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Multiple monogenic benign skin tumours v1.5 TSC1 Arina Puzriakova Tag curated_removed tag was added to gene: TSC1.
Multiple monogenic benign skin tumours v1.5 TMC8 Arina Puzriakova Tag curated_removed tag was added to gene: TMC8.
Multiple monogenic benign skin tumours v1.5 TMC6 Arina Puzriakova Tag curated_removed tag was added to gene: TMC6.
Multiple monogenic benign skin tumours v1.5 SUFU Arina Puzriakova Tag curated_removed tag was added to gene: SUFU.
Multiple monogenic benign skin tumours v1.5 STK11 Arina Puzriakova Tag curated_removed tag was added to gene: STK11.
Multiple monogenic benign skin tumours v1.5 SASH1 Arina Puzriakova Tag curated_removed tag was added to gene: SASH1.
Multiple monogenic benign skin tumours v1.5 SAMD9 Arina Puzriakova Tag curated_removed tag was added to gene: SAMD9.
Multiple monogenic benign skin tumours v1.5 PTEN Arina Puzriakova Tag curated_removed tag was added to gene: PTEN.
Multiple monogenic benign skin tumours v1.5 PTCH2 Arina Puzriakova Tag curated_removed tag was added to gene: PTCH2.
Multiple monogenic benign skin tumours v1.5 PTCH1 Arina Puzriakova Tag curated_removed tag was added to gene: PTCH1.
Multiple monogenic benign skin tumours v1.5 PRKAR1A Arina Puzriakova Tag curated_removed tag was added to gene: PRKAR1A.
Multiple monogenic benign skin tumours v1.5 PORCN Arina Puzriakova Tag curated_removed tag was added to gene: PORCN.
Multiple monogenic benign skin tumours v1.5 PIK3CA Arina Puzriakova Tag curated_removed tag was added to gene: PIK3CA.
Multiple monogenic benign skin tumours v1.5 PDGFRB Arina Puzriakova Tag curated_removed tag was added to gene: PDGFRB.
Multiple monogenic benign skin tumours v1.5 NRAS Arina Puzriakova Tag curated_removed tag was added to gene: NRAS.
Multiple monogenic benign skin tumours v1.5 NF1 Arina Puzriakova Tag curated_removed tag was added to gene: NF1.
Multiple monogenic benign skin tumours v1.5 MC1R Arina Puzriakova Tag curated_removed tag was added to gene: MC1R.
Multiple monogenic benign skin tumours v1.5 LEF1 Arina Puzriakova Tag curated_removed tag was added to gene: LEF1.
Multiple monogenic benign skin tumours v1.5 KRT17 Arina Puzriakova Tag curated_removed tag was added to gene: KRT17.
Multiple monogenic benign skin tumours v1.5 KRAS Arina Puzriakova Tag curated_removed tag was added to gene: KRAS.
Multiple monogenic benign skin tumours v1.5 JAK2 Arina Puzriakova Tag curate was removed from gene: JAK2.
Tag curated_removed tag was added to gene: JAK2.
Multiple monogenic benign skin tumours v1.5 JAK2 Arina Puzriakova Tag curate tag was added to gene: JAK2.
Multiple monogenic benign skin tumours v1.5 IRF4 Arina Puzriakova Tag curated_removed tag was added to gene: IRF4.
Multiple monogenic benign skin tumours v1.5 HRAS Arina Puzriakova Tag curated_removed tag was added to gene: HRAS.
Multiple monogenic benign skin tumours v1.5 GLA Arina Puzriakova Tag curated_removed tag was added to gene: GLA.
Multiple monogenic benign skin tumours v1.5 GALNT3 Arina Puzriakova Tag curated_removed tag was added to gene: GALNT3.
Multiple monogenic benign skin tumours v1.5 FGFR3 Arina Puzriakova Tag curated_removed tag was added to gene: FGFR3.
Multiple monogenic benign skin tumours v1.5 FGFR2 Arina Puzriakova Tag curated_removed tag was added to gene: FGFR2.
Multiple monogenic benign skin tumours v1.5 FGF23 Arina Puzriakova Tag curated_removed tag was added to gene: FGF23.
Multiple monogenic benign skin tumours v1.5 CTNNB1 Arina Puzriakova Tag curated_removed tag was added to gene: CTNNB1.
Multiple monogenic benign skin tumours v1.5 CIB1 Arina Puzriakova Tag curated_removed tag was added to gene: CIB1.
Multiple monogenic benign skin tumours v1.5 CDKN2A Arina Puzriakova Tag curated_removed tag was added to gene: CDKN2A.
Multiple monogenic benign skin tumours v1.5 CDK4 Arina Puzriakova Tag curated_removed tag was added to gene: CDK4.
Multiple monogenic benign skin tumours v1.5 BRAF Arina Puzriakova Tag curated_removed tag was added to gene: BRAF.
Multiple monogenic benign skin tumours v1.5 APC Arina Puzriakova Tag curated_removed tag was added to gene: APC.
Multiple monogenic benign skin tumours v1.5 ACTRT1 Arina Puzriakova Tag curated_removed tag was added to gene: ACTRT1.
Mosaic skin disorders - deep sequencing v1.5 TYRP1 Arina Puzriakova Tag curated_removed tag was added to gene: TYRP1.
Mosaic skin disorders - deep sequencing v1.5 TYR Arina Puzriakova Tag curated_removed tag was added to gene: TYR.
Mosaic skin disorders - deep sequencing v1.5 TERT Arina Puzriakova Tag curated_removed tag was added to gene: TERT.
Mosaic skin disorders - deep sequencing v1.5 NOD2 Arina Puzriakova Tag curated_removed tag was added to gene: NOD2.
Mosaic skin disorders - deep sequencing v1.5 NDUFB11 Arina Puzriakova Tag curated_removed tag was added to gene: NDUFB11.
Mosaic skin disorders - deep sequencing v1.5 MVK Arina Puzriakova Tag curated_removed tag was added to gene: MVK.
Mosaic skin disorders - deep sequencing v1.5 KITLG Arina Puzriakova Tag curated_removed tag was added to gene: KITLG.
Mosaic skin disorders - deep sequencing v1.5 JAK2 Arina Puzriakova Tag removed tag was added to gene: JAK2.
Mosaic skin disorders - deep sequencing v1.5 HCCS Arina Puzriakova Tag curated_removed tag was added to gene: HCCS.
Mosaic skin disorders - deep sequencing v1.5 COX7B Arina Puzriakova Tag curated_removed tag was added to gene: COX7B.
Mosaic skin disorders - deep sequencing v1.5 AKT3 Arina Puzriakova Tag curated_removed tag was added to gene: AKT3.
Mosaic skin disorders - deep sequencing v1.5 AKT2 Arina Puzriakova Tag curated_removed tag was added to gene: AKT2.
Limb disorders v2.36 WDR35 Arina Puzriakova Tag curated_removed tag was added to gene: WDR35.
Limb disorders v2.36 WDR34 Arina Puzriakova Tag curated_removed tag was added to gene: WDR34.
Limb disorders v2.36 WDR19 Arina Puzriakova Tag curated_removed tag was added to gene: WDR19.
Limb disorders v2.36 TTC21B Arina Puzriakova Tag curated_removed tag was added to gene: TTC21B.
Limb disorders v2.36 TRAF3IP1 Arina Puzriakova Tag curated_removed tag was added to gene: TRAF3IP1.
Limb disorders v2.36 TMEM237 Arina Puzriakova Tag curated_removed tag was added to gene: TMEM237.
Limb disorders v2.36 TMEM231 Arina Puzriakova Tag curated_removed tag was added to gene: TMEM231.
Limb disorders v2.36 TMEM216 Arina Puzriakova Tag curated_removed tag was added to gene: TMEM216.
Limb disorders v2.36 TMEM138 Arina Puzriakova Tag curated_removed tag was added to gene: TMEM138.
Limb disorders v2.36 TCTN3 Arina Puzriakova Tag curated_removed tag was added to gene: TCTN3.
Limb disorders v2.36 TCTN2 Arina Puzriakova Tag curated_removed tag was added to gene: TCTN2.
Limb disorders v2.36 TCTEX1D2 Arina Puzriakova Tag curated_removed tag was added to gene: TCTEX1D2.
Limb disorders v2.36 RPGRIP1L Arina Puzriakova Tag curated_removed tag was added to gene: RPGRIP1L.
Limb disorders v2.36 OFD1 Arina Puzriakova Tag curated_removed tag was added to gene: OFD1.
Limb disorders v2.36 NPHP3 Arina Puzriakova Tag curated_removed tag was added to gene: NPHP3.
Limb disorders v2.36 NEK1 Arina Puzriakova Tag curated_removed tag was added to gene: NEK1.
Limb disorders v2.36 KIF7 Arina Puzriakova Tag curated_removed tag was added to gene: KIF7.
Limb disorders v2.36 KIAA0586 Arina Puzriakova Tag curated_removed tag was added to gene: KIAA0586.
Limb disorders v2.36 INPP5E Arina Puzriakova Tag curated_removed tag was added to gene: INPP5E.
Limb disorders v2.36 IFT80 Arina Puzriakova Tag curated_removed tag was added to gene: IFT80.
Limb disorders v2.36 IFT52 Arina Puzriakova Tag curated_removed tag was added to gene: IFT52.
Limb disorders v2.36 IFT172 Arina Puzriakova Tag curated_removed tag was added to gene: IFT172.
Limb disorders v2.36 IFT140 Arina Puzriakova Tag curated_removed tag was added to gene: IFT140.
Limb disorders v2.36 ICK Arina Puzriakova Tag curated_removed tag was added to gene: ICK.
Limb disorders v2.36 HYLS1 Arina Puzriakova Tag curated_removed tag was added to gene: HYLS1.
Limb disorders v2.36 EVC2 Arina Puzriakova Tag curated_removed tag was added to gene: EVC2.
Limb disorders v2.36 EVC Arina Puzriakova Tag curated_removed tag was added to gene: EVC.
Limb disorders v2.36 DYNC2LI1 Arina Puzriakova Tag curated_removed tag was added to gene: DYNC2LI1.
Limb disorders v2.36 DYNC2H1 Arina Puzriakova Tag curated_removed tag was added to gene: DYNC2H1.
Limb disorders v2.36 CSPP1 Arina Puzriakova Tag curated_removed tag was added to gene: CSPP1.
Limb disorders v2.36 CEP41 Arina Puzriakova Tag curated_removed tag was added to gene: CEP41.
Limb disorders v2.36 CEP164 Arina Puzriakova Tag curated_removed tag was added to gene: CEP164.
Limb disorders v2.36 CEP120 Arina Puzriakova Tag curated_removed tag was added to gene: CEP120.
Limb disorders v2.36 CC2D2A Arina Puzriakova Tag curated_removed tag was added to gene: CC2D2A.
Limb disorders v2.36 C5orf42 Arina Puzriakova Tag curated_removed tag was added to gene: C5orf42.
Limb disorders v2.36 C2CD3 Arina Puzriakova Tag curated_removed tag was added to gene: C2CD3.
Limb disorders v2.36 B9D2 Arina Puzriakova Tag curated_removed tag was added to gene: B9D2.
Limb disorders v2.36 ALMS1 Arina Puzriakova Tag curated_removed tag was added to gene: ALMS1.
Limb disorders v2.36 AHI1 Arina Puzriakova Tag curated_removed tag was added to gene: AHI1.
Inherited renal cancer v1.4 PMS2 Arina Puzriakova Tag curated_removed tag was added to gene: PMS2.
Inherited renal cancer v1.4 MSH6 Arina Puzriakova Tag curated_removed tag was added to gene: MSH6.
Inherited renal cancer v1.4 MSH2 Arina Puzriakova Tag curated_removed tag was added to gene: MSH2.
Inherited renal cancer v1.4 MLH1 Arina Puzriakova Tag curated_removed tag was added to gene: MLH1.
Haematological malignancies cancer susceptibility v2.15 HPLH1 Arina Puzriakova Tag curated_removed tag was added to gene: HPLH1.
Early onset or syndromic epilepsy v2.303 PROSC Arina Puzriakova Tag curated_removed tag was added to gene: PROSC.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 TSC2 Arina Puzriakova Tag curated_removed tag was added to gene: TSC2.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 TSC1 Arina Puzriakova Tag curated_removed tag was added to gene: TSC1.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 SMAD4 Arina Puzriakova Tag curated_removed tag was added to gene: SMAD4.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 SERPINA1 Arina Puzriakova Tag curated_removed tag was added to gene: SERPINA1.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 PKD2 Arina Puzriakova Tag curated_removed tag was added to gene: PKD2.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 MED12 Arina Puzriakova Tag curated_removed tag was added to gene: MED12.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 GGCX Arina Puzriakova Tag curated_removed tag was added to gene: GGCX.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 COL9A3 Arina Puzriakova Tag curated_removed tag was added to gene: COL9A3.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 COL9A2 Arina Puzriakova Tag curated_removed tag was added to gene: COL9A2.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 COL9A1 Arina Puzriakova Tag curated_removed tag was added to gene: COL9A1.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 COL2A1 Arina Puzriakova Tag curated_removed tag was added to gene: COL2A1.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 COL11A2 Arina Puzriakova Tag curated_removed tag was added to gene: COL11A2.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 COL11A1 Arina Puzriakova Tag curated_removed tag was added to gene: COL11A1.
Ehlers Danlos syndrome with a likely monogenic cause v2.4 ABCC6 Arina Puzriakova Tag curated_removed tag was added to gene: ABCC6.
Monogenic diabetes v2.4 WRN Arina Puzriakova Tag curated_removed tag was added to gene: WRN.
Monogenic diabetes v2.4 TFR2 Arina Puzriakova Tag curated_removed tag was added to gene: TFR2.
Monogenic diabetes v2.4 STAT3 Arina Puzriakova Tag curated_removed tag was added to gene: STAT3.
Monogenic diabetes v2.4 STAT1 Arina Puzriakova Tag curated_removed tag was added to gene: STAT1.
Monogenic diabetes v2.4 SLC40A1 Arina Puzriakova Tag curated_removed tag was added to gene: SLC40A1.
Monogenic diabetes v2.4 SLC2A2 Arina Puzriakova Tag curated_removed tag was added to gene: SLC2A2.
Monogenic diabetes v2.4 SLC19A2 Arina Puzriakova Tag curated_removed tag was added to gene: SLC19A2.
Monogenic diabetes v2.4 PTF1A Arina Puzriakova Tag curated_removed tag was added to gene: PTF1A.
Monogenic diabetes v2.4 PSMB8 Arina Puzriakova Tag curated_removed tag was added to gene: PSMB8.
Monogenic diabetes v2.4 PPP1R3A Arina Puzriakova Tag curated_removed tag was added to gene: PPP1R3A.
Monogenic diabetes v2.4 POC1A Arina Puzriakova Tag curated_removed tag was added to gene: POC1A.
Monogenic diabetes v2.4 PCYT1A Arina Puzriakova Tag curated_removed tag was added to gene: PCYT1A.
Monogenic diabetes v2.4 PCNT Arina Puzriakova Tag curated_removed tag was added to gene: PCNT.
Monogenic diabetes v2.4 PAX4 Arina Puzriakova Tag curated_removed tag was added to gene: PAX4.
Monogenic diabetes v2.4 NSMCE2 Arina Puzriakova Tag curated_removed tag was added to gene: NSMCE2.
Monogenic diabetes v2.4 NKX2-2 Arina Puzriakova Tag curated_removed tag was added to gene: NKX2-2.
Monogenic diabetes v2.4 NEUROG3 Arina Puzriakova Tag curated_removed tag was added to gene: NEUROG3.
Monogenic diabetes v2.4 MNX1 Arina Puzriakova Tag curated_removed tag was added to gene: MNX1.
Monogenic diabetes v2.4 LRBA Arina Puzriakova Tag curated_removed tag was added to gene: LRBA.
Monogenic diabetes v2.4 LIPC Arina Puzriakova Tag curated_removed tag was added to gene: LIPC.
Monogenic diabetes v2.4 KLF11 Arina Puzriakova Tag curated_removed tag was added to gene: KLF11.
Monogenic diabetes v2.4 IL2RA Arina Puzriakova Tag curated_removed tag was added to gene: IL2RA.
Monogenic diabetes v2.4 IER3IP1 Arina Puzriakova Tag curated_removed tag was added to gene: IER3IP1.
Monogenic diabetes v2.4 HFE2 Arina Puzriakova Tag curated_removed tag was added to gene: HFE2.
Monogenic diabetes v2.4 HFE Arina Puzriakova Tag curated_removed tag was added to gene: HFE.
Monogenic diabetes v2.4 HAMP Arina Puzriakova Tag curated_removed tag was added to gene: HAMP.
Monogenic diabetes v2.4 GLIS3 Arina Puzriakova Tag curated_removed tag was added to gene: GLIS3.
Monogenic diabetes v2.4 FOXP3 Arina Puzriakova Tag curated_removed tag was added to gene: FOXP3.
Monogenic diabetes v2.4 FOXC2 Arina Puzriakova Tag curated_removed tag was added to gene: FOXC2.
Monogenic diabetes v2.4 FGFR3 Arina Puzriakova Tag curated_removed tag was added to gene: FGFR3.
Monogenic diabetes v2.4 ENPP1 Arina Puzriakova Tag curated_removed tag was added to gene: ENPP1.
Monogenic diabetes v2.4 EIF2AK3 Arina Puzriakova Tag curated_removed tag was added to gene: EIF2AK3.
Monogenic diabetes v2.4 DMXL2 Arina Puzriakova Tag curated_removed tag was added to gene: DMXL2.
Monogenic diabetes v2.4 CAVIN1 Arina Puzriakova Tag curated_removed tag was added to gene: CAVIN1.
Monogenic diabetes v2.4 BSCL2 Arina Puzriakova Tag curated_removed tag was added to gene: BSCL2.
Monogenic diabetes v2.4 BLM Arina Puzriakova Tag curated_removed tag was added to gene: BLM.
Monogenic diabetes v2.4 BLK Arina Puzriakova Tag curated_removed tag was added to gene: BLK.
Monogenic diabetes v2.4 ALMS1 Arina Puzriakova Tag curated_removed tag was added to gene: ALMS1.
Monogenic diabetes v2.4 AGPAT2 Arina Puzriakova Tag curated_removed tag was added to gene: AGPAT2.
Rare syndromic craniosynostosis or isolated multisuture synostosis v2.23 KANSL1-AS1 Arina Puzriakova Tag curated_removed tag was added to gene: KANSL1-AS1.
Clefting v2.24 FSHMD1A Arina Puzriakova Tag curated_removed tag was added to gene: FSHMD1A.
Cholestasis v1.81 TMEM67 Arina Puzriakova Tag curated_removed tag was added to gene: TMEM67.
Cholestasis v1.81 RPGRIP1L Arina Puzriakova Tag curated_removed tag was added to gene: RPGRIP1L.
Cholestasis v1.81 CC2D2A Arina Puzriakova Tag curated_removed tag was added to gene: CC2D2A.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TY Arina Puzriakova Tag curated_removed tag was added to gene: MT-TY.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TW Arina Puzriakova Tag curated_removed tag was added to gene: MT-TW.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TV Arina Puzriakova Tag curated_removed tag was added to gene: MT-TV.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TT Arina Puzriakova Tag curated_removed tag was added to gene: MT-TT.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TS2 Arina Puzriakova Tag curated_removed tag was added to gene: MT-TS2.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TS1 Arina Puzriakova Tag curated_removed tag was added to gene: MT-TS1.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TR Arina Puzriakova Tag curated_removed tag was added to gene: MT-TR.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TQ Arina Puzriakova Tag curated_removed tag was added to gene: MT-TQ.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TP Arina Puzriakova Tag curated_removed tag was added to gene: MT-TP.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TN Arina Puzriakova Tag curated_removed tag was added to gene: MT-TN.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TM Arina Puzriakova Tag curated_removed tag was added to gene: MT-TM.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TL2 Arina Puzriakova Tag curated_removed tag was added to gene: MT-TL2.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TL1 Arina Puzriakova Tag curated_removed tag was added to gene: MT-TL1.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TK Arina Puzriakova Tag curated_removed tag was added to gene: MT-TK.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TI Arina Puzriakova Tag curated_removed tag was added to gene: MT-TI.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TH Arina Puzriakova Tag curated_removed tag was added to gene: MT-TH.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TG Arina Puzriakova Tag curated_removed tag was added to gene: MT-TG.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TF Arina Puzriakova Tag curated_removed tag was added to gene: MT-TF.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TE Arina Puzriakova Tag curated_removed tag was added to gene: MT-TE.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TD Arina Puzriakova Tag curated_removed tag was added to gene: MT-TD.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TC Arina Puzriakova Tag curated_removed tag was added to gene: MT-TC.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-TA Arina Puzriakova Tag curated_removed tag was added to gene: MT-TA.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-RNR2 Arina Puzriakova Tag curated_removed tag was added to gene: MT-RNR2.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-RNR1 Arina Puzriakova Tag curated_removed tag was added to gene: MT-RNR1.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-ND6 Arina Puzriakova Tag curated_removed tag was added to gene: MT-ND6.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-ND5 Arina Puzriakova Tag curated_removed tag was added to gene: MT-ND5.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-ND4L Arina Puzriakova Tag curated_removed tag was added to gene: MT-ND4L.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-ND4 Arina Puzriakova Tag curated_removed tag was added to gene: MT-ND4.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-ND3 Arina Puzriakova Tag curated_removed tag was added to gene: MT-ND3.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-ND2 Arina Puzriakova Tag curated_removed tag was added to gene: MT-ND2.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-ND1 Arina Puzriakova Tag curated_removed tag was added to gene: MT-ND1.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-CYB Arina Puzriakova Tag curated_removed tag was added to gene: MT-CYB.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-CO3 Arina Puzriakova Tag curated_removed tag was added to gene: MT-CO3.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-CO2 Arina Puzriakova Tag curated_removed tag was added to gene: MT-CO2.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-CO1 Arina Puzriakova Tag curated_removed tag was added to gene: MT-CO1.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-ATP8 Arina Puzriakova Tag curated_removed tag was added to gene: MT-ATP8.
Childhood onset dystonia, chorea or related movement disorder v1.83 MT-ATP6 Arina Puzriakova Tag curated_removed tag was added to gene: MT-ATP6.
Cerebral vascular malformations v2.8 MYMY3 Arina Puzriakova Tag curated_removed tag was added to gene: MYMY3.
Cerebral vascular malformations v2.8 MYMY1 Arina Puzriakova Tag curated_removed tag was added to gene: MYMY1.
Cerebral vascular malformations v2.8 ANIB1 Arina Puzriakova Tag curated_removed tag was added to gene: ANIB1.
Bardet Biedl syndrome v1.9 ALMS1 Arina Puzriakova Tag curated_removed tag was added to gene: ALMS1.
Familial diabetes v1.59 ENPP1 Arina Puzriakova Classified gene: ENPP1 as No list
Familial diabetes v1.59 ENPP1 Arina Puzriakova Gene: enpp1 has been removed from the panel.
Intellectual disability v3.966 KCNN3 Arina Puzriakova changed review comment from: Comment on mode of pathogenicity: Gain-of-function variants identified in all patients, reported to date.; to: Comment on mode of pathogenicity: Gain-of-function variants identified in all patients reported to date.
Intellectual disability v3.966 KCNN3 Arina Puzriakova Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome 3; OMIM# 618658 to Zimmermann-Laband syndrome 3, OMIM:618658
Intellectual disability v3.965 KCNH1 Arina Puzriakova Publications for gene: KCNH1 were set to 25420144
Intellectual disability v3.964 KCNH1 Arina Puzriakova Phenotypes for gene: KCNH1 were changed from TEMPLE BARRAISTER SYNDROME to Temple-Baraitser syndrome, OMIM:611816; Temple-Baraitser syndrome, MONDO:0012735; Zimmermann-Laband syndrome 1, OMIM:135500; Zimmermann-Laband syndrome 1, MONDO:0024526
Intellectual disability v3.963 ERBB4 Arina Puzriakova Tag Q2_21_NHS_review tag was added to gene: ERBB4.
Arthrogryposis v3.74 MYLPF Arina Puzriakova Tag watchlist tag was added to gene: MYLPF.
Arthrogryposis v3.74 MYLPF Arina Puzriakova edited their review of gene: MYLPF: Changed rating: AMBER
Arthrogryposis v3.74 MYLPF Arina Puzriakova Classified gene: MYLPF as Amber List (moderate evidence)
Arthrogryposis v3.74 MYLPF Arina Puzriakova Added comment: Comment on list classification: Given there are 6 families and different ethnic backgrounds, the biallelic form technically reaches the threshold for inclusion as Green. However, it should be considered that only the residue Cys157 has been implicated to date and the mechanism of pathogenicity is not clear.

