review
Mendeliome v0.11004 SPATA16 Paul De Fazio reviewed gene: SPATA16: Rating: AMBER; Mode of pathogenicity: None; Publications: 17847006, 27086357, 29065458; Phenotypes: ?Spermatogenic failure 6 MIM#102530, Spermatogenic failure 6 MONDO:0007060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11004 TNFRSF10B Paul De Fazio reviewed gene: TNFRSF10B: Rating: RED; Mode of pathogenicity: None; Publications: 9721851; Phenotypes: Squamous cell carcinoma, head and neck MIM#275355; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11004 MAPK8IP1 Paul De Fazio reviewed gene: MAPK8IP1: Rating: RED; Mode of pathogenicity: None; Publications: 10700186; Phenotypes: Susceptibility to diabetes mellitus, noninsulin-dependent MIM#125853; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.11004 SMIM1 Paul De Fazio reviewed gene: SMIM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Blood group, Vel system MIM#615264; Mode of inheritance: Unknown; Current diagnostic: yes
Mendeliome v0.11004 ACKR1 Paul De Fazio reviewed gene: ACKR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Blood group, Duffy system MIM#110700; Mode of inheritance: Unknown; Current diagnostic: yes
Mendeliome v0.11004 OGG1 Paul De Fazio reviewed gene: OGG1: Rating: RED; Mode of pathogenicity: None; Publications: 10987279, 29305130; Phenotypes: Renal cell carcinoma, clear cell, somatic MIM#144700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.11004 B3GALNT1 Paul De Fazio reviewed gene: B3GALNT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Blood group, globoside system MIM#615021; Mode of inheritance: Unknown; Current diagnostic: yes
Mendeliome v0.11004 SERPINA7 Paul De Fazio reviewed gene: SERPINA7: Rating: GREEN; Mode of pathogenicity: None; Publications: 34126618, 32266677, 17887925, 28553659, 29733970, 16947003; Phenotypes: Thyroxine-binding globulin QTL MIM#300932, Thyroxine-binding globulin deficiency; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Congenital diaphragmatic hernia v1.5 PBX1 Zornitza Stark Marked gene: PBX1 as ready
Congenital diaphragmatic hernia v1.5 PBX1 Zornitza Stark Gene: pbx1 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.5 PBX1 Zornitza Stark Classified gene: PBX1 as Green List (high evidence)
Congenital diaphragmatic hernia v1.5 PBX1 Zornitza Stark Gene: pbx1 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.4 PBX1 Zornitza Stark gene: PBX1 was added
gene: PBX1 was added to Congenital diaphragmatic hernia. Sources: Expert Review
Mode of inheritance for gene: PBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PBX1 were set to 28566479; 29036646; 29966037
Phenotypes for gene: PBX1 were set to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MIM# 617641
Review for gene: PBX1 was set to GREEN
Added comment: CAKUTHED is an autosomal dominant highly pleiotropic developmental disorder characterized mainly by variable congenital anomalies of the kidney and urinary tract, sometimes resulting in renal dysfunction or failure, dysmorphic facial features, and abnormalities of the outer ear, often with hearing loss. Most individuals have global developmental delay. More than 10 unrelated families reported.

CDH reported in several.
Sources: Expert Review
Mendeliome v0.11004 Zornitza Stark removed gene:TBK1 from the panel
Incidentalome v0.85 TBK1 Zornitza Stark Marked gene: TBK1 as ready
Incidentalome v0.85 TBK1 Zornitza Stark Gene: tbk1 has been classified as Green List (High Evidence).
Incidentalome v0.85 TBK1 Zornitza Stark Classified gene: TBK1 as Green List (high evidence)
Incidentalome v0.85 TBK1 Zornitza Stark Gene: tbk1 has been classified as Green List (High Evidence).
Incidentalome v0.84 TBK1 Zornitza Stark gene: TBK1 was added
gene: TBK1 was added to Incidentalome. Sources: Expert Review
Mode of inheritance for gene: TBK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBK1 were set to 25803835; 26581300; 31000212; 25943890
Phenotypes for gene: TBK1 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (MIM#616439), AD
Review for gene: TBK1 was set to GREEN
Added comment: Well established gene-disease association for an adult-onset neurodegenerative disorder.
Sources: Expert Review
Fetal anomalies v0.3709 ITGA7 Zornitza Stark Marked gene: ITGA7 as ready
Fetal anomalies v0.3709 ITGA7 Zornitza Stark Gene: itga7 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3709 ITGA7 Zornitza Stark Phenotypes for gene: ITGA7 were changed from CONGENITAL MUSCULAR DYSTROPHY to Muscular dystrophy, congenital, due to ITGA7 deficiency, MIM# 613204
Fetal anomalies v0.3708 ITGA7 Zornitza Stark changed review comment from: Primarily a muscle phenotype, accompanied by gross motor delay as expected. One out of 3 reported individuals had intellectual disability.; to: Primarily a muscle phenotype, typically presents post-natally.
Fetal anomalies v0.3708 ITGA7 Zornitza Stark edited their review of gene: ITGA7: Changed rating: RED
Fetal anomalies v0.3708 IQSEC2 Zornitza Stark Marked gene: IQSEC2 as ready
Fetal anomalies v0.3708 IQSEC2 Zornitza Stark Gene: iqsec2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3708 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from MENTAL RETARDATION X-LINKED TYPE 1 to Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Fetal anomalies v0.3707 IQSEC2 Zornitza Stark Publications for gene: IQSEC2 were set to
Fetal anomalies v0.3706 IQSEC2 Zornitza Stark changed review comment from: More than 20 unrelated families reported.; to: More than 20 unrelated families reported. Clinical presentation is typically post-natal.
Fetal anomalies v0.3706 IQSEC2 Zornitza Stark edited their review of gene: IQSEC2: Changed rating: RED
Fetal anomalies v0.3706 HYDIN Zornitza Stark Marked gene: HYDIN as ready
Fetal anomalies v0.3706 HYDIN Zornitza Stark Gene: hydin has been classified as Red List (Low Evidence).
Fetal anomalies v0.3706 HYDIN Zornitza Stark Phenotypes for gene: HYDIN were changed from CILIARY DYSKINESIA, PRIMARY, 5 to Ciliary dyskinesia, primary, 5 (MIM#08647)
Fetal anomalies v0.3705 HYDIN Zornitza Stark Publications for gene: HYDIN were set to 30712880
Fetal anomalies v0.3704 HNRNPU Zornitza Stark Marked gene: HNRNPU as ready
Fetal anomalies v0.3704 HNRNPU Zornitza Stark Gene: hnrnpu has been classified as Red List (Low Evidence).
Fetal anomalies v0.3704 HNRNPU Zornitza Stark Phenotypes for gene: HNRNPU were changed from EPILEPTIC ENCEPHALOPATHY to Epileptic encephalopathy, early infantile, 54, MIM#617391
Fetal anomalies v0.3703 HNRNPU Zornitza Stark Publications for gene: HNRNPU were set to
Fetal anomalies v0.3702 HNRNPU Zornitza Stark Mode of inheritance for gene: HNRNPU was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3701 HNRNPU Zornitza Stark commented on gene: HNRNPU: Clinical presentation is typically post-natal.
Fetal anomalies v0.3701 HNRNPU Zornitza Stark edited their review of gene: HNRNPU: Changed rating: RED
Fetal anomalies v0.3701 HECW2 Zornitza Stark Marked gene: HECW2 as ready
Fetal anomalies v0.3701 HECW2 Zornitza Stark Gene: hecw2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3701 HECW2 Zornitza Stark Phenotypes for gene: HECW2 were changed from HECW2 to Neurodevelopmental disorder with hypotonia, seizures, and absent language (MIM#617268)
Fetal anomalies v0.3700 HECW2 Zornitza Stark Publications for gene: HECW2 were set to
Fetal anomalies v0.3699 HECW2 Zornitza Stark Mode of pathogenicity for gene: HECW2 was changed from to Other
Fetal anomalies v0.3698 HECW2 Zornitza Stark Mode of inheritance for gene: HECW2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3697 HECW2 Zornitza Stark changed review comment from: Typically denovo missense variants in the HECT domain.
PMID: 29807643 - R1191Q single case with severe D/ID, EE and regression
PMID: 29395664 - single case with regression, loss of swallowing, increased abnormal movements/hand stereotypies, Rett like, cortical visual impairment and EE
PMID: 27334371 - propose GOF or dominant negative; 1 case plus references 5 previous cases
PMID: 27389779 - four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. p. Arg1330Trp, p.Glu1445Gly reported >1 case.
Regression reported in the context of refractory EE; to: Clinical presentation is typically post-natal.

Typically denovo missense variants in the HECT domain.
PMID: 29807643 - R1191Q single case with severe D/ID, EE and regression
PMID: 29395664 - single case with regression, loss of swallowing, increased abnormal movements/hand stereotypies, Rett like, cortical visual impairment and EE
PMID: 27334371 - propose GOF or dominant negative; 1 case plus references 5 previous cases
PMID: 27389779 - four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. p. Arg1330Trp, p.Glu1445Gly reported >1 case.
Regression reported in the context of refractory EE
Fetal anomalies v0.3697 HECW2 Zornitza Stark edited their review of gene: HECW2: Changed rating: RED
Fetal anomalies v0.3697 HDAC4 Zornitza Stark Marked gene: HDAC4 as ready
Fetal anomalies v0.3697 HDAC4 Zornitza Stark Gene: hdac4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3697 HDAC4 Zornitza Stark Phenotypes for gene: HDAC4 were changed from BRACHYDACTYLY-MENTAL RETARDATION SYNDROME to Brachydactyly mental retardation syndrome; Brachydactyly without intellectual disability
Fetal anomalies v0.3696 HDAC4 Zornitza Stark Publications for gene: HDAC4 were set to
Fetal anomalies v0.3695 HDAC4 Zornitza Stark Mode of inheritance for gene: HDAC4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3694 HDAC4 Zornitza Stark Classified gene: HDAC4 as Amber List (moderate evidence)
Fetal anomalies v0.3694 HDAC4 Zornitza Stark Gene: hdac4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3693 HDAC4 Zornitza Stark changed review comment from: Contradictory evidence: deletions linked to brachydactyly-MR but note some individuals reported without MR. Only two reports of intragenic variants (still structural rather than SNVs).; to: Contradictory evidence: deletions linked to brachydactyly-MR but note some individuals reported without MR. Only two reports of intragenic variants (still structural rather than SNVs).

Subtle brain abnormalities, hip dislocation reported in PMID 33537682.
Fetal anomalies v0.3693 HADH Zornitza Stark Marked gene: HADH as ready
Fetal anomalies v0.3693 HADH Zornitza Stark Gene: hadh has been classified as Red List (Low Evidence).
Fetal anomalies v0.3693 HADH Zornitza Stark Phenotypes for gene: HADH were changed from 3-HYDROXYACYL-COENZYME A DEHYDROGENASE DEFICIENCY to 3-hydroxyacyl-CoA dehydrogenase deficiency, MIM#231530; Hyperinsulinemic hypoglycemia, familial, 4, MIM#609975
Fetal anomalies v0.3692 HADH Zornitza Stark changed review comment from: Metabolic encephalopathy rather than ID; to: Metabolic encephalopathy, typically presents post-natally.
Fetal anomalies v0.3692 HACE1 Zornitza Stark Marked gene: HACE1 as ready
Fetal anomalies v0.3692 HACE1 Zornitza Stark Gene: hace1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3692 HACE1 Zornitza Stark Phenotypes for gene: HACE1 were changed from HACE1 related disorder to Spastic paraplegia and psychomotor retardation with or without seizures, 616756; MONDO:0014764
Fetal anomalies v0.3691 HACE1 Zornitza Stark Publications for gene: HACE1 were set to
Fetal anomalies v0.3690 HACE1 Zornitza Stark Classified gene: HACE1 as Amber List (moderate evidence)
Fetal anomalies v0.3690 HACE1 Zornitza Stark Gene: hace1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3689 HACE1 Zornitza Stark edited their review of gene: HACE1: Changed rating: AMBER
Fetal anomalies v0.3689 H3F3A Zornitza Stark Marked gene: H3F3A as ready
Fetal anomalies v0.3689 H3F3A Zornitza Stark Gene: h3f3a has been classified as Green List (High Evidence).
Fetal anomalies v0.3689 H3F3A Zornitza Stark Phenotypes for gene: H3F3A were changed from Craniofacial with neurodevelopment disorders to Bryant-Li-Bhoj neurodevelopmental syndrome 1, MIM# 619720
Fetal anomalies v0.3688 H3F3A Zornitza Stark Publications for gene: H3F3A were set to
Fetal anomalies v0.3687 H3F3A Zornitza Stark Mode of inheritance for gene: H3F3A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3686 H3F3A Zornitza Stark Classified gene: H3F3A as Green List (high evidence)
Fetal anomalies v0.3686 H3F3A Zornitza Stark Gene: h3f3a has been classified as Green List (High Evidence).
Fetal anomalies v0.3685 H3F3A Zornitza Stark changed review comment from: 33 unrelated individuals reported with missense variants in H3F3A. Phenotype primarily comprised intellectual disability and minor congenital anomalies, regression in significant proportion. Seizures in 50%.; to: 33 unrelated individuals reported with missense variants in H3F3A. Phenotype primarily comprised intellectual disability and minor congenital anomalies, including micro/macrocephaly, craniosynostosis, contractures, congenital heart disease.
Fetal anomalies v0.3685 H19 Zornitza Stark Marked gene: H19 as ready
Fetal anomalies v0.3685 H19 Zornitza Stark Gene: h19 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3685 H19 Zornitza Stark changed review comment from: Part of the BWS/RSS locus but ID not a feature.; to: Methylation changes rather than sequence variation are associated with BWS/RSS.
Mackenzie's Mission_Reproductive Carrier Screening v0.104 NDUFA11 Zornitza Stark reviewed gene: NDUFA11: Rating: RED; Mode of pathogenicity: None; Publications: 18306244, 31074871; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, MIM#618236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.123 NDUFA11 Zornitza Stark Marked gene: NDUFA11 as ready
Cardiomyopathy_Paediatric v0.123 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.123 NDUFA11 Zornitza Stark Publications for gene: NDUFA11 were set to
Cardiomyopathy_Paediatric v0.122 NDUFA11 Zornitza Stark Classified gene: NDUFA11 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.122 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.121 NDUFA11 Zornitza Stark reviewed gene: NDUFA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 18306244, 31074871; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, MIM#618236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.403 NDUFA11 Zornitza Stark Marked gene: NDUFA11 as ready
Regression v0.403 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Red List (Low Evidence).
Regression v0.403 NDUFA11 Zornitza Stark Phenotypes for gene: NDUFA11 were changed from Mitochondrial complex I deficiency, nuclear type 14, MIM#618236 to Mitochondrial complex I deficiency, nuclear type 14, MIM#618236
Regression v0.402 NDUFA11 Zornitza Stark Phenotypes for gene: NDUFA11 were changed from to Mitochondrial complex I deficiency, nuclear type 14, MIM#618236
Regression v0.401 NDUFA11 Zornitza Stark Publications for gene: NDUFA11 were set to 18306244; 31074871
Regression v0.401 NDUFA11 Zornitza Stark Publications for gene: NDUFA11 were set to
Regression v0.400 NDUFA11 Zornitza Stark Mode of inheritance for gene: NDUFA11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.399 NDUFA11 Zornitza Stark Classified gene: NDUFA11 as Red List (low evidence)
Regression v0.399 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Red List (Low Evidence).
Regression v0.398 NDUFA11 Zornitza Stark reviewed gene: NDUFA11: Rating: RED; Mode of pathogenicity: None; Publications: 18306244, 31074871; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, MIM#618236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.361 NDUFA11 Zornitza Stark Marked gene: NDUFA11 as ready
Callosome v0.361 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Red List (Low Evidence).
Callosome v0.361 NDUFA11 Zornitza Stark Phenotypes for gene: NDUFA11 were changed from to Mitochondrial complex I deficiency, nuclear type 14, MIM#618236
Callosome v0.360 NDUFA11 Zornitza Stark Publications for gene: NDUFA11 were set to
Callosome v0.359 NDUFA11 Zornitza Stark Mode of inheritance for gene: NDUFA11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.358 NDUFA11 Zornitza Stark Classified gene: NDUFA11 as Red List (low evidence)
Callosome v0.358 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Red List (Low Evidence).
Callosome v0.357 NDUFA11 Zornitza Stark reviewed gene: NDUFA11: Rating: RED; Mode of pathogenicity: None; Publications: 18306244, 31074871; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, MIM#618236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.698 NDUFA11 Zornitza Stark Marked gene: NDUFA11 as ready
Mitochondrial disease v0.698 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.698 NDUFA11 Zornitza Stark Phenotypes for gene: NDUFA11 were changed from to Mitochondrial complex I deficiency, nuclear type 14, MIM#618236
Mitochondrial disease v0.697 NDUFA11 Zornitza Stark Publications for gene: NDUFA11 were set to
Mitochondrial disease v0.696 NDUFA11 Zornitza Stark Mode of inheritance for gene: NDUFA11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.695 NDUFA11 Zornitza Stark Classified gene: NDUFA11 as Amber List (moderate evidence)
Mitochondrial disease v0.695 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.694 NDUFA11 Zornitza Stark reviewed gene: NDUFA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 18306244, 31074871; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, MIM#618236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11003 NDUFA11 Zornitza Stark Marked gene: NDUFA11 as ready
Mendeliome v0.11003 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11003 NDUFA11 Zornitza Stark Phenotypes for gene: NDUFA11 were changed from to Mitochondrial complex I deficiency, nuclear type 14, MIM#618236
Mendeliome v0.11002 NDUFA11 Zornitza Stark Publications for gene: NDUFA11 were set to
Mendeliome v0.11001 NDUFA11 Zornitza Stark Mode of inheritance for gene: NDUFA11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11000 NDUFA11 Zornitza Stark Classified gene: NDUFA11 as Amber List (moderate evidence)
Mendeliome v0.11000 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10999 NDUFA11 Zornitza Stark reviewed gene: NDUFA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 18306244, 31074871; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, MIM#618236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10999 TBK1 Chern Lim reviewed gene: TBK1: Rating: RED; Mode of pathogenicity: None; Publications: 25803835, 26581300; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (MIM#616439), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3685 GRIN2A Zornitza Stark Marked gene: GRIN2A as ready
Fetal anomalies v0.3685 GRIN2A Zornitza Stark Gene: grin2a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3685 GRIN2A Zornitza Stark Phenotypes for gene: GRIN2A were changed from EPILEPSY WITH NEURODEVELOPMENTAL DEFECTS; LANDAU-KLEFFNER SYNDROME to Epilepsy, focal, with speech disorder and with or without mental retardation, MIM# 245570
Fetal anomalies v0.3684 GRIN2A Zornitza Stark Publications for gene: GRIN2A were set to
Fetal anomalies v0.3683 GRIN2A Zornitza Stark Mode of pathogenicity for gene: GRIN2A was changed from to Other
Fetal anomalies v0.3682 GRIN2A Zornitza Stark Mode of inheritance for gene: GRIN2A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3681 GRIN2A Zornitza Stark changed review comment from: Large cohort of 248 individuals reported in PMID: 30544257: The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. Pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes. Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function.; to: Large cohort of 248 individuals reported in PMID: 30544257: The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. Pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes. Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function.

Clinical presentation is typically postnatal.
Fetal anomalies v0.3681 GRIN2A Zornitza Stark edited their review of gene: GRIN2A: Changed rating: RED
Fetal anomalies v0.3681 GRIK2 Zornitza Stark Marked gene: GRIK2 as ready
Fetal anomalies v0.3681 GRIK2 Zornitza Stark Gene: grik2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3681 GRIK2 Zornitza Stark Phenotypes for gene: GRIK2 were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 6 to Neurodevelopmental disorder with impaired language and ataxia and with or without seizures, MIM# 619580
Fetal anomalies v0.3680 GRIK2 Zornitza Stark Publications for gene: GRIK2 were set to
Fetal anomalies v0.3679 GRIK2 Zornitza Stark Mode of inheritance for gene: GRIK2 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3678 GRIK2 Zornitza Stark Classified gene: GRIK2 as Amber List (moderate evidence)
Fetal anomalies v0.3678 GRIK2 Zornitza Stark Gene: grik2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3677 GRIK2 Zornitza Stark reviewed gene: GRIK2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with impaired language and ataxia and with or without seizures, MIM# 619580; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3677 GRIA3 Zornitza Stark Marked gene: GRIA3 as ready
Fetal anomalies v0.3677 GRIA3 Zornitza Stark Gene: gria3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3677 GRIA3 Zornitza Stark Phenotypes for gene: GRIA3 were changed from MENTAL RETARDATION X-LINKED TYPE 94 to Intellectual developmental disorder, X-linked, syndromic, Wu type (MIM#300699)
Fetal anomalies v0.3676 GRIA3 Zornitza Stark Publications for gene: GRIA3 were set to
Fetal anomalies v0.3675 GRIA3 Zornitza Stark Classified gene: GRIA3 as Amber List (moderate evidence)
Fetal anomalies v0.3675 GRIA3 Zornitza Stark Gene: gria3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3674 GRIA3 Zornitza Stark reviewed gene: GRIA3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked, syndromic, Wu type (MIM#300699); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3674 GMPPA Zornitza Stark Marked gene: GMPPA as ready
Fetal anomalies v0.3674 GMPPA Zornitza Stark Gene: gmppa has been classified as Red List (Low Evidence).
Fetal anomalies v0.3674 GMPPA Zornitza Stark Phenotypes for gene: GMPPA were changed from GLYCOSYLATION DISORDER CHARACTERIZED BY INTELLECTUAL DISABILITY AND AUTONOMIC DYSFUNCTION to Alacrima, achalasia, and mental retardation syndrome (MIM# 615510)
Fetal anomalies v0.3673 GMPPA Zornitza Stark Publications for gene: GMPPA were set to
Fetal anomalies v0.3672 GMPPA Zornitza Stark reviewed gene: GMPPA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alacrima, achalasia, and mental retardation syndrome (MIM# 615510); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3672 GLUD1 Zornitza Stark Marked gene: GLUD1 as ready
Fetal anomalies v0.3672 GLUD1 Zornitza Stark Gene: glud1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3672 GLUD1 Zornitza Stark Phenotypes for gene: GLUD1 were changed from HYPERINSULINISM-HYPERAMMONEMIA SYNDROME to Hyperinsulinism-hyperammonemia syndrome, MIM#606762
Fetal anomalies v0.3671 GLUD1 Zornitza Stark Mode of inheritance for gene: GLUD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3670 GLUD1 Zornitza Stark changed review comment from: ID is not typically a feature.; to: Clinical presentation is typically postnatal.
Fetal anomalies v0.3670 GHR Zornitza Stark Marked gene: GHR as ready
Fetal anomalies v0.3670 GHR Zornitza Stark Gene: ghr has been classified as Green List (High Evidence).
Fetal anomalies v0.3670 GHR Zornitza Stark Phenotypes for gene: GHR were changed from PITUITARY DWARFISM II to Growth hormone insensitivity, partial, MIM#604271; Laron dwarfism, MIM#262500
Fetal anomalies v0.3669 GHR Zornitza Stark Publications for gene: GHR were set to
Fetal anomalies v0.3668 GHR Zornitza Stark Mode of inheritance for gene: GHR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3667 GHR Zornitza Stark Classified gene: GHR as Green List (high evidence)
Fetal anomalies v0.3667 GHR Zornitza Stark Gene: ghr has been classified as Green List (High Evidence).
Fetal anomalies v0.3666 GHR Zornitza Stark Deleted their comment
Fetal anomalies v0.3666 GHR Zornitza Stark edited their review of gene: GHR: Added comment: Birth weight and length are significantly decreased in the more severe, bi-allelic disorder (Laron).; Changed rating: GREEN; Changed publications: 9360502
Fetal anomalies v0.3666 GDF2 Zornitza Stark Marked gene: GDF2 as ready
Fetal anomalies v0.3666 GDF2 Zornitza Stark Gene: gdf2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3666 DDOST Zornitza Stark Marked gene: DDOST as ready
Fetal anomalies v0.3666 DDOST Zornitza Stark Gene: ddost has been classified as Red List (Low Evidence).
Fetal anomalies v0.3666 DDOST Zornitza Stark Phenotypes for gene: DDOST were changed from CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IR to Congenital disorder of glycosylation, type Ir, MIM# 614507
Fetal anomalies v0.3665 DDOST Zornitza Stark Publications for gene: DDOST were set to
Fetal anomalies v0.3664 DDOST Zornitza Stark edited their review of gene: DDOST: Changed rating: RED
Fetal anomalies v0.3664 CSTB Zornitza Stark Marked gene: CSTB as ready
Fetal anomalies v0.3664 CSTB Zornitza Stark Gene: cstb has been classified as Red List (Low Evidence).
Fetal anomalies v0.3664 CSTB Zornitza Stark Phenotypes for gene: CSTB were changed from UNVERRICHT-LUNDBORG DISEASE to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), MIM# 254800
Fetal anomalies v0.3663 CSTB Zornitza Stark Publications for gene: CSTB were set to
Fetal anomalies v0.3662 CSTB Zornitza Stark changed review comment from: Myoclonic epilepsy of Unverricht and Lundborg is an autosomal recessive disorder characterized by onset of neurodegeneration between 6 and 13 years of age. Not appropriate for the ID panel.; to: Myoclonic epilepsy of Unverricht and Lundborg is an autosomal recessive disorder characterized by onset of neurodegeneration between 6 and 13 years of age. Not appropriate for the Fetal Anomalies panel.
Fetal anomalies v0.3662 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Fetal anomalies v0.3662 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3662 GATM Zornitza Stark Marked gene: GATM as ready
Fetal anomalies v0.3662 GATM Zornitza Stark Gene: gatm has been classified as Red List (Low Evidence).
Fetal anomalies v0.3662 GATM Zornitza Stark Phenotypes for gene: GATM were changed from ARGININE:GLYCINE AMIDINOTRANSFERASE DEFICIENCY to Cerebral creatine deficiency syndrome 3, MIM# 612718
Fetal anomalies v0.3661 GATM Zornitza Stark Publications for gene: GATM were set to
Fetal anomalies v0.3660 GATM Zornitza Stark changed review comment from: Bi-allelic variants cause a disorder characterized by developmental delay/regression, intellectual disability, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. At least four unrelated families reported.; to: Bi-allelic variants cause a disorder characterized by developmental delay/regression, intellectual disability, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. At least four unrelated families reported.