Therefore rating Amber awaiting additional cases/functional evidence and further assessment by the GMS expert team to determine the most appropriate rating in view of the current evidence (tagged for 'expert-review')
Arthrogryposis v3.74 MYLPF Arina Puzriakova Gene: mylpf has been classified as Amber List (Moderate Evidence).
Arthrogryposis v3.73 MYLPF Arina Puzriakova Tag Q2_21_expert_review tag was added to gene: MYLPF.
Arthrogryposis v3.73 MYLPF Arina Puzriakova Added comment: Comment on mode of inheritance: Following consultation with Helen Brittain (Genomics England Clinical Team) it was agreed that in view of only 2 families with arthrogryposis and monoallelic variants in this gene there is currently not enough evidence to support inclusion of the monoallelic form. More cases or a delineation of the mechanism of pathogenicity are required before considering adding this as an MOI.
Arthrogryposis v3.73 MYLPF Arina Puzriakova Mode of inheritance for gene: MYLPF was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v3.72 MYLPF Arina Puzriakova reviewed gene: MYLPF: Rating: ; Mode of pathogenicity: None; Publications: 32707087; Phenotypes: Arthrogryposis, distal, type 1C, OMIM:619110, Arthrogryposis, distal, type 1C, MONDO:0030847; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe microcephaly v2.102 C7orf43 Arina Puzriakova changed review comment from: Added new-gene-name tag, new approved HGNC gene symbol for C7orf43 is MAP11; to: Added new-gene-name tag, new approved HGNC gene symbol for C7orf43 is TRAPPC14
Proteinuric renal disease v2.48 LCAT Ania Koziell reviewed gene: LCAT: Rating: GREEN; Mode of pathogenicity: None; Publications: Muthusethupathi MA, Padmanabhan R, Date A, Jayakumar M, Rajendran S, Vijayakumar R. Familial Lecithin:cholesterol acyltransferase deficiency with renal failure in two siblings. First case report from India. Nephron. 1999 Jan, 81(1):89-93. doi: 10.1159/000045253. PMID: 9884427.; Phenotypes: proteinuric renal disease, pseudo-membranous nephropathy, unexplained renal failure in young adults; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pancreatitis v2.7 CELA3B Miranda Durkie gene: CELA3B was added
gene: CELA3B was added to Pancreatitis. Sources: Literature
Mode of inheritance for gene: CELA3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CELA3B were set to Chronic Pancreatitis; Diabetes; Pancreatic cancer
Penetrance for gene: CELA3B were set to Incomplete
Mode of pathogenicity for gene: CELA3B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: CELA3B was set to GREEN
Added comment: PMID: 31369399 - 1 large family with 17 affected family members across 4 generations. Exome sequencing identified c.268C>T p.(Arg90Cys) in CELA3B gene in affected mother and affected daughter (not present in unaffected son). Does not segregate with disease in a further 6 unaffected family members. Functional studies showed both this variant and p.(Arg90Leu) variants cause translational upregulation of CELA3B, which, upon secretion and activation by
trypsin, leads to uncontrolled proteolysis and recurrent pancreatitis.
PMID: 33565216 - Sequenced CELA3B in 644 genetically unexplained French chronic pancreatitis (CP) patients (all unrelated) and 566 controls. No loss of function variants found, however found p.Arg90Leu (c.269G>T) in four patients but no controls.
Therefore 5 families identified with p.(Arg90Cys) or p.(Arg90Leu) and supporting functional assay for these variants only.
Sources: Literature
Dilated and arrhythmogenic cardiomyopathy v1.13 NRAP Ivone Leong Classified gene: NRAP as Amber List (moderate evidence)
Dilated and arrhythmogenic cardiomyopathy v1.13 NRAP Ivone Leong Gene: nrap has been classified as Amber List (Moderate Evidence).
Dilated and arrhythmogenic cardiomyopathy v1.12 NRAP Ivone Leong gene: NRAP was added
gene: NRAP was added to Dilated cardiomyopathy - adult and teen. Sources: Literature
Q2_21_rating tags were added to gene: NRAP.
Mode of inheritance for gene: NRAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRAP were set to 30384889; 33534821; 28611399; https://doi.org/10.1101/2020.10.12.20211474
Phenotypes for gene: NRAP were set to Dilated cardiomyopathy, MONDO:0005021
Review for gene: NRAP was set to GREEN
Added comment: This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There are >3 unrelated cases of patients with variants in this gene and having DCM.

https://doi.org/10.1101/2020.10.12.20211474 also describes a CRISPR knockout zebrafish which had a cardiac phenotype.