Clinical presentation is typically post-natal.
Fetal anomalies v0.3660 GATM Zornitza Stark edited their review of gene: GATM: Changed rating: RED
Fetal anomalies v0.3660 GATAD2B Zornitza Stark Marked gene: GATAD2B as ready
Fetal anomalies v0.3660 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3660 GATAD2B Zornitza Stark Phenotypes for gene: GATAD2B were changed from NONSPECIFIC SEVERE ID to GAND syndrome, MIM# 615074
Fetal anomalies v0.3659 GATAD2B Zornitza Stark Publications for gene: GATAD2B were set to
Fetal anomalies v0.3658 GATAD2B Zornitza Stark Mode of inheritance for gene: GATAD2B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3657 GATAD2B Zornitza Stark Classified gene: GATAD2B as Amber List (moderate evidence)
Fetal anomalies v0.3657 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3656 GATAD2B Zornitza Stark reviewed gene: GATAD2B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: GAND syndrome 615074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3656 MYH6 Zornitza Stark Marked gene: MYH6 as ready
Fetal anomalies v0.3656 MYH6 Zornitza Stark Gene: myh6 has been classified as Green List (High Evidence).
Fetal anomalies v0.3656 MYH6 Zornitza Stark Phenotypes for gene: MYH6 were changed from ATRIAL SEPTAL DEFECT TYPE 3; CARDIOMYOPATHY FAMILIAL HYPERTROPHIC TYPE 14; CARDIOMYOPATHY DILATED TYPE 1EE to Atrial septal defect 3 (MIM#614089)
Fetal anomalies v0.3655 MYH6 Zornitza Stark Publications for gene: MYH6 were set to
Fetal anomalies v0.3654 GAS8 Zornitza Stark Marked gene: GAS8 as ready
Fetal anomalies v0.3654 GAS8 Zornitza Stark Gene: gas8 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3654 GAS8 Zornitza Stark Phenotypes for gene: GAS8 were changed from PRIMARY CILIARY DYSKINESIA to Ciliary dyskinesia, primary, 33, MIM# 616726
Fetal anomalies v0.3653 GAS8 Zornitza Stark Publications for gene: GAS8 were set to 30166424
Fetal anomalies v0.3652 GALT Zornitza Stark Marked gene: GALT as ready
Fetal anomalies v0.3652 GALT Zornitza Stark Gene: galt has been classified as Red List (Low Evidence).
Fetal anomalies v0.3652 GALT Zornitza Stark Phenotypes for gene: GALT were changed from GALACTOSEMIA to Galactosaemia, MIM#230400
Fetal anomalies v0.3651 GALT Zornitza Stark changed review comment from: Clinical presentation is typically postnatal.; to: Clinical presentation is typically postnatal.
Fetal anomalies v0.3651 GALT Zornitza Stark changed review comment from: Most cases should be detected by newborn screening where available, but ID is part of the phenotype.; to: Clinical presentation is typically postnatal.
Fetal anomalies v0.3651 GALT Zornitza Stark edited their review of gene: GALT: Changed phenotypes: Galactosaemia, MIM#230400
Fetal anomalies v0.3651 GALT Zornitza Stark edited their review of gene: GALT: Changed rating: RED
Fetal anomalies v0.3651 GABRB3 Zornitza Stark Marked gene: GABRB3 as ready
Fetal anomalies v0.3651 GABRB3 Zornitza Stark Gene: gabrb3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3651 GABRB3 Zornitza Stark Phenotypes for gene: GABRB3 were changed from CHILDHOOD ABSENCE EPILEPSY TYPE 5; EPILEPTIC ENCEPHALOPATHIES to Epileptic encephalopathy, early infantile, 43, MIM# 617113
Fetal anomalies v0.3650 GABRB3 Zornitza Stark Publications for gene: GABRB3 were set to
Fetal anomalies v0.3649 GABRB3 Zornitza Stark Mode of inheritance for gene: GABRB3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3648 GABRB3 Zornitza Stark edited their review of gene: GABRB3: Changed rating: RED
Fetal anomalies v0.3648 FTSJ1 Zornitza Stark Marked gene: FTSJ1 as ready
Fetal anomalies v0.3648 FTSJ1 Zornitza Stark Gene: ftsj1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3648 FTSJ1 Zornitza Stark Phenotypes for gene: FTSJ1 were changed from MENTAL RETARDATION X-LINKED TYPE 44 to Intellectual developmental disorder, X-linked 9, MIM# 309549
Fetal anomalies v0.3647 FTSJ1 Zornitza Stark Publications for gene: FTSJ1 were set to
Fetal anomalies v0.3646 FOXP1 Zornitza Stark Marked gene: FOXP1 as ready
Fetal anomalies v0.3646 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3646 FOXP1 Zornitza Stark Phenotypes for gene: FOXP1 were changed from MENTAL RETARDATION WITH LANGUAGE IMPAIRMENT AND AUTISTIC FEATURES to Mental retardation with language impairment and with or without autistic features, MIM# 613670
Fetal anomalies v0.3645 FOXP1 Zornitza Stark Publications for gene: FOXP1 were set to
Fetal anomalies v0.3644 FOXP1 Zornitza Stark Mode of inheritance for gene: FOXP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3643 FOXP1 Zornitza Stark changed review comment from: Single individual reported as part of a CDH cohort.
Sources: Literature; to: Single individual reported as part of a CDH cohort. Otherwise clinical presentation is typically post-natal.
Sources: Literature
Fetal anomalies v0.3643 FLVCR1 Zornitza Stark Marked gene: FLVCR1 as ready
Fetal anomalies v0.3643 FLVCR1 Zornitza Stark Gene: flvcr1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3643 FLVCR1 Zornitza Stark Phenotypes for gene: FLVCR1 were changed from ATAXIA, POSTERIOR COLUMN, WITH RETINITIS PIGMENTOSA to Ataxia, posterior column, with retinitis pigmentosa, MIM#609033
Fetal anomalies v0.3642 FLVCR1 Zornitza Stark changed review comment from: progressive neurological condition, ID is not really part of the phenotype.; to: progressive neurological condition, postnatal onset.
Fetal anomalies v0.3642 FGF12 Zornitza Stark Marked gene: FGF12 as ready
Fetal anomalies v0.3642 FGF12 Zornitza Stark Gene: fgf12 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3642 FGF12 Zornitza Stark Phenotypes for gene: FGF12 were changed from EPILEPTIC ENCEPHALOPATHY to Developmental and epileptic encephalopathy 47, MIM# 617166
Fetal anomalies v0.3641 FGF12 Zornitza Stark Publications for gene: FGF12 were set to
Fetal anomalies v0.3640 FGF12 Zornitza Stark Mode of inheritance for gene: FGF12 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3639 FGF12 Zornitza Stark edited their review of gene: FGF12: Changed rating: RED
Fetal anomalies v0.3639 FBXO11 Zornitza Stark Marked gene: FBXO11 as ready
Fetal anomalies v0.3639 FBXO11 Zornitza Stark Gene: fbxo11 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3639 FBXO11 Zornitza Stark Phenotypes for gene: FBXO11 were changed from Variable Neurodevelopmental Disorder to Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 618089
Fetal anomalies v0.3638 FBXO11 Zornitza Stark Publications for gene: FBXO11 were set to 30057029
Fetal anomalies v0.3637 FBXO11 Zornitza Stark Mode of inheritance for gene: FBXO11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3636 FBXO11 Zornitza Stark reviewed gene: FBXO11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 618089; Mode of inheritance: None
Fetal anomalies v0.3636 FARS2 Zornitza Stark Marked gene: FARS2 as ready
Fetal anomalies v0.3636 FARS2 Zornitza Stark Gene: fars2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3636 FARS2 Zornitza Stark Phenotypes for gene: FARS2 were changed from Neurometabolic disorder due to FARS2 deficiency to Combined oxidative phosphorylation deficiency 14, MIM#614946
Fetal anomalies v0.3635 FARS2 Zornitza Stark Mode of inheritance for gene: FARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3634 FARS2 Zornitza Stark changed review comment from: Severe neurologic phenotype described.; to: Clinical presentation is typically postnatal.
Fetal anomalies v0.3634 FARS2 Zornitza Stark edited their review of gene: FARS2: Changed rating: RED
Fetal anomalies v0.3634 ERCC6L2 Zornitza Stark Marked gene: ERCC6L2 as ready
Fetal anomalies v0.3634 ERCC6L2 Zornitza Stark Gene: ercc6l2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3634 ERCC6L2 Zornitza Stark Phenotypes for gene: ERCC6L2 were changed from BONE MARROW FAILURE SYNDROME 2 to Bone marrow failure syndrome 2, MIM# 615715
Fetal anomalies v0.3633 ERCC6L2 Zornitza Stark Publications for gene: ERCC6L2 were set to
Fetal anomalies v0.3632 ERCC6L2 Zornitza Stark Classified gene: ERCC6L2 as Amber List (moderate evidence)
Fetal anomalies v0.3632 ERCC6L2 Zornitza Stark Gene: ercc6l2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3631 ERCC6L2 Zornitza Stark reviewed gene: ERCC6L2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24507776, 27185855; Phenotypes: Bone marrow failure syndrome 2, MIM# 615715; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3631 Zornitza Stark removed gene:EPHX1 from the panel
Fetal anomalies v0.3630 ENPP1 Zornitza Stark Marked gene: ENPP1 as ready
Fetal anomalies v0.3630 ENPP1 Zornitza Stark Gene: enpp1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3630 ENPP1 Zornitza Stark Phenotypes for gene: ENPP1 were changed from HYPOPHOSPHATEMIC RICKETS, AUTOSOMAL RECESSIVE, 2; ARTERIAL CALCIFICATION, GENERALIZED, OF INFANCY, 1 to Arterial calcification, generalized, of infancy, 1, MIM3 208000; Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312
Fetal anomalies v0.3629 ENPP1 Zornitza Stark Publications for gene: ENPP1 were set to
Fetal anomalies v0.3628 ENPP1 Zornitza Stark Classified gene: ENPP1 as Amber List (moderate evidence)
Fetal anomalies v0.3628 ENPP1 Zornitza Stark Gene: enpp1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3627 ENPP1 Zornitza Stark reviewed gene: ENPP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 19521093; Phenotypes: Arterial calcification, generalized, of infancy, 1, MIM3 208000, Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3627 EGR2 Zornitza Stark Marked gene: EGR2 as ready
Fetal anomalies v0.3627 EGR2 Zornitza Stark Gene: egr2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3627 EGR2 Zornitza Stark Phenotypes for gene: EGR2 were changed from NEUROPATHY, CONGENITAL HYPOMYELINATING, 1 to Charcot-Marie-Tooth disease, type 1D, MIM# 607678; Dejerine-Sottas disease, MIM# 145900; Hypomyelinating neuropathy, congenital, 1, MIM# 605253
Fetal anomalies v0.3626 EGR2 Zornitza Stark Mode of inheritance for gene: EGR2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3625 EGR2 Zornitza Stark reviewed gene: EGR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 1D, MIM# 607678, Dejerine-Sottas disease, MIM# 145900, Hypomyelinating neuropathy, congenital, 1, MIM# 605253; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3625 DUSP6 Zornitza Stark Marked gene: DUSP6 as ready
Fetal anomalies v0.3625 DUSP6 Zornitza Stark Gene: dusp6 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3625 DUSP6 Zornitza Stark Publications for gene: DUSP6 were set to
Fetal anomalies v0.3624 DUSP6 Zornitza Stark Mode of inheritance for gene: DUSP6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3623 DMP1 Zornitza Stark Marked gene: DMP1 as ready
Fetal anomalies v0.3623 DMP1 Zornitza Stark Gene: dmp1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3623 DMP1 Zornitza Stark Phenotypes for gene: DMP1 were changed from HYPOPHOSPHATEMIC RICKETS, AR to Hypophosphatemic rickets, AR MIM#241520
Fetal anomalies v0.3622 DMP1 Zornitza Stark Publications for gene: DMP1 were set to
Fetal anomalies v0.3621 DLG3 Zornitza Stark Marked gene: DLG3 as ready
Fetal anomalies v0.3621 DLG3 Zornitza Stark Gene: dlg3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3621 DLG3 Zornitza Stark Phenotypes for gene: DLG3 were changed from MENTAL RETARDATION X-LINKED TYPE 90 to Mental retardation, X-linked 90, MIM#300850
Fetal anomalies v0.3620 DLG3 Zornitza Stark Publications for gene: DLG3 were set to
Fetal anomalies v0.3619 DLG3 Zornitza Stark changed review comment from: At least 6 unrelated families reported. Some females have mild symptoms.; to: At least 6 unrelated families reported. Clinical presentation is typically post-natal.
Fetal anomalies v0.3619 DLG3 Zornitza Stark edited their review of gene: DLG3: Changed rating: RED
Fetal anomalies v0.3619 DLAT Zornitza Stark Marked gene: DLAT as ready
Fetal anomalies v0.3619 DLAT Zornitza Stark Gene: dlat has been classified as Red List (Low Evidence).
Fetal anomalies v0.3619 DLAT Zornitza Stark Phenotypes for gene: DLAT were changed from PYRUVATE DEHYDROGENASE E2 DEFICIENCY to Pyruvate dehydrogenase E2 deficiency, MIM#245348
Fetal anomalies v0.3618 DLAT Zornitza Stark Publications for gene: DLAT were set to
Fetal anomalies v0.3617 DLAT Zornitza Stark changed review comment from: Only two families with ID reported; third individual had paroxysmal dyskinesia.; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.3617 DLAT Zornitza Stark edited their review of gene: DLAT: Changed rating: RED
Fetal anomalies v0.3617 DEAF1 Zornitza Stark Marked gene: DEAF1 as ready
Fetal anomalies v0.3617 DEAF1 Zornitza Stark Gene: deaf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3617 DEAF1 Zornitza Stark Phenotypes for gene: DEAF1 were changed from Autism, intellectual disability, basal ganglia dysfunction and epilepsy; MENTAL RETARDATION, AUTOSOMAL DOMINANT 24 to Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171; Vulto-van Silfout-de Vries syndrome 615828
Fetal anomalies v0.3616 DEAF1 Zornitza Stark Publications for gene: DEAF1 were set to
Fetal anomalies v0.3615 DEAF1 Zornitza Stark Mode of inheritance for gene: DEAF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3614 DEAF1 Zornitza Stark Classified gene: DEAF1 as Green List (high evidence)
Fetal anomalies v0.3614 DEAF1 Zornitza Stark Gene: deaf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3613 DEAF1 Zornitza Stark changed review comment from: Bi-allelic disease is through LOF mechanism (PTVs and missense). Mono-allelic disease described in association with de novo missense variants only.

LOF and Dominant-negative
- De novo missense in the SAND domain tend to have a dominant-negative effect
- Biallelic variants in the SAND domain lead to partial loss of function - missense (reduced function), NMD (haploinsufficiency)
- Heterozygous deletions have no phenotype.; to: Bi-allelic disease is through LOF mechanism (PTVs and missense). Mono-allelic disease described in association with de novo missense variants only.

LOF and Dominant-negative
- De novo missense in the SAND domain tend to have a dominant-negative effect
- Biallelic variants in the SAND domain lead to partial loss of function - missense (reduced function), NMD (haploinsufficiency)
- Heterozygous deletions have no phenotype.

Brain abnormalities on imaging, particularly with AD disorder.
Fetal anomalies v0.3613 ST3GAL5 Zornitza Stark Marked gene: ST3GAL5 as ready
Fetal anomalies v0.3613 ST3GAL5 Zornitza Stark Gene: st3gal5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3613 ST3GAL5 Zornitza Stark Phenotypes for gene: ST3GAL5 were changed from AMISH INFANTILE EPILEPSY SYNDROME to Salt and pepper developmental regression syndrome; OMIM #609056
Fetal anomalies v0.3612 ST3GAL5 Zornitza Stark Publications for gene: ST3GAL5 were set to
Fetal anomalies v0.3611 ST3GAL5 Zornitza Stark Classified gene: ST3GAL5 as Red List (low evidence)
Fetal anomalies v0.3611 ST3GAL5 Zornitza Stark Gene: st3gal5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3610 ST3GAL5 Zornitza Stark changed review comment from: Salt and pepper developmental regression syndrome, also known as Amish infantile epilepsy syndrome, is an autosomal recessive neurocutaneous disorder characterised by infantile onset of refractory and recurrent seizures associated with profoundly delayed psychomotor development and/or developmental regression as well as abnormal movements and visual loss. Affected individuals develop hypo- or hyperpigmented skin macules on the trunk, face, and extremities in early childhood. Although initially reported in the Amish (founder variant p.Arg288Ter), families from other ethnicities have also been reported.; to: Salt and pepper developmental regression syndrome, also known as Amish infantile epilepsy syndrome, is an autosomal recessive neurocutaneous disorder characterised by infantile onset of refractory and recurrent seizures associated with profoundly delayed psychomotor development and/or developmental regression as well as abnormal movements and visual loss. Affected individuals develop hypo- or hyperpigmented skin macules on the trunk, face, and extremities in early childhood. Although initially reported in the Amish (founder variant p.Arg288Ter), families from other ethnicities have also been reported.

Clinical presentation is typically post-natal.
Fetal anomalies v0.3610 ST3GAL5 Zornitza Stark edited their review of gene: ST3GAL5: Changed rating: RED
Fetal anomalies v0.3610 RSPRY1 Zornitza Stark Marked gene: RSPRY1 as ready
Fetal anomalies v0.3610 RSPRY1 Zornitza Stark Gene: rspry1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3610 RSPRY1 Zornitza Stark Phenotypes for gene: RSPRY1 were changed from PROGRESSIVE SPONDYLOEPIMETAPHYSEAL DYSPLASIA to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585
Fetal anomalies v0.3609 RSPRY1 Zornitza Stark Publications for gene: RSPRY1 were set to
Fetal anomalies v0.3608 RSPRY1 Zornitza Stark changed review comment from: Two unrelated individuals reported, some functional evidence. Dev delay/autism part of the phenotype.
Sources: Expert list; to: Two unrelated individuals reported, some functional evidence. Multiple skeletal anomalies.
Sources: Expert list
Fetal anomalies v0.3608 RSPH9 Zornitza Stark Marked gene: RSPH9 as ready
Fetal anomalies v0.3608 RSPH9 Zornitza Stark Gene: rsph9 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3608 RSPH9 Zornitza Stark Phenotypes for gene: RSPH9 were changed from Ciliary dyskinesia, primary 612650 to Ciliary dyskinesia, primary, MIM# 612650
Fetal anomalies v0.3607 RSPH9 Zornitza Stark Publications for gene: RSPH9 were set to
Fetal anomalies v0.3606 RSPH9 Zornitza Stark Classified gene: RSPH9 as Red List (low evidence)
Fetal anomalies v0.3606 RSPH9 Zornitza Stark Gene: rsph9 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3605 RSPH4A Zornitza Stark Marked gene: RSPH4A as ready
Fetal anomalies v0.3605 RSPH4A Zornitza Stark Gene: rsph4a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3605 RSPH4A Zornitza Stark Publications for gene: RSPH4A were set to
Fetal anomalies v0.3604 RSPH4A Zornitza Stark Classified gene: RSPH4A as Red List (low evidence)
Fetal anomalies v0.3604 RSPH4A Zornitza Stark Gene: rsph4a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3603 RRAS2 Zornitza Stark Marked gene: RRAS2 as ready
Fetal anomalies v0.3603 RRAS2 Zornitza Stark Gene: rras2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3603 RRAS2 Zornitza Stark Publications for gene: RRAS2 were set to
Fetal anomalies v0.3602 RRAS2 Zornitza Stark Mode of inheritance for gene: RRAS2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3601 RRAS2 Zornitza Stark Classified gene: RRAS2 as Green List (high evidence)
Fetal anomalies v0.3601 RRAS2 Zornitza Stark Gene: rras2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3600 RRAS Zornitza Stark Marked gene: RRAS as ready
Fetal anomalies v0.3600 RRAS Zornitza Stark Gene: rras has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3600 RRAS Zornitza Stark Phenotypes for gene: RRAS were changed from ATYPICAL NOONAN SYNDROME to Noonan syndrome
Fetal anomalies v0.3599 RRAS Zornitza Stark Publications for gene: RRAS were set to
Fetal anomalies v0.3598 RRAS Zornitza Stark Mode of inheritance for gene: RRAS was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3597 RPS7 Zornitza Stark Marked gene: RPS7 as ready
Fetal anomalies v0.3597 RPS7 Zornitza Stark Gene: rps7 has been classified as Green List (High Evidence).
Fetal anomalies v0.3597 RPS7 Zornitza Stark Publications for gene: RPS7 were set to
Fetal anomalies v0.3596 RPS7 Zornitza Stark Mode of inheritance for gene: RPS7 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3595 RPS7 Zornitza Stark Classified gene: RPS7 as Green List (high evidence)
Fetal anomalies v0.3595 RPS7 Zornitza Stark Gene: rps7 has been classified as Green List (High Evidence).
Fetal anomalies v0.3594 RPS24 Zornitza Stark Marked gene: RPS24 as ready
Fetal anomalies v0.3594 RPS24 Zornitza Stark Gene: rps24 has been classified as Green List (High Evidence).
Fetal anomalies v0.3594 RPS24 Zornitza Stark Mode of inheritance for gene: RPS24 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3593 RPS24 Zornitza Stark Classified gene: RPS24 as Green List (high evidence)
Fetal anomalies v0.3593 RPS24 Zornitza Stark Gene: rps24 has been classified as Green List (High Evidence).
Fetal anomalies v0.3592 RPS23 Zornitza Stark Marked gene: RPS23 as ready
Fetal anomalies v0.3592 RPS23 Zornitza Stark Gene: rps23 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3592 RPS23 Zornitza Stark Phenotypes for gene: RPS23 were changed from Microcephaly, hearing loss, and dysmorphic features to Brachycephaly, trichomegaly, and developmental delay, MIM# 617412
Fetal anomalies v0.3591 RPS23 Zornitza Stark Publications for gene: RPS23 were set to
Fetal anomalies v0.3590 RPS23 Zornitza Stark Mode of inheritance for gene: RPS23 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3589 RPS23 Zornitza Stark changed review comment from: Two unrelated individuals and some functional data.; to: Two unrelated individuals and some functional data. Microcephaly; cleft palate in one.
Fetal anomalies v0.3589 MYH3 Zornitza Stark Mode of inheritance for gene: MYH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3588 MYH3 Zornitza Stark reviewed gene: MYH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM #193700, Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM #618436, Contractures, pterygia, and variable skeletal fusions syndrome 1A, OMIM #178110, Contractures, pterygia, and variable skeletal fusions syndrome 1B, OMIM #618469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3588 MYH6 Alison Yeung Mode of inheritance for gene: MYH6 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3587 MYH3 Alison Yeung Marked gene: MYH3 as ready
Fetal anomalies v0.3587 MYH3 Alison Yeung Gene: myh3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3587 MYH3 Alison Yeung Phenotypes for gene: MYH3 were changed from DISTAL ARTHROGRYPOSIS TYPE 2A; DISTAL ARTHROGRYPOSIS TYPE 2B to Arthrogryposis, distal, type 2A (Freeman-Sheldon) MIM# 193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall) MIM# 618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, MIM#178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, MIM# 618469
Fetal anomalies v0.3586 MYH3 Alison Yeung Publications for gene: MYH3 were set to
Fetal anomalies v0.3585 RPL35A Zornitza Stark Marked gene: RPL35A as ready
Fetal anomalies v0.3585 RPL35A Zornitza Stark Gene: rpl35a has been classified as Green List (High Evidence).
Fetal anomalies v0.3585 RPL35A Zornitza Stark Publications for gene: RPL35A were set to
Fetal anomalies v0.3584 RPL35A Zornitza Stark Mode of inheritance for gene: RPL35A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3583 RPL35A Zornitza Stark Classified gene: RPL35A as Green List (high evidence)
Fetal anomalies v0.3583 RPL35A Zornitza Stark Gene: rpl35a has been classified as Green List (High Evidence).
Fetal anomalies v0.3582 RPL10 Zornitza Stark Marked gene: RPL10 as ready
Fetal anomalies v0.3582 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Fetal anomalies v0.3582 RPL10 Zornitza Stark Publications for gene: RPL10 were set to
Fetal anomalies v0.3581 RPL10 Zornitza Stark Classified gene: RPL10 as Green List (high evidence)
Fetal anomalies v0.3581 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Fetal anomalies v0.3580 RPL10 Zornitza Stark changed review comment from: At least three families reported. Progressive microcephaly, up to -9.6 SD described.
Sources: Expert list; to: At least three families reported. Progressive microcephaly, up to -9.6 SD described. IUGR, congenital heart disease.