Therefore, there is enough evidence to support a gene-disease association and this gene is recommended to be promoted Green at the next panel review.
Sources: Literature
Intellectual disability v3.963 CXorf56 Catherine Snow Tag new-gene-name tag was added to gene: CXorf56.
Intellectual disability v3.963 CXorf56 Catherine Snow commented on gene: CXorf56
Intellectual disability v3.963 MPP5 Catherine Snow Tag new-gene-name tag was added to gene: MPP5.
Intellectual disability v3.963 MPP5 Catherine Snow commented on gene: MPP5
COVID-19 research v1.76 MPP5 Catherine Snow Tag new-gene-name tag was added to gene: MPP5.
COVID-19 research v1.76 MPP5 Catherine Snow commented on gene: MPP5
DDG2P v2.21 TTC25 Catherine Snow Tag new-gene-name tag was added to gene: TTC25.
DDG2P v2.21 TTC25 Catherine Snow commented on gene: TTC25
Fetal anomalies v1.628 TTC25 Catherine Snow Tag new-gene-name tag was added to gene: TTC25.
Fetal anomalies v1.628 TTC25 Catherine Snow commented on gene: TTC25
Respiratory ciliopathies including non-CF bronchiectasis v1.43 TTC25 Catherine Snow Tag new-gene-name tag was added to gene: TTC25.
Respiratory ciliopathies including non-CF bronchiectasis v1.43 TTC25 Catherine Snow commented on gene: TTC25
Laterality disorders and isomerism v1.21 TTC25 Catherine Snow Tag new-gene-name tag was added to gene: TTC25.
Laterality disorders and isomerism v1.21 TTC25 Catherine Snow commented on gene: TTC25
Rare multisystem ciliopathy disorders v1.139 CCDC151 Catherine Snow Tag new-gene-name tag was added to gene: CCDC151.
Rare multisystem ciliopathy disorders v1.139 CCDC151 Catherine Snow commented on gene: CCDC151
DDG2P v2.21 CCDC151 Catherine Snow Tag new-gene-name tag was added to gene: CCDC151.
DDG2P v2.21 CCDC151 Catherine Snow commented on gene: CCDC151
Fetal anomalies v1.628 CCDC151 Catherine Snow Tag new-gene-name tag was added to gene: CCDC151.
Fetal anomalies v1.628 CCDC151 Catherine Snow commented on gene: CCDC151
Respiratory ciliopathies including non-CF bronchiectasis v1.43 CCDC151 Catherine Snow Tag new-gene-name tag was added to gene: CCDC151.
Respiratory ciliopathies including non-CF bronchiectasis v1.43 CCDC151 Catherine Snow commented on gene: CCDC151
Laterality disorders and isomerism v1.21 CCDC151 Catherine Snow Tag new-gene-name tag was added to gene: CCDC151.
Laterality disorders and isomerism v1.21 CCDC151 Catherine Snow commented on gene: CCDC151
Primary ciliary disorders v1.29 CCDC151 Catherine Snow Tag new-gene-name tag was added to gene: CCDC151.
Primary ciliary disorders v1.29 CCDC151 Catherine Snow commented on gene: CCDC151
Rare multisystem ciliopathy disorders v1.139 ARMC4 Catherine Snow Tag new-gene-name tag was added to gene: ARMC4.
Rare multisystem ciliopathy disorders v1.139 ARMC4 Catherine Snow commented on gene: ARMC4
Intellectual disability v3.963 ARMC4 Catherine Snow Tag new-gene-name tag was added to gene: ARMC4.
Intellectual disability v3.963 ARMC4 Catherine Snow commented on gene: ARMC4
DDG2P v2.21 ARMC4 Catherine Snow Tag new-gene-name tag was added to gene: ARMC4.
DDG2P v2.21 ARMC4 Catherine Snow commented on gene: ARMC4
Fetal anomalies v1.628 ARMC4 Catherine Snow Tag new-gene-name tag was added to gene: ARMC4.
Fetal anomalies v1.628 ARMC4 Catherine Snow commented on gene: ARMC4
Respiratory ciliopathies including non-CF bronchiectasis v1.43 ARMC4 Catherine Snow Tag new-gene-name tag was added to gene: ARMC4.
Respiratory ciliopathies including non-CF bronchiectasis v1.43 ARMC4 Catherine Snow commented on gene: ARMC4
Laterality disorders and isomerism v1.21 ARMC4 Catherine Snow Tag new-gene-name tag was added to gene: ARMC4.
Laterality disorders and isomerism v1.21 ARMC4 Catherine Snow commented on gene: ARMC4
Primary ciliary disorders v1.29 ARMC4 Catherine Snow Tag new-gene-name tag was added to gene: ARMC4.
Primary ciliary disorders v1.29 ARMC4 Catherine Snow commented on gene: ARMC4
Rare multisystem ciliopathy disorders v1.139 CCDC114 Catherine Snow Tag new-gene-name tag was added to gene: CCDC114.
Rare multisystem ciliopathy disorders v1.139 CCDC114 Catherine Snow commented on gene: CCDC114
Intellectual disability v3.963 CCDC114 Catherine Snow Tag new-gene-name tag was added to gene: CCDC114.
Intellectual disability v3.963 CCDC114 Catherine Snow commented on gene: CCDC114
DDG2P v2.21 CCDC114 Catherine Snow Tag new-gene-name tag was added to gene: CCDC114.
DDG2P v2.21 CCDC114 Catherine Snow commented on gene: CCDC114
Fetal anomalies v1.628 CCDC114 Catherine Snow Tag new-gene-name tag was added to gene: CCDC114.
Fetal anomalies v1.628 CCDC114 Catherine Snow commented on gene: CCDC114
Respiratory ciliopathies including non-CF bronchiectasis v1.43 CCDC114 Catherine Snow Tag new-gene-name tag was added to gene: CCDC114.
Respiratory ciliopathies including non-CF bronchiectasis v1.43 CCDC114 Catherine Snow commented on gene: CCDC114
Laterality disorders and isomerism v1.21 CCDC114 Catherine Snow Tag new-gene-name tag was added to gene: CCDC114.
Laterality disorders and isomerism v1.21 CCDC114 Catherine Snow commented on gene: CCDC114
Primary ciliary disorders v1.29 CCDC114 Catherine Snow Tag new-gene-name tag was added to gene: CCDC114.
Primary ciliary disorders v1.29 CCDC114 Catherine Snow commented on gene: CCDC114
Ductal plate malformation v1.16 CCDC114 Catherine Snow Tag new-gene-name tag was added to gene: CCDC114.
Ductal plate malformation v1.16 CCDC114 Catherine Snow commented on gene: CCDC114
Childhood onset dystonia, chorea or related movement disorder v1.83 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Childhood onset dystonia, chorea or related movement disorder v1.83 C12orf65 Catherine Snow commented on gene: C12orf65
Hereditary neuropathy or pain disorder v1.23 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Hereditary neuropathy or pain disorder v1.23 C12orf65 Catherine Snow commented on gene: C12orf65
Retinal disorders v2.172 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Retinal disorders v2.172 C12orf65 Catherine Snow commented on gene: C12orf65
Mitochondrial disorders v2.19 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Mitochondrial disorders v2.19 C12orf65 Catherine Snow commented on gene: C12orf65
Intellectual disability v3.963 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Intellectual disability v3.963 C12orf65 Catherine Snow commented on gene: C12orf65
Hereditary neuropathy v1.383 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Hereditary neuropathy v1.383 C12orf65 Catherine Snow commented on gene: C12orf65
DDG2P v2.21 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
DDG2P v2.21 C12orf65 Catherine Snow commented on gene: C12orf65
Fetal anomalies v1.628 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Fetal anomalies v1.628 C12orf65 Catherine Snow commented on gene: C12orf65
Possible mitochondrial disorder - nuclear genes v1.37 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Possible mitochondrial disorder - nuclear genes v1.37 C12orf65 Catherine Snow commented on gene: C12orf65
Likely inborn error of metabolism v2.101 C12orf65 Catherine Snow commented on gene: C12orf65
Likely inborn error of metabolism v2.101 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Undiagnosed metabolic disorders v1.447 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Undiagnosed metabolic disorders v1.447 C12orf65 Catherine Snow commented on gene: C12orf65
Adult onset neurodegenerative disorder v2.39 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Adult onset neurodegenerative disorder v2.39 C12orf65 Catherine Snow commented on gene: C12orf65
Adult onset hereditary spastic paraplegia v1.16 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Adult onset hereditary spastic paraplegia v1.16 C12orf65 Catherine Snow commented on gene: C12orf65
Childhood onset hereditary spastic paraplegia v2.28 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Childhood onset hereditary spastic paraplegia v2.28 C12orf65 Catherine Snow commented on gene: C12orf65
Arthrogryposis v3.72 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Arthrogryposis v3.72 C12orf65 Catherine Snow commented on gene: C12orf65
Optic neuropathy v2.35 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Optic neuropathy v2.35 C12orf65 Catherine Snow commented on gene: C12orf65
Hereditary spastic paraplegia v1.219 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Hereditary spastic paraplegia v1.219 C12orf65 Catherine Snow commented on gene: C12orf65
Primary immunodeficiency or monogenic inflammatory bowel disease v2.401 MAP1LC3B2 Boaz Palterer gene: MAP1LC3B2 was added
gene: MAP1LC3B2 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: MAP1LC3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAP1LC3B2 were set to 33310865
Phenotypes for gene: MAP1LC3B2 were set to Mollaret’s meningitis; recurrent HSV2 meningitis
Penetrance for gene: MAP1LC3B2 were set to unknown
Review for gene: MAP1LC3B2 was set to RED
Added comment: Hait et al. described a single patient with a rare heterozygous variant in MAP1LC3B2 presenting with recurrent HSV2 meningitis (Mollaret's meningitis). They showed that the mutations caused impaired HSV2-induced autophagy leading to increased viral replication and apoptosis of patient fibroblasts. The defect was rescued by the introduction of WT MAP1LC3B2 into patient fibroblasts.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.401 ATG4A Boaz Palterer gene: ATG4A was added
gene: ATG4A was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: ATG4A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATG4A were set to 33310865
Phenotypes for gene: ATG4A were set to Mollaret’s meningitis; recurrent HSV2 meningitis
Penetrance for gene: ATG4A were set to unknown
Review for gene: ATG4A was set to RED
Added comment: Hait et al. described a single patient with a rare heterozygous variant in ATG4 presenting with recurrent HSV2 meningitis (Mollaret's meningitis). They showed that the mutations caused impaired HSV2-induced autophagy leading to increased viral replication and apoptosis of patient fibroblasts. The defect was rescued by the introduction of WT ATG4 into patient fibroblasts.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.401 RAD50 Boaz Palterer gene: RAD50 was added
gene: RAD50 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: RAD50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAD50 were set to 33378670
Phenotypes for gene: RAD50 were set to bone marrow failure; immunodeficiency; developmental defect
Penetrance for gene: RAD50 were set to unknown
Review for gene: RAD50 was set to RED
Added comment: Chansel-Da Cruz et al. identified a single patient with bone marrow failure, immunodeficiency and developmental defect caused by compound heterozygous mutations in RAD50. The first mutations generate a null allele, the second is hypothesized to be hypomorphic because of the loss of a single amino acid residue in the coiled-coil domain of RAD50.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.401 POU2AF1 Boaz Palterer gene: POU2AF1 was added
gene: POU2AF1 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: POU2AF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POU2AF1 were set to 33571536
Phenotypes for gene: POU2AF1 were set to Agammaglobulinemia; Immunodeficiency; Bob1 deficiency
Penetrance for gene: POU2AF1 were set to unknown
Review for gene: POU2AF1 was set to RED
Added comment: Kury et al. described a single patient from consanguineous parents carrying a homozygous frameshift mutation in POU2AF1, encoding for Bob1, presenting with agammaglobulinemia with normal B cells. Functional data showed that Bob1 deficiency ex vivo and in a mouse KO model reduced B-cell responsiveness, impaired plasmablast formation and immunoglobulin secretion.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.401 GIMAP5 Boaz Palterer gene: GIMAP5 was added
gene: GIMAP5 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: GIMAP5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GIMAP5 were set to lymphopenia; autoimmunity; immunodeficiency; liver disease
Penetrance for gene: GIMAP5 were set to unknown
Review for gene: GIMAP5 was set to RED
Added comment: Park et al. (https://www.biorxiv.org/content/10.1101/2021.02.22.432146v1.full.pdf) identified biallelic mutations in GIMAP5 in 10 subjects from 4 kindreds with severe progressive
lymphopenia, autoimmunity, immunodeficiency, and liver disease
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v1.83 G6PC Catherine Snow Tag new-gene-name tag was added to gene: G6PC.
Childhood onset dystonia, chorea or related movement disorder v1.83 G6PC Catherine Snow commented on gene: G6PC
Mitochondrial disorders v2.19 G6PC Catherine Snow Tag new-gene-name tag was added to gene: G6PC.
Mitochondrial disorders v2.19 G6PC Catherine Snow commented on gene: G6PC
Possible mitochondrial disorder - nuclear genes v1.37 G6PC Catherine Snow Tag new-gene-name tag was added to gene: G6PC.
Possible mitochondrial disorder - nuclear genes v1.37 G6PC Catherine Snow commented on gene: G6PC
Likely inborn error of metabolism v2.101 G6PC Catherine Snow Tag new-gene-name tag was added to gene: G6PC.
Likely inborn error of metabolism v2.101 G6PC Catherine Snow commented on gene: G6PC
Undiagnosed metabolic disorders v1.447 G6PC Catherine Snow Tag new-gene-name tag was added to gene: G6PC.
Undiagnosed metabolic disorders v1.447 G6PC Catherine Snow commented on gene: G6PC
Glycogen storage disease v1.4 G6PC Catherine Snow Tag new-gene-name tag was added to gene: G6PC.
Glycogen storage disease v1.4 G6PC Catherine Snow commented on gene: G6PC
Hyperammonaemia v1.8 G6PC Catherine Snow Tag new-gene-name tag was added to gene: G6PC.
Hyperammonaemia v1.8 G6PC Catherine Snow commented on gene: G6PC
Ketotic hypoglycaemia v1.4 G6PC Catherine Snow Tag new-gene-name tag was added to gene: G6PC.
Ketotic hypoglycaemia v1.4 G6PC Catherine Snow commented on gene: G6PC
Intellectual disability v3.963 FAM160B1 Catherine Snow Tag new-gene-name tag was added to gene: FAM160B1.
Intellectual disability v3.963 FAM160B1 Catherine Snow commented on gene: FAM160B1
Childhood onset dystonia, chorea or related movement disorder v1.83 TCTEX1D2 Catherine Snow Tag new-gene-name tag was added to gene: TCTEX1D2.
Childhood onset dystonia, chorea or related movement disorder v1.83 TCTEX1D2 Catherine Snow commented on gene: TCTEX1D2
Skeletal ciliopathies v1.10 TCTEX1D2 Catherine Snow Tag new-gene-name tag was added to gene: TCTEX1D2.
Skeletal ciliopathies v1.10 TCTEX1D2 Catherine Snow commented on gene: TCTEX1D2
Rare multisystem ciliopathy disorders v1.139 TCTEX1D2 Catherine Snow Tag new-gene-name tag was added to gene: TCTEX1D2.
Rare multisystem ciliopathy disorders v1.139 TCTEX1D2 Catherine Snow commented on gene: TCTEX1D2
Fetal anomalies v1.628 TCTEX1D2 Catherine Snow Tag new-gene-name tag was added to gene: TCTEX1D2.
Fetal anomalies v1.628 TCTEX1D2 Catherine Snow commented on gene: TCTEX1D2
Skeletal dysplasia v2.83 TCTEX1D2 Catherine Snow Tag new-gene-name tag was added to gene: TCTEX1D2.
Skeletal dysplasia v2.83 TCTEX1D2 Catherine Snow commented on gene: TCTEX1D2
Limb disorders v2.36 TCTEX1D2 Catherine Snow Tag new-gene-name tag was added to gene: TCTEX1D2.
Limb disorders v2.36 TCTEX1D2 Catherine Snow commented on gene: TCTEX1D2
Thoracic dystrophies v1.12 TCTEX1D2 Catherine Snow Tag new-gene-name tag was added to gene: TCTEX1D2.
Thoracic dystrophies v1.12 TCTEX1D2 Catherine Snow commented on gene: TCTEX1D2
Rare multisystem ciliopathy disorders v1.139 LRRC6 Catherine Snow Tag new-gene-name tag was added to gene: LRRC6.
Rare multisystem ciliopathy disorders v1.139 LRRC6 Catherine Snow commented on gene: LRRC6
Intellectual disability v3.963 LRRC6 Catherine Snow Tag new-gene-name tag was added to gene: LRRC6.
Intellectual disability v3.963 LRRC6 Catherine Snow commented on gene: LRRC6
DDG2P v2.21 LRRC6 Catherine Snow Tag new-gene-name tag was added to gene: LRRC6.
DDG2P v2.21 LRRC6 Catherine Snow commented on gene: LRRC6
Fetal anomalies v1.628 LRRC6 Catherine Snow Tag new-gene-name tag was added to gene: LRRC6.
Fetal anomalies v1.628 LRRC6 Catherine Snow commented on gene: LRRC6
Respiratory ciliopathies including non-CF bronchiectasis v1.43 LRRC6 Catherine Snow Tag new-gene-name tag was added to gene: LRRC6.
Respiratory ciliopathies including non-CF bronchiectasis v1.43 LRRC6 Catherine Snow commented on gene: LRRC6
Laterality disorders and isomerism v1.21 LRRC6 Catherine Snow Tag new-gene-name tag was added to gene: LRRC6.
Laterality disorders and isomerism v1.21 LRRC6 Catherine Snow commented on gene: LRRC6
Primary ciliary disorders v1.29 LRRC6 Catherine Snow Tag new-gene-name tag was added to gene: LRRC6.
Primary ciliary disorders v1.29 LRRC6 Catherine Snow commented on gene: LRRC6
Ductal plate malformation v1.16 LRRC6 Catherine Snow Tag new-gene-name tag was added to gene: LRRC6.
Ductal plate malformation v1.16 LRRC6 Catherine Snow commented on gene: LRRC6
Mitochondrial disorders v2.19 USMG5 Catherine Snow commented on gene: USMG5
Mitochondrial disorders v2.19 USMG5 Catherine Snow Tag new-gene-name tag was added to gene: USMG5.
Intellectual disability v3.963 CDK19 Sarah Leigh edited their review of gene: CDK19: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN
Early onset or syndromic epilepsy v2.303 CDK19 Julia Baptista reviewed gene: CDK19: Rating: GREEN; Mode of pathogenicity: None; Publications: 33495529, 33568421, 32330417; Phenotypes: developmental delay, hypotonia, seizures, autism/autistic traits; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Unexplained kidney failure in young people v1.92 TRIM8 Julia Baptista gene: TRIM8 was added
gene: TRIM8 was added to Unexplained kidney failure in young people. Sources: Literature
Mode of inheritance for gene: TRIM8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM8 were set to 33508234
Phenotypes for gene: TRIM8 were set to nephrotic syndrome; epilepsy
Mode of pathogenicity for gene: TRIM8 was set to Other
Review for gene: TRIM8 was set to GREEN
Added comment: Eight families with NFS, six confirmed de novo heterozygous variants clustering within the last exon between residues 390 and 487 of the 551 amino acid protein, indicating a correlation between this syndrome and loss of the TRIM8 C-terminal region. Gain-of-function is the proposed disease mechanism.
Sources: Literature
Intellectual disability v3.963 ERBB4 Julia Baptista gene: ERBB4 was added
gene: ERBB4 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: ERBB4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERBB4 were set to 33603162
Phenotypes for gene: ERBB4 were set to intellectual disability; epilepsy
Penetrance for gene: ERBB4 were set to Incomplete
Review for gene: ERBB4 was set to GREEN
Added comment: Heterozygous intragenic multi-exonic ERBB4 deletions were identified in nine individuals from five unrelated families. Affected individuals had either non-syndromic ID or generalised epilepsy.
The deletion segregated with the phenotype in five affected individuals in one family, it was de novo in a second family and the inheritance was unknown in two families. In the fifth family, the deletion was inherited from a normal parent.
Sources: Literature
Renal ciliopathies v1.40 DLG5 Julia Baptista reviewed gene: DLG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32631816; Phenotypes: Cystic kidneys, hydrocephalus, retinal abnormality, cleft palate, rhizomelic limb shortening; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.963 KCNH1 Julia Baptista reviewed gene: KCNH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33594261; Phenotypes: Temple-Baraitser syndrome, Zimmermann-Laband syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.963 KCNN3 Julia Baptista reviewed gene: KCNN3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 33594261; Phenotypes: developmental delay, ID, hypotonia, gingival enlargement, hypertrichosis, nail anomalies; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Osteogenesis imperfecta v2.13 UNC45A Julia Baptista reviewed gene: UNC45A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29429573; Phenotypes: cholestasis, diarrhea, bone fragility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v3.963 CDK19 Julia Baptista changed review comment from: De novo missense variants mapped to the kinase domain of CDK19 were described in 11 unrelated individuals (age range: 9 months to 14 years).Two recurrent changes at residues Tyr32 and Gly28 were identified.
One additional case report (PMID:33568421) described a 10-month-old male patient who presented with a neurodevelopmental syndrome characterized by infantile spasms and a de novo missense variant c.92C>A (p.Thr31Asn) (also in the kinase domain). This brings the total of cases reported in the literature to 15.; to: De novo missense variants mapped to the kinase domain of CDK19 were described in 11 unrelated individuals (age range: 9 months to 14 years).Two recurrent changes at residues Tyr32 and Gly28 were identified.
One additional case report (PMID:33568421) described a 10-month-old male patient who presented with a neurodevelopmental syndrome characterized by infantile spasms and a de novo missense variant c.92C>A (p.Thr31Asn) (also in the kinase domain). This brings the total of cases reported in the literature to 15.
Intellectual disability v3.963 CDK19 Julia Baptista reviewed gene: CDK19: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33495529, 33568421, 32330417; Phenotypes: developmental delay, hypotonia, seizures, autism/autistic traits; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Early onset or syndromic epilepsy v2.303 SCAMP5 Sarah Leigh Tag Q2_21_rating tag was added to gene: SCAMP5.
Early onset or syndromic epilepsy v2.303 SCAMP5 Sarah Leigh edited their review of gene: SCAMP5: Added comment: Not associated with relevant phenotype in OMIM or Gen2Phen (18/02/2021). At single heterozygous variant (NM_001178111.1: c.538G>T, p.Gly180Trp) has been reported to be associated with intellectual disability; seizures; autism in at least six unrelated cases (PMID 33390987; 31439720).; Changed rating: GREEN
Early onset or syndromic epilepsy v2.303 SCAMP5 Sarah Leigh Classified gene: SCAMP5 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v2.303 SCAMP5 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v2.303 SCAMP5 Sarah Leigh Gene: scamp5 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v2.302 SCAMP5 Sarah Leigh Added comment: Comment on phenotypes: OMIM does not have a phenotype associated with variants in this gene (18/02/21).
Early onset or syndromic epilepsy v2.302 SCAMP5 Sarah Leigh Phenotypes for gene: SCAMP5 were changed from Global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology; Behavioral abnormality to Global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology; Behavioral abnormality
Early onset or syndromic epilepsy v2.301 SCAMP5 Sarah Leigh Publications for gene: SCAMP5 were set to 31439720; 20071347; 32020363
Adult onset dystonia, chorea or related movement disorder v1.20 PPP2R5D Sarah Leigh Phenotypes for gene: PPP2R5D were changed from Early onset Parkinsonism; Mental retardation, autosomal dominant 35, MIM# 616355 to Mental retardation, autosomal dominant 35 OMIM:616355; intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome MONDO:0014602
Adult onset dystonia, chorea or related movement disorder v1.19 PPP2R5D Sarah Leigh changed review comment from: Associated with OMIM 616355 and as confirmed Gen2Phen gene for intellectual disability. Early-onset Parkinsonism has recently been associated with two PPP2R5D variants in four unrelated cases (NM_006245.3: c.592G > A, p.Glu198Lys (one case) c.598G>A, p.Glu200Lys (three cases)).; to: Associated with OMIM 616355 and as confirmed Gen2Phen gene for intellectual disability. Early-onset Parkinsonism has recently been associated with two PPP2R5D variants in four unrelated cases (NM_006245.3: c.592G > A, p.Glu198Lys (one case) c.598G>A, p.Glu200Lys (four cases)).
Adult onset dystonia, chorea or related movement disorder v1.19 PPP2R5D Sarah Leigh edited their review of gene: PPP2R5D: Added comment: Associated with OMIM 616355 and as confirmed Gen2Phen gene for intellectual disability. Early-onset Parkinsonism has recently been associated with two PPP2R5D variants in four unrelated cases (NM_006245.3: c.592G > A, p.Glu198Lys (one case) c.598G>A, p.Glu200Lys (three cases)).; Changed rating: GREEN
Adult onset dystonia, chorea or related movement disorder v1.19 PPP2R5D Sarah Leigh Classified gene: PPP2R5D as Amber List (moderate evidence)
Adult onset dystonia, chorea or related movement disorder v1.19 PPP2R5D Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset dystonia, chorea or related movement disorder v1.19 PPP2R5D Sarah Leigh Gene: ppp2r5d has been classified as Amber List (Moderate Evidence).
Adult onset dystonia, chorea or related movement disorder v1.18 PPP2R5D Sarah Leigh Tag Q2_21_phenotype tag was added to gene: PPP2R5D.
Adult onset dystonia, chorea or related movement disorder v1.18 PPP2R5D Sarah Leigh Publications for gene: PPP2R5D were set to 33338668; 32743835
Hereditary ataxia v1.211 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from Pontocerebellar hypoplasia 10 (#615803) to Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349
Hereditary ataxia v1.210 CLP1 Sarah Leigh Publications for gene: CLP1 were set to
Hereditary ataxia v1.209 CLP1 Sarah Leigh Classified gene: CLP1 as Green List (high evidence)
Hereditary ataxia v1.209 CLP1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. A single variant was reported in Turkish families who shared an 11.5 Mb haplotype in the CLP1 region, this did not suggest a recent ancestory amongst seemingly unrelated families (PMID 24766809). Supportive functional studies and a mouse model were also reported.
Hereditary ataxia v1.209 CLP1 Sarah Leigh Gene: clp1 has been classified as Green List (High Evidence).
DDG2P v2.21 CLP1 Sarah Leigh Publications for gene: CLP1 were set to 24766809
DDG2P v2.20 CLP1 Sarah Leigh Classified gene: CLP1 as Amber List (moderate evidence)
DDG2P v2.20 CLP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
DDG2P v2.20 CLP1 Sarah Leigh Gene: clp1 has been classified as Amber List (Moderate Evidence).
DDG2P v2.19 CLP1 Sarah Leigh Tag Q2_21_rating tag was added to gene: CLP1.
DDG2P v2.19 CLP1 Sarah Leigh reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v1.628 CLP1 Sarah Leigh reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.48 CLP1 Sarah Leigh edited their review of gene: CLP1: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. A single variant was reported in Turkish families who shared an 11.5 Mb haplotype in the CLP1 region, this did not suggest a recent ancestory amongst seemingly unrelated families (PMID 24766809). Supportive functional studies and a mouse model were also reported.; Changed rating: GREEN; Changed publications: 24766810
Ataxia and cerebellar anomalies - narrow panel v2.48 CLP1 Sarah Leigh Tag Q2_21_rating tag was added to gene: CLP1.
Ataxia and cerebellar anomalies - narrow panel v2.48 CLP1 Sarah Leigh Classified gene: CLP1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.48 CLP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.48 CLP1 Sarah Leigh Gene: clp1 has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - deep sequencing v1.5 MVD Zornitza Stark reviewed gene: MVD: Rating: GREEN; Mode of pathogenicity: None; Publications: 33491095; Phenotypes: Porokeratosis 7, multiple types, MIM# 614714; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v1.5 IKBKG Zornitza Stark reviewed gene: IKBKG: Rating: GREEN; Mode of pathogenicity: None; Publications: 32908217, 29077987; Phenotypes: Incontinentia pigmenti, 308300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mosaic skin disorders - deep sequencing v1.5 FGFR2 Zornitza Stark reviewed gene: FGFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31937562, 30580445; Phenotypes: Keratinocytic epidermal naevi; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v1.5 ATP2A2 Zornitza Stark reviewed gene: ATP2A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30085326, 26154588, 21720150, 12890216; Phenotypes: Darier disease, MIM# 124200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v2.172 ZFYVE26 Ivone Leong Classified gene: ZFYVE26 as Amber List (moderate evidence)
Retinal disorders v2.172 ZFYVE26 Ivone Leong Added comment: Comment on list classification: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Retinal disorders v2.172 ZFYVE26 Ivone Leong Gene: zfyve26 has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.171 ZFYVE26 Ivone Leong Tag Q2_21_rating tag was added to gene: ZFYVE26.
Retinal disorders v2.171 ZFYVE26 Ivone Leong Publications for gene: ZFYVE26 were set to 18394578; 14409555; 19805727
Retinal disorders v2.170 ZFYVE26 Ivone Leong Publications for gene: ZFYVE26 were set to 18394578; 14409555
Retinal disorders v2.169 ZFYVE26 Ivone Leong Phenotypes for gene: ZFYVE26 were changed from Spastic paraplegia 15, autosomal recessive MIM#270700 to Spastic paraplegia 15, autosomal recessive OMIM:270700
Retinal disorders v2.168 UNC119 Ivone Leong Classified gene: UNC119 as Amber List (moderate evidence)
Retinal disorders v2.168 UNC119 Ivone Leong Added comment: Comment on list classification: This gene is associated with a relevant phenotype in Gene2Phenotype but not in OMIM. Based on the available evidence there are 2 independent cases with an animal model, therefore there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Retinal disorders v2.168 UNC119 Ivone Leong Gene: unc119 has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.167 UNC119 Ivone Leong Tag Q2_21_rating tag was added to gene: UNC119.
Retinal disorders v2.167 WDPCP Ivone Leong Phenotypes for gene: WDPCP were changed from Eye Disorders to Bardet-Biedl syndrome 15, OMIM:615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, OMIM:217085
Retinal disorders v2.166 WDPCP Ivone Leong Added comment: Comment on publications: New publications added
Retinal disorders v2.166 WDPCP Ivone Leong Publications for gene: WDPCP were set to
Retinal disorders v2.165 UNC119 Ivone Leong Publications for gene: UNC119 were set to
Hereditary ataxia with onset in adulthood v2.25 CHMP1A Sarah Leigh Phenotypes for gene: CHMP1A were changed from Pontocerebellar hypoplasia, type 8, 614961; Pontocerebellar hypoplasia type 8, 614961 to Pontocerebellar hypoplasia, type 8 OMIM:614961; pontocerebellar hypoplasia type 8 MONDO:0013990
Hereditary ataxia with onset in adulthood v2.24 CHMP1A Sarah Leigh Publications for gene: CHMP1A were set to
Hereditary ataxia with onset in adulthood v2.23 CHMP1A Sarah Leigh reviewed gene: CHMP1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary ataxia with onset in adulthood v2.23 CHMP1A Sarah Leigh Tag Q2_21_phenotype tag was added to gene: CHMP1A.
Ataxia and cerebellar anomalies - narrow panel v2.47 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349 to Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349
Intellectual disability v3.963 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from PONTOCEREBELLAR HYPOPLASIA, TYPE 10 to Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349
Intellectual disability v3.962 CLP1 Sarah Leigh Tag founder-effect tag was added to gene: CLP1.
DDG2P v2.19 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from PONTOCEREBELLAR HYPOPLASIA, TYPE 10 615803 to Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349
DDG2P v2.18 CLP1 Sarah Leigh Tag founder-effect tag was added to gene: CLP1.
Cerebellar hypoplasia v1.43 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from Pontocerebellar Hypoplasia type 10; Pontocerebellar HypoplasiaPontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349 to Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349
Cerebellar hypoplasia v1.42 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from Pontocerebellar Hypoplasia type 10; Pontocerebellar Hypoplasia to Pontocerebellar Hypoplasia type 10; Pontocerebellar HypoplasiaPontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349
Fetal anomalies v1.628 CLP1 Sarah Leigh Tag founder-effect tag was added to gene: CLP1.
Ataxia and cerebellar anomalies - narrow panel v2.46 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 10 OMIM:615803 to Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349
Cerebellar hypoplasia v1.41 CLP1 Sarah Leigh Tag founder-effect tag was added to gene: CLP1.
Hereditary ataxia v1.208 CLP1 Sarah Leigh Tag founder-effect tag was added to gene: CLP1.
Ataxia and cerebellar anomalies - narrow panel v2.45 CLP1 Sarah Leigh Tag founder-effect tag was added to gene: CLP1.
Hereditary ataxia with onset in adulthood v2.23 CLP1 Sarah Leigh changed review comment from: Zornitza Stark has reviewed this gene as red on this panel, as the phenotype associated with variants in CLP1 is evident in childhood. Furthermore, only a single Founder variant has been reported, in patients.; to: Zornitza Stark has reviewed this gene as red on this panel, as the phenotype associated with variants in CLP1 is evident in childhood. Furthermore, only a single (founder) variant has been reported, in patients.
Hereditary ataxia with onset in adulthood v2.23 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from Pontocerebellar hypoplasia type 10, 615803 to Pontocerebellar hypoplasia type 10 OMIM:615803
Ataxia and cerebellar anomalies - narrow panel v2.45 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 10 (#615803); Pontocerebellar Hypoplasia type 10 to Pontocerebellar Hypoplasia; Pontocerebellar hypoplasia 10 OMIM:615803
Ataxia and cerebellar anomalies - narrow panel v2.44 CLP1 Sarah Leigh Publications for gene: CLP1 were set to PMID: 24766810
Hereditary ataxia with onset in adulthood v2.22 CLP1 Sarah Leigh Publications for gene: CLP1 were set to
Hereditary ataxia with onset in adulthood v2.21 CLP1 Sarah Leigh Tag founder-effect tag was added to gene: CLP1.
Hereditary ataxia with onset in adulthood v2.21 CLP1 Sarah Leigh reviewed gene: CLP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary ataxia with onset in adulthood v2.21 CLP1 Sarah Leigh Tag Q2_21_phenotype tag was added to gene: CLP1.
Early onset or syndromic epilepsy v2.300 SLC7A6OS Sarah Leigh Classified gene: SLC7A6OS as Red List (low evidence)
Early onset or syndromic epilepsy v2.300 SLC7A6OS Sarah Leigh Added comment: Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one variant reported in two familes, shown to share common ancestors by haplotype analysis (PMID 33085104).
Early onset or syndromic epilepsy v2.300 SLC7A6OS Sarah Leigh Gene: slc7a6os has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v2.299 SLC7A6OS Sarah Leigh Publications for gene: SLC7A6OS were set to 33085104
Early onset or syndromic epilepsy v2.298 SLC7A6OS Sarah Leigh Tag founder-effect tag was added to gene: SLC7A6OS.
Mitochondrial disorders v2.19 NFS1 Sarah Leigh edited their review of gene: NFS1: Added comment: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one variant reported in six cases from two unrelated families, together with supportive functional studies.; Changed rating: GREEN
Mitochondrial disorders v2.19 NFS1 Sarah Leigh Tag Q2_21_rating tag was added to gene: NFS1.
Mitochondrial disorders v2.19 NFS1 Sarah Leigh Added comment: Comment on phenotypes: PMID: 24498631 describes the phenotype as "infantile mitochondrial complex II/III deficiency"
Mitochondrial disorders v2.19 NFS1 Sarah Leigh Phenotypes for gene: NFS1 were changed from No OMIM phenotype to No OMIM phenotype
Mitochondrial disorders v2.18 NFS1 Sarah Leigh Classified gene: NFS1 as Amber List (moderate evidence)
Mitochondrial disorders v2.18 NFS1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v2.18 NFS1 Sarah Leigh Gene: nfs1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.17 NFS1 Sarah Leigh Publications for gene: NFS1 were set to 24498631; 33457206
Mitochondrial disorders v2.16 NFS1 Sarah Leigh Publications for gene: NFS1 were set to 24498631
Retinal disorders v2.164 TUBB4B Ivone Leong Tag Q2_21_rating tag was added to gene: TUBB4B.
Retinal disorders v2.164 TUBB4B Ivone Leong Classified gene: TUBB4B as Amber List (moderate evidence)
Retinal disorders v2.164 TUBB4B Ivone Leong Added comment: Comment on list classification: This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be made Green at the next review.
Retinal disorders v2.164 TUBB4B Ivone Leong Gene: tubb4b has been classified as Amber List (Moderate Evidence).
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.15 EPAS1 Ivone Leong Classified gene: EPAS1 as Amber List (moderate evidence)
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.15 EPAS1 Ivone Leong Gene: epas1 has been classified as Amber List (Moderate Evidence).
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.14 EPAS1 Ivone Leong gene: EPAS1 was added
gene: EPAS1 was added to Inherited phaeochromocytoma and paraganglioma excluding NF1. Sources: Expert list
Q2_21_phenotype tags were added to gene: EPAS1.
Mode of inheritance for gene: EPAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EPAS1 were set to 22931260; 23418310; 33300499
Phenotypes for gene: EPAS1 were set to Erythrocytosis, familial, 4, OMIM:611783
Review for gene: EPAS1 was set to AMBER
Added comment: This gene was suggested to be added and given a Green rating by Ruth Casey (Cambridge University Hospital). No other evidence was provided.

This gene is associated with a phenotype in OMIM. It has been reported as somatic gain of function variants in patients who present with PPGL and sporadic tumours (PMID: 22931260, 23418310).

PMID: 33300499 looked at EPAS1 germline variants in patients who has PPGL. Half of them have germline variants in EPAS1 and a known PPGL gene, other half has just EPAS1 variants. There are no details about whether these people had a family history of PPGL.
Sources: Expert list
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.13 NF1 Ivone Leong Classified gene: NF1 as Amber List (moderate evidence)
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.13 NF1 Ivone Leong Gene: nf1 has been classified as Amber List (Moderate Evidence).
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.12 NF1 Ivone Leong gene: NF1 was added
gene: NF1 was added to Inherited phaeochromocytoma and paraganglioma excluding NF1. Sources: Expert list
Q2_21_phenotype tags were added to gene: NF1.
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NF1 were set to 22429592; 16735498
Phenotypes for gene: NF1 were set to NF1
Review for gene: NF1 was set to GREEN
Added comment: This gene was suggested to be added and given a Green rating by Ruth Casey (Cambridge University Hospital).

This gene is Green on the Inherited phaeochromocytoma and paraganglioma (Version 1.6). This gene should be reconsidered for inclusion in this panel by the GMS specialist group.
Sources: Expert list
Endocrine neoplasia v1.22 PMS2 Ivone Leong Classified gene: PMS2 as Amber List (moderate evidence)
Endocrine neoplasia v1.22 PMS2 Ivone Leong Gene: pms2 has been classified as Amber List (Moderate Evidence).
Endocrine neoplasia v1.21 PMS2 Ivone Leong gene: PMS2 was added
gene: PMS2 was added to Endocrine neoplasms. Sources: Expert Review
Q2_21_phenotype tags were added to gene: PMS2.
Mode of inheritance for gene: PMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: PMS2 was set to AMBER
Added comment: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service). No further evidence was provided.

This gene has been given an Amber rating and will reviewed by GMS before Green status is given.
Sources: Expert Review
Endocrine neoplasia v1.20 MSH6 Ivone Leong Classified gene: MSH6 as Amber List (moderate evidence)
Endocrine neoplasia v1.20 MSH6 Ivone Leong Gene: msh6 has been classified as Amber List (Moderate Evidence).
Endocrine neoplasia v1.19 MSH6 Ivone Leong gene: MSH6 was added
gene: MSH6 was added to Endocrine neoplasms. Sources: Expert list
Q2_21_phenotype tags were added to gene: MSH6.
Mode of inheritance for gene: MSH6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: MSH6 was set to AMBER
Added comment: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service). No further evidence was provided.

This gene has been given an Amber rating and will reviewed by GMS before Green status is given.
Sources: Expert list
Endocrine neoplasia v1.18 MSH2 Ivone Leong Classified gene: MSH2 as Amber List (moderate evidence)
Endocrine neoplasia v1.18 MSH2 Ivone Leong Gene: msh2 has been classified as Amber List (Moderate Evidence).
Endocrine neoplasia v1.17 MSH2 Ivone Leong gene: MSH2 was added
gene: MSH2 was added to Endocrine neoplasms. Sources: Expert list
Q2_21_phenotype tags were added to gene: MSH2.
Mode of inheritance for gene: MSH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: MSH2 was set to AMBER
Added comment: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service). No further evidence was provided.

This gene has been given an Amber rating and will reviewed by GMS before Green status is given.
Sources: Expert list
Endocrine neoplasia v1.16 MLH1 Ivone Leong Classified gene: MLH1 as Amber List (moderate evidence)
Endocrine neoplasia v1.16 MLH1 Ivone Leong Gene: mlh1 has been classified as Amber List (Moderate Evidence).
Endocrine neoplasia v1.15 MLH1 Ivone Leong gene: MLH1 was added
gene: MLH1 was added to Endocrine neoplasms. Sources: Expert list
Q2_21_phenotype tags were added to gene: MLH1.
Mode of inheritance for gene: MLH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: MLH1 was set to AMBER
Added comment: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service). No further evidence was provided.

This gene has been given an Amber rating and will reviewed by GMS before Green status is given.
Sources: Expert list
Endocrine neoplasia v1.14 VHL Ivone Leong changed review comment from: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review; to: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service). No further evidence was provided.

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review
Endocrine neoplasia v1.14 TP53 Ivone Leong changed review comment from: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review; to: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service). No further evidence was provided.

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review
Endocrine neoplasia v1.14 PRKAR1A Ivone Leong changed review comment from: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review; to: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service). No further evidence was provided.