Sources: Expert list
Fetal anomalies v0.3580 RORA Zornitza Stark Marked gene: RORA as ready
Fetal anomalies v0.3580 RORA Zornitza Stark Gene: rora has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3580 RORA Zornitza Stark Phenotypes for gene: RORA were changed from INTELLECTUAL DISABILITY to Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, MIM#618060
Fetal anomalies v0.3579 RORA Zornitza Stark Publications for gene: RORA were set to
Fetal anomalies v0.3578 RORA Zornitza Stark Mode of pathogenicity for gene: RORA was changed from Other to None
Fetal anomalies v0.3577 RORA Zornitza Stark Mode of pathogenicity for gene: RORA was changed from to Other
Fetal anomalies v0.3576 RORA Zornitza Stark Mode of inheritance for gene: RORA was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3575 RORA Zornitza Stark changed review comment from: Eleven unrelated individuals with de novo variants in this gene; postulated that some variants exert dominant-negative effect resulting in a more severe phenotype than the LoF variants.
Sources: Expert list; to: Eleven unrelated individuals with de novo variants in this gene; postulated that some variants exert dominant-negative effect resulting in a more severe phenotype than the LoF variants.

Clinical presentation is generally post-natal, but pontocerebellar hypoplasia rarely reported.

Sources: Expert list
Fetal anomalies v0.3575 RORA Zornitza Stark edited their review of gene: RORA: Changed rating: AMBER
Fetal anomalies v0.3575 ROBO3 Zornitza Stark Marked gene: ROBO3 as ready
Fetal anomalies v0.3575 ROBO3 Zornitza Stark Gene: robo3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3575 ROBO3 Zornitza Stark Publications for gene: ROBO3 were set to
Fetal anomalies v0.3574 ROBO3 Zornitza Stark Classified gene: ROBO3 as Green List (high evidence)
Fetal anomalies v0.3574 ROBO3 Zornitza Stark Gene: robo3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3573 RMND1 Zornitza Stark Marked gene: RMND1 as ready
Fetal anomalies v0.3573 RMND1 Zornitza Stark Gene: rmnd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3573 RMND1 Zornitza Stark Phenotypes for gene: RMND1 were changed from ENCEPHALOPATHY ASSOCIATED WITH MULTIPLE OXIDATIVE PHOSPHORYLATION COMPLEX DEFICIENCIES AND A MITOCHONDRIAL TRANSLATION DEFECT to Combined oxidative phosphorylation deficiency 11, MIM# MIM#614922
Fetal anomalies v0.3572 RMND1 Zornitza Stark Publications for gene: RMND1 were set to
Fetal anomalies v0.3571 RMND1 Zornitza Stark Classified gene: RMND1 as Green List (high evidence)
Fetal anomalies v0.3571 RMND1 Zornitza Stark Gene: rmnd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3570 RMND1 Zornitza Stark reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 11, MIM# MIM#614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3570 RLIM Zornitza Stark Marked gene: RLIM as ready
Fetal anomalies v0.3570 RLIM Zornitza Stark Gene: rlim has been classified as Green List (High Evidence).
Fetal anomalies v0.3570 RLIM Zornitza Stark Phenotypes for gene: RLIM were changed from INTELLECTUAL DISABILITY to Tonne-Kalscheuer syndrome, MIM# 300978
Fetal anomalies v0.3569 RLIM Zornitza Stark Publications for gene: RLIM were set to
Fetal anomalies v0.3568 RLIM Zornitza Stark Classified gene: RLIM as Green List (high evidence)
Fetal anomalies v0.3568 RLIM Zornitza Stark Gene: rlim has been classified as Green List (High Evidence).
Fetal anomalies v0.3567 RIN2 Zornitza Stark Marked gene: RIN2 as ready
Fetal anomalies v0.3567 RIN2 Zornitza Stark Gene: rin2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3567 RIN2 Zornitza Stark Phenotypes for gene: RIN2 were changed from MACROCEPHALY, ALOPECIA, CUTIS LAXA, AND SCOLIOSIS TALL FOREHEAD, SPARSE HAIR, SKIN HYPEREXTENSIBILITY, AND SCOLIOSIS to Macrocephaly, alopecia, cutis laxa, and scoliosis, MIM#613075
Fetal anomalies v0.3566 RIN2 Zornitza Stark Publications for gene: RIN2 were set to
Fetal anomalies v0.3565 RIN2 Zornitza Stark Classified gene: RIN2 as Green List (high evidence)
Fetal anomalies v0.3565 RIN2 Zornitza Stark Gene: rin2 has been classified as Green List (High Evidence).
Mendeliome v0.10999 RIN2 Zornitza Stark Marked gene: RIN2 as ready
Mendeliome v0.10999 RIN2 Zornitza Stark Gene: rin2 has been classified as Green List (High Evidence).
Mendeliome v0.10999 RIN2 Zornitza Stark Phenotypes for gene: RIN2 were changed from to Macrocephaly, alopecia, cutis laxa, and scoliosis, MIM#613075
Mendeliome v0.10998 RIN2 Zornitza Stark Publications for gene: RIN2 were set to
Mendeliome v0.10997 RIN2 Zornitza Stark Mode of inheritance for gene: RIN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10996 RIN2 Zornitza Stark reviewed gene: RIN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19631308, 20424861, 20954239, 24449201, 30769224; Phenotypes: Macrocephaly, alopecia, cutis laxa, and scoliosis, MIM#613075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3564 RIN2 Zornitza Stark changed review comment from: Macrocephaly, subcortical cysts and other brain abnormalities are a feature.; to: Macrocephaly, subcortical cysts and other brain abnormalities are a feature. More than 5 unrelated families reported.
Fetal anomalies v0.3564 RIN2 Zornitza Stark edited their review of gene: RIN2: Changed publications: 19631308, 20424861, 20954239, 24449201, 30769224
Fetal anomalies v0.3564 RIN2 Zornitza Stark changed review comment from: ID is not a key feature of this syndrome, most individuals described as having normal/borderline intellect.; to: Macrocephaly, subcortical cysts and other brain abnormalities are a feature.
Fetal anomalies v0.3564 RIN2 Zornitza Stark edited their review of gene: RIN2: Changed rating: GREEN
Fetal anomalies v0.3564 RFT1 Zornitza Stark Marked gene: RFT1 as ready
Fetal anomalies v0.3564 RFT1 Zornitza Stark Gene: rft1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3564 RFT1 Zornitza Stark Publications for gene: RFT1 were set to
Fetal anomalies v0.3563 RFT1 Zornitza Stark changed review comment from: Bi-allelic variants are associated with DD/ID, seizures, deafness. More than 10 unrelated families reported.; to: Bi-allelic variants are associated with DD/ID, seizures, deafness. More than 10 unrelated families reported.

Clinical presentation is typically post-natal, though age of onset of microcephaly is uncertain.
Fetal anomalies v0.3563 RFT1 Zornitza Stark edited their review of gene: RFT1: Changed rating: AMBER
Fetal anomalies v0.3563 RBM10 Zornitza Stark Marked gene: RBM10 as ready
Fetal anomalies v0.3563 RBM10 Zornitza Stark Gene: rbm10 has been classified as Green List (High Evidence).
Fetal anomalies v0.3563 RBM10 Zornitza Stark Publications for gene: RBM10 were set to
Fetal anomalies v0.3562 RBM10 Zornitza Stark Classified gene: RBM10 as Green List (high evidence)
Fetal anomalies v0.3562 RBM10 Zornitza Stark Gene: rbm10 has been classified as Green List (High Evidence).
Fetal anomalies v0.3561 RBM10 Zornitza Stark Deleted their comment
Fetal anomalies v0.3561 RBM10 Zornitza Stark edited their review of gene: RBM10: Added comment: Well established gene-disease association, multiple congenital anomalies.; Changed rating: GREEN; Changed publications: 20451169, 24259342, 30450804, 30189253
Fetal anomalies v0.3561 DUSP6 Belinda Chong reviewed gene: DUSP6: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 19 with or without anosmia MIM615269; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3561 RBBP8 Zornitza Stark Marked gene: RBBP8 as ready
Fetal anomalies v0.3561 RBBP8 Zornitza Stark Gene: rbbp8 has been classified as Green List (High Evidence).
Fetal anomalies v0.3561 RBBP8 Zornitza Stark Phenotypes for gene: RBBP8 were changed from Seckel syndrome 2, MONDO:0011715; Seckel syndrome 2, OMIM:606744 to Jawad syndrome, MIM# 251255; Seckel syndrome 2, MONDO:0011715; Seckel syndrome 2, OMIM:606744
Fetal anomalies v0.3560 RBBP8 Zornitza Stark Publications for gene: RBBP8 were set to
Fetal anomalies v0.3559 RBBP8 Zornitza Stark Classified gene: RBBP8 as Green List (high evidence)
Fetal anomalies v0.3559 RBBP8 Zornitza Stark Gene: rbbp8 has been classified as Green List (High Evidence).
Fetal anomalies v0.3558 RAD51C Zornitza Stark Marked gene: RAD51C as ready
Fetal anomalies v0.3558 RAD51C Zornitza Stark Gene: rad51c has been classified as Green List (High Evidence).
Fetal anomalies v0.3558 RAD51C Zornitza Stark Phenotypes for gene: RAD51C were changed from FANCONI ANEMIA, COMPLEMENTATION GROUP 0 to Fanconi anemia, complementation group O, MIM# 613390
Fetal anomalies v0.3557 RAD51C Zornitza Stark Publications for gene: RAD51C were set to
Fetal anomalies v0.3556 RAD51C Zornitza Stark Classified gene: RAD51C as Green List (high evidence)
Fetal anomalies v0.3556 RAD51C Zornitza Stark Gene: rad51c has been classified as Green List (High Evidence).
Fetal anomalies v0.3555 RAD51 Zornitza Stark Marked gene: RAD51 as ready
Fetal anomalies v0.3555 RAD51 Zornitza Stark Gene: rad51 has been classified as Green List (High Evidence).
Fetal anomalies v0.3555 RAD51 Zornitza Stark Phenotypes for gene: RAD51 were changed from MIRROR MOVEMENTS 2 to Fanconi anaemia, complementation group R, MIM# 617244
Fetal anomalies v0.3554 RAD51 Zornitza Stark Publications for gene: RAD51 were set to
Fetal anomalies v0.3553 RAD51 Zornitza Stark Mode of inheritance for gene: RAD51 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3552 RAD51 Zornitza Stark Classified gene: RAD51 as Green List (high evidence)
Fetal anomalies v0.3552 RAD51 Zornitza Stark Gene: rad51 has been classified as Green List (High Evidence).
Fetal anomalies v0.3551 RAD51 Zornitza Stark changed review comment from: Three unrelated individuals reported with de novo variants in this gene and FA phenotype. However, only one had radial ray abnormalities.
Sources: Expert Review; to: Three unrelated individuals reported with de novo variants in this gene and FA phenotype.
Sources: Expert Review
Fetal anomalies v0.3551 RAD51 Zornitza Stark edited their review of gene: RAD51: Changed rating: GREEN
Fetal anomalies v0.3551 RAB11B Zornitza Stark Marked gene: RAB11B as ready
Fetal anomalies v0.3551 RAB11B Zornitza Stark Gene: rab11b has been classified as Green List (High Evidence).
Fetal anomalies v0.3551 RAB11B Zornitza Stark Phenotypes for gene: RAB11B were changed from INTELLECTUAL DISABILITY to Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, MIM# 617807
Fetal anomalies v0.3550 RAB11B Zornitza Stark Publications for gene: RAB11B were set to
Fetal anomalies v0.3549 RAB11B Zornitza Stark Mode of inheritance for gene: RAB11B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3548 RAB11B Zornitza Stark Classified gene: RAB11B as Green List (high evidence)
Fetal anomalies v0.3548 RAB11B Zornitza Stark Gene: rab11b has been classified as Green List (High Evidence).
Fetal anomalies v0.3547 RAB11A Zornitza Stark Marked gene: RAB11A as ready
Fetal anomalies v0.3547 RAB11A Zornitza Stark Gene: rab11a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3547 RAB11A Zornitza Stark Publications for gene: RAB11A were set to
Fetal anomalies v0.3546 RAB11A Zornitza Stark Mode of inheritance for gene: RAB11A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3545 RAB11A Zornitza Stark Classified gene: RAB11A as Red List (low evidence)
Fetal anomalies v0.3545 RAB11A Zornitza Stark Gene: rab11a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3544 RAB11A Zornitza Stark changed review comment from: Five individuals reported with DNMs and neurodevelopmental phenotypes as part of this paper; however, clinical details are sparse. Emerging gene, phenotype not yet clearly delineated.
Sources: Literature; to: Five individuals reported with DNMs and neurodevelopmental phenotypes as part of this paper; however, clinical details are sparse. Emerging gene, phenotype not yet clearly delineated.

Clinical presentation is post-natal.
Sources: Literature
Fetal anomalies v0.3544 RAB11A Zornitza Stark edited their review of gene: RAB11A: Changed rating: RED
Fetal anomalies v0.3544 DMP1 Belinda Chong reviewed gene: DMP1: Rating: RED; Mode of pathogenicity: None; Publications: 17033625, 17033621, 31843680; Phenotypes: Hypophosphatemic rickets, AR MIM#241520; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hypertension and Aldosterone disorders v1.5 CYP11B1 Chirag Patel Classified gene: CYP11B1 as Green List (high evidence)
Hypertension and Aldosterone disorders v1.5 CYP11B1 Chirag Patel Gene: cyp11b1 has been classified as Green List (High Evidence).
Hypertension and Aldosterone disorders v1.4 CYP11B1 Chirag Patel reviewed gene: CYP11B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.10996 DLD Zornitza Stark Marked gene: DLD as ready
Mendeliome v0.10996 DLD Zornitza Stark Gene: dld has been classified as Green List (High Evidence).
Mendeliome v0.10996 DLD Zornitza Stark Phenotypes for gene: DLD were changed from to Dihydrolipoamide dehydrogenase deficiency MIM#246900
Mendeliome v0.10995 DLD Zornitza Stark Publications for gene: DLD were set to
Mendeliome v0.10994 DLD Zornitza Stark Mode of inheritance for gene: DLD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3544 DLD Zornitza Stark Marked gene: DLD as ready
Fetal anomalies v0.3544 DLD Zornitza Stark Gene: dld has been classified as Red List (Low Evidence).
Fetal anomalies v0.3544 DLD Zornitza Stark Phenotypes for gene: DLD were changed from LEIGH SYNDROME; DIHYDROLIPOAMIDE DEHYDROGENASE (E3) DEFICIENCY to Dihydrolipoamide dehydrogenase deficiency MIM#246900
Fetal anomalies v0.3543 DLD Zornitza Stark Publications for gene: DLD were set to
Fetal anomalies v0.3542 WNT9B Zornitza Stark Marked gene: WNT9B as ready
Fetal anomalies v0.3542 WNT9B Zornitza Stark Gene: wnt9b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3542 WNT9B Zornitza Stark Classified gene: WNT9B as Amber List (moderate evidence)
Fetal anomalies v0.3542 WNT9B Zornitza Stark Gene: wnt9b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4507 KIAA0391 Zornitza Stark Phenotypes for gene: KIAA0391 were changed from Combined oxidative phosphorylation deficiency 54, MIM# 619737 to Combined oxidative phosphorylation deficiency 54, MIM# 619737
Intellectual disability syndromic and non-syndromic v0.4507 KIAA0391 Zornitza Stark Phenotypes for gene: KIAA0391 were changed from Hearing loss, intellectual disability; Mitochondrial disorder to Combined oxidative phosphorylation deficiency 54, MIM# 619737
Intellectual disability syndromic and non-syndromic v0.4506 KIAA0391 Zornitza Stark Tag new gene name tag was added to gene: KIAA0391.
Intellectual disability syndromic and non-syndromic v0.4506 KIAA0391 Zornitza Stark edited their review of gene: KIAA0391: Changed phenotypes: Combined oxidative phosphorylation deficiency 54, MIM# 619737
Deafness_IsolatedAndComplex v1.117 KIAA0391 Zornitza Stark Phenotypes for gene: KIAA0391 were changed from Hearing loss, intellectual disability; Mitochondrial disorder to Combined oxidative phosphorylation deficiency 54, MIM# 619737
Deafness_IsolatedAndComplex v1.116 KIAA0391 Zornitza Stark Tag new gene name tag was added to gene: KIAA0391.
Deafness_IsolatedAndComplex v1.116 KIAA0391 Zornitza Stark edited their review of gene: KIAA0391: Changed phenotypes: Combined oxidative phosphorylation deficiency 54, MIM# 619737
Mitochondrial disease v0.694 KIAA0391 Zornitza Stark Tag new gene name tag was added to gene: KIAA0391.
Mitochondrial disease v0.694 KIAA0391 Zornitza Stark Phenotypes for gene: KIAA0391 were changed from Hearing loss, intellectual disability; Mitochondrial disorder to Combined oxidative phosphorylation deficiency 54, MIM# 619737
Mitochondrial disease v0.693 KIAA0391 Zornitza Stark edited their review of gene: KIAA0391: Changed phenotypes: Combined oxidative phosphorylation deficiency 54, MIM# 619737
Mendeliome v0.10993 KIAA0391 Zornitza Stark Tag new gene name tag was added to gene: KIAA0391.
Mendeliome v0.10993 KIAA0391 Zornitza Stark changed review comment from: Comment when marking as ready: Note gene is referred to as PRORP in the manuscript, but HGNC approved name is KIAA0391.; to: HGNC approved name is now PRORP.
Mendeliome v0.10993 KIAA0391 Zornitza Stark Phenotypes for gene: KIAA0391 were changed from Mitochondrial disorder to Combined oxidative phosphorylation deficiency 54, MIM# 619737
Mendeliome v0.10992 DLD Belinda Chong reviewed gene: DLD: Rating: GREEN; Mode of pathogenicity: None; Publications: 3769994, 8506365, 9934985, 17404228, 21558426, 21930696; Phenotypes: Dihydrolipoamide dehydrogenase deficiency MIM#246900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3541 DLD Belinda Chong reviewed gene: DLD: Rating: RED; Mode of pathogenicity: None; Publications: 3769994, 8506365, 9934985, 17404228, 21558426, 21930696; Phenotypes: Dihydrolipoamide dehydrogenase deficiency MIM#246900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3541 WNT9B Krithika Murali gene: WNT9B was added
gene: WNT9B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WNT9B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT9B were set to 34145744
Phenotypes for gene: WNT9B were set to Renal agenesis/hypoplasia/dysplasia, no OMIM #
Review for gene: WNT9B was set to AMBER
Added comment: Now new publications since last PanelApp review Sept 2021

---

WNT9B plays a key role in the development of the mammalian urogenital system. It is essential for the induction of mesonephric and metanephric tubules, the regulation of renal tubule morphogenesis, and the regulation of renal progenitor cell expansion and differentiation. WNT9B−/− mice have renal agenesis/hypoplasia and reproductive tract abnormalities.

Lemire et al. (2021) report 4 individuals from 2 unrelated consanguineous families with bilateral renal agenesis/hypoplasia/dysplasia and homozygous variants in WNT9B. The proband from Family 1 had bilateral renal cystic dysplasia and chronic kidney disease, with 2 deceased siblings with bilateral renal hypoplasia/agenesis. The 3 affected family members were homozygous for a Gly317Arg missense variant in WNT9B. Proband from Family 2 had renal hypoplasia/dysplasia, chronic kidney disease, and was homozygous for a Pro5Alafs*52 nonsense variant in WNT9B. The proband's unaffected brother is also homozygous for the nonsense variant in WNT9B, suggesting nonpenetrance.
Sources: Literature
Hereditary Neuropathy - complex v0.120 POLR3B Zornitza Stark Phenotypes for gene: POLR3B were changed from Ataxia, spasticity, and demyelinating neuropathy to Charcot-Marie-Tooth disease, demyelinating, type 1I, MIM# 619742
Hereditary Neuropathy - complex v0.119 POLR3B Zornitza Stark edited their review of gene: POLR3B: Changed rating: GREEN; Changed phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1I, MIM# 619742; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10992 POLR3B Zornitza Stark Phenotypes for gene: POLR3B were changed from Ataxia, spasticity, and demyelinating neuropathy; Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism MIM#614381 to Charcot-Marie-Tooth disease, demyelinating, type 1I, MIM# 619742; Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381
Mendeliome v0.10991 POLR3B Zornitza Stark edited their review of gene: POLR3B: Changed phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1I, MIM# 619742, Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3541 TBCK Zornitza Stark Marked gene: TBCK as ready
Fetal anomalies v0.3541 TBCK Zornitza Stark Gene: tbck has been classified as Green List (High Evidence).
Fetal anomalies v0.3541 TBCK Zornitza Stark Phenotypes for gene: TBCK were changed from Severe Infantile Syndromic Encephalopathy to Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, MIM# 616900
Fetal anomalies v0.3540 TBCK Zornitza Stark Publications for gene: TBCK were set to
Fetal anomalies v0.3539 TBCK Zornitza Stark reviewed gene: TBCK: Rating: GREEN; Mode of pathogenicity: None; Publications: 27040692, 30103036, 27040691; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, MIM# 616900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3539 TBL1XR1 Zornitza Stark Marked gene: TBL1XR1 as ready
Fetal anomalies v0.3539 TBL1XR1 Zornitza Stark Gene: tbl1xr1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3539 TBL1XR1 Zornitza Stark Phenotypes for gene: TBL1XR1 were changed from Intellectual disability with autism spectrum disorder; Pierpont syndrome to Mental retardation, autosomal dominant 41, MIM# 616944; Pierpont syndrome, MIM# 602342
Fetal anomalies v0.3538 TBL1XR1 Zornitza Stark Mode of inheritance for gene: TBL1XR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3537 TBL1XR1 Zornitza Stark changed review comment from: Well established gene-disease association. However, few if any significant congenital anomalies associated.; to: Well established gene-disease associations. However, few if any significant congenital anomalies associated.
Fetal anomalies v0.3537 TBL1XR1 Zornitza Stark reviewed gene: TBL1XR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal dominant 41, MIM# 616944, Pierpont syndrome, MIM# 602342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10991 TBX15 Zornitza Stark Marked gene: TBX15 as ready
Mendeliome v0.10991 TBX15 Zornitza Stark Gene: tbx15 has been classified as Green List (High Evidence).
Mendeliome v0.10991 TBX15 Zornitza Stark Phenotypes for gene: TBX15 were changed from to Cousin syndrome, MIM# 260660
Mendeliome v0.10990 TBX15 Zornitza Stark Publications for gene: TBX15 were set to
Mendeliome v0.10989 TBX15 Zornitza Stark Mode of inheritance for gene: TBX15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10988 TBX15 Zornitza Stark reviewed gene: TBX15: Rating: GREEN; Mode of pathogenicity: None; Publications: 19068278, 24039145; Phenotypes: Cousin syndrome, MIM# 260660; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3537 TBX15 Zornitza Stark Marked gene: TBX15 as ready
Fetal anomalies v0.3537 TBX15 Zornitza Stark Gene: tbx15 has been classified as Green List (High Evidence).
Fetal anomalies v0.3537 TBX15 Zornitza Stark Phenotypes for gene: TBX15 were changed from Cousin Syndrome; Craniofacial Dysmorphism, Hypoplasia of Scapula and Pelvis, and Short Stature to Cousin syndrome, MIM# 260660; Craniofacial Dysmorphism, Hypoplasia of Scapula and Pelvis, and Short Stature
Fetal anomalies v0.3536 TBX15 Zornitza Stark Publications for gene: TBX15 were set to
Fetal anomalies v0.3535 TBX15 Zornitza Stark reviewed gene: TBX15: Rating: GREEN; Mode of pathogenicity: None; Publications: 19068278, 24039145; Phenotypes: Cousin syndrome, MIM# 260660; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.100 TBX18 Zornitza Stark Marked gene: TBX18 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.100 TBX18 Zornitza Stark Gene: tbx18 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.100 TBX18 Zornitza Stark Phenotypes for gene: TBX18 were changed from to Congenital anomalies of kidney and urinary tract 2, MIM# 143400
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.99 TBX18 Zornitza Stark Publications for gene: TBX18 were set to
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.98 TBX18 Zornitza Stark Mode of inheritance for gene: TBX18 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.97 TBX18 Zornitza Stark reviewed gene: TBX18: Rating: GREEN; Mode of pathogenicity: None; Publications: 26235987; Phenotypes: Congenital anomalies of kidney and urinary tract 2, MIM# 143400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10988 TBX18 Zornitza Stark Marked gene: TBX18 as ready
Mendeliome v0.10988 TBX18 Zornitza Stark Gene: tbx18 has been classified as Green List (High Evidence).
Mendeliome v0.10988 TBX18 Zornitza Stark Phenotypes for gene: TBX18 were changed from to Congenital anomalies of kidney and urinary tract 2, MIM# 143400
Mendeliome v0.10987 TBX18 Zornitza Stark Publications for gene: TBX18 were set to
Mendeliome v0.10986 TBX18 Zornitza Stark Mode of inheritance for gene: TBX18 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10985 TBX18 Zornitza Stark reviewed gene: TBX18: Rating: GREEN; Mode of pathogenicity: None; Publications: 26235987; Phenotypes: Congenital anomalies of kidney and urinary tract 2, MIM# 143400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3535 TBX18 Zornitza Stark Marked gene: TBX18 as ready
Fetal anomalies v0.3535 TBX18 Zornitza Stark Gene: tbx18 has been classified as Green List (High Evidence).
Fetal anomalies v0.3535 TBX18 Zornitza Stark Phenotypes for gene: TBX18 were changed from CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT 2 to Congenital anomalies of kidney and urinary tract 2, MIM# 143400
Fetal anomalies v0.3534 TBX18 Zornitza Stark Publications for gene: TBX18 were set to
Fetal anomalies v0.3533 TBX18 Zornitza Stark Mode of inheritance for gene: TBX18 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3532 TBX18 Zornitza Stark reviewed gene: TBX18: Rating: GREEN; Mode of pathogenicity: None; Publications: 26235987; Phenotypes: Congenital anomalies of kidney and urinary tract 2, MIM# 143400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3532 TBX20 Zornitza Stark Marked gene: TBX20 as ready
Fetal anomalies v0.3532 TBX20 Zornitza Stark Gene: tbx20 has been classified as Green List (High Evidence).
Fetal anomalies v0.3532 TBX20 Zornitza Stark Phenotypes for gene: TBX20 were changed from ATRIAL SEPTAL DEFECT TYPE 4 to Atrial septal defect 4, MIM# 611363
Fetal anomalies v0.3531 TBX20 Zornitza Stark Publications for gene: TBX20 were set to
Fetal anomalies v0.3530 TBX20 Zornitza Stark Mode of inheritance for gene: TBX20 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3529 TBX20 Zornitza Stark reviewed gene: TBX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 17668378, 19762328, 33585493, 29089047; Phenotypes: Atrial septal defect 4, MIM# 611363; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3529 TBX4 Zornitza Stark Marked gene: TBX4 as ready
Fetal anomalies v0.3529 TBX4 Zornitza Stark Gene: tbx4 has been classified as Green List (High Evidence).
Mendeliome v0.10985 TBX4 Zornitza Stark Phenotypes for gene: TBX4 were changed from Posterior amelia with pelvis and pulmonary hypoplasia; small patella syndrome to Amelia, posterior, with pelvic and pulmonary hypoplasia syndrome, MIM# 601360; Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension, MIM# 147891
Mendeliome v0.10984 TBX4 Zornitza Stark Mode of inheritance for gene: TBX4 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.10983 TBX4 Zornitza Stark edited their review of gene: TBX4: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v0.3529 TBX4 Zornitza Stark Phenotypes for gene: TBX4 were changed from Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension, OMIM:147891 to Amelia, posterior, with pelvic and pulmonary hypoplasia syndrome, MIM# 601360; Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension, MIM# 147891
Fetal anomalies v0.3528 TBX4 Zornitza Stark Publications for gene: TBX4 were set to
Fetal anomalies v0.3527 TBX4 Zornitza Stark Mode of inheritance for gene: TBX4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3526 TBX4 Zornitza Stark reviewed gene: TBX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23592887, 31151956, 31761294, 31965066; Phenotypes: Amelia, posterior, with pelvic and pulmonary hypoplasia syndrome, MIM# 601360, Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension, MIM# 147891; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3526 TCF12 Zornitza Stark Marked gene: TCF12 as ready
Fetal anomalies v0.3526 TCF12 Zornitza Stark Gene: tcf12 has been classified as Green List (High Evidence).
Fetal anomalies v0.3526 TCF12 Zornitza Stark Phenotypes for gene: TCF12 were changed from CORONAL CRANIOSYNOSTOSIS to Craniosynostosis 3, MIM# 615314
Fetal anomalies v0.3525 TCF12 Zornitza Stark Publications for gene: TCF12 were set to
Fetal anomalies v0.3524 TCF12 Zornitza Stark Mode of inheritance for gene: TCF12 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3523 TCF12 Zornitza Stark reviewed gene: TCF12: Rating: GREEN; Mode of pathogenicity: None; Publications: 23354436; Phenotypes: Craniosynostosis 3, MIM# 615314; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3523 TBX6 Zornitza Stark Marked gene: TBX6 as ready
Fetal anomalies v0.3523 TBX6 Zornitza Stark Gene: tbx6 has been classified as Green List (High Evidence).
Fetal anomalies v0.3523 TBX6 Zornitza Stark Phenotypes for gene: TBX6 were changed from Spondylocostal dysostosis 5 122600 to Spondylocostal dysostosis 5 , MIM#122600
Fetal anomalies v0.3522 TBX6 Zornitza Stark Publications for gene: TBX6 were set to
Fetal anomalies v0.3521 TBX6 Zornitza Stark Mode of inheritance for gene: TBX6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3520 TCOF1 Zornitza Stark Marked gene: TCOF1 as ready
Fetal anomalies v0.3520 TCOF1 Zornitza Stark Gene: tcof1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3520 TCOF1 Zornitza Stark Phenotypes for gene: TCOF1 were changed from TREACHER COLLINS SYNDROME TYPE 1 to Treacher Collins syndrome 1, MIM# 154500
Fetal anomalies v0.3519 TCOF1 Zornitza Stark Mode of inheritance for gene: TCOF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3518 TCOF1 Zornitza Stark reviewed gene: TCOF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Treacher Collins syndrome 1, MIM# 154500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10983 TGDS Zornitza Stark Marked gene: TGDS as ready
Mendeliome v0.10983 TGDS Zornitza Stark Gene: tgds has been classified as Green List (High Evidence).
Mendeliome v0.10983 TGDS Zornitza Stark Phenotypes for gene: TGDS were changed from to Catel-Manzke syndrome, MIM# 616145
Mendeliome v0.10982 TGDS Zornitza Stark Publications for gene: TGDS were set to
Mendeliome v0.10981 TGDS Zornitza Stark Mode of inheritance for gene: TGDS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10980 TGDS Zornitza Stark reviewed gene: TGDS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25480037; Phenotypes: Catel-Manzke syndrome, MIM# 616145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3518 TGDS Zornitza Stark Marked gene: TGDS as ready
Fetal anomalies v0.3518 TGDS Zornitza Stark Gene: tgds has been classified as Green List (High Evidence).
Fetal anomalies v0.3518 TGDS Zornitza Stark Phenotypes for gene: TGDS were changed from CATEL-MANZKE SYNDROME to Catel-Manzke syndrome, MIM# 616145
Fetal anomalies v0.3517 TGDS Zornitza Stark Publications for gene: TGDS were set to
Fetal anomalies v0.3516 TGDS Zornitza Stark reviewed gene: TGDS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25480037; Phenotypes: Catel-Manzke syndrome, MIM# 616145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3516 TGFB2 Zornitza Stark Marked gene: TGFB2 as ready
Fetal anomalies v0.3516 TGFB2 Zornitza Stark Gene: tgfb2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3516 TGFB2 Zornitza Stark Phenotypes for gene: TGFB2 were changed from LOEYS-DIETZ SYNDROME, TYPE 4 to Loeys-Dietz syndrome 4, MIM# 614816
Fetal anomalies v0.3515 TGFB2 Zornitza Stark Mode of inheritance for gene: TGFB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3514 TGFB2 Zornitza Stark reviewed gene: TGFB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 4, MIM# 614816; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3514 TGFB3 Zornitza Stark Marked gene: TGFB3 as ready
Fetal anomalies v0.3514 TGFB3 Zornitza Stark Gene: tgfb3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3514 TGFB3 Zornitza Stark Phenotypes for gene: TGFB3 were changed from LOEYS-DIETZ SYNDROME to Loeys-Dietz syndrome 5, MIM# 615582
Fetal anomalies v0.3513 TGFB3 Zornitza Stark Mode of inheritance for gene: TGFB3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3512 TGFB3 Zornitza Stark reviewed gene: TGFB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 5, MIM# 615582; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4506 THOC6 Zornitza Stark Marked gene: THOC6 as ready
Intellectual disability syndromic and non-syndromic v0.4506 THOC6 Zornitza Stark Gene: thoc6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4506 THOC6 Zornitza Stark Phenotypes for gene: THOC6 were changed from to Beaulieu-Boycott-Innes syndrome, MIM# 613680
Intellectual disability syndromic and non-syndromic v0.4505 THOC6 Zornitza Stark Publications for gene: THOC6 were set to
Intellectual disability syndromic and non-syndromic v0.4504 THOC6 Zornitza Stark Mode of inheritance for gene: THOC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4503 THOC6 Zornitza Stark reviewed gene: THOC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23621916, 26739162, 27102954, 30238602, 30476144; Phenotypes: Beaulieu-Boycott-Innes syndrome, MIM# 613680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10980 THOC6 Zornitza Stark Marked gene: THOC6 as ready
Mendeliome v0.10980 THOC6 Zornitza Stark Gene: thoc6 has been classified as Green List (High Evidence).
Mendeliome v0.10980 THOC6 Zornitza Stark Phenotypes for gene: THOC6 were changed from to Beaulieu-Boycott-Innes syndrome, MIM# 613680
Mendeliome v0.10979 THOC6 Zornitza Stark Publications for gene: THOC6 were set to
Mendeliome v0.10978 THOC6 Zornitza Stark Mode of inheritance for gene: THOC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10977 THOC6 Zornitza Stark reviewed gene: THOC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23621916, 26739162, 27102954, 30238602, 30476144; Phenotypes: Beaulieu-Boycott-Innes syndrome, MIM# 613680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3512 THOC6 Zornitza Stark Marked gene: THOC6 as ready
Fetal anomalies v0.3512 THOC6 Zornitza Stark Gene: thoc6 has been classified as Green List (High Evidence).
Fetal anomalies v0.3512 THOC6 Zornitza Stark Phenotypes for gene: THOC6 were changed from Beaulieu-Boycott-Innes syndrome to Beaulieu-Boycott-Innes syndrome, MIM# 613680
Fetal anomalies v0.3511 THOC6 Zornitza Stark Publications for gene: THOC6 were set to
Fetal anomalies v0.3510 THOC6 Zornitza Stark reviewed gene: THOC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23621916, 26739162, 27102954, 30238602, 30476144; Phenotypes: Beaulieu-Boycott-Innes syndrome, MIM# 613680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3510 TBC1D1 Krithika Murali gene: TBC1D1 was added
gene: TBC1D1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TBC1D1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBC1D1 were set to 26572137
Phenotypes for gene: TBC1D1 were set to CAKUT
Review for gene: TBC1D1 was set to GREEN
Added comment: No new publications since last PanelApp review included below