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review
Hereditary ataxia with onset in adulthood v2.21 CLP1 Zornitza Stark reviewed gene: CLP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia type 10, 615803; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.43 CLP1 Zornitza Stark reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24766809, 29307788; Phenotypes: Pontocerebellar hypoplasia, type 10, MIM# 615803; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v2.21 CHMP1A Zornitza Stark reviewed gene: CHMP1A: Rating: RED; Mode of pathogenicity: None; Publications: 23023333; Phenotypes: Pontocerebellar hypoplasia, type 8, MIM# 614961; Mode of inheritance: None
Differences in sex development v2.16 PAX8 Zornitza Stark gene: PAX8 was added
gene: PAX8 was added to Disorders of sex development. Sources: Literature
Mode of inheritance for gene: PAX8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAX8 were set to 33434492
Phenotypes for gene: PAX8 were set to Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS)
Review for gene: PAX8 was set to AMBER
Added comment: Variants in this gene are associated with congenital hypothyroidism.

5 individuals identified in large cohorts with MRKHS and likely deleterious variants in PAX8. At least one of the individuals had congenital hypothyroidism together with features of MRKHS, suggesting this is phenotype expansion. Amber rating suggested due to limited case-level data.
Sources: Literature
Leber hereditary optic neuropathy v1.7 DNAJC30 Zornitza Stark reviewed gene: DNAJC30: Rating: GREEN; Mode of pathogenicity: None; Publications: 33465056; Phenotypes: Leber Hereditary Optic Neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v2.15 NFS1 Zornitza Stark edited their review of gene: NFS1: Added comment: PMID 33457206: Second paper reporting another family (consanguineous) with three affected children and supportive functional data.
Homozygous for the same missense variant as reported in the 2014 paper - this family of Christian Arab descent; the family in the previous report of Mennonite background.
Suggests this is a mutation hotspot.; Changed rating: GREEN; Changed publications: 24498631, 33457206; Changed phenotypes: progressive hypotonia, lactic acidosis, acute metabolic crises, liver dysfunction, increased CPK
Early onset or syndromic epilepsy v2.298 SLC7A6OS Zornitza Stark gene: SLC7A6OS was added
gene: SLC7A6OS was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: SLC7A6OS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A6OS were set to 33085104
Phenotypes for gene: SLC7A6OS were set to Progressive myoclonus epilepsy
Review for gene: SLC7A6OS was set to RED
Added comment: Two unrelated families reported with same homozygous splice site variant, shared haplotype (founder effect). Limited functional data.
Sources: Literature
Intellectual disability v3.962 ATCAY Catherine Snow Source: Expert Review Amber was removed from gene: ATCAY
Intellectual disability v3.961 ANO3 Catherine Snow Source: Expert Review Amber was removed from gene: ANO3
Intellectual disability v3.960 ADGRV1 Catherine Snow Source: Expert Review Amber was removed from gene: ADGRV1
Intellectual disability v3.959 ABHD12 Catherine Snow Source: Expert Review Amber was removed from gene: ABHD12
Intellectual disability v3.958 CDK16 Catherine Snow Source: Expert Review Red was removed from gene: CDK16
Intellectual disability v3.957 ZC3H14 Catherine Snow Source: Expert Review Red was removed from gene: ZC3H14
Intellectual disability v3.956 XPA Catherine Snow Source: Expert Review Red was removed from gene: XPA
Intellectual disability v3.955 USP27X Catherine Snow Source: Expert Review Red was removed from gene: USP27X
Intellectual disability v3.953 TUBGCP4 Catherine Snow Source: Expert Review Red was removed from gene: TUBGCP4
Intellectual disability v3.952 TRAPPC11 Catherine Snow Source: Expert Review Red was removed from gene: TRAPPC11
CAKUT v1.160 WBP11 Eleanor Williams Classified gene: WBP11 as Green List (high evidence)
CAKUT v1.160 WBP11 Eleanor Williams Added comment: Comment on list classification: Added to the panel at the suggestion of Genomics England clinicians. Promoting from red to green based on 4 unrelated cases with a renal phenotype.
CAKUT v1.160 WBP11 Eleanor Williams Gene: wbp11 has been classified as Green List (High Evidence).
Intellectual disability v3.951 TMEM231 Catherine Snow Source: Expert Review Red was removed from gene: TMEM231
CAKUT v1.159 WBP11 Eleanor Williams changed review comment from: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.
Sources: Literature; to: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.

A renal phenotype was seen in 5/13 patients from 4 families.
Sources: Literature
Intellectual disability v3.950 SRGAP3 Catherine Snow Source: Expert Review Red was removed from gene: SRGAP3
CAKUT v1.159 WBP11 Eleanor Williams gene: WBP11 was added
gene: WBP11 was added to CAKUT. Sources: Literature
Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WBP11 were set to 33276377
Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems
Review for gene: WBP11 was set to GREEN
Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.
Sources: Literature
Intellectual disability v3.949 SMARCD2 Catherine Snow Source: Expert Review Red was removed from gene: SMARCD2
Intellectual disability v3.947 SACS Catherine Snow Source: Expert Review Red was removed from gene: SACS
VACTERL-like phenotypes v1.29 WBP11 Eleanor Williams Classified gene: WBP11 as Green List (high evidence)
VACTERL-like phenotypes v1.29 WBP11 Eleanor Williams Added comment: Comment on list classification: Promoting from red to green as there are 5 cases from 3 families in which patients affected had features in three component organs
VACTERL-like phenotypes v1.29 WBP11 Eleanor Williams Gene: wbp11 has been classified as Green List (High Evidence).
VACTERL-like phenotypes v1.28 WBP11 Eleanor Williams gene: WBP11 was added
gene: WBP11 was added to VACTERL-like phenotypes. Sources: Literature
Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WBP11 were set to 33276377
Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems
Review for gene: WBP11 was set to GREEN
Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.
Sources: Literature
Paediatric disorders - additional genes v1.84 WBP11 Eleanor Williams Classified gene: WBP11 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.84 WBP11 Eleanor Williams Added comment: Comment on list classification: Promoting to amber but with a recommendation for green rating at the next GMS review.
Paediatric disorders - additional genes v1.84 WBP11 Eleanor Williams Gene: wbp11 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.83 WBP11 Eleanor Williams Tag Q2_21_rating tag was added to gene: WBP11.
Paediatric disorders - additional genes v1.83 WBP11 Eleanor Williams gene: WBP11 was added
gene: WBP11 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WBP11 were set to 33276377
Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems
Review for gene: WBP11 was set to GREEN
Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.
Sources: Literature
Skeletal dysplasia v2.83 WBP11 Eleanor Williams Tag Q2_21_rating tag was added to gene: WBP11.
Skeletal dysplasia v2.83 WBP11 Eleanor Williams Classified gene: WBP11 as Amber List (moderate evidence)
Skeletal dysplasia v2.83 WBP11 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber with recommendation for a green rating following GMS review.
Skeletal dysplasia v2.83 WBP11 Eleanor Williams Gene: wbp11 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.82 WBP11 Eleanor Williams gene: WBP11 was added
gene: WBP11 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WBP11 were set to 33276377
Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems
Review for gene: WBP11 was set to GREEN
Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.

Vertebral anomalies were noted in 6/13 patients from 5 families. One patient had congenital scoliosis and one abnormalities of the right upper ribs. Genomics England clinical team suggest it just meets the threshold for the skeletal dysplasia panel.
Sources: Literature
Fetal anomalies v1.628 WBP11 Eleanor Williams Tag Q2_21_rating tag was added to gene: WBP11.
Fetal anomalies v1.628 WBP11 Eleanor Williams Classified gene: WBP11 as Amber List (moderate evidence)
Fetal anomalies v1.628 WBP11 Eleanor Williams Added comment: Comment on list classification: Promoting to amber but with a recommendation for green rating at the next GMS review.
Fetal anomalies v1.628 WBP11 Eleanor Williams Gene: wbp11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.627 WBP11 Eleanor Williams gene: WBP11 was added
gene: WBP11 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WBP11 were set to 33276377
Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems
Review for gene: WBP11 was set to GREEN
Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.
Sources: Literature
Limb disorders v2.36 FSTL5 Eleanor Williams gene: FSTL5 was added
gene: FSTL5 was added to Limb disorders. Sources: Literature
Mode of inheritance for gene: FSTL5 was set to Unknown
Publications for gene: FSTL5 were set to 33105483
Phenotypes for gene: FSTL5 were set to isolated club-foot; iTEV; Talipes equinovarus
Review for gene: FSTL5 was set to RED
Added comment: PMID: 33105483 - Khanshour et al 20201 - GWAS study of isolated Talipes equinovarus (clubfoot, iTEV) identified an associated locus within FSTL5. They show that Fstl5 is expressed in the embryonic hindlimb in bats, chicks and mice. However, Fstl5 was expressed more highly in neural tissues in mice, and rats lacking Fstl5 showed no gross developmental malformations. Conditional overexpression of Fstl5 in osteochondroprogenitors resulted in sexually dimorphic differences in skeletal development in mice.

Not sure about the phenotypic fit for the limb disorders panel but adding as red and will wait for the cases where the clinical phenotype is reported in cases with variants in FSTL5.
Sources: Literature
Monogenic hearing loss v2.149 NCOA3 Eleanor Williams gene: NCOA3 was added
gene: NCOA3 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: NCOA3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NCOA3 were set to 33326993
Phenotypes for gene: NCOA3 were set to non-syndromic hearing loss
Review for gene: NCOA3 was set to RED
Added comment: PMID: 33326993 - Salazar da Silva et al 2020 - report a 5 generation Brazilian family with 15 individuals with non-syndromic, bilateral and progressive hearing loss. Using linkage analysis and then exome sequencing they identified a heterozygous variant in NCOA3 (NM_181659, c.2810C > G; p.Ser937Cys) that was found in the 7 analysed affected individuals. It was also found in 4 unaffected individuals but they are within the range of onset of hearing loss observed in the family. Expression of nco3 was found in the inner ear of mice and zebrafish. ncoa3-/- zebrafish showed subtle alterations in cartilage, mineral density and abnormal adult swimming behaviour, which may suggest the mechanism of pathogenicity.
Sources: Literature
Intellectual disability v3.946 RAX Catherine Snow Source: Expert Review Red was removed from gene: RAX
Intellectual disability v3.945 WT1 Arina Puzriakova Source: Expert Review Amber was removed from gene: WT1
Intellectual disability v3.944 NUP62 Catherine Snow Source: Expert Review Red was removed from gene: NUP62
Intellectual disability v3.943 NDUFAF2 Catherine Snow Source: Expert Review Red was removed from gene: NDUFAF2
Intellectual disability v3.942 MIR17HG Catherine Snow Source: Expert Review Red was removed from gene: MIR17HG
Intellectual disability v3.941 VPS35 Arina Puzriakova Source: Expert Review Amber was removed from gene: VPS35
Intellectual disability v3.940 TTPA Arina Puzriakova Source: Expert Review Amber was removed from gene: TTPA
Intellectual disability v3.939 MAPK10 Catherine Snow Source: Expert Review Red was removed from gene: MAPK10
Intellectual disability v3.938 TTC7A Arina Puzriakova Source: Expert Review Amber was removed from gene: TTC7A
Intellectual disability v3.937 TTBK2 Arina Puzriakova Source: Expert Review Amber was removed from gene: TTBK2
Intellectual disability v3.936 KLHL15 Catherine Snow Source: Expert Review Red was removed from gene: KLHL15
Intellectual disability v3.935 HAX1 Catherine Snow Source: Expert Review Red was removed from gene: HAX1
Intellectual disability v3.934 TGM6 Arina Puzriakova Source: Expert Review Amber was removed from gene: TGM6
Intellectual disability v3.933 TFG Arina Puzriakova Source: Expert Review Amber was removed from gene: TFG
Intellectual disability v3.932 TFAP2B Arina Puzriakova Source: Expert Review Amber was removed from gene: TFAP2B
Intellectual disability v3.931 TFAP2A Arina Puzriakova Source: Expert Review Amber was removed from gene: TFAP2A
Intellectual disability v3.930 TBP Arina Puzriakova Source: Expert Review Amber was removed from gene: TBP
Intellectual disability v3.929 TARDBP Arina Puzriakova Source: Expert Review Amber was removed from gene: TARDBP
Intellectual disability v3.928 STUB1 Arina Puzriakova Source: Expert Review Amber was removed from gene: STUB1
Intellectual disability v3.927 PLEC Sarah Leigh Source: Expert Review Amber was removed from gene: PLEC
Intellectual disability v3.926 SPG7 Arina Puzriakova Source: Expert Review Amber was removed from gene: SPG7
Intellectual disability v3.926 PLCE1 Sarah Leigh Source: Expert Review Amber was removed from gene: PLCE1
Intellectual disability v3.925 SPG21 Arina Puzriakova Source: Expert Review Amber was removed from gene: SPG21
Intellectual disability v3.924 PINK1 Sarah Leigh Source: Expert Review Amber was removed from gene: PINK1
Intellectual disability v3.923 SNCA Arina Puzriakova Source: Expert Review Amber was removed from gene: SNCA
Intellectual disability v3.922 PDYN Sarah Leigh Source: Expert Review Amber was removed from gene: PDYN
Intellectual disability v3.922 SMO Arina Puzriakova Source: Expert Review Amber was removed from gene: SMO
Intellectual disability v3.922 PDGFB Sarah Leigh Source: Expert Review Amber was removed from gene: PDGFB
Intellectual disability v3.921 PCYT1A Sarah Leigh Source: Expert Review Amber was removed from gene: PCYT1A
Intellectual disability v3.921 SLC20A2 Arina Puzriakova Source: Expert Review Amber was removed from gene: SLC20A2
Intellectual disability v3.920 PARK7 Sarah Leigh Source: Expert Review Amber was removed from gene: PARK7
Intellectual disability v3.919 SIGMAR1 Arina Puzriakova Source: Expert Review Amber was removed from gene: SIGMAR1
Intellectual disability v3.919 PALB2 Sarah Leigh Source: Expert Review Amber was removed from gene: PALB2
Intellectual disability v3.918 NPHS2 Sarah Leigh Source: Expert Review Amber was removed from gene: NPHS2
Intellectual disability v3.917 NOP56 Sarah Leigh Source: Expert Review Amber was removed from gene: NOP56
Intellectual disability v3.916 SH3TC2 Arina Puzriakova Source: Expert Review Amber was removed from gene: SH3TC2
Intellectual disability v3.915 SGCE Arina Puzriakova Source: Expert Review Amber was removed from gene: SGCE
Intellectual disability v3.914 NIPA1 Sarah Leigh Source: Expert Review Amber was removed from gene: NIPA1
Intellectual disability v3.913 SETX Arina Puzriakova Source: Expert Review Amber was removed from gene: SETX
Intellectual disability v3.912 NHLRC1 Sarah Leigh Source: Expert Review Amber was removed from gene: NHLRC1
Intellectual disability v3.911 SCN9A Arina Puzriakova Source: Expert Review Amber was removed from gene: SCN9A
Intellectual disability v3.911 NHEJ1 Sarah Leigh Source: Expert Review Amber was removed from gene: NHEJ1
Intellectual disability v3.910 SCARB2 Arina Puzriakova Source: Expert Review Amber was removed from gene: SCARB2
Intellectual disability v3.909 NEFL Sarah Leigh Source: Expert Review Amber was removed from gene: NEFL
Intellectual disability v3.908 SBF2 Arina Puzriakova Source: Expert Review Amber was removed from gene: SBF2
Intellectual disability v3.908 NDRG1 Sarah Leigh Source: Expert Review Amber was removed from gene: NDRG1
Intellectual disability v3.907 MTPAP Sarah Leigh Source: Expert Review Amber was removed from gene: MTPAP
Intellectual disability v3.906 RTN2 Arina Puzriakova Source: Expert Review Amber was removed from gene: RTN2
Intellectual disability v3.906 MTMR2 Sarah Leigh Source: Expert Review Amber was removed from gene: MTMR2
Intellectual disability v3.905 RNF216 Arina Puzriakova Source: Expert Review Amber was removed from gene: RNF216
Intellectual disability v3.904 RIPK4 Arina Puzriakova Source: Expert Review Amber was removed from gene: RIPK4
Intellectual disability v3.903 RFX6 Arina Puzriakova Source: Expert Review Amber was removed from gene: RFX6
Intellectual disability v3.902 REEP2 Arina Puzriakova Source: Expert Review Amber was removed from gene: REEP2
Intellectual disability v3.901 REEP1 Arina Puzriakova Source: Expert Review Amber was removed from gene: REEP1
Intellectual disability v3.900 MPZ Sarah Leigh Source: Expert Review Amber was removed from gene: MPZ
Intellectual disability v3.899 PSEN1 Arina Puzriakova Source: Expert Review Amber was removed from gene: PSEN1
Intellectual disability v3.899 MMP21 Sarah Leigh Source: Expert Review Amber was removed from gene: MMP21
Intellectual disability v3.898 MITF Sarah Leigh Source: Expert Review Amber was removed from gene: MITF
Intellectual disability v3.897 PRX Arina Puzriakova Source: Expert Review Amber was removed from gene: PRX
Intellectual disability v3.896 MECR Sarah Leigh Source: Expert Review Amber was removed from gene: MECR
Intellectual disability v3.895 MARS2 Sarah Leigh Source: Expert Review Amber was removed from gene: MARS2
Intellectual disability v3.894 PRKRA Arina Puzriakova Source: Expert Review Amber was removed from gene: PRKRA
Intellectual disability v3.894 MAFB Sarah Leigh Source: Expert Review Amber was removed from gene: MAFB
Intellectual disability v3.893 LRRK2 Sarah Leigh Source: Expert Review Amber was removed from gene: LRRK2
Intellectual disability v3.893 PRKN Arina Puzriakova Source: Expert Review Amber was removed from gene: PRKN
Intellectual disability v3.893 LOXHD1 Sarah Leigh Source: Expert Review Amber was removed from gene: LOXHD1
Intellectual disability v3.892 PRKCG Arina Puzriakova Source: Expert Review Amber was removed from gene: PRKCG
Intellectual disability v3.892 LITAF Sarah Leigh Source: Expert Review Amber was removed from gene: LITAF
Intellectual disability v3.891 PRICKLE2 Arina Puzriakova Source: Expert Review Amber was removed from gene: PRICKLE2
Intellectual disability v3.891 KIF1C Sarah Leigh Source: Expert Review Amber was removed from gene: KIF1C
Intellectual disability v3.890 KCNE1 Sarah Leigh Source: Expert Review Amber was removed from gene: KCNE1
Intellectual disability v3.889 PRICKLE1 Arina Puzriakova Source: Expert Review Amber was removed from gene: PRICKLE1
Intellectual disability v3.889 KCNA1 Sarah Leigh Source: Expert Review Amber was removed from gene: KCNA1
Intellectual disability v3.888 ITGA3 Sarah Leigh Source: Expert Review Amber was removed from gene: ITGA3
Intellectual disability v3.887 PPP2R2B Arina Puzriakova Source: Expert Review Amber was removed from gene: PPP2R2B
Intellectual disability v3.886 IGHMBP2 Sarah Leigh Source: Expert Review Amber was removed from gene: IGHMBP2
Intellectual disability v3.885 PNKD Arina Puzriakova Source: Expert Review Amber was removed from gene: PNKD
Intellectual disability v3.884 DCTN1 Sarah Leigh Source: Expert Review Amber was removed from gene: DCTN1
Unexplained young onset end-stage renal disease v1.15 OCRL Arina Puzriakova Source: Expert Review Red was removed from gene: OCRL
Intellectual disability v3.883 DHODH Sarah Leigh Source: Expert Review Amber was removed from gene: DHODH
Unexplained young onset end-stage renal disease v1.14 BSND Arina Puzriakova Source: Expert Review Red was removed from gene: BSND
Intellectual disability v3.882 DNM2 Sarah Leigh Source: Expert Review Amber was removed from gene: DNM2
Intellectual disability v3.881 EFHC1 Sarah Leigh Source: Expert Review Amber was removed from gene: EFHC1
Undiagnosed metabolic disorders v1.447 CD320 Arina Puzriakova Source: Expert Review Amber was removed from gene: CD320
Undiagnosed metabolic disorders v1.446 SLC36A2 Arina Puzriakova Source: Expert Review Amber was removed from gene: SLC36A2
Sarcoma susceptibility v1.11 EXT2 Arina Puzriakova Source: Expert Review Amber was removed from gene: EXT2
Intellectual disability v3.880 EIF4G1 Sarah Leigh Source: Expert Review Amber was removed from gene: EIF4G1
Intellectual disability v3.879 ELOVL5 Sarah Leigh Source: Expert Review Amber was removed from gene: ELOVL5
Intellectual disability v3.878 EPM2A Sarah Leigh Source: Expert Review Amber was removed from gene: EPM2A
Intellectual disability v3.877 FAM111B Sarah Leigh Source: Expert Review Amber was removed from gene: FAM111B
Intellectual disability v3.876 GDAP1 Sarah Leigh Source: Expert Review Amber was removed from gene: GDAP1
Intellectual disability v3.875 GNAL Sarah Leigh Source: Expert Review Amber was removed from gene: GNAL
Intellectual disability v3.874 GORAB Sarah Leigh Source: Expert Review Amber was removed from gene: GORAB
Intellectual disability v3.873 GOSR2 Sarah Leigh Source: Expert Review Amber was removed from gene: GOSR2
Intellectual disability v3.872 GRN Sarah Leigh Source: Expert Review Amber was removed from gene: GRN
Intellectual disability v3.871 MDH2 Ivone Leong Source: Expert Review Amber was removed from gene: MDH2
Intellectual disability v3.870 KNL1 Ivone Leong Source: Expert Review Amber was removed from gene: KNL1
Intellectual disability v3.869 KIAA0586 Ivone Leong Source: Expert Review Amber was removed from gene: KIAA0586
Intellectual disability v3.868 HECW2 Ivone Leong commented on gene: HECW2
Intellectual disability v3.868 HECW2 Ivone Leong Phenotypes for gene: HECW2 were changed from Neurodevelopmental disorder with hypotonia, seizures, and absent language to Neurodevelopmental disorder with hypotonia, seizures, and absent language, OMIM:617268
Intellectual disability v3.867 HECW2 Ivone Leong Mode of pathogenicity for gene: HECW2 was changed from to Other
Intellectual disability v3.866 HECW2 Ivone Leong Publications for gene: HECW2 were set to
Intellectual disability v3.865 HECW2 Ivone Leong gene: HECW2 was added
gene: HECW2 was added to Intellectual disability. Sources: Expert Review Green,BRIDGE study SPEED NEURO Tier1 Gene,Victorian Clinical Genetics Services
Mode of inheritance for gene: HECW2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: HECW2 were set to Neurodevelopmental disorder with hypotonia, seizures, and absent language
Intellectual disability v3.864 IFT140 Sarah Leigh Source: Expert Review Amber was removed from gene: IFT140
Intellectual disability v3.863 FLAD1 Sarah Leigh Source: Expert Review Amber was removed from gene: FLAD1
Intellectual disability v3.862 DNMT1 Sarah Leigh Source: Expert Review Amber was removed from gene: DNMT1
Intellectual disability v3.861 Ivone Leong removed gene:HECW2 from the panel
Intellectual disability v3.860 HACE1 Ivone Leong Source: Expert Review Amber was removed from gene: HACE1
Intellectual disability v3.859 GRID2 Ivone Leong Source: Expert Review Amber was removed from gene: GRID2
Intellectual disability v3.858 GLIS3 Ivone Leong Source: Expert Review Amber was removed from gene: GLIS3
Intellectual disability v3.857 FGF12 Ivone Leong Source: Expert Review Amber was removed from gene: FGF12
Intellectual disability v3.857 GJB1 Catherine Snow Source: Expert Review Red was removed from gene: GJB1
Intellectual disability v3.856 EBF3 Ivone Leong Source: Expert Review Amber was removed from gene: EBF3
Intellectual disability v3.855 CHD4 Ivone Leong Source: Expert Review Amber was removed from gene: CHD4
Intellectual disability v3.854 BRPF1 Ivone Leong Source: Expert Review Amber was removed from gene: BRPF1
Intellectual disability v3.854 GBA2 Catherine Snow Source: Expert Review Red was removed from gene: GBA2
Intellectual disability v3.853 BMP4 Ivone Leong Source: Expert Review Amber was removed from gene: BMP4
Intellectual disability v3.852 ACADS Ivone Leong Source: Expert Review Amber was removed from gene: ACADS
Intellectual disability v3.851 AAAS Ivone Leong Source: Expert Review Amber was removed from gene: AAAS
Intellectual disability v3.851 FRAS1 Catherine Snow Source: Expert Review Red was removed from gene: FRAS1
Intellectual disability v3.850 FAM120C Catherine Snow Source: Expert Review Red was removed from gene: FAM120C
Intellectual disability v3.850 MBTPS2 Ivone Leong Source: Expert Review Red was removed from gene: MBTPS2
Intellectual disability v3.850 CSF1R Sarah Leigh Source: Expert Review Amber was removed from gene: CSF1R
Intellectual disability v3.849 FAAH2 Catherine Snow Source: Expert Review Red was removed from gene: FAAH2
Likely inborn error of metabolism v2.101 IDH3B Eleanor Williams Source: Expert Review Amber was removed from gene: IDH3B
Intellectual disability v3.849 UBTF Ivone Leong Source: Expert Review Red was removed from gene: UBTF
Intellectual disability v3.848 ERMARD Catherine Snow Source: Expert Review Red was removed from gene: ERMARD
Intellectual disability v3.847 THOC2 Ivone Leong Source: Expert Review Red was removed from gene: THOC2
Intellectual disability v3.847 CRYGC Sarah Leigh Source: Expert Review Amber was removed from gene: CRYGC
Likely inborn error of metabolism v2.100 SDHB Eleanor Williams Source: Expert Review Amber was removed from gene: SDHB
Intellectual disability v3.846 TECPR2 Ivone Leong Source: Expert Review Red was removed from gene: TECPR2
Intellectual disability v3.845 EPB41L1 Catherine Snow Source: Expert Review Red was removed from gene: EPB41L1
Likely inborn error of metabolism v2.99 TANGO2 Eleanor Williams Source: Expert Review Red was removed from gene: TANGO2
Intellectual disability v3.844 TAF1 Ivone Leong Source: Expert Review Red was removed from gene: TAF1
Intellectual disability v3.843 EEF1B2 Catherine Snow Source: Expert Review Red was removed from gene: EEF1B2
Likely inborn error of metabolism v2.98 SLC52A3 Eleanor Williams Source: Expert Review Red was removed from gene: SLC52A3
Intellectual disability v3.843 SZT2 Ivone Leong Source: Expert Review Red was removed from gene: SZT2
Likely inborn error of metabolism v2.97 SLC52A2 Eleanor Williams Source: Expert Review Red was removed from gene: SLC52A2
Intellectual disability v3.842 DPM3 Catherine Snow Source: Expert Review Red was removed from gene: DPM3
Intellectual disability v3.842 ST3GAL5 Ivone Leong Source: Expert Review Red was removed from gene: ST3GAL5
Likely inborn error of metabolism v2.96 SLC25A22 Eleanor Williams Source: Expert Review Red was removed from gene: SLC25A22
Intellectual disability v3.841 DLG2 Catherine Snow Source: Expert Review Red was removed from gene: DLG2
Intellectual disability v3.840 SMC3 Ivone Leong Source: Expert Review Red was removed from gene: SMC3
Likely inborn error of metabolism v2.95 SLC25A20 Eleanor Williams Source: Expert Review Red was removed from gene: SLC25A20
Intellectual disability v3.840 DLG1 Catherine Snow Source: Expert Review Red was removed from gene: DLG1
Intellectual disability v3.839 SMAD4 Ivone Leong Source: Expert Review Red was removed from gene: SMAD4
Likely inborn error of metabolism v2.94 SLC22A5 Eleanor Williams Source: Expert Review Red was removed from gene: SLC22A5
Intellectual disability v3.838 DIP2B Catherine Snow Source: Expert Review Red was removed from gene: DIP2B
Intellectual disability v3.838 SLC33A1 Ivone Leong Source: Expert Review Red was removed from gene: SLC33A1
Intellectual disability v3.837 DDX53 Catherine Snow Source: Expert Review Red was removed from gene: DDX53
Likely inborn error of metabolism v2.93 SAMHD1 Eleanor Williams Source: Expert Review Red was removed from gene: SAMHD1
Intellectual disability v3.836 SERAC1 Ivone Leong Source: Expert Review Red was removed from gene: SERAC1
Intellectual disability v3.835 RTTN Ivone Leong Source: Expert Review Red was removed from gene: RTTN
Likely inborn error of metabolism v2.92 PYCR1 Eleanor Williams Source: Expert Review Red was removed from gene: PYCR1
Intellectual disability v3.834 CYP7B1 Catherine Snow Source: Expert Review Red was removed from gene: CYP7B1
Intellectual disability v3.834 RLIM Ivone Leong Source: Expert Review Red was removed from gene: RLIM
Likely inborn error of metabolism v2.91 PPOX Eleanor Williams Source: Expert Review Red was removed from gene: PPOX
Intellectual disability v3.833 QARS Ivone Leong Source: Expert Review Red was removed from gene: QARS
Intellectual disability v3.833 CHL1 Catherine Snow Source: Expert Review Red was removed from gene: CHL1
Likely inborn error of metabolism v2.90 OXCT1 Eleanor Williams Source: Expert Review Red was removed from gene: OXCT1
Intellectual disability v3.832 PYCR2 Ivone Leong Source: Expert Review Red was removed from gene: PYCR2
Intellectual disability v3.831 CEP63 Catherine Snow Source: Expert Review Red was removed from gene: CEP63
Likely inborn error of metabolism v2.89 L2HGDH Eleanor Williams Source: Expert Review Red was removed from gene: L2HGDH
Intellectual disability v3.831 PYCR1 Ivone Leong Source: Expert Review Red was removed from gene: PYCR1
Intellectual disability v3.830 CD96 Catherine Snow Source: Expert Review Red was removed from gene: CD96
Likely inborn error of metabolism v2.88 IER3IP1 Eleanor Williams Source: Expert Review Red was removed from gene: IER3IP1
Intellectual disability v3.829 PUS1 Ivone Leong Source: Expert Review Red was removed from gene: PUS1
Likely inborn error of metabolism v2.87 HMGCS2 Eleanor Williams Source: Expert Review Red was removed from gene: HMGCS2
Intellectual disability v3.828 C9orf72 Catherine Snow Source: Expert Review Amber was removed from gene: C9orf72
Intellectual disability v3.828 PUF60 Ivone Leong Source: Expert Review Red was removed from gene: PUF60
Likely inborn error of metabolism v2.86 HMGCL Eleanor Williams Source: Expert Review Red was removed from gene: HMGCL
Intellectual disability v3.827 PEX11B Ivone Leong Source: Expert Review Red was removed from gene: PEX11B
Likely inborn error of metabolism v2.85 HADHB Eleanor Williams Source: Expert Review Red was removed from gene: HADHB
Intellectual disability v3.827 BEAN1 Catherine Snow Source: Expert Review Amber was removed from gene: BEAN1
Likely inborn error of metabolism v2.84 HADHA Eleanor Williams Source: Expert Review Red was removed from gene: HADHA
Intellectual disability v3.826 NTRK1 Ivone Leong Source: Expert Review Red was removed from gene: NTRK1
Likely inborn error of metabolism v2.83 GLUD1 Eleanor Williams Source: Expert Review Red was removed from gene: GLUD1
Intellectual disability v3.826 CRYBA4 Sarah Leigh Source: Expert Review Amber was removed from gene: CRYBA4
Intellectual disability v3.825 NFIA Ivone Leong Source: Expert Review Red was removed from gene: NFIA
Likely inborn error of metabolism v2.82 GATM Eleanor Williams Source: Expert Review Red was removed from gene: GATM
Intellectual disability v3.824 ATXN7 Catherine Snow Source: Expert Review Amber was removed from gene: ATXN7
Likely inborn error of metabolism v2.81 ETFB Eleanor Williams Source: Expert Review Red was removed from gene: ETFB
Intellectual disability v3.823 ATXN3 Catherine Snow Source: Expert Review Amber was removed from gene: ATXN3
Likely inborn error of metabolism v2.80 ETFA Eleanor Williams Source: Expert Review Red was removed from gene: ETFA
Intellectual disability v3.822 ATXN2 Catherine Snow Source: Expert Review Amber was removed from gene: ATXN2
Likely inborn error of metabolism v2.79 DHTKD1 Eleanor Williams Source: Expert Review Red was removed from gene: DHTKD1
Likely inborn error of metabolism v2.78 DARS Eleanor Williams Source: Expert Review Red was removed from gene: DARS
Intellectual disability v3.821 ATXN10 Catherine Snow Source: Expert Review Amber was removed from gene: ATXN10
Intellectual disability v3.820 ATXN1 Catherine Snow Source: Expert Review Amber was removed from gene: ATXN1
Likely inborn error of metabolism v2.77 D2HGDH Eleanor Williams Source: Expert Review Red was removed from gene: D2HGDH
Likely inborn error of metabolism v2.76 CPT2 Eleanor Williams Source: Expert Review Red was removed from gene: CPT2
Intellectual disability v3.819 NDST1 Ivone Leong Source: Expert Review Red was removed from gene: NDST1
Likely inborn error of metabolism v2.75 CPT1A Eleanor Williams Source: Expert Review Red was removed from gene: CPT1A
Intellectual disability v3.817 UNC80 Catherine Snow Source: Expert Review Amber was removed from gene: UNC80
Intellectual disability v3.816 LONP1 Ivone Leong Source: Expert Review Red was removed from gene: LONP1
Likely inborn error of metabolism v2.74 CHKB Eleanor Williams Source: Expert Review Red was removed from gene: CHKB
Intellectual disability v3.815 KMT2C Ivone Leong Source: Expert Review Red was removed from gene: KMT2C
Intellectual disability v3.815 UBA5 Catherine Snow Source: Expert Review Amber was removed from gene: UBA5
Likely inborn error of metabolism v2.73 C19orf12 Eleanor Williams Source: Expert Review Red was removed from gene: C19orf12
Intellectual disability v3.814 CDC45 Sarah Leigh Source: Expert Review Amber was removed from gene: CDC45
Likely inborn error of metabolism v2.72 ACAT1 Eleanor Williams Source: Expert Review Red was removed from gene: ACAT1
Intellectual disability v3.813 IER3IP1 Ivone Leong Source: Expert Review Red was removed from gene: IER3IP1
Intellectual disability v3.812 TRMT10A Catherine Snow Source: Expert Review Amber was removed from gene: TRMT10A
Intellectual disability v3.812 HIVEP2 Ivone Leong Source: Expert Review Red was removed from gene: HIVEP2
Likely inborn error of metabolism v2.71 ACADVL Eleanor Williams Source: Expert Review Red was removed from gene: ACADVL
Intellectual disability v3.811 TMEM240 Catherine Snow Source: Expert Review Amber was removed from gene: TMEM240
Intellectual disability v3.810 GMPPB Ivone Leong Source: Expert Review Red was removed from gene: GMPPB
Intellectual disability v3.810 TBCD Catherine Snow Source: Expert Review Amber was removed from gene: TBCD
Likely inborn error of metabolism v2.70 ACADSB Eleanor Williams Source: Expert Review Red was removed from gene: ACADSB
Intellectual disability v3.809 GFER Ivone Leong Source: Expert Review Red was removed from gene: GFER
Intellectual disability v3.808 EMX2 Ivone Leong Source: Expert Review Red was removed from gene: EMX2
Likely inborn error of metabolism v2.69 ACADS Eleanor Williams Source: Expert Review Red was removed from gene: ACADS
Intellectual disability v3.808 SPTBN2 Catherine Snow Source: Expert Review Amber was removed from gene: SPTBN2
Intellectual disability v3.807 ELP2 Ivone Leong Source: Expert Review Red was removed from gene: ELP2
Familial diabetes v1.58 STAT1 Eleanor Williams Source: Expert Review Removed was removed from gene: STAT1
Intellectual disability v3.806 DNAJC19 Ivone Leong Source: Expert Review Red was removed from gene: DNAJC19
Likely inborn error of metabolism v2.68 ACADM Eleanor Williams Source: Expert Review Red was removed from gene: ACADM
Intellectual disability v3.805 DAG1 Ivone Leong Source: Expert Review Red was removed from gene: DAG1
Familial diabetes v1.57 IL2RA Eleanor Williams Source: Expert Review Removed was removed from gene: IL2RA
Intellectual disability v3.803 CRADD Ivone Leong Source: Expert Review Red was removed from gene: CRADD
Intellectual disability v3.803 SPART Catherine Snow Source: Expert Review Amber was removed from gene: SPART
Familial diabetes v1.56 PAX4 Eleanor Williams Source: Expert Review Removed was removed from gene: PAX4
Familial diabetes v1.55 LIPC Eleanor Williams Source: Expert Review Removed was removed from gene: LIPC
Intellectual disability v3.802 COG5 Ivone Leong Source: Expert Review Red was removed from gene: COG5
Familial diabetes v1.54 KLF11 Eleanor Williams Source: Expert Review Removed was removed from gene: KLF11
Intellectual disability v3.801 SON Catherine Snow Source: Expert Review Amber was removed from gene: SON
Familial diabetes v1.53 BLK Eleanor Williams Source: Expert Review Removed was removed from gene: BLK
Intellectual disability v3.801 CLCN4 Ivone Leong Source: Expert Review Red was removed from gene: CLCN4
Familial diabetes v1.52 LRBA Eleanor Williams Source: Expert Review Removed was removed from gene: LRBA
Familial diabetes v1.51 BSCL2 Eleanor Williams Source: Expert Review Removed was removed from gene: BSCL2
Intellectual disability v3.800 CHMP1A Ivone Leong Source: Expert Review Red was removed from gene: CHMP1A
Intellectual disability v3.800 CCDC115 Sarah Leigh Source: Expert Review Amber was removed from gene: CCDC115
Familial diabetes v1.50 AGPAT2 Eleanor Williams Source: Expert Review Removed was removed from gene: AGPAT2
Familial diabetes v1.49 STAT3 Eleanor Williams Source: Expert Review Removed was removed from gene: STAT3
Familial diabetes v1.48 SLC2A2 Eleanor Williams Source: Expert Review Removed was removed from gene: SLC2A2
Intellectual disability v3.798 CAMK2A Ivone Leong Source: Expert Review Red was removed from gene: CAMK2A
Intellectual disability v3.798 PRUNE1 Catherine Snow Source: Expert Review Amber was removed from gene: PRUNE1
Familial diabetes v1.47 SLC19A2 Eleanor Williams Source: Expert Review Removed was removed from gene: SLC19A2
Intellectual disability v3.797 CACNA1S Sarah Leigh Source: Expert Review Amber was removed from gene: CACNA1S
Intellectual disability v3.797 CACNA1D Ivone Leong Source: Expert Review Red was removed from gene: CACNA1D
Familial diabetes v1.46 PTF1A Eleanor Williams Source: Expert Review Removed was removed from gene: PTF1A
Intellectual disability v3.796 CACNA1A Ivone Leong Source: Expert Review Red was removed from gene: CACNA1A
Intellectual disability v3.795 PGAP1 Catherine Snow Source: Expert Review Amber was removed from gene: PGAP1
Intellectual disability v3.795 BRCA2 Sarah Leigh Source: Expert Review Amber was removed from gene: BRCA2
Intellectual disability v3.794 BSCL2 Ivone Leong Source: Expert Review Red was removed from gene: BSCL2
Familial diabetes v1.45 NEUROG3 Eleanor Williams Source: Expert Review Removed was removed from gene: NEUROG3
Familial diabetes v1.44 MNX1 Eleanor Williams Source: Expert Review Removed was removed from gene: MNX1
Familial diabetes v1.43 IER3IP1 Eleanor Williams Source: Expert Review Removed was removed from gene: IER3IP1
Intellectual disability v3.792 PNPLA6 Catherine Snow Source: Expert Review Amber was removed from gene: PNPLA6
Familial diabetes v1.42 GLIS3 Eleanor Williams Source: Expert Review Removed was removed from gene: GLIS3
Sarcoma susceptibility v1.8 NF1 Arina Puzriakova Source: Expert Review Amber was removed from gene: NF1
Familial diabetes v1.41 FOXP3 Eleanor Williams Source: Expert Review Removed was removed from gene: FOXP3
Intellectual disability v3.791 ATP6V0A2 Ivone Leong Source: Expert Review Red was removed from gene: ATP6V0A2
Sarcoma susceptibility v1.6 PDGFRA Arina Puzriakova Source: Expert Review Green was removed from gene: PDGFRA
Familial diabetes v1.40 EIF2AK3 Eleanor Williams Source: Expert Review Removed was removed from gene: EIF2AK3
Intellectual disability v3.790 PDE4D Catherine Snow Source: Expert Review Amber was removed from gene: PDE4D
Intellectual disability v3.789 ASL Ivone Leong Source: Expert Review Red was removed from gene: ASL
COVID-19 research v1.76 FCGR3A Eleanor Williams Source: Expert Review Amber was removed from gene: FCGR3A
Intellectual disability v3.789 ATP7B Sarah Leigh Source: Expert Review Amber was removed from gene: ATP7B
COVID-19 research v1.75 TRAF3 Eleanor Williams Source: Expert Review Red was removed from gene: TRAF3
Intellectual disability v3.787 PARN Catherine Snow Source: Expert Review Amber was removed from gene: PARN
Intellectual disability v3.787 ARL13B Ivone Leong Source: Expert Review Red was removed from gene: ARL13B
COVID-19 research v1.74 IRF7 Eleanor Williams Source: Expert Review Amber was removed from gene: IRF7
Possible mitochondrial disorder - nuclear genes v1.37 TIMM50 Arina Puzriakova Source: Expert Review Amber was removed from gene: TIMM50
Intellectual disability v3.786 ARID2 Ivone Leong Source: Expert Review Red was removed from gene: ARID2
Cholestasis v1.81 BCS1L Eleanor Williams Source: Expert Review Amber was removed from gene: BCS1L
Possible mitochondrial disorder - nuclear genes v1.36 IER3IP1 Arina Puzriakova Source: Expert Review Green was removed from gene: IER3IP1
Intellectual disability v3.785 OPA3 Catherine Snow Source: Expert Review Amber was removed from gene: OPA3
Possible mitochondrial disorder - nuclear genes v1.35 HMGCL Arina Puzriakova Source: Expert Review Green was removed from gene: HMGCL
Intellectual disability v3.784 AP3B1 Ivone Leong Source: Expert Review Red was removed from gene: AP3B1
Cholestasis v1.80 PEX2 Eleanor Williams Source: Expert Review Green was removed from gene: PEX2
Intellectual disability v3.783 PMP22 Arina Puzriakova Source: Expert Review Amber was removed from gene: PMP22
Cholestasis v1.79 CYP7A1 Eleanor Williams Source: Expert Review Red was removed from gene: CYP7A1
Intellectual disability v3.782 ADK Ivone Leong Source: Expert Review Red was removed from gene: ADK
Mitochondrial disorders v2.15 SLC44A1 Arina Puzriakova Mode of inheritance for gene: SLC44A1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.43 SLC44A1 Arina Puzriakova Phenotypes for gene: SLC44A1 were changed from progressive ataxia; tremor; cognitive decline; dysphagia; optic atrophy; dysarthria to Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, OMIM:618868; Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, MONDO:0030028
Intellectual disability v3.781 CCDC186 Sarah Leigh Classified gene: CCDC186 as Amber List (moderate evidence)
Intellectual disability v3.781 CCDC186 Sarah Leigh Gene: ccdc186 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.780 CCDC186 Sarah Leigh changed review comment from: Not associated with relevant phenotype in OMIM or Gen2Phen. At least 2 terminating variants reported in unrelated cases.
Sources: Literature; to: Not associated with a relevant phenotype in OMIM or Gen2Phen. At least 2 terminating variants reported in cases with failure to thrive and developmental delay.
Sources: Literature
Intellectual disability v3.780 CCDC186 Sarah Leigh gene: CCDC186 was added
gene: CCDC186 was added to Intellectual disability. Sources: Literature
watchlist tags were added to gene: CCDC186.
Mode of inheritance for gene: CCDC186 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC186 were set to 33259146; 28600779
Phenotypes for gene: CCDC186 were set to failure to thrive and developmental delay
Review for gene: CCDC186 was set to AMBER
Added comment: Not associated with relevant phenotype in OMIM or Gen2Phen. At least 2 terminating variants reported in unrelated cases.
Sources: Literature
Early onset or syndromic epilepsy v2.298 CCDC186 Sarah Leigh Tag watchlist tag was added to gene: CCDC186.
Early onset or syndromic epilepsy v2.298 CCDC186 Sarah Leigh Classified gene: CCDC186 as Red List (low evidence)
Early onset or syndromic epilepsy v2.298 CCDC186 Sarah Leigh Added comment: Comment on list classification: Not associated with a relevant phenotype in OMIM or Gen2Phen. At least 2 terminating variants reported in cases with failure to thrive and developmental delay, epileptic encephalopathy was rerported in one case (PMID33259146).
Early onset or syndromic epilepsy v2.298 CCDC186 Sarah Leigh Gene: ccdc186 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v2.297 CCDC186 Sarah Leigh Publications for gene: CCDC186 were set to 33259146
Endocrine neoplasia v1.14 PTEN Ivone Leong changed review comment from: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service). No further evidence was provided.

This gene has been given an Amber rating and will be given Green status pending decision by the GMS review panel.
Sources: Expert list; to: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service). No further evidence was provided.

This gene has been given an Amber rating and will reviewed by GMS before Green status is given.
Sources: Expert list
Endocrine neoplasia v1.14 PTEN Ivone Leong Classified gene: PTEN as Amber List (moderate evidence)
Endocrine neoplasia v1.14 PTEN Ivone Leong Gene: pten has been classified as Amber List (Moderate Evidence).
Endocrine neoplasia v1.13 PTEN Ivone Leong gene: PTEN was added
gene: PTEN was added to Endocrine neoplasms. Sources: Expert list
Q2_21_phenotype tags were added to gene: PTEN.
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Review for gene: PTEN was set to AMBER
Added comment: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service). No further evidence was provided.

This gene has been given an Amber rating and will be given Green status pending decision by the GMS review panel.
Sources: Expert list
Monogenic hearing loss v2.148 PDSS1 Ivone Leong Classified gene: PDSS1 as Amber List (moderate evidence)
Monogenic hearing loss v2.148 PDSS1 Ivone Leong Gene: pdss1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.147 PDSS1 Ivone Leong gene: PDSS1 was added
gene: PDSS1 was added to Hearing loss. Sources: Literature
watchlist tags were added to gene: PDSS1.
Mode of inheritance for gene: PDSS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDSS1 were set to 33285023; 17332895
Phenotypes for gene: PDSS1 were set to Coenzyme Q10 deficiency, primary, 2, OMIM:614651
Review for gene: PDSS1 was set to AMBER
Added comment: Reviews copied from Optic neuropathy panel (Version 2.35).