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1 heterozygous de novo frameshift variant in TBC1D1 in 1 CAKUT.
3 further CAKUT cases with three novel or rare inherited heterozygous TBC1D1 missense variants predicted to be pathogenic. TBC1D1 mutations affected Ser237-phosphorylation or protein stability and thereby act as hypomorphs. Tbc1d1 showed widespread expression in the developing murine urogenital system. A mild CAKUT spectrum phenotype, including anomalies observed in patients carrying TBC1D1 mutations, was found in kidneys of some Tbc1d1 (-/-) mice. Significantly reduced Glut4 levels were detected in kidneys of Tbc1d1 (-/-) mice and the dysplastic kidney of a TBC1D1 mutation carrier versus controls. TBC1D1 and SLC2A4 encoding GLUT4 were highly expressed in human fetal kidney. These data demonstrate heterozygous deactivating TBC1D1 mutations in CAKUT patients with a similar renal and ureteral phenotype, and provide evidence that TBC1D1 mutations may contribute to CAKUT pathogenesis, possibly via a role in glucose homeostasis.
Sources: Literature
Fetal anomalies v0.3510 THRA Zornitza Stark edited their review of gene: THRA: Changed publications: 22168587, 22494134, 25670821
Fetal anomalies v0.3510 THRA Zornitza Stark Marked gene: THRA as ready
Fetal anomalies v0.3510 THRA Zornitza Stark Gene: thra has been classified as Green List (High Evidence).
Fetal anomalies v0.3510 THRA Zornitza Stark Phenotypes for gene: THRA were changed from HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 6 to Hypothyroidism, congenital, nongoitrous, 6, MIM# 614450
Fetal anomalies v0.3509 THRA Zornitza Stark Publications for gene: THRA were set to
Fetal anomalies v0.3508 SRGAP1 Krithika Murali gene: SRGAP1 was added
gene: SRGAP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SRGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRGAP1 were set to 26026792
Phenotypes for gene: SRGAP1 were set to congenital anomalies of the kidney and urinary tract
Review for gene: SRGAP1 was set to AMBER
Added comment: PMID 26026792 Hwang et al report 2 unrelated families with heterozygous SRGAP1 variants.
- Family 1 - proband with prenatally diagnosed multicystic dysplastic kidney, affected mother with right duplex kidney
- Family 2 - proband with horseshoe kidney with a multicystic dysplastic right upper pole. Variant paternally inherited, father not available for renal ultrasound

Supportive mouse models
Sources: Literature
Fetal anomalies v0.3508 THRA Zornitza Stark Mode of inheritance for gene: THRA was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3507 THRA Zornitza Stark reviewed gene: THRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypothyroidism, congenital, nongoitrous, 6, MIM# 614450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3507 TMCO1 Zornitza Stark Marked gene: TMCO1 as ready
Fetal anomalies v0.3507 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3507 TMCO1 Zornitza Stark Phenotypes for gene: TMCO1 were changed from CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION SYNDROME to Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980
Fetal anomalies v0.3506 TMCO1 Zornitza Stark Publications for gene: TMCO1 were set to
Fetal anomalies v0.3505 TMCO1 Zornitza Stark changed review comment from: Multiple families reported. Although some have the same recurrent founder variants, sufficient number of families from different ethnicities and with different variants reported for Green rating.; to: Multiple families reported. Although some have the same recurrent founder variants, sufficient number of families from different ethnicities and with different variants reported for Green rating.

Skeletal abnormalities are pertinent to this panel.
Fetal anomalies v0.3505 TMCO1 Zornitza Stark reviewed gene: TMCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20018682, 23320496, 24194475, 30556256, 31102500; Phenotypes: Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3505 TPM3 Zornitza Stark Marked gene: TPM3 as ready
Fetal anomalies v0.3505 TPM3 Zornitza Stark Gene: tpm3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3505 TPM3 Zornitza Stark Phenotypes for gene: TPM3 were changed from Congenital fiber-type disproportion myopathy 255310 to Myopathy, congenital, with fiber-type disproportion, MIM# 255310
Fetal anomalies v0.3504 TPM3 Zornitza Stark reviewed gene: TPM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, congenital, with fiber-type disproportion, MIM# 255310; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3504 TREX1 Zornitza Stark Marked gene: TREX1 as ready
Fetal anomalies v0.3504 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3504 TREX1 Zornitza Stark Phenotypes for gene: TREX1 were changed from AICARDI-GOUTIERES SYNDROME 1, DOMINANT AND RECESSIVE to Aicardi-Goutieres syndrome 1, dominant and recessive, MIM# 225750
Fetal anomalies v0.3503 TREX1 Zornitza Stark Publications for gene: TREX1 were set to
Fetal anomalies v0.3502 TREX1 Zornitza Stark reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33527515; Phenotypes: Aicardi-Goutieres syndrome 1, dominant and recessive, MIM# 225750; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3502 SLIT2 Krithika Murali gene: SLIT2 was added
gene: SLIT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SLIT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLIT2 were set to 26026792; 15130495
Phenotypes for gene: SLIT2 were set to CAKUT; vesicoureteric reflux
Review for gene: SLIT2 was set to AMBER
Added comment: PMID 26026792 Hwang et al 2019 - identified three unrelated individuals with CAKUT and different heterozygous SLIT2 missense mutations.
- 1 patient presented with multiple bilateral subcortical renal cysts
- 1 patient presented with multicystic dysplastic kidneys
- 1 patient had right renal agenesis

Authors provide supportive variant-specific mouse models.

PMID: 34059960 Liu et al 2021 - 3 unrelated children from a Chinese Kidney Disease Database with vesicoureteric reflux had SLIT3 VUS identified