"Two families reported where optic atrophy and deafness are part of the phenotype. Sources: Literature
Zornitza Stark (Australian Genomics), 1 Feb 2021"

"Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. As there are only 2 cases there is not enough evidence to support a gene-disease association. Therefore, this gene has been given an Amber rating.
Ivone Leong (Genomics England Curator), 9 Feb 2021"
Sources: Literature
Early onset or syndromic epilepsy v2.296 LMBRD2 Sarah Leigh Added comment: Comment on mode of pathogenicity: Both of the references for this entry suggest a gain-of-function action for LMBRD2 variants.
Early onset or syndromic epilepsy v2.296 LMBRD2 Sarah Leigh Mode of pathogenicity for gene: LMBRD2 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v3.779 LMBRD2 Sarah Leigh Added comment: Comment on mode of pathogenicity: Both of the references for this entry suggest a gain-of-function action for LMBRD2 variants.
Intellectual disability v3.779 LMBRD2 Sarah Leigh Mode of pathogenicity for gene: LMBRD2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v3.778 ADAM22 Sarah Leigh Classified gene: ADAM22 as Amber List (moderate evidence)
Intellectual disability v3.778 ADAM22 Sarah Leigh Added comment: Comment on list classification: There is just enough evidence for this gene to be rated GREEN at the next major review, which may make it a boarderline case.
Intellectual disability v3.778 ADAM22 Sarah Leigh Gene: adam22 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v2.295 ADAM22 Sarah Leigh changed review comment from: Comment on list classification: There is just enough evidence for this gene to be rated GREEN at the next major review, which may make it a boarderline case.; to: Comment on list classification: There is just enough evidence for this gene to be rated GREEN at the next major review, which may make it a borderline case.
Early onset or syndromic epilepsy v2.295 ADAM22 Sarah Leigh Classified gene: ADAM22 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v2.295 ADAM22 Sarah Leigh Added comment: Comment on list classification: There is just enough evidence for this gene to be rated GREEN at the next major review, which may make it a boarderline case.
Early onset or syndromic epilepsy v2.295 ADAM22 Sarah Leigh Gene: adam22 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.42 KCNN2 Arina Puzriakova Classified gene: KCNN2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.42 KCNN2 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to promote this gene to Green at the next GMS panel update - cerebellar ataxia, with an early onset from childhood to adolescence, was reported in 4/10 individuals with distinct KCNN2 variants. Pathogenicity of variants was supported by functional data.
Ataxia and cerebellar anomalies - narrow panel v2.42 KCNN2 Arina Puzriakova Gene: kcnn2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.41 KCNN2 Arina Puzriakova gene: KCNN2 was added
gene: KCNN2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q2_21_rating tags were added to gene: KCNN2.
Mode of inheritance for gene: KCNN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNN2 were set to 33242881
Phenotypes for gene: KCNN2 were set to Intellectual disability; seizures; movement disorder
Review for gene: KCNN2 was set to GREEN
Added comment: - PMID: 33242881 (2020) - 10 patients with de novo KCNN2 variants and one individual with a heterozygous missense variant inherited from an affected parent, detected by WES. Patch-clamp functional studies showed that all but one variant (p.Glu30Gln) tested, which was reclassified VUS, led to to a loss-of-function of SK2 channels.

Excluding the case with the VUS, one patient displayed DD, 4 patients exhibited mild ID, 3 patients had moderate ID, and 2 had severe ID. Other clinical characteristics include a movement disorder (6/10) including tremor (5), cerebellar ataxia (4), and extrapyramidal symptoms (4); epilepsy (2/10); white matter abnormalities (3/6). Authors note that the 4 individuals without a movement disorder were under the age of 16 years at the time of the study and there is a possibility that this manifestation may arise later in life.
Sources: Literature
Intellectual disability v3.777 KCNN2 Arina Puzriakova Classified gene: KCNN2 as Amber List (moderate evidence)
Intellectual disability v3.777 KCNN2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. There is enough evidence to promote this gene to Green at the next GMS panel update - variable degrees of cognitive impairment were a universal feature amongst individuals with KCNN2 variants (at least 10 unrelated cases with unique variants). Pathogenicity was supported by functional data.
Intellectual disability v3.777 KCNN2 Arina Puzriakova Gene: kcnn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.776 KCNN2 Arina Puzriakova Tag Q2_21_rating tag was added to gene: KCNN2.
Intellectual disability v3.776 KCNN2 Arina Puzriakova reviewed gene: KCNN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33242881; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v2.294 SATB1 Arina Puzriakova Classified gene: SATB1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v2.294 SATB1 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to promote this gene to Green at the next major review.
Early onset or syndromic epilepsy v2.294 SATB1 Arina Puzriakova Gene: satb1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v2.293 SATB1 Arina Puzriakova gene: SATB1 was added
gene: SATB1 was added to Genetic epilepsy syndromes. Sources: Literature
Q2_21_rating tags were added to gene: SATB1.
Mode of inheritance for gene: SATB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SATB1 were set to 33513338
Phenotypes for gene: SATB1 were set to Neurodevelopmental disorder
Review for gene: SATB1 was set to GREEN
Added comment: Currently not associated with any phenotype in OMIM (last edited: 30/09/2020) but has a 'confirmed' disease confidence rating for 'SATB1-related developmental disorder (monoallelic)' in Gene2Phenotype.

- Den Hoed et al. 2021 (PMID: 33513338) - Total of 42 individuals from 35 families with SATB1 variants (including previously reported cases) - 30 patients harboured 15 unique SATB1 missense variants, including three recurrent variants; 10 had premature protein truncating variants; and and 2 individuals carried a (partial) gene deletion. 28 variants occurred de novo, 3 were inherited from an affected parent, 5 resulted from suspected parental mosaicism (2 inherited from an unaffected parent indicating reduced penetrance), and unknown inheritance in remaining 4 variants.

Phenotypes include neurodevelopmental delay (35/36, 97%), intellectual disability (28/31, 90%), muscle tone abnormalities (abnormal tone 28/37, 76%; hypotonia 28/37, 76%; spasticity 10/36, 28%), epilepsy (22/36, 61%), facial dysmorphisms (24/36, 67%), and dental abnormalities (24/34, 71%). Variable seizure phenotypes described but multiple refractory early-onset cases.

Missense variants were associated with a more severe phenotype - for instance, 57% of individuals with a missense variant had severe/profound ID whereas this level of ID was not observed for any individuals with truncating variants.
Sources: Literature
Intellectual disability v3.776 SATB1 Arina Puzriakova Publications for gene: SATB1 were set to 33057194
Intellectual disability v3.775 SATB1 Arina Puzriakova Deleted their comment
Intellectual disability v3.775 SATB1 Arina Puzriakova Classified gene: SATB1 as Amber List (moderate evidence)
Intellectual disability v3.775 SATB1 Arina Puzriakova Added comment: Comment on list classification: There is now enough evidence to promote this gene to Green at the next major review.
Intellectual disability v3.775 SATB1 Arina Puzriakova Gene: satb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.775 SATB1 Arina Puzriakova Classified gene: SATB1 as Amber List (moderate evidence)
Intellectual disability v3.775 SATB1 Arina Puzriakova Added comment: Comment on list classification: There is now enough evidence to promote this gene to Green at the next major review.
Intellectual disability v3.775 SATB1 Arina Puzriakova Gene: satb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.774 SATB1 Arina Puzriakova Tag watchlist was removed from gene: SATB1.
Tag Q2_21_rating tag was added to gene: SATB1.
Intellectual disability v3.774 SATB1 Arina Puzriakova reviewed gene: SATB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33513338; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric disorders - additional genes v1.82 OTUD5 Arina Puzriakova Classified gene: OTUD5 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.82 OTUD5 Arina Puzriakova Added comment: Comment on list classification: This panel is relevant in view of the multiple congenital malformations associated with OTUD5 variants and therefore this gene may be promoted to Green at the next major review - at least 8 unrelated families reported with distinct hemizygous variants (PMIDs: 33131077 and 33523931).
Paediatric disorders - additional genes v1.82 OTUD5 Arina Puzriakova Gene: otud5 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.81 OTUD5 Arina Puzriakova gene: OTUD5 was added
gene: OTUD5 was added to Paediatric disorders - additional genes. Sources: Expert Review
Q2_21_rating tags were added to gene: OTUD5.
Mode of inheritance for gene: OTUD5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OTUD5 were set to 33131077; 33523931
Phenotypes for gene: OTUD5 were set to Multiple congenital anomalies-neurodevelopmental syndrome, X-linked, OMIM:301056
Review for gene: OTUD5 was set to GREEN
Added comment: OTUD5 is associated with a relevant phenotype in OMIM but not yet in Gene2Phenotype.

- PMID: 33131077 (2021) - 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with IUGR, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. WGS in four individuals identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals.

- PMID: 33523931 (2021) - Another 10 individuals from 7 families reported. Key features include poor growth, global developmental delay with impaired intellectual development, and variable abnormalities of the cardiac, skeletal, and genitourinary systems. Most affected individuals also have hypotonia and dysmorphic craniofacial features. Brain imaging typically shows enlarged ventricles and thin corpus callosum; some have microcephaly, whereas others have hydrocephalus. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade.
Sources: Expert Review
Fetal anomalies v1.626 OTUD5 Arina Puzriakova Classified gene: OTUD5 as Amber List (moderate evidence)
Fetal anomalies v1.626 OTUD5 Arina Puzriakova Added comment: Comment on list classification: At least 8 families reported with a multiple congenital anomaly disorder and distinct hemizygous variants in this gene (PMIDs: 33131077 and 33523931). Phenotype may conceivably be detected prenatally and therefore this gene should be promoted to Green at the next GMS panel update.
Fetal anomalies v1.626 OTUD5 Arina Puzriakova Gene: otud5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.625 OTUD5 Arina Puzriakova gene: OTUD5 was added
gene: OTUD5 was added to Fetal anomalies. Sources: Expert Review
Q2_21_rating tags were added to gene: OTUD5.
Mode of inheritance for gene: OTUD5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OTUD5 were set to 33131077; 33523931
Phenotypes for gene: OTUD5 were set to Multiple congenital anomalies-neurodevelopmental syndrome, X-linked, OMIM:301056
Review for gene: OTUD5 was set to GREEN
Added comment: OTUD5 is associated with a relevant phenotype in OMIM but not yet in Gene2Phenotype.

- PMID: 33131077 (2021) - 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with IUGR, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. WGS in four individuals identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals.

- PMID: 33523931 (2021) - Another 10 individuals from 7 families reported. Key features include poor growth, global developmental delay with impaired intellectual development, and variable abnormalities of the cardiac, skeletal, and genitourinary systems. Most affected individuals also have hypotonia and dysmorphic craniofacial features. Brain imaging typically shows enlarged ventricles and thin corpus callosum; some have microcephaly, whereas others have hydrocephalus. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade.
Sources: Expert Review
Intellectual disability v3.774 OTUD5 Arina Puzriakova Classified gene: OTUD5 as Amber List (moderate evidence)
Intellectual disability v3.774 OTUD5 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. There is enough evidence to rate this gene Green at the next GMS panel update.

At least 8 families reported with a multiple congenital anomaly disorder and distinct hemizygous variants in this gene. GDD/ID is part of the disease presentation and was noted in all cases of relevant age (PMIDs: 33131077 and 33523931).
Intellectual disability v3.774 OTUD5 Arina Puzriakova Gene: otud5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.773 OTUD5 Arina Puzriakova Tag Q2_21_rating tag was added to gene: OTUD5.
Intellectual disability v3.773 OTUD5 Zornitza Stark changed review comment from: PMID 33523931: Another 10 individuals from 7 families reported, promote to Green. X-linked multiple congenital anomalies-neurodevelopmental syndrome (MCAND) is an X-linked recessive congenital multisystemic disorder characterized by poor growth, global developmental delay with impaired intellectual development, and variable abnormalities of the cardiac, skeletal, and genitourinary systems. Most affected individuals also have hypotonia and dysmorphic craniofacial features. Brain imaging typically shows enlarged ventricles and thin corpus callosum; some have microcephaly, whereas others have hydrocephalus. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade.; to: PMID 33523931: Another 10 individuals from 7 families reported. Key features include poor growth, global developmental delay with impaired intellectual development, and variable abnormalities of the cardiac, skeletal, and genitourinary systems. Most affected individuals also have hypotonia and dysmorphic craniofacial features. Brain imaging typically shows enlarged ventricles and thin corpus callosum; some have microcephaly, whereas others have hydrocephalus. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade.
Intellectual disability v3.773 OTUD5 Zornitza Stark edited their review of gene: OTUD5: Added comment: PMID 33523931: Another 10 individuals from 7 families reported, promote to Green. X-linked multiple congenital anomalies-neurodevelopmental syndrome (MCAND) is an X-linked recessive congenital multisystemic disorder characterized by poor growth, global developmental delay with impaired intellectual development, and variable abnormalities of the cardiac, skeletal, and genitourinary systems. Most affected individuals also have hypotonia and dysmorphic craniofacial features. Brain imaging typically shows enlarged ventricles and thin corpus callosum; some have microcephaly, whereas others have hydrocephalus. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade.; Changed rating: GREEN; Changed publications: 33131077, 33523931
Intellectual disability v3.773 PIGF Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Zornitza Stark. Rating Red as 2 families with the same (likely founder) variant reported at present (PMID: 33386993). Phenotypes did include severe ID or DD, respectively - but additional cases with other variants in the LRRC32 gene required to substantiate causation (added founder-effect tag); to: Comment on list classification: New gene added by Zornitza Stark. Rating Red as 2 families with the same (likely founder) variant reported at present (PMID: 33386993). Phenotypes did include severe ID or DD, respectively - but additional cases with other variants in the PIGF gene required to substantiate causation (added founder-effect tag)
Intellectual disability v3.773 PIGF Arina Puzriakova Tag founder-effect tag was added to gene: PIGF.
Intellectual disability v3.773 PIGF Arina Puzriakova Classified gene: PIGF as Red List (low evidence)
Intellectual disability v3.773 PIGF Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Rating Red as 2 families with the same (likely founder) variant reported at present (PMID: 33386993). Phenotypes did include severe ID or DD, respectively - but additional cases with other variants in the LRRC32 gene required to substantiate causation (added founder-effect tag)
Intellectual disability v3.773 PIGF Arina Puzriakova Gene: pigf has been classified as Red List (Low Evidence).
Likely inborn error of metabolism v2.67 NDUFC2 Sarah Leigh Mode of inheritance for gene: NDUFC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v2.66 NDUFC2 Sarah Leigh Tag Q2_21_rating tag was added to gene: NDUFC2.
Intellectual disability v3.772 OTUD5 Arina Puzriakova Publications for gene: OTUD5 were set to 33131077
Likely inborn error of metabolism v2.66 NDUFC2 Sarah Leigh Classified gene: NDUFC2 as Amber List (moderate evidence)
Likely inborn error of metabolism v2.66 NDUFC2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v2.66 NDUFC2 Sarah Leigh Gene: ndufc2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v2.65 NDUFC2 Sarah Leigh edited their review of gene: NDUFC2: Added comment: Associated with relevant phenotype in OMIM, but not Gen2Phen. At least 2 variants have been reported in two unrelated cases, together with supportive functional evidence (PMID 32969598). There are also 2 families with complex I deficiency with reported by Carl Fratter (10 May 2019, Oxford University Hospitals NHS Trust).; Changed rating: GREEN
Possible mitochondrial disorder - nuclear genes v1.34 NDUFC2 Sarah Leigh changed review comment from: Not associated with relevant phenotype in OMIM or in Gen2Phen. At least 2 variants have been reported in two unrelated cases, together with supportive functional evidence (PMID 32969598). There are also 2 families with complex I deficiency with reported by Carl Fratter (review below 10 May 2019).; to: Associated with relevant phenotype in OMIM, but not Gen2Phen. At least 2 variants have been reported in two unrelated cases, together with supportive functional evidence (PMID 32969598). There are also 2 families with complex I deficiency with reported by Carl Fratter (review below 10 May 2019).
Mitochondrial disorder with complex I deficiency v1.9 NDUFC2 Sarah Leigh changed review comment from: Not associated with relevant phenotype in OMIM or in Gen2Phen. At least 2 variants have been reported in two unrelated cases, together with supportive functional evidence (PMID 32969598). There are also 2 families with complex I deficiency with reported by Carl Fratter (review below 10 May 2019).; to: Associated with relevant phenotype in OMIM, but not Gen2Phen. At least 2 variants have been reported in two unrelated cases, together with supportive functional evidence (PMID 32969598). There are also 2 families with complex I deficiency with reported by Carl Fratter (review below 10 May 2019).
Undiagnosed metabolic disorders v1.445 NDUFC2 Sarah Leigh Classified gene: NDUFC2 as Amber List (moderate evidence)
Undiagnosed metabolic disorders v1.445 NDUFC2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Undiagnosed metabolic disorders v1.445 NDUFC2 Sarah Leigh Gene: ndufc2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.771 OTUD5 Arina Puzriakova Phenotypes for gene: OTUD5 were changed from X-linked severe neurodevelopmental delay, hydrocephalus, and early lethality to Multiple congenital anomalies-neurodevelopmental syndrome, X-linked, OMIM:301056
Undiagnosed metabolic disorders v1.444 NDUFC2 Sarah Leigh Tag Q2_21_rating tag was added to gene: NDUFC2.
Undiagnosed metabolic disorders v1.444 NDUFC2 Sarah Leigh commented on gene: NDUFC2: Associated with relevant phenotype in OMIM, but not Gen2Phen. At least 2 variants have been reported in two unrelated cases, together with supportive functional evidence (PMID 32969598). There are also 2 families with complex I deficiency with reported by Carl Fratter (10 May 2019, Oxford University Hospitals NHS Trust).
Likely inborn error of metabolism v2.65 NDUFC2 Sarah Leigh Publications for gene: NDUFC2 were set to
Intellectual disability v3.770 METAP1 Arina Puzriakova Classified gene: METAP1 as Red List (low evidence)
Intellectual disability v3.770 METAP1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Rating Red as only one family reported at present (PMID:32764695). Phenotypes do include ID/DD, but additional cases required to corroborate this gene-disease association.
Intellectual disability v3.770 METAP1 Arina Puzriakova Gene: metap1 has been classified as Red List (Low Evidence).
Mitochondrial disorder with complex I deficiency v1.9 NDUFC2 Sarah Leigh Added comment: Comment on phenotypes: Assigned a phenotype by OMIM 02/02/2021
Mitochondrial disorder with complex I deficiency v1.9 NDUFC2 Sarah Leigh Phenotypes for gene: NDUFC2 were changed from Mitochondrial complex I deficiency, nuclear type 36 OMIM:619170 to Mitochondrial complex I deficiency, nuclear type 36 OMIM:619170
Likely inborn error of metabolism v2.64 NDUFC2 Sarah Leigh Added comment: Comment on phenotypes: Assigned a phenotype by OMIM 02/02/2021
Likely inborn error of metabolism v2.64 NDUFC2 Sarah Leigh Phenotypes for gene: NDUFC2 were changed from No OMIM phenotype; Isolated complex I deficiency to Mitochondrial complex I deficiency, nuclear type 36 OMIM:619170
Possible mitochondrial disorder - nuclear genes v1.34 NDUFC2 Sarah Leigh changed review comment from: Comment on phenotypes: Assigned a OMIM phenotype 02/02/2021; to: Comment on phenotypes: Assigned a phenotype by OMIM 02/02/2021
Possible mitochondrial disorder - nuclear genes v1.34 NDUFC2 Sarah Leigh Added comment: Comment on phenotypes: Assigned a OMIM phenotype 02/02/2021
Possible mitochondrial disorder - nuclear genes v1.34 NDUFC2 Sarah Leigh Phenotypes for gene: NDUFC2 were changed from No OMIM phenotype; early-onset Leigh syndrome and stalled biogenesis of complex I to Mitochondrial complex I deficiency, nuclear type 36 OMIM:619170
Mitochondrial disorder with complex I deficiency v1.8 NDUFC2 Sarah Leigh Phenotypes for gene: NDUFC2 were changed from No OMIM phenotype; early-onset Leigh syndrome and stalled biogenesis of complex I to Mitochondrial complex I deficiency, nuclear type 36 OMIM:619170
Undiagnosed metabolic disorders v1.444 NDUFC2 Sarah Leigh Publications for gene: NDUFC2 were set to
Severe microcephaly v2.102 HPDL Arina Puzriakova changed review comment from: Comment on list classification: HPDL was added to this panel following with clinical feedback from Helen Brittain (Genomics England Clinical Team). There is enough evidence for this gene to be rated Green at the next major review.; to: Comment on list classification: HPDL was added to this panel following clinical feedback from Helen Brittain (Genomics England Clinical Team). There is enough evidence for this gene to be rated Green at the next major review.
Undiagnosed metabolic disorders v1.443 NDUFC2 Sarah Leigh gene: NDUFC2 was added
gene: NDUFC2 was added to Undiagnosed metabolic disorders. Sources: Literature
Mode of inheritance for gene: NDUFC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFC2 were set to Mitochondrial complex I deficiency, nuclear type 36 OMIM:619170
Review for gene: NDUFC2 was set to GREEN
Added comment: Sources: Literature
Severe microcephaly v2.102 HPDL Arina Puzriakova Classified gene: HPDL as Amber List (moderate evidence)
Severe microcephaly v2.102 HPDL Arina Puzriakova Added comment: Comment on list classification: HPDL was added to this panel following with clinical feedback from Helen Brittain (Genomics England Clinical Team). There is enough evidence for this gene to be rated Green at the next major review.
Severe microcephaly v2.102 HPDL Arina Puzriakova Gene: hpdl has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.101 HPDL Arina Puzriakova gene: HPDL was added
gene: HPDL was added to Severe microcephaly. Sources: Literature
Q2_21_rating tags were added to gene: HPDL.
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 32707086; 33188300
Phenotypes for gene: HPDL were set to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613
Review for gene: HPDL was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and has a 'probable' disease confidence for 'HPDL Neurodegenerative Disease' in Gene2Phenotype.

At least 34 cases from 21 unrelated families with a paediatric-onset spastic movement disorder and biallelic variants in this gene (PMIDs: 32707086 and 33188300). There is broad clinical variability ranging from severe, neonatal-onset neurodevelopmental delay with neuroimaging findings resembling mitochondrial encephalopathy to milder manifestation of adolescent-onset, isolated HSP. Microcephaly of relevant severity (HC ≤ 3 SD) was observed in 13/30 cases.

Supportive functional studies were reported, including localization of HPDL protein to the mitochondria and muscle fibre abnormalities and a KO mouse model displaying features of seizures, early lethality, smaller brain sizes, and cellular apoptosis.
Sources: Literature
Mitochondrial disorders v2.14 HPDL Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 16 variants reported in 17 cases from 13 unrelated families, supportive functional studies were reported, including localization of HPDL protein to the mitochrondria and muscle fibre abnormalies in some cases tested (PMID 32707086).; to: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 16 variants reported in 17 cases from 11 unrelated families, supportive functional studies were reported, including localization of HPDL protein to the mitochrondria and muscle fibre abnormalies in some cases tested (PMID 32707086).
Possible mitochondrial disorder - nuclear genes v1.33 HPDL Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 16 variants reported in 17 cases from 13 unrelated families, supportive functional studies were reported, including localization of HPDL protein to the mitochrondria and muscle fibre abnormalies in some cases tested (PMID 32707086).; to: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 16 variants reported in 17 cases from 11 unrelated families, supportive functional studies were reported, including localization of HPDL protein to the mitochrondria and muscle fibre abnormalies in some cases tested (PMID 32707086).
Early onset or syndromic epilepsy v2.292 HPDL Arina Puzriakova Phenotypes for gene: HPDL were changed from spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613
Early onset or syndromic epilepsy v2.291 HPDL Arina Puzriakova Publications for gene: HPDL were set to PMID: 32707086; 33188300
Early onset or syndromic epilepsy v2.290 HPDL Arina Puzriakova Classified gene: HPDL as Amber List (moderate evidence)
Early onset or syndromic epilepsy v2.290 HPDL Arina Puzriakova Added comment: Comment on list classification: New gene added by Evan Reid (University of Cambridge). There is enough evidence for this gene to be rated Green at the next major review.
Early onset or syndromic epilepsy v2.290 HPDL Arina Puzriakova Gene: hpdl has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v2.289 HPDL Arina Puzriakova Tag Q2_21_rating tag was added to gene: HPDL.
Early onset or syndromic epilepsy v2.289 HPDL Arina Puzriakova reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: 32707086, 33188300; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026, Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v2.28 HPDL Arina Puzriakova Phenotypes for gene: HPDL were changed from spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual and motor disability to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613; Spastic paraplegia 83, autosomal recessive, OMIM:619027; Spastic paraplegia 83, autosomal recessive, MONDO:0033614
Childhood onset hereditary spastic paraplegia v2.27 HPDL Arina Puzriakova Publications for gene: HPDL were set to PMID: 32707086; 33188300
Childhood onset hereditary spastic paraplegia v2.26 HPDL Arina Puzriakova Classified gene: HPDL as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v2.26 HPDL Arina Puzriakova Added comment: Comment on list classification: New gene added by Evan Reid (University of Cambridge). There is enough evidence for this gene to be rated Green at the next major review.
Childhood onset hereditary spastic paraplegia v2.26 HPDL Arina Puzriakova Gene: hpdl has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v2.25 HPDL Arina Puzriakova Tag Q2_21_rating tag was added to gene: HPDL.
Childhood onset hereditary spastic paraplegia v2.25 HPDL Arina Puzriakova reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: 32707086, 33188300; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026, Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613, Spastic paraplegia 83, autosomal recessive, OMIM:619027, Spastic paraplegia 83, autosomal recessive, MONDO:0033614; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.769 HPDL Arina Puzriakova Classified gene: HPDL as Amber List (moderate evidence)
Intellectual disability v3.769 HPDL Arina Puzriakova Added comment: Comment on list classification: New gene added by Evan Reid (University of Cambridge). There is enough evidence for this gene to be rated Green at the next major review.
Intellectual disability v3.769 HPDL Arina Puzriakova Gene: hpdl has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.768 HPDL Arina Puzriakova Publications for gene: HPDL were set to PMID: 32707086; 33188300
Intellectual disability v3.767 HPDL Arina Puzriakova Tag Q2_21_rating tag was added to gene: HPDL.
Intellectual disability v3.767 HPDL Arina Puzriakova reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: 32707086, 33188300; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026, Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.767 HPDL Arina Puzriakova Phenotypes for gene: HPDL were changed from spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613
Optic neuropathy v2.35 PDSS1 Ivone Leong Tag watchlist tag was added to gene: PDSS1.
Optic neuropathy v2.35 PDSS1 Ivone Leong Classified gene: PDSS1 as Amber List (moderate evidence)
Optic neuropathy v2.35 PDSS1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. As there are only 2 cases there is not enough evidence to support a gene-disease association. Therefore, this gene has been given an Amber rating.
Optic neuropathy v2.35 PDSS1 Ivone Leong Gene: pdss1 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.34 PDSS1 Ivone Leong Publications for gene: PDSS1 were set to 33285023
Intellectual disability v3.766 HIRA Arina Puzriakova Classified gene: HIRA as Amber List (moderate evidence)
Intellectual disability v3.766 HIRA Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. At least 4 unrelated individuals with heterozygous variants in this gene - however, only 1 presented moderate ID (2 had ASD rather than ID, while the phenotype is unclear for the fourth individual). HIRA is a good candidate for neurodevelopmental impairment, supported by an animal model, but additional cases are required to ascertain the relevance of ID.

Therefore, at present there is only enough evidence to rate Amber awaiting further cases/clinical evidence (added 'watchlist' tag)
Intellectual disability v3.766 HIRA Arina Puzriakova Gene: hira has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.33 PDSS1 Ivone Leong Phenotypes for gene: PDSS1 were changed from Coenzyme Q10 deficiency, primary, 2, MIM# 614651 to Coenzyme Q10 deficiency, primary, 2, OMIM:614651
Intellectual disability v3.765 HIRA Arina Puzriakova Tag watchlist tag was added to gene: HIRA.
Intellectual disability v3.765 HIRA Arina Puzriakova reviewed gene: HIRA: Rating: AMBER; Mode of pathogenicity: None; Publications: 25363760, 28135719, 33417013; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v2.32 SSBP1 Ivone Leong Phenotypes for gene: SSBP1 were changed from Autosomal dominant optic atrophy with variable retinal degeneration to Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510; Autosomal dominant optic atrophy with variable retinal degeneration; Optic atrophy with retinal degeneration (+-systemic features)
Optic neuropathy v2.31 SSBP1 Ivone Leong Publications for gene: SSBP1 were set to 31298765
Intellectual disability v3.765 VPS4A Arina Puzriakova Phenotypes for gene: VPS4A were changed from developmental delay; intellectual disability; cerebellar hypoplasia; pontine hypoplasia; thin corpus callosum; microcephaly; growth retardation; congenital anaemia; dyserythropeoitic anaemia; dystonia; congenital cataracts; deafness to CIMDAG syndrome
Rare anaemia v1.14 VPS4A Arina Puzriakova Phenotypes for gene: VPS4A were changed from developmental delay; intellectual disability; cerebellar hypoplasia; pontine hypoplasia; thin corpus callosum; microcephaly; growth retardation; congenital anaemia; dyserythropeoitic anaemia; dystonia; congenital cataracts; deafness to CIMDAG syndrome
Congenital disorders of glycosylation v2.65 TMEM199 Sarah Leigh Phenotypes for gene: TMEM199 were changed from Congenital disorder of glycosylation, type IIp 616829 to Congenital disorder of glycosylation, type IIp OMIM:616829; TMEM199-CDG MONDO:0014790
Congenital disorders of glycosylation v2.64 TMEM199 Sarah Leigh Publications for gene: TMEM199 were set to 26833330
Congenital disorders of glycosylation v2.63 TMEM199 Sarah Leigh Classified gene: TMEM199 as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.63 TMEM199 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital disorders of glycosylation v2.63 TMEM199 Sarah Leigh Gene: tmem199 has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v2.62 SLC35A2 Sarah Leigh Classified gene: SLC35A2 as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.62 SLC35A2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital disorders of glycosylation v2.62 SLC35A2 Sarah Leigh Gene: slc35a2 has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v2.61 SLC35A2 Sarah Leigh Phenotypes for gene: SLC35A2 were changed from Congenital disorder of glycosylation, type IIm 300896 to Congenital disorder of glycosylation, type IIm OMIM:300896; Developmental and epileptic encephalopathy-22 OMIM:300896; SLC35A2-CDG MONDO:0010478
Congenital disorders of glycosylation v2.60 SLC35A2 Sarah Leigh Deleted their comment
Congenital disorders of glycosylation v2.60 SLC35A2 Sarah Leigh Added comment: Comment on phenotypes: Congenital disorder of glycosylation, type IIm OMIM:300896;Developmental and epileptic encephalopathy-22 OMIM:300896;SLC35A2-CDG MONDO:0010478
Congenital disorders of glycosylation v2.60 SLC35A2 Sarah Leigh Phenotypes for gene: SLC35A2 were changed from Congenital disorder of glycosylation, type IIm OMIM:300896; developmental and epileptic encephalopathy-22 OMIM:300896; SLC35A2-CDG MONDO:0010478 to Congenital disorder of glycosylation, type IIm 300896
Congenital disorders of glycosylation v2.59 SLC35A2 Sarah Leigh Publications for gene: SLC35A2 were set to 23561849; 24115232; 27743886; 25778940; 30817854
Congenital disorders of glycosylation v2.58 SLC35A2 Sarah Leigh Tag Q2_21_rating tag was added to gene: SLC35A2.
Congenital disorders of glycosylation v2.58 SLC35A2 Sarah Leigh Phenotypes for gene: SLC35A2 were changed from Congenital disorder of glycosylation, type IIm OMIM:300896; SLC35A2-CDG MONDO:0010478 to Congenital disorder of glycosylation, type IIm OMIM:300896; developmental and epileptic encephalopathy-22 OMIM:300896; SLC35A2-CDG MONDO:0010478
Congenital disorders of glycosylation v2.57 SLC35A2 Sarah Leigh Phenotypes for gene: SLC35A2 were changed from Congenital disorder of glycosylation, type IIm 300896 to Congenital disorder of glycosylation, type IIm OMIM:300896; SLC35A2-CDG MONDO:0010478
Congenital disorders of glycosylation v2.56 SLC35A2 Sarah Leigh Publications for gene: SLC35A2 were set to 25778940; 27743886; 23561849
Likely inborn error of metabolism v2.63 POMK Sarah Leigh Classified gene: POMK as Amber List (moderate evidence)
Likely inborn error of metabolism v2.63 POMK Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v2.63 POMK Sarah Leigh Gene: pomk has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v2.55 POMK Sarah Leigh Classified gene: POMK as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.55 POMK Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital disorders of glycosylation v2.55 POMK Sarah Leigh Gene: pomk has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v2.62 POMK Sarah Leigh Tag Q2_21_rating tag was added to gene: POMK.
Congenital disorders of glycosylation v2.54 POMK Sarah Leigh Classified gene: POMK as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.54 POMK Sarah Leigh Gene: pomk has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v2.53 POMK Sarah Leigh Tag Q2_21_rating tag was added to gene: POMK.
Congenital disorders of glycosylation v2.53 POMK Sarah Leigh reviewed gene: POMK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Likely inborn error of metabolism v2.62 POMK Sarah Leigh reviewed gene: POMK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Likely inborn error of metabolism v2.62 POMK Sarah Leigh Phenotypes for gene: POMK were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 (MIM #615249) to ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12 OMIM:616094; limb-girdle muscular dystrophy due to POMK deficiencyMONDO:0014489; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 OMIM:615249; muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 MONDO:0014101
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v2.18 POMK Sarah Leigh Phenotypes for gene: POMK were changed from ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12, 616094; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, 615249; limb girdle muscular dystrophy; congenital muscular dystrophy to ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12 OMIM:616094; limb-girdle muscular dystrophy due to POMK deficiencyMONDO:0014489; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 OMIM:615249; muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 MONDO:0014101
Congenital disorders of glycosylation v2.53 POMK Sarah Leigh Phenotypes for gene: POMK were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 OMIM:615249 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 OMIM:615249; muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 MONDO:0014101
Likely inborn error of metabolism v2.61 POMK Sarah Leigh Publications for gene: POMK were set to 23519211; 24556084; 24925318
Congenital disorders of glycosylation v2.52 POMK Sarah Leigh Publications for gene: POMK were set to 23519211; 24556084; 24925318
Arthrogryposis v3.72 MYLPF Arina Puzriakova Tag watchlist was removed from gene: MYLPF.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v2.17 POMK Sarah Leigh Publications for gene: POMK were set to 24925318; 24556084; 29910097
Congenital disorders of glycosylation v2.51 POMK Sarah Leigh Phenotypes for gene: POMK were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 (MIM #615249) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 OMIM:615249
Undiagnosed metabolic disorders v1.442 MAGT1 Sarah Leigh Phenotypes for gene: MAGT1 were changed from Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853 to Congenital disorder of glycosylation, type Icc OMIM:301031; congenital disorder of glycosylation, type ICC MONDO:0026729; Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia OMIM:300853; X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia MONDO:0010455
Congenital disorders of glycosylation v2.50 MAGT1 Sarah Leigh Added comment: Comment on phenotypes: Congenital disorder of glycosylation, type Icc OMIM:301031; congenital disorder of glycosylation, type ICC MONDO:0026729;Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia OMIM:300853;X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia MONDO:0010455
Congenital disorders of glycosylation v2.50 MAGT1 Sarah Leigh Phenotypes for gene: MAGT1 were changed from Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853; IAP-CDG (Disorders of protein N-glycosylation) to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853; IAP-CDG (Disorders of protein N-glycosylation)
Undiagnosed metabolic disorders v1.441 MAGT1 Sarah Leigh commented on gene: MAGT1: PMID 31036665 and PMID 31714901 demonstrate that variants in MAGT1 can result in disruption of glycosylation. This effect could be rescued in vitro by transfection of MAGT1 mRNA (PMID 31714901).
This gene is subject to skewed X-inactivation.
Undiagnosed metabolic disorders v1.441 MAGT1 Sarah Leigh Tag Skewed X-inactivation tag was added to gene: MAGT1.
Congenital disorders of glycosylation v2.49 MAGT1 Sarah Leigh edited their review of gene: MAGT1: Added comment: PMID 31036665 and PMID 31714901 demonstrate that variants in MAGT1 can result in disruption of glycosylation. This effect could be rescued in vitro by transfection of MAGT1 mRNA (PMID 31714901).
This gene is subject to skewed X-inactivation.; Changed rating: GREEN
Arthrogryposis v3.72 MYLPF Arina Puzriakova Tag watchlist tag was added to gene: MYLPF.
Arthrogryposis v3.72 MYLPF Arina Puzriakova Phenotypes for gene: MYLPF were changed from Distal arthrogryoposis to Arthrogryposis, distal, type 1C, OMIM:619110; Arthrogryposis, distal, type 1C, MONDO:0030847
Congenital disorders of glycosylation v2.49 MAGT1 Sarah Leigh Tag Skewed X-inactivation tag was added to gene: MAGT1.
Tag Q2_21_phenotype tag was added to gene: MAGT1.
Congenital disorders of glycosylation v2.49 MAGT1 Sarah Leigh Classified gene: MAGT1 as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.49 MAGT1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital disorders of glycosylation v2.49 MAGT1 Sarah Leigh Gene: magt1 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia v1.208 SYNE1 Arina Puzriakova Phenotypes for gene: SYNE1 were changed from Cerebellar Ataxia ; Spinocerebellar ataxia, autosomal recessive 8 to Spinocerebellar ataxia, autosomal recessive 8, OMIM:610743; Autosomal recessive ataxia, Beauce type, MONDO:0012549
Hereditary ataxia with onset in adulthood v2.21 SYNE1 Arina Puzriakova Phenotypes for gene: SYNE1 were changed from Cerebellar Ataxia; Spinocerebellar ataxia, autosomal recessive 8; Autosomal recessive spinocerebellar ataxia type 8 to Spinocerebellar ataxia, autosomal recessive 8, OMIM:610743; Autosomal recessive ataxia, Beauce type, MONDO:0012549
Ataxia and cerebellar anomalies - narrow panel v2.40 SYNE1 Arina Puzriakova Phenotypes for gene: SYNE1 were changed from Cerebellar Ataxia; Spinocerebellar ataxia, autosomal recessive 8 to Spinocerebellar ataxia, autosomal recessive 8, OMIM:610743; Autosomal recessive ataxia, Beauce type, MONDO:0012549
Fetal anomalies v1.624 SYNE1 Arina Puzriakova Phenotypes for gene: SYNE1 were changed from SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 8; EMERY-DREIFUSS MUSCULAR DYSTROPHY 4, AUTOSOMAL RECESSIVE to Arthrogryposis multiplex congenita 3, myogenic type, OMIM:618484; Arthrogryposis multiplex congenita 3, myogenic type, MONDO:0032778
Fetal anomalies v1.623 SYNE1 Arina Puzriakova Publications for gene: SYNE1 were set to
Fetal anomalies v1.622 SYNE1 Arina Puzriakova Classified gene: SYNE1 as Amber List (moderate evidence)
Fetal anomalies v1.622 SYNE1 Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but there is sufficient evidence to promote to Green at the next GMS panel update - at least 3 unrelated cases with arthrogryposis multiplex congenita (AMC) which may be detected prenatally.
Fetal anomalies v1.622 SYNE1 Arina Puzriakova Gene: syne1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.621 SYNE1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: SYNE1.
Fetal anomalies v1.621 SYNE1 Arina Puzriakova reviewed gene: SYNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19542096, 24319099, 27782104; Phenotypes: Arthrogryposis multiplex congenita 3, myogenic type, OMIM:618484, Arthrogryposis multiplex congenita 3, myogenic type, MONDO:0032778; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v3.71 SYNE1 Arina Puzriakova Publications for gene: SYNE1 were set to
Arthrogryposis v3.70 SYNE1 Arina Puzriakova Classified gene: SYNE1 as Amber List (moderate evidence)
Arthrogryposis v3.70 SYNE1 Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but there is sufficient evidence to promote to Green at the next GMS panel update.
Arthrogryposis v3.70 SYNE1 Arina Puzriakova Gene: syne1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v3.69 SYNE1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: SYNE1.
Arthrogryposis v3.69 SYNE1 Arina Puzriakova reviewed gene: SYNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19542096, 24319099, 27782104; Phenotypes: Arthrogryposis multiplex congenita 3, myogenic type, OMIM:618484, Arthrogryposis multiplex congenita 3, myogenic type, MONDO:0032778; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v2.48 MAGT1 Sarah Leigh Publications for gene: MAGT1 were set to 27604308; 27393411
Likely inborn error of metabolism v2.60 GORAB Sarah Leigh Phenotypes for gene: GORAB were changed from Geroderma osteodysplasticum OMIM:231070; geroderma osteodysplastica MONDO:0009271 to Geroderma osteodysplasticum OMIM:231070; geroderma osteodysplastica MONDO:0009271
Likely inborn error of metabolism v2.59 GORAB Sarah Leigh edited their review of gene: GORAB: Added comment: PMID 30631079 demonstrates that disrupting variants in GORAB result in "impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor". The authors conclude that this finding supports the view that "defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica".
Therefore variants in GORAB are relevant to this panel based on this mechanism.; Changed rating: GREEN
Likely inborn error of metabolism v2.59 GORAB Sarah Leigh Publications for gene: GORAB were set to 26000619; 18348262; 28807865; 30631079
Congenital disorders of glycosylation v2.47 GORAB Sarah Leigh edited their review of gene: GORAB: Added comment: PMID 30631079 demonstrates that disrupting variants in GORAB result in "impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor". The authors conclude that this finding supports the view that "defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica".
Therefore variants in GORAB are relevant to this panel based on this mechanism.; Changed rating: GREEN
Likely inborn error of metabolism v2.58 GORAB Sarah Leigh Phenotypes for gene: GORAB were changed from Geroderma osteodysplasticum to Geroderma osteodysplasticum OMIM:231070; geroderma osteodysplastica MONDO:0009271
Likely inborn error of metabolism v2.57 GORAB Sarah Leigh Publications for gene: GORAB were set to 26000619; 18348262; 28807865; 30631079
Likely inborn error of metabolism v2.57 GORAB Sarah Leigh Publications for gene: GORAB were set to 26000619; 18348262; 28807865; 30631079
Likely inborn error of metabolism v2.57 GORAB Sarah Leigh Publications for gene: GORAB were set to 26000619
Congenital disorders of glycosylation v2.47 GORAB Sarah Leigh Publications for gene: GORAB were set to 26000619; 18348262; 28807865; 30631079
Likely inborn error of metabolism v2.56 GORAB Sarah Leigh Classified gene: GORAB as Amber List (moderate evidence)
Likely inborn error of metabolism v2.56 GORAB Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v2.56 GORAB Sarah Leigh Gene: gorab has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v2.55 GORAB Sarah Leigh Tag Q2_21_phenotype tag was added to gene: GORAB.
Congenital disorders of glycosylation v2.46 GORAB Sarah Leigh Classified gene: GORAB as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.46 GORAB Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital disorders of glycosylation v2.46 GORAB Sarah Leigh Gene: gorab has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v2.45 GORAB Sarah Leigh Tag Q2_21_phenotype tag was added to gene: GORAB.
Congenital disorders of glycosylation v2.45 GORAB Sarah Leigh Phenotypes for gene: GORAB were changed from Geroderma osteodysplasticum 231070 to Geroderma osteodysplasticum OMIM:231070; geroderma osteodysplastica MONDO:0009271
Congenital disorders of glycosylation v2.44 GORAB Sarah Leigh Publications for gene: GORAB were set to 26000619
Congenital disorders of glycosylation v2.43 G6PC3 Sarah Leigh Tag Q2_21_rating tag was added to gene: G6PC3.
Congenital disorders of glycosylation v2.43 G6PC3 Sarah Leigh Classified gene: G6PC3 as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.43 G6PC3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital disorders of glycosylation v2.43 G6PC3 Sarah Leigh Gene: g6pc3 has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v2.42 G6PC3 Sarah Leigh Publications for gene: G6PC3 were set to 19118303; 21385794
Congenital disorders of glycosylation v2.41 G6PC3 Sarah Leigh Publications for gene: G6PC3 were set to 21385794
Congenital disorders of glycosylation v2.40 G6PC3 Sarah Leigh reviewed gene: G6PC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Infantile enterocolitis & monogenic inflammatory bowel disease v1.19 G6PC3 Sarah Leigh Phenotypes for gene: G6PC3 were changed from Congenital neutropenia to Dursun syndrome OMIM:612541; Neutropenia, severe congenital 4, autosomal recessive OMIM:612541; autosomal recessive severe congenital neutropenia due to G6PC3 deficiency MONDO:0012930
Congenital disorders of glycosylation v2.40 G6PC3 Sarah Leigh Phenotypes for gene: G6PC3 were changed from Dursun syndrome 612541; Neutropenia, severe congenital 4, autosomal recessive 612541 to Dursun syndrome OMIM:612541; Neutropenia, severe congenital 4, autosomal recessive OMIM:612541; autosomal recessive severe congenital neutropenia due to G6PC3 deficiency MONDO:0012930
Early onset or syndromic epilepsy v2.289 FUK Sarah Leigh Phenotypes for gene: FUK were changed from Seizures; Generalized hypotonia; Feeding difficulties; Intellectual disability; Global developmental delay; Abnormality of vision; Congenital disorder of glycosylation with defective fucosylation 2, 618324 to Congenital disorder of glycosylation with defective fucosylation 2 OMIM:618324; congenital disorder of glycosylation with defective fucosylation 2 MONDO:0020777
Congenital disorders of glycosylation v2.39 FUK Sarah Leigh Phenotypes for gene: FUK were changed from Congenital disorder of glycosylation with defective fucosylation 2, MIM# 618324 to Congenital disorder of glycosylation with defective fucosylation 2 OMIM:618324; congenital disorder of glycosylation with defective fucosylation 2 MONDO:0020777
Congenital disorders of glycosylation v2.38 FUK Sarah Leigh edited their review of gene: FUK: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least three variants reported in two unrelated cases.; Changed rating: AMBER
Congenital disorders of glycosylation v2.38 FUK Sarah Leigh Classified gene: FUK as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.38 FUK Sarah Leigh Gene: fuk has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v2.37 FUK Sarah Leigh Tag watchlist tag was added to gene: FUK.
Congenital disorders of glycosylation v2.37 FUK Sarah Leigh commented on gene: FUK
Congenital disorders of glycosylation v2.37 FUK Sarah Leigh Tag new-gene-name tag was added to gene: FUK.
Congenital disorders of glycosylation v2.37 EOGT Sarah Leigh Phenotypes for gene: EOGT were changed from Adams-Oliver syndrome 4, MIM# 615297 to Adams-Oliver syndrome 4 OMIM:615297; Adams-Oliver syndrome 4 MONDO:0014124
Congenital disorders of glycosylation v2.36 EOGT Sarah Leigh Tag Q2_21_rating tag was added to gene: EOGT.
Congenital disorders of glycosylation v2.36 EOGT Sarah Leigh edited their review of gene: EOGT: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in five unrelated cases.; Changed rating: GREEN
Congenital disorders of glycosylation v2.36 EOGT Sarah Leigh Classified gene: EOGT as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.36 EOGT Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital disorders of glycosylation v2.36 EOGT Sarah Leigh Gene: eogt has been classified as Amber List (Moderate Evidence).
Arthrogryposis v3.69 SYNE1 Arina Puzriakova Phenotypes for gene: SYNE1 were changed from Emery-Dreifuss Muscular Dystrophy; Spinocerebellar ataxia, autosomal recessive 8, 610743 to Arthrogryposis multiplex congenita 3, myogenic type, OMIM:618484; Arthrogryposis multiplex congenita 3, myogenic type, MONDO:0032778
Arthrogryposis v3.68 SYNE1 Arina Puzriakova Mode of inheritance for gene: SYNE1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v2.35 B4GALNT1 Sarah Leigh Tag Q2_21_rating tag was added to gene: B4GALNT1.
Congenital disorders of glycosylation v2.35 B4GALNT1 Sarah Leigh Classified gene: B4GALNT1 as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.35 B4GALNT1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital disorders of glycosylation v2.35 B4GALNT1 Sarah Leigh Gene: b4galnt1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.764 B4GALNT1 Sarah Leigh Classified gene: B4GALNT1 as Green List (high evidence)
Intellectual disability v3.764 B4GALNT1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least eight variants reported in at least eight unrelated cases.
Intellectual disability v3.764 B4GALNT1 Sarah Leigh Gene: b4galnt1 has been classified as Green List (High Evidence).
Congenital disorders of glycosylation v2.34 B4GALNT1 Sarah Leigh reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.763 B4GALNT1 Sarah Leigh Publications for gene: B4GALNT1 were set to
Intellectual disability v3.762 B4GALNT1 Sarah Leigh Phenotypes for gene: B4GALNT1 were changed from ID; Spastic paraplegia 26, autosomal recessive to Spastic paraplegia 26, autosomal recessive OMIM:609195; hereditary spastic paraplegia 26 MONDO:0012213
Congenital disorders of glycosylation v2.34 B4GALNT1 Sarah Leigh Phenotypes for gene: B4GALNT1 were changed from Spastic paraplegia 26, autosomal recessive (MIM #609195) to Spastic paraplegia 26, autosomal recessive OMIM:609195; hereditary spastic paraplegia 26 MONDO:0012213
Arthrogryposis v3.67 SCN4A Arina Puzriakova Phenotypes for gene: SCN4A were changed from Congenital Myasthenic Syndrome, Recessive; Hyperkalemic periodic paralysis, type 2, 170500 to Myasthenic syndrome, congenital, 16, OMIM:614198, Congenital myasthenic syndrome 16, MONDO:0013620
Arthrogryposis v3.66 SCN4A Arina Puzriakova commented on gene: SCN4A
Likely inborn error of metabolism v2.55 TRAPPC11 Sarah Leigh Publications for gene: TRAPPC11 were set to 23830518; 26322222; 29855340; 30105108; 26912795; 27707803; 27862579; 28484880
Likely inborn error of metabolism v2.54 TRAPPC11 Sarah Leigh Phenotypes for gene: TRAPPC11 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 18 OMIM:615356; autosomal recessive limb-girdle muscular dystrophy type 2S MONDO:0014144 to Muscular dystrophy, limb-girdle, autosomal recessive 18 OMIM:615356; autosomal recessive limb-girdle muscular dystrophy type 2S MONDO:0014144
Likely inborn error of metabolism v2.53 TRAPPC11 Sarah Leigh Publications for gene: TRAPPC11 were set to 23830518; 26912795
Likely inborn error of metabolism v2.53 TRAPPC11 Sarah Leigh Phenotypes for gene: TRAPPC11 were changed from Muscular dystrophy, limb-girdle, type 2S to Muscular dystrophy, limb-girdle, autosomal recessive 18 OMIM:615356; autosomal recessive limb-girdle muscular dystrophy type 2S MONDO:0014144
Congenital disorders of glycosylation v2.33 TRAPPC11 Sarah Leigh Phenotypes for gene: TRAPPC11 were changed from Muscular dystrophy, limb-girdle, type 2S 615356 to Muscular dystrophy, limb-girdle, autosomal recessive 18 OMIM:615356; autosomal recessive limb-girdle muscular dystrophy type 2S MONDO:0014144
Congenital disorders of glycosylation v2.32 TRAPPC11 Sarah Leigh Deleted their comment
Congenital disorders of glycosylation v2.32 TRAPPC11 Sarah Leigh Added comment: Comment on phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 18 OMIM:615356;autosomal recessive limb-girdle muscular dystrophy type 2S MONDO:0014144
Congenital disorders of glycosylation v2.32 TRAPPC11 Sarah Leigh Phenotypes for gene: TRAPPC11 were changed from Muscular dystrophy, limb-girdle, type 2S 615356 to Muscular dystrophy, limb-girdle, type 2S 615356
Congenital disorders of glycosylation v2.31 TRAPPC11 Sarah Leigh Publications for gene: TRAPPC11 were set to 26912795; 23830518
Arthrogryposis v3.66 MYL1 Arina Puzriakova Publications for gene: MYL1 were set to
Arthrogryposis v3.65 MYL1 Arina Puzriakova Classified gene: MYL1 as Green List (high evidence)
Arthrogryposis v3.65 MYL1 Arina Puzriakova Added comment: Comment on list classification: Only mild contractures described in 1/2 individuals with variants in this gene. Therefore, there is only enough evidence for a RED rating on this panel at present. These cases would still expected to be picked up via the 'Congenital myopathy' or 'Fetal anomalies' routes for which this gene is Green.
Arthrogryposis v3.65 MYL1 Arina Puzriakova Gene: myl1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism v2.52 TRAPPC11 Sarah Leigh Classified gene: TRAPPC11 as Amber List (moderate evidence)
Likely inborn error of metabolism v2.52 TRAPPC11 Sarah Leigh Gene: trappc11 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v2.51 TRAPPC11 Sarah Leigh reviewed gene: TRAPPC11: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital disorders of glycosylation v2.30 TRAPPC11 Sarah Leigh edited their review of gene: TRAPPC11: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least four variants reported in four unrelated cases. Animal model suggestive of involvement in glycosylation.; Changed rating: AMBER
Arthrogryposis v3.64 MYL1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: MYL1.
Arthrogryposis v3.64 MYL1 Arina Puzriakova commented on gene: MYL1
Congenital disorders of glycosylation v2.30 TRAPPC11 Sarah Leigh Classified gene: TRAPPC11 as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.30 TRAPPC11 Sarah Leigh Gene: trappc11 has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v2.29 PIGW Sarah Leigh Tag Q2_21_rating tag was added to gene: PIGW.
Fetal anomalies v1.621 MYL9 Arina Puzriakova Publications for gene: MYL9 were set to 29453416
Fetal anomalies v1.620 MYL9 Arina Puzriakova Classified gene: MYL9 as Amber List (moderate evidence)
Fetal anomalies v1.620 MYL9 Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber as there are now two unrelated families presenting features of MMIHS, associated with different biallelic variants in the MYL9 gene (PMIDs: 29453416; 33031641).