PMID 19350278 Zu et al 2009 - x2 unrelated individuals with SLIT2 variants - not segregating with disease in either family
Sources: Literature
Fetal anomalies v0.3502 NEK9 Zornitza Stark Marked gene: NEK9 as ready
Fetal anomalies v0.3502 NEK9 Zornitza Stark Gene: nek9 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3502 NEK9 Zornitza Stark Phenotypes for gene: NEK9 were changed from Arthrogryposis, Perthes disease, and upward gaze palsy, MONDO:0013660; NEK9-related lethal skeletal dysplasia, MONDO:0014870; Lethal congenital contracture syndrome 10, OMIM:617022; ?Arthrogryposis, Perthes disease, and upward gaze palsy, OMIM:614262 to Arthrogryposis, Perthes disease, and upward gaze palsy, MONDO:0013660; NEK9-related lethal skeletal dysplasia, MONDO:0014870; Lethal congenital contracture syndrome 10, OMIM:617022; Arthrogryposis, Perthes disease, and upward gaze palsy, OMIM:614262
Fetal anomalies v0.3501 NEK9 Zornitza Stark edited their review of gene: NEK9: Changed rating: AMBER; Changed phenotypes: Lethal congenital contracture syndrome 10, MIM# 617022, Skeletal dysplasia
Fetal anomalies v0.3501 NEK8 Zornitza Stark Marked gene: NEK8 as ready
Fetal anomalies v0.3501 NEK8 Zornitza Stark Gene: nek8 has been classified as Green List (High Evidence).
Fetal anomalies v0.3501 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MONDO:0014174; Renal-hepatic-pancreatic dysplasia 2, OMIM:615415; ?Nephronophthisis 9, OMIM:613824; Nephronophthisis 9, MONDO:0013444 to Renal-hepatic-pancreatic dysplasia 2, MONDO:0014174; Renal-hepatic-pancreatic dysplasia 2, OMIM:615415; Nephronophthisis 9, OMIM:613824; Nephronophthisis 9, MONDO:0013444
Fetal anomalies v0.3500 NEK8 Zornitza Stark Classified gene: NEK8 as Green List (high evidence)
Fetal anomalies v0.3500 NEK8 Zornitza Stark Gene: nek8 has been classified as Green List (High Evidence).
Fetal anomalies v0.3499 NEDD4L Zornitza Stark Marked gene: NEDD4L as ready
Fetal anomalies v0.3499 NEDD4L Zornitza Stark Gene: nedd4l has been classified as Green List (High Evidence).
Fetal anomalies v0.3499 NEDD4L Zornitza Stark Publications for gene: NEDD4L were set to
Fetal anomalies v0.3498 NEDD4L Zornitza Stark Mode of inheritance for gene: NEDD4L was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3497 NEDD4L Zornitza Stark Classified gene: NEDD4L as Green List (high evidence)
Fetal anomalies v0.3497 NEDD4L Zornitza Stark Gene: nedd4l has been classified as Green List (High Evidence).
Fetal anomalies v0.3496 NDUFAF2 Zornitza Stark Marked gene: NDUFAF2 as ready
Fetal anomalies v0.3496 NDUFAF2 Zornitza Stark Gene: ndufaf2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3496 NDUFAF2 Zornitza Stark Phenotypes for gene: NDUFAF2 were changed from LEIGH SYNDROME to Mitochondrial complex I deficiency, nuclear type 10, MIM#618233
Fetal anomalies v0.3495 NDUFAF2 Zornitza Stark Publications for gene: NDUFAF2 were set to
Fetal anomalies v0.3494 NDUFAF2 Zornitza Stark Classified gene: NDUFAF2 as Red List (low evidence)
Fetal anomalies v0.3494 NDUFAF2 Zornitza Stark Gene: ndufaf2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3493 NDUFAF2 Zornitza Stark changed review comment from: At least four unrelated families reported, complex neurological presentation with optic atrophy, nystagmus, ataxia in some, others described as ventilator-dependent. ID is unlikely to be the presenting or main feature.; to: At least four unrelated families reported, complex neurological presentation with optic atrophy, nystagmus, ataxia in some, others described as ventilator-dependent. Clinical presentation is typically post-natal.
Fetal anomalies v0.3493 NDUFAF2 Zornitza Stark edited their review of gene: NDUFAF2: Changed rating: RED
Fetal anomalies v0.3493 NDUFA10 Zornitza Stark Marked gene: NDUFA10 as ready
Fetal anomalies v0.3493 NDUFA10 Zornitza Stark Gene: ndufa10 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3493 NDUFA10 Zornitza Stark Phenotypes for gene: NDUFA10 were changed from LEIGH SYNDROME DUP to Mitochondrial complex I deficiency, nuclear type 22, MIM#618243
Fetal anomalies v0.3492 NDUFA10 Zornitza Stark Publications for gene: NDUFA10 were set to
Fetal anomalies v0.3491 NDUFA10 Zornitza Stark changed review comment from: Two families, functional data, but phenotypic description only available for one, IUGR reported.; to: Two families, functional data, IUGR reported.
Fetal anomalies v0.3491 NDUFA10 Zornitza Stark changed review comment from: Two families, functional data, but phenotypic description only available for one (DD/ID part of the phenotype).; to: Two families, functional data, but phenotypic description only available for one, IUGR reported.
Fetal anomalies v0.3491 NAA15 Zornitza Stark Marked gene: NAA15 as ready
Fetal anomalies v0.3491 NAA15 Zornitza Stark Gene: naa15 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3491 NAA15 Zornitza Stark Phenotypes for gene: NAA15 were changed from CONGENITAL HEART DISEASE and NEURODEVELOPMENTAL DISORDER to Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities, MIM 617787
Fetal anomalies v0.3490 NAA15 Zornitza Stark Publications for gene: NAA15 were set to
Fetal anomalies v0.3489 NAA15 Zornitza Stark Mode of inheritance for gene: NAA15 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3488 NAA15 Zornitza Stark Classified gene: NAA15 as Red List (low evidence)
Fetal anomalies v0.3488 NAA15 Zornitza Stark Gene: naa15 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3487 NAA15 Zornitza Stark reviewed gene: NAA15: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities, MIM 617787; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.156 SEMA3A Zornitza Stark Marked gene: SEMA3A as ready
Skeletal dysplasia v0.156 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Skeletal dysplasia v0.156 SEMA3A Zornitza Stark Phenotypes for gene: SEMA3A were changed from {Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897; congenital heart disease; short stature to {Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897; congenital heart disease; skeletal anomalies
Skeletal dysplasia v0.155 SEMA3A Zornitza Stark Mode of inheritance for gene: SEMA3A was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.154 SEMA3A Zornitza Stark Classified gene: SEMA3A as Green List (high evidence)
Skeletal dysplasia v0.154 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Congenital Heart Defect v0.191 SEMA3A Zornitza Stark Marked gene: SEMA3A as ready
Congenital Heart Defect v0.191 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Congenital Heart Defect v0.191 SEMA3A Zornitza Stark Mode of inheritance for gene: SEMA3A was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.190 SEMA3A Zornitza Stark Classified gene: SEMA3A as Green List (high evidence)
Congenital Heart Defect v0.190 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Fetal anomalies v0.3487 SEMA3A Zornitza Stark Mode of inheritance for gene: SEMA3A 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 v0.3486 SEMA3A Zornitza Stark Phenotypes for gene: SEMA3A were changed from {Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897; congenital heart disease to {Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897; congenital heart disease; skeletal anomalies
Fetal anomalies v0.3485 SEMA3A Zornitza Stark Classified gene: SEMA3A as Green List (high evidence)
Fetal anomalies v0.3485 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Skeletal dysplasia v0.153 SEMA3A Krithika Murali gene: SEMA3A was added
gene: SEMA3A was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: SEMA3A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SEMA3A were set to 28075028; 33369061; 20301509; 21059704; 24124006; 22927827
Phenotypes for gene: SEMA3A were set to {Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897; congenital heart disease; short stature
Review for gene: SEMA3A was set to GREEN
Added comment: Heterozygous variants associated with isolated GnRH deficiency with or without anosmia (Kallman syndrome like). More severe phenotype with biallelic SEMA3A variants reported including postnatal short stature and congenital heart defects in 3/3 published, unrelated individuals.

PMID 33369061 Gileta et al 2021 - report x1 patient. Female proband was compound heterozygote for a nonsense variant and a multiexonic deletion of SEMA3A. Presents with postnatal short stature, congenital cardiac anomalies, dysmorphic features, hypogonadotrophic hypogonadism and anosmia.

PMID 28075028 Baumann et al 2017 - report x1 patient. Homozygous LoF variants identified in a proband from a consanguineous Turkish family. Noted at birth to have a high-positioned scapulae, deformed ribs and a lateral clavicular hook. The patient also had upper/lower limb contractures and aberrant right subclavian artery. Mild facial dysmorphism, micropenis and hypogonadotrophic hypogonadism also noted in the first week of life. Postnatal short stature (length 50cm at term birth)

PMID 24124006 Hofmann et al 2013 - first reported biallelic variants in a proband with postnatal short stature, skeletal anomalies of the thorax, congenital heart
defect and camptodactyly
Sources: Literature
Congenital Heart Defect v0.189 SEMA3A Krithika Murali gene: SEMA3A was added
gene: SEMA3A was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: SEMA3A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SEMA3A were set to 28075028; 33369061; 20301509; 21059704; 24124006; 22927827
Phenotypes for gene: SEMA3A were set to {Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897; congenital heart disease; short stature
Review for gene: SEMA3A was set to GREEN
Added comment: Heterozygous variants associated with isolated GnRH deficiency with or without anosmia (Kallman syndrome like). More severe phenotype with biallelic SEMA3A variants including postnatal short stature and congenital heart defects in 3/3 published, unrelated individuals.

PMID 33369061 Gileta et al 2021 - report x1 patient. Female proband was compound heterozygote for a nonsense variant and a multiexonic deletion of SEMA3A. Presents with postnatal short stature, congenital cardiac anomalies, dysmorphic features, hypogonadotrophic hypogonadism and anosmia.

PMID 28075028 Baumann et al 2017 - report x1 patient. Homozygous LoF variants identified in a proband from a consanguineous Turkish family. Noted at birth to have a high-positioned scapulae, deformed ribs and a lateral clavicular hook. The patient also had upper/lower limb contractures and aberrant right subclavian artery. Mild facial dysmorphism, micropenis and hypogonadotrophic hypogonadism also noted in the first week of life. Postnatal short stature (length 50cm at term birth)

PMID 24124006 Hofmann et al 2013 - first reported biallelic variants in a proband with postnatal short stature, skeletal anomalies of the thorax, congenital heart
defect and camptodactyly
Sources: Literature
Fetal anomalies v0.3484 SEMA3A Krithika Murali gene: SEMA3A was added
gene: SEMA3A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SEMA3A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SEMA3A were set to 28075028; 33369061; 20301509; 21059704; 24124006; 22927827
Phenotypes for gene: SEMA3A were set to {Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897; congenital heart disease
Review for gene: SEMA3A was set to GREEN
Added comment: Heterozygous variants associated with isolated GnRH deficiency with or without anosmia (Kallman syndrome like). Anomalies such as unilateral renal aplasia which can be detected antenatally reported with Kallman syndrome but not published with heterozygous SEMA3A variants.

More severe phenotype with biallelic SEMA3A variants reported with features detectable antenatally.

PMID 33369061 Gileta et al 2021 - report x1 patient. Female proband was compound heterozygote for a nonsense variant and a multiexonic deletion of SEMA3A. Presents with postnatal short stature, congenital cardiac anomalies, dysmorphic features, hypogonadotrophic hypogonadism and anosmia.

PMID 28075028 Baumann et al 2017 - report x1 patient. Homozygous LoF variants identified in a proband from a consanguineous Turkish family. Noted at birth to have a high-positioned scapulae, deformed ribs and a lateral clavicular hook. The patient also had upper/lower limb contractures and aberrant right subclavian artery. Mild facial dysmorphism, micropenis and hypogonadotrophic hypogonadism also noted in the first week of life. Postnatal short stature (length 50cm at term birth)

PMID 24124006 Hofmann et al 2013 - first reported biallelic variants in a proband with postnatal short stature, skeletal anomalies of the thorax, congenital heart
defect and camptodactyly
Sources: Literature
Mendeliome v0.10977 DRC1 Zornitza Stark Phenotypes for gene: DRC1 were changed from Ciliary dyskinesia, primary, 21, MIM# 615294 to Ciliary dyskinesia, primary, 21, MIM# 615294; Male infertility
Mendeliome v0.10976 DRC1 Zornitza Stark Publications for gene: DRC1 were set to 31960620
Mendeliome v0.10975 DRC1 Zornitza Stark edited their review of gene: DRC1: Added comment: PMID 34169321: two individuals reported with homozygous variants and morphological abnormalities of sperm/male infertility.; Changed publications: 31960620, 34169321; Changed phenotypes: Ciliary dyskinesia, primary, 21, MIM# 615294, Male infertility
Fetal anomalies v0.3484 ROBO2 Zornitza Stark Marked gene: ROBO2 as ready
Fetal anomalies v0.3484 ROBO2 Zornitza Stark Gene: robo2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3484 ROBO2 Zornitza Stark Classified gene: ROBO2 as Green List (high evidence)
Fetal anomalies v0.3484 ROBO2 Zornitza Stark Gene: robo2 has been classified as Green List (High Evidence).
Mendeliome v0.10975 HOXB6 Zornitza Stark Publications for gene: HOXB6 were set to 22371315
Mendeliome v0.10974 HOXB6 Zornitza Stark Classified gene: HOXB6 as Red List (low evidence)
Mendeliome v0.10974 HOXB6 Zornitza Stark Gene: hoxb6 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3483 HOXB6 Zornitza Stark Marked gene: HOXB6 as ready
Fetal anomalies v0.3483 HOXB6 Zornitza Stark Gene: hoxb6 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3483 HOXB6 Zornitza Stark Classified gene: HOXB6 as Red List (low evidence)
Fetal anomalies v0.3483 HOXB6 Zornitza Stark Gene: hoxb6 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3482 COQ7 Zornitza Stark Marked gene: COQ7 as ready
Fetal anomalies v0.3482 COQ7 Zornitza Stark Gene: coq7 has been classified as Green List (High Evidence).
Fetal anomalies v0.3482 COQ7 Zornitza Stark Classified gene: COQ7 as Green List (high evidence)
Fetal anomalies v0.3482 COQ7 Zornitza Stark Gene: coq7 has been classified as Green List (High Evidence).
Fetal anomalies v0.3481 CDX2 Zornitza Stark Marked gene: CDX2 as ready
Fetal anomalies v0.3481 CDX2 Zornitza Stark Gene: cdx2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3481 CDX2 Zornitza Stark Classified gene: CDX2 as Amber List (moderate evidence)
Fetal anomalies v0.3481 CDX2 Zornitza Stark Gene: cdx2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3480 TLK2 Zornitza Stark Marked gene: TLK2 as ready
Fetal anomalies v0.3480 TLK2 Zornitza Stark Gene: tlk2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3480 TLK2 Zornitza Stark Classified gene: TLK2 as Green List (high evidence)
Fetal anomalies v0.3480 TLK2 Zornitza Stark Gene: tlk2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3479 STAT3 Zornitza Stark Marked gene: STAT3 as ready
Fetal anomalies v0.3479 STAT3 Zornitza Stark Gene: stat3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3479 STAT3 Zornitza Stark Classified gene: STAT3 as Green List (high evidence)
Fetal anomalies v0.3479 STAT3 Zornitza Stark Gene: stat3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3478 STAT3 Zornitza Stark reviewed gene: STAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyper-IgE recurrent infection syndrome - MIM#147060, Autoimmune disease, multisystem, infantile-onset, 1 - MIM#615952; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3478 RNU12 Zornitza Stark Marked gene: RNU12 as ready
Fetal anomalies v0.3478 RNU12 Zornitza Stark Gene: rnu12 has been classified as Green List (High Evidence).
Fetal anomalies v0.3478 RNU12 Zornitza Stark Classified gene: RNU12 as Green List (high evidence)
Fetal anomalies v0.3478 RNU12 Zornitza Stark Gene: rnu12 has been classified as Green List (High Evidence).
Fetal anomalies v0.3477 PJA1 Zornitza Stark Marked gene: PJA1 as ready
Fetal anomalies v0.3477 PJA1 Zornitza Stark Gene: pja1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3477 PJA1 Zornitza Stark Classified gene: PJA1 as Amber List (moderate evidence)
Fetal anomalies v0.3477 PJA1 Zornitza Stark Gene: pja1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3476 PHEX Zornitza Stark Marked gene: PHEX as ready
Fetal anomalies v0.3476 PHEX Zornitza Stark Gene: phex has been classified as Green List (High Evidence).
Fetal anomalies v0.3476 PHEX Zornitza Stark Classified gene: PHEX as Green List (high evidence)
Fetal anomalies v0.3476 PHEX Zornitza Stark Gene: phex has been classified as Green List (High Evidence).
Fetal anomalies v0.3475 LTBP1 Zornitza Stark Marked gene: LTBP1 as ready
Fetal anomalies v0.3475 LTBP1 Zornitza Stark Gene: ltbp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3475 LTBP1 Zornitza Stark Classified gene: LTBP1 as Green List (high evidence)
Fetal anomalies v0.3475 LTBP1 Zornitza Stark Gene: ltbp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3474 EFNA4 Zornitza Stark Marked gene: EFNA4 as ready
Fetal anomalies v0.3474 EFNA4 Zornitza Stark Gene: efna4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3474 EFNA4 Zornitza Stark Classified gene: EFNA4 as Amber List (moderate evidence)
Fetal anomalies v0.3474 EFNA4 Zornitza Stark Gene: efna4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3473 DHH Zornitza Stark Marked gene: DHH as ready
Fetal anomalies v0.3473 DHH Zornitza Stark Gene: dhh has been classified as Red List (Low Evidence).
Fetal anomalies v0.3473 DHH Zornitza Stark Phenotypes for gene: DHH were changed from 46XY partial gonadal dysgenesis, with minifascicular neuropathy; 46XY sex reversal 7 to 46XY gonadal dysgenesis with minifascicular neuropathy MIM#607080
Fetal anomalies v0.3472 DHH Zornitza Stark Publications for gene: DHH were set to
Fetal anomalies v0.3471 DEPDC5 Zornitza Stark Marked gene: DEPDC5 as ready
Fetal anomalies v0.3471 DEPDC5 Zornitza Stark Gene: depdc5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3471 DEPDC5 Zornitza Stark Phenotypes for gene: DEPDC5 were changed from FAMILIAL FOCAL EPILEPSY WITH VARIABLE FOCI to Epilepsy, familial focal, with variable foci 1 MIM#604364
Fetal anomalies v0.3470 DEPDC5 Zornitza Stark Publications for gene: DEPDC5 were set to
Fetal anomalies v0.3469 DEPDC5 Zornitza Stark Mode of inheritance for gene: DEPDC5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3468 DDHD2 Zornitza Stark Marked gene: DDHD2 as ready
Fetal anomalies v0.3468 DDHD2 Zornitza Stark Gene: ddhd2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3468 DDHD2 Zornitza Stark Phenotypes for gene: DDHD2 were changed from COMPLEX HEREDITARY SPASTIC PARAPLEGIA to Spastic paraplegia 54, autosomal recessive, MIM# 615033; MONDO:0014018
Fetal anomalies v0.3467 DDHD2 Zornitza Stark Publications for gene: DDHD2 were set to
Fetal anomalies v0.3466 DDHD1 Zornitza Stark Marked gene: DDHD1 as ready
Fetal anomalies v0.3466 DDHD1 Zornitza Stark Gene: ddhd1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3466 DDHD1 Zornitza Stark Phenotypes for gene: DDHD1 were changed from HEREDITARY SPASTIC PARAPLEGIA to Spastic paraplegia 28, autosomal recessive, 609340; MONDO:0012256
Fetal anomalies v0.3465 DDHD1 Zornitza Stark Publications for gene: DDHD1 were set to
Fetal anomalies v0.3464 ROBO2 Krithika Murali gene: ROBO2 was added
gene: ROBO2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ROBO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ROBO2 were set to 18235093; 19350278; 24429398; 17357069; 26026792; 29194579; 34059960
Phenotypes for gene: ROBO2 were set to Vesicoureteral reflux 2 - MIM#610878; CAKUT
Review for gene: ROBO2 was set to GREEN
Added comment: Known association with familial vesicoureteral reflux and congenital anomalies of the kidney and urinary tract.
Sources: Literature
Mendeliome v0.10973 HOXB6 Krithika Murali reviewed gene: HOXB6: Rating: RED; Mode of pathogenicity: None; Publications: 17003840, 22371315; Phenotypes: Hypospadias; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3464 HOXB6 Krithika Murali gene: HOXB6 was added
gene: HOXB6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HOXB6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HOXB6 were set to 17003840; 22371315
Phenotypes for gene: HOXB6 were set to Hypospadias
Review for gene: HOXB6 was set to RED
Added comment: PMID 17003840 Chen et al 2007 report 2 babies with hypospadias and heterozygous HOXB6 variants. Cohort of 90 unrelated Chinese patients with hypospadias and 380 controls.

x1 patient - heterozygous, maternally inherited HOXB6 c.124C>A p.P42T in a child with scrotal, micropenis, bifid scrotum, cryptorchidism. Baby also has maternally inherited SRD5A2 and de novo MID1 variant. The HOXB6 variant is absent from gnomad v2, v3, not previously reported in ClinVar, minor GS change (38), moderately conserved (change in non-placental mammals), not in a region of missense constraint.

x1 patient - penile hypospadias, heterozygous HOXB6 c.367T>C p.C123R. No segregation information. 5 hets (East Asian, gnomad v2), 2 hets (East Asian, gnomad v3). GS 180, conserved in mammals (changed in birds), not in a region of missense constraint, not previously reported in ClinVar, predicted to escape NMD.

x2 patients with hypospadias from a single study, variants of uncertain significance.
Sources: Literature
Fetal anomalies v0.3464 DDC Zornitza Stark Marked gene: DDC as ready
Fetal anomalies v0.3464 DDC Zornitza Stark Gene: ddc has been classified as Red List (Low Evidence).
Fetal anomalies v0.3464 DDC Zornitza Stark Publications for gene: DDC were set to
Fetal anomalies v0.3463 DDB2 Zornitza Stark Marked gene: DDB2 as ready
Fetal anomalies v0.3463 DDB2 Zornitza Stark Gene: ddb2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3463 DDB2 Zornitza Stark Phenotypes for gene: DDB2 were changed from XERODERMA PIGMENTOSUM, GROUP E, DDB-NEGATIVE SUBTYPE to Xeroderma pigmentosum, group E, DDB-negative subtype MIM#278740
Fetal anomalies v0.3462 DDB2 Zornitza Stark Publications for gene: DDB2 were set to
Fetal anomalies v0.3461 FUZ Zornitza Stark Marked gene: FUZ as ready
Fetal anomalies v0.3461 FUZ Zornitza Stark Gene: fuz has been classified as Red List (Low Evidence).
Fetal anomalies v0.3461 FUZ Zornitza Stark Publications for gene: FUZ were set to
Fetal anomalies v0.3460 FUZ Zornitza Stark Mode of inheritance for gene: FUZ was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10973 FUZ Zornitza Stark Marked gene: FUZ as ready
Mendeliome v0.10973 FUZ Zornitza Stark Gene: fuz has been classified as Red List (Low Evidence).
Mendeliome v0.10973 FUZ Zornitza Stark Classified gene: FUZ as Red List (low evidence)
Mendeliome v0.10973 FUZ Zornitza Stark Gene: fuz has been classified as Red List (Low Evidence).
Fetal anomalies v0.3459 DBT Zornitza Stark Marked gene: DBT as ready
Fetal anomalies v0.3459 DBT Zornitza Stark Gene: dbt has been classified as Red List (Low Evidence).
Fetal anomalies v0.3459 DBT Zornitza Stark Phenotypes for gene: DBT were changed from MAPLE SYRUP URINE DISEASEQ to Maple syrup urine disease, type II (MIM#248600)
Fetal anomalies v0.3458 DBT Zornitza Stark Publications for gene: DBT were set to
Fetal anomalies v0.3457 DARS2 Zornitza Stark Marked gene: DARS2 as ready
Fetal anomalies v0.3457 DARS2 Zornitza Stark Gene: dars2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3457 DARS2 Zornitza Stark Phenotypes for gene: DARS2 were changed from LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105
Fetal anomalies v0.3456 DARS2 Zornitza Stark Publications for gene: DARS2 were set to
Fetal anomalies v0.3455 TTC19 Zornitza Stark Marked gene: TTC19 as ready
Fetal anomalies v0.3455 TTC19 Zornitza Stark Gene: ttc19 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3455 TTC19 Zornitza Stark Phenotypes for gene: TTC19 were changed from MITOCHONDRIAL COMPLEX III DEFICIENCY to Mitochondrial complex III deficiency, nuclear type 2 (MIM#615157)
Fetal anomalies v0.3454 TTC19 Zornitza Stark Publications for gene: TTC19 were set to
Fetal anomalies v0.3453 CYP19A1 Zornitza Stark Marked gene: CYP19A1 as ready
Fetal anomalies v0.3453 CYP19A1 Zornitza Stark Gene: cyp19a1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3453 CYP19A1 Zornitza Stark Phenotypes for gene: CYP19A1 were changed from Aromatase deficiency 613546; Aromatase excess syndrome 139300 to Aromatase deficiency (MIM#613546), AR; Aromatase excess syndrome (MIM#139300), AD
Fetal anomalies v0.3452 CYP19A1 Zornitza Stark Publications for gene: CYP19A1 were set to
Fetal anomalies v0.3451 CYP19A1 Zornitza Stark Mode of inheritance for gene: CYP19A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3450 TNXB Zornitza Stark Marked gene: TNXB as ready
Fetal anomalies v0.3450 TNXB Zornitza Stark Gene: tnxb has been classified as Red List (Low Evidence).
Fetal anomalies v0.3450 TNXB Zornitza Stark Publications for gene: TNXB were set to
Fetal anomalies v0.3449 TNXB Zornitza Stark reviewed gene: TNXB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Vesicoureteral reflux 8, MIM#615963; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10972 FTSJ1 Zornitza Stark Marked gene: FTSJ1 as ready
Mendeliome v0.10972 FTSJ1 Zornitza Stark Gene: ftsj1 has been classified as Green List (High Evidence).
Mendeliome v0.10972 FTSJ1 Zornitza Stark Phenotypes for gene: FTSJ1 were changed from to Intellectual developmental disorder, X-linked 9 MIM#309549
Mendeliome v0.10971 FTSJ1 Zornitza Stark Publications for gene: FTSJ1 were set to
Mendeliome v0.10970 FTSJ1 Zornitza Stark Mode of inheritance for gene: FTSJ1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3449 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Fetal anomalies v0.3449 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3449 FLRT3 Zornitza Stark Phenotypes for gene: FLRT3 were changed from Hypogonadotropic hypogonadism 21 with anosmia 615271 to Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)
Fetal anomalies v0.3448 FLRT3 Zornitza Stark Publications for gene: FLRT3 were set to
Fetal anomalies v0.3447 FLRT3 Zornitza Stark Mode of inheritance for gene: FLRT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3446 TMEM126B Zornitza Stark Marked gene: TMEM126B as ready
Fetal anomalies v0.3446 TMEM126B Zornitza Stark Gene: tmem126b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3446 TMEM126B Zornitza Stark Phenotypes for gene: TMEM126B were changed from Muscle Weakness and Isolated Complex I Deficiency to Mitochondrial complex I deficiency, nuclear type 29 (MIM#618250)
Fetal anomalies v0.3445 TMEM126B Zornitza Stark Publications for gene: TMEM126B were set to
Fetal anomalies v0.3444 TMEM126B Zornitza Stark Classified gene: TMEM126B as Amber List (moderate evidence)
Fetal anomalies v0.3444 TMEM126B Zornitza Stark Gene: tmem126b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10969 FLAD1 Zornitza Stark Marked gene: FLAD1 as ready
Mendeliome v0.10969 FLAD1 Zornitza Stark Gene: flad1 has been classified as Green List (High Evidence).
Mendeliome v0.10969 FLAD1 Zornitza Stark Phenotypes for gene: FLAD1 were changed from to Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency MIM#255100
Mendeliome v0.10968 FLAD1 Zornitza Stark Publications for gene: FLAD1 were set to
Mendeliome v0.10967 FLAD1 Zornitza Stark Mode of inheritance for gene: FLAD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3443 FLAD1 Zornitza Stark Marked gene: FLAD1 as ready
Fetal anomalies v0.3443 FLAD1 Zornitza Stark Gene: flad1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3443 FLAD1 Zornitza Stark Phenotypes for gene: FLAD1 were changed from Riboflavin-Responsive and Non-responsive Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency. to Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency MIM#255100
Fetal anomalies v0.3442 FLAD1 Zornitza Stark Publications for gene: FLAD1 were set to
Fetal anomalies v0.3441 TK2 Zornitza Stark Marked gene: TK2 as ready
Fetal anomalies v0.3441 TK2 Zornitza Stark Gene: tk2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3441 TK2 Zornitza Stark Phenotypes for gene: TK2 were changed from MITOCHONDRIAL DNA DEPLETION SYNDROME, MYOPATHIC FORM to Mitochondrial DNA depletion syndrome 2 (myopathic type) (MIM#609560)
Fetal anomalies v0.3440 FGF20 Zornitza Stark Marked gene: FGF20 as ready
Fetal anomalies v0.3440 FGF20 Zornitza Stark Gene: fgf20 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3440 FGF20 Zornitza Stark Phenotypes for gene: FGF20 were changed from ?Renal hypodysplasia/aplasia 2, 615721 to Renal hypodysplasia/aplasia 2, MIM#615721
Fetal anomalies v0.3439 FGF20 Zornitza Stark Classified gene: FGF20 as Amber List (moderate evidence)
Fetal anomalies v0.3439 FGF20 Zornitza Stark Gene: fgf20 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3438 FGF17 Zornitza Stark Marked gene: FGF17 as ready
Fetal anomalies v0.3438 FGF17 Zornitza Stark Gene: fgf17 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3438 FGF17 Zornitza Stark Publications for gene: FGF17 were set to
Fetal anomalies v0.3437 FGF17 Zornitza Stark Mode of inheritance for gene: FGF17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3436 TEK Zornitza Stark Marked gene: TEK as ready
Fetal anomalies v0.3436 TEK Zornitza Stark Gene: tek has been classified as Red List (Low Evidence).
Fetal anomalies v0.3436 TEK Zornitza Stark Phenotypes for gene: TEK were changed from VENOUS MALFORMATIONS, MULTIPLE CUTANEOUS AND MUCOSAL to Glaucoma 3, primary congenital, E (MIM#617272); Venous malformations, multiple cutaneous and mucosal (MIM#600195)
Fetal anomalies v0.3435 TEK Zornitza Stark Publications for gene: TEK were set to
Mendeliome v0.10966 FGF17 Zornitza Stark Marked gene: FGF17 as ready
Mendeliome v0.10966 FGF17 Zornitza Stark Gene: fgf17 has been classified as Green List (High Evidence).
Mendeliome v0.10966 FGF17 Zornitza Stark Phenotypes for gene: FGF17 were changed from to Hypogonadotropic hypogonadism 20 with or without anosmia MIM#615270
Mendeliome v0.10965 FGF17 Zornitza Stark Publications for gene: FGF17 were set to
Mendeliome v0.10964 FGF17 Zornitza Stark Mode of inheritance for gene: FGF17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3434 TBXAS1 Zornitza Stark Phenotypes for gene: TBXAS1 were changed from Ghosal hematodiaphyseal syndrome (MIM#231095) to Ghosal haematodiaphyseal syndrome (MIM#231095)
Fetal anomalies v0.3433 TBXAS1 Zornitza Stark Marked gene: TBXAS1 as ready
Fetal anomalies v0.3433 TBXAS1 Zornitza Stark Gene: tbxas1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3433 TBXAS1 Zornitza Stark Phenotypes for gene: TBXAS1 were changed from GHOSAL HEMATODIAPHYSEAL SYNDROME to Ghosal hematodiaphyseal syndrome (MIM#231095)
Fetal anomalies v0.3432 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
Fetal anomalies v0.3432 TANGO2 Zornitza Stark Gene: tango2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3432 TANGO2 Zornitza Stark Phenotypes for gene: TANGO2 were changed from Infancy-Onset Recurrent Metabolic Crises with Encephalocardiomyopathy to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MIM#616878)
Fetal anomalies v0.3431 TANGO2 Zornitza Stark Publications for gene: TANGO2 were set to
Fetal anomalies v0.3430 TANGO2 Zornitza Stark reviewed gene: TANGO2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MIM#616878); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3430 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Fetal anomalies v0.3430 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3430 ZFYVE26 Zornitza Stark Phenotypes for gene: ZFYVE26 were changed from SPASTIC PARAPLEGIA AUTOSOMAL RECESSIVE TYPE 15 to Spastic paraplegia 15, autosomal recessive MIM#270700
Fetal anomalies v0.3429 ZFYVE26 Zornitza Stark Publications for gene: ZFYVE26 were set to
Fetal anomalies v0.3428 ZFYVE26 Zornitza Stark reviewed gene: ZFYVE26: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 15, autosomal recessive MIM#270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4503 SYP Zornitza Stark Marked gene: SYP as ready
Intellectual disability syndromic and non-syndromic v0.4503 SYP Zornitza Stark Gene: syp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4503 SYP Zornitza Stark Phenotypes for gene: SYP were changed from to Mental retardation, X-linked 96 MIM#300802
Intellectual disability syndromic and non-syndromic v0.4502 SYP Zornitza Stark Publications for gene: SYP were set to
Intellectual disability syndromic and non-syndromic v0.4501 SYP Zornitza Stark Mode of inheritance for gene: SYP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.4500 SYP Zornitza Stark reviewed gene: SYP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23966691, 19377476; Phenotypes: Mental retardation, X-linked 96 MIM#300802; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.10963 SYP Zornitza Stark Marked gene: SYP as ready
Mendeliome v0.10963 SYP Zornitza Stark Gene: syp has been classified as Green List (High Evidence).
Mendeliome v0.10963 SYP Zornitza Stark Phenotypes for gene: SYP were changed from to Mental retardation, X-linked 96 MIM#300802
Mendeliome v0.10962 SYP Zornitza Stark Publications for gene: SYP were set to
Mendeliome v0.10961 SYP Zornitza Stark Mode of pathogenicity for gene: SYP was changed from to None
Mendeliome v0.10960 SYP Zornitza Stark Mode of inheritance for gene: SYP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3428 SYP Zornitza Stark Marked gene: SYP as ready
Fetal anomalies v0.3428 SYP Zornitza Stark Gene: syp has been classified as Red List (Low Evidence).
Fetal anomalies v0.3428 SYP Zornitza Stark Phenotypes for gene: SYP were changed from MENTAL RETARDATION X-LINKED SYP-RELATED to Intellectual developmental disorder, X-linked 96 (MIM#300802)
Fetal anomalies v0.3427 SYP Zornitza Stark Publications for gene: SYP were set to
Fetal anomalies v0.3426 SYP Zornitza Stark reviewed gene: SYP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3426 CYC1 Zornitza Stark Marked gene: CYC1 as ready
Fetal anomalies v0.3426 CYC1 Zornitza Stark Gene: cyc1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3426 CYC1 Zornitza Stark Phenotypes for gene: CYC1 were changed from MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 6 to Mitochondrial complex III deficiency, nuclear type 6, MIM# 615453
Fetal anomalies v0.3425 CYC1 Zornitza Stark Publications for gene: CYC1 were set to
Mendeliome v0.10959 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Mendeliome v0.10959 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).