Additional cases/functional evidence required prior to inclusion as diagnostic-grade.
Fetal anomalies v1.620 MYL9 Arina Puzriakova Gene: myl9 has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v2.29 PIGW Sarah Leigh edited their review of gene: PIGW: Added comment: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least six variants reported in at least four unrelated cases.; Changed rating: GREEN
Fetal anomalies v1.619 GDF6 Arina Puzriakova Phenotypes for gene: GDF6 were changed from MICROPHTHALMIA ISOLATED TYPE 4; KLIPPEL-FEIL SYNDROME TYPE 1 to MICROPHTHALMIA ISOLATED TYPE 4; KLIPPEL-FEIL SYNDROME TYPE 1; Syndromic CAKUT
Fetal anomalies v1.618 GDF6 Arina Puzriakova Publications for gene: GDF6 were set to
Congenital disorders of glycosylation v2.29 PIGW Sarah Leigh Classified gene: PIGW as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.29 PIGW Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital disorders of glycosylation v2.29 PIGW Sarah Leigh Gene: pigw has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v2.28 PIGW Sarah Leigh Phenotypes for gene: PIGW were changed from ?Hyperphosphatasia with mental retardation syndrome 5 616025 to Glycosylphosphatidylinositol biosynthesis defect 11 OMIM:616025; hyperphosphatasia with intellectual disability syndrome 5 MONDO:0014457
Congenital disorders of glycosylation v2.27 PIGW Sarah Leigh Publications for gene: PIGW were set to 24367057
Fetal anomalies v1.617 SLC20A1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: SLC20A1.
Fetal anomalies v1.617 SLC20A1 Arina Puzriakova Classified gene: SLC20A1 as Amber List (moderate evidence)
Fetal anomalies v1.617 SLC20A1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Rating Amber but there is sufficient evidence to promote to Green.

At least three unrelated families with a BEEC phenotype (fetally-relevant) and different heterozygous variants in this gene (PMID: 32850778). In vitro assays and zebrafish model support pathogenicity.
Fetal anomalies v1.617 SLC20A1 Arina Puzriakova Gene: slc20a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v2.51 ACSF3 Zornitza Stark reviewed gene: ACSF3: Rating: AMBER; Mode of pathogenicity: None; Publications: 21841779, 30740739; Phenotypes: Combined malonic and methylmalonic aciduria MIM#614265; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v2.51 AASS Zornitza Stark reviewed gene: AASS: Rating: AMBER; Mode of pathogenicity: None; Publications: 23570448; Phenotypes: Hyperlysinemia, MIM# 238700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.761 PIGF Zornitza Stark gene: PIGF was added
gene: PIGF was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: PIGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGF were set to 33386993
Phenotypes for gene: PIGF were set to Glycosylphosphatidylinositol deficiency, onychodystrophy, osteodystrophy, intellectual disability, and seizures
Review for gene: PIGF was set to RED
Added comment: The same homozygous missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness. Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated.

Rated Red as the two families are likely to be related (founder mutation?).
Sources: Literature
Laterality disorders and isomerism v1.21 BRWD1 Zornitza Stark gene: BRWD1 was added
gene: BRWD1 was added to Laterality disorders and isomerism. Sources: Literature
Mode of inheritance for gene: BRWD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRWD1 were set to 33389130
Phenotypes for gene: BRWD1 were set to Primary ciliary dyskinesia, asthenoteratozoospermia
Review for gene: BRWD1 was set to GREEN
Added comment: Biallelic missense variants reported in 3 unrelated individuals. Apart from asthenoteratozoospermia, all 3 had PCD or "PCD-like" symptoms of reccurring airway infections, bronchiectasis, and rhinosinusitis. One individual had situs inversus. Studies on cells from one indivdidual showed abnormal respiratory cilia structure. BRWD1 staining was absent from respiratory cilia in this individual (present in controls).
Sources: Literature
Likely inborn error of metabolism v2.51 PNPLA2 Zornitza Stark gene: PNPLA2 was added
gene: PNPLA2 was added to Inborn errors of metabolism. Sources: Expert Review
Mode of inheritance for gene: PNPLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA2 were set to 18952067; 25287355; 25956450
Phenotypes for gene: PNPLA2 were set to Neutral lipid storage disease with myopathy MIM#610717
Review for gene: PNPLA2 was set to GREEN
Added comment: PLPLA2 is a triglyceride lipase and this is a lipid storage disorder.
Sources: Expert Review
Likely inborn error of metabolism v2.51 POMK Zornitza Stark gene: POMK was added
gene: POMK was added to Inborn errors of metabolism. Sources: Expert Review
Mode of inheritance for gene: POMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMK were set to 23519211; 24556084; 24925318
Phenotypes for gene: POMK were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 (MIM #615249)
Review for gene: POMK was set to GREEN
gene: POMK was marked as current diagnostic
Added comment: Other enzyme deficiencies causing dystroglycanopathies are included in the panel.
Sources: Expert Review
Clefting v2.24 ACBD5 Zornitza Stark reviewed gene: ACBD5: Rating: RED; Mode of pathogenicity: None; Publications: 27799409, 23105016, 33427402; Phenotypes: Retinal dystrophy with leukodystrophy, MIM# 618863; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare multisystem ciliopathy disorders v1.139 LAMA1 John Sayer gene: LAMA1 was added
gene: LAMA1 was added to Rare multisystem ciliopathy disorders. Sources: Expert Review
Mode of inheritance for gene: LAMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA1 were set to https://www.ncbi.nlm.nih.gov/pubmed/25105227
Phenotypes for gene: LAMA1 were set to cerebellar cysts; myopia; cerebellar vermis hypoplasia; gaze palsy; retinitis pigments
Penetrance for gene: LAMA1 were set to Complete
Review for gene: LAMA1 was set to GREEN
Added comment: LAMA1 causes Poretti-Boltshauser syndrome - but this is often misdiagnosed as Joubert syndrome so the ciliopathies panel needs to include LAMA1
Sources: Expert Review
Ataxia and cerebellar anomalies - narrow panel v2.39 LAMA1 John Sayer reviewed gene: LAMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://www.ncbi.nlm.nih.gov/pubmed/25105227; Phenotypes: cerebellar dysplasia, cerebellar vermis atrophy, myopia, cerebellar cysts, abnormal eye movements; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.761 DDX58 Arina Puzriakova reviewed gene: DDX58: Rating: ; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.761 DDX58 Arina Puzriakova Mode of inheritance for gene: DDX58 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v1.47 DDX58 Arina Puzriakova Publications for gene: DDX58 were set to 25620203; 30574673
Structural eye disease v1.46 DDX58 Arina Puzriakova Phenotypes for gene: DDX58 were changed from Atypical Singleton-Merton syndrome (AD) - glaucoma and skeletal abnormalities. to Singleton-Merten syndrome 2, OMIM:616298; Singleton-Merten syndrome 2, MONDO:0014575
Structural eye disease v1.45 DDX58 Arina Puzriakova Mode of pathogenicity for gene: DDX58 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
Structural eye disease v1.44 DDX58 Arina Puzriakova edited their review of gene: DDX58: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Structural eye disease v1.44 DDX58 Arina Puzriakova reviewed gene: DDX58: Rating: GREEN; Mode of pathogenicity: None; Publications: 25620203, 30574673, 33495304; Phenotypes: Singleton-Merten syndrome 2, OMIM:616298, Singleton-Merten syndrome 2, MONDO:0014575; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Glaucoma (developmental) v1.12 DDX58 Arina Puzriakova Publications for gene: DDX58 were set to 2509; 3588; 25620203
Glaucoma (developmental) v1.11 DDX58 Arina Puzriakova Classified gene: DDX58 as Green List (high evidence)
Glaucoma (developmental) v1.11 DDX58 Arina Puzriakova Added comment: Comment on list classification: At least 4 gain-of-function variants identified in 5 unrelated families with Singleton-Merten syndrome 2, including glaucoma in all affected individuals (PMIDs: 25620203; 30574673; 33495304). Therefore, this now reaches threshold for a rating upgrade from Amber to Green.
Glaucoma (developmental) v1.11 DDX58 Arina Puzriakova Gene: ddx58 has been classified as Green List (High Evidence).
Glaucoma (developmental) v1.10 DDX58 Arina Puzriakova reviewed gene: DDX58: Rating: GREEN; Mode of pathogenicity: None; Publications: 25620203, 30574673, 33495304; Phenotypes: Singleton-Merten syndrome 2, OMIM:616298, Singleton-Merten syndrome 2, MONDO:0014575; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v2.30 FDXR Ivone Leong Publications for gene: FDXR were set to 30250212; 28965846; 29040572; 32499495
Differences in sex development v2.16 ISCA-46302-Gain Catherine Snow Tag for-review tag was added to Region: ISCA-46302-Gain.
Differences in sex development v2.16 ISCA-46302-Gain Catherine Snow Classified Region: ISCA-46302-Gain as Amber List (moderate evidence)
Differences in sex development v2.16 ISCA-46302-Gain Catherine Snow Added comment: Comment on list classification: Addition of region inline with ClinGen regions classifications. Reviewed by GEL clinical team for panel phenotype, NR0B1 green on panel so CNV should be added too and phenotype of gonadal dysgenesis relevant to this panel.
Differences in sex development v2.16 ISCA-46302-Gain Catherine Snow Region: isca-46302-gain has been classified as Amber List (Moderate Evidence).
Differences in sex development v2.15 ISCA-46302-Gain Catherine Snow Region: ISCA-46302-Gain was added
Region: ISCA-46302-Gain was added to Disorders of sex development. Sources: ClinGen
Mode of inheritance for Region: ISCA-46302-Gain was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for Region: ISCA-46302-Gain were set to 22518125; 17504899; 20685758
Phenotypes for Region: ISCA-46302-Gain were set to gonadal dysgenesis
Review for Region: ISCA-46302-Gain was set to AMBER
Added comment: Sources: ClinGen
Fetal anomalies v1.616 ISCA-46302-Gain Catherine Snow Classified Region: ISCA-46302-Gain as Amber List (moderate evidence)
Fetal anomalies v1.616 ISCA-46302-Gain Catherine Snow Region: isca-46302-gain has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.615 ISCA-46302-Gain Catherine Snow changed review comment from: Addition of region inline with ClinGen region. Reviewed by GEL clinical for application for panel the phenotype, may escape detection in fetal life. The fetal team have rated the gene NR0B1 green, the CNV should be added too.
Sources: ClinGen; to: Addition of region inline with ClinGen regions classifications. Reviewed by GEL clinical team for panel phenotype, noted that this may escape detection in fetal life, however as the fetal team have rated the gene NR0B1 green, the CNV should be added too.
Sources: ClinGen
Fetal anomalies v1.615 ISCA-46302-Gain Catherine Snow Classified Region: ISCA-46302-Gain as Red List (low evidence)
Fetal anomalies v1.615 ISCA-46302-Gain Catherine Snow Region: isca-46302-gain has been classified as Red List (Low Evidence).
Fetal anomalies v1.614 ISCA-46302-Gain Catherine Snow Region: ISCA-46302-Gain was added
Region: ISCA-46302-Gain was added to Fetal anomalies. Sources: ClinGen
for-review tags were added to Region: ISCA-46302-Gain.
Mode of inheritance for Region: ISCA-46302-Gain was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for Region: ISCA-46302-Gain were set to 22518125; 17504899; 20685758
Phenotypes for Region: ISCA-46302-Gain were set to gonadal dysgenesis
Review for Region: ISCA-46302-Gain was set to AMBER
Added comment: Addition of region inline with ClinGen region. Reviewed by GEL clinical for application for panel the phenotype, may escape detection in fetal life. The fetal team have rated the gene NR0B1 green, the CNV should be added too.
Sources: ClinGen
Early onset or syndromic epilepsy v2.288 HPDL Evan Reid gene: HPDL was added
gene: HPDL was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to PMID: 32707086; 33188300
Phenotypes for gene: HPDL were set to spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability
Penetrance for gene: HPDL were set to Complete
Review for gene: HPDL was set to GREEN
Added comment: Newly identified gene that can give a phenotype ranging from infantile epileptic encephalopathy to juvenile onset progressive spastic paraplegia.
Sources: Literature
Intellectual disability v3.760 HPDL Evan Reid gene: HPDL was added
gene: HPDL was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to PMID: 32707086; 33188300
Phenotypes for gene: HPDL were set to spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability
Penetrance for gene: HPDL were set to Complete
Review for gene: HPDL was set to GREEN
Added comment: Newly identified gene that can give a phenotype ranging from infantile epileptic encephalopathy with severe developmental delay/intellectual disability to juvenile onset progressive spastic paraplegia.
Sources: Literature
Childhood onset hereditary spastic paraplegia v2.25 HPDL Evan Reid gene: HPDL was added
gene: HPDL was added to Hereditary spastic paraplegia - childhood onset. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to PMID: 32707086; 33188300
Phenotypes for gene: HPDL were set to spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual and motor disability
Penetrance for gene: HPDL were set to Complete
Review for gene: HPDL was set to GREEN
Added comment: Newly identified gene that can give a phenotype ranging from infantile epileptic encephalopathy to juvenile onset progressive spastic paraplegia.
Sources: Literature
Glaucoma (developmental) v1.10 DDX58 Arina Puzriakova Phenotypes for gene: DDX58 were changed from Atypical Singleton-Merton syndrome (AD) - glaucoma and skeletal abnormalities. to Singleton-Merten syndrome 2, OMIM:616298; Singleton-Merten syndrome 2, MONDO:0014575
Skeletal dysplasia v2.81 TBXAS1 Ivone Leong Tag for-review tag was added to gene: TBXAS1.
Optic neuropathy v2.29 FDXR Neringa Jurkute reviewed gene: FDXR: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 28965846, 32499495, 30250212, 33348459, 29040572; Phenotypes: Optic atrophy and sensorineural hearing loss, mitochondrial disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Endocrine neoplasia v1.12 EGFR Eleanor Williams Classified gene: EGFR as Amber List (moderate evidence)
Endocrine neoplasia v1.12 EGFR Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. More than one case of patient with ACC and germline variants in EGFR. But no family history/segregation data to further confirm the disease association.
Endocrine neoplasia v1.12 EGFR Eleanor Williams Gene: egfr has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.29 SSBP1 Neringa Jurkute reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 31298765, PMID: 31550240, PMID: 31550237, PMID: 30412255; Phenotypes: Optic atrophy with retinal degeneration (+-systemic features); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leber hereditary optic neuropathy v1.7 DNAJC30 Neringa Jurkute reviewed gene: DNAJC30: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33465056; Phenotypes: LHON-like; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leber hereditary optic neuropathy v1.7 DNAJC30 Neringa Jurkute Deleted their review
Skeletal dysplasia v2.81 GZF1 Ivone Leong Tag for-review tag was added to gene: GZF1.
Fetal anomalies v1.613 SCLT1 Ivone Leong Tag for-review tag was added to gene: SCLT1.
Fetal anomalies v1.613 CASR Ivone Leong Tag for-review tag was added to gene: CASR.
Endocrine neoplasia v1.11 EGFR Eleanor Williams changed review comment from: PMID: 33326033 - Akhavanfard et al 2020 - identified a heterozygous germline variant in EGFR (c.3238 G>A, p.Asp1080Asn) in a 21 year old female with metastatic bilateral Adrenocortical carcinoma (ACC). Then they analyzed germline exome data from 21 children, 32 adolescents and young adults (15-39y), and 60 adult participants with ACC. 3.5% of all 113 ACC cases had at least a highly prioritized VUS germline EGFR variant, compared to only 0.3% in a non-TCGA (The Cancer Genome Atlas) ExAC control group (P < 0.0001). No segregation data.
Sources: Literature; to: PMID: 33326033 - Akhavanfard et al 2020 - identified a heterozygous germline variant in EGFR (c.3238 G>A, p.Asp1080Asn) in a 21 year old female with metastatic bilateral Adrenocortical carcinoma (ACC). Then they analyzed germline exome data from 21 children, 32 adolescents and young adults (15-39y), and 60 adult participants with ACC. 3.5% of all 113 ACC cases had at least a highly prioritized VUS germline EGFR variant, compared to only 0.3% in a non-TCGA (The Cancer Genome Atlas) ExAC control group (P < 0.0001). In the adolescents and young adults group 6.2% had ECGR variants. No segregation data.
Sources: Literature
Endocrine neoplasia v1.11 EGFR Eleanor Williams gene: EGFR was added
gene: EGFR was added to Endocrine neoplasms. Sources: Literature
Mode of inheritance for gene: EGFR was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EGFR were set to 33326033
Phenotypes for gene: EGFR were set to Adrenocortical carcinoma
Review for gene: EGFR was set to AMBER
Added comment: PMID: 33326033 - Akhavanfard et al 2020 - identified a heterozygous germline variant in EGFR (c.3238 G>A, p.Asp1080Asn) in a 21 year old female with metastatic bilateral Adrenocortical carcinoma (ACC). Then they analyzed germline exome data from 21 children, 32 adolescents and young adults (15-39y), and 60 adult participants with ACC. 3.5% of all 113 ACC cases had at least a highly prioritized VUS germline EGFR variant, compared to only 0.3% in a non-TCGA (The Cancer Genome Atlas) ExAC control group (P < 0.0001). No segregation data.
Sources: Literature
Intellectual disability v3.760 TCTN3 Arina Puzriakova Publications for gene: TCTN3 were set to
Intellectual disability v3.759 TCTN3 Arina Puzriakova changed review comment from: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag).

At least 3 unrelated cases with Joubert syndrome, presenting with ID, and biallelic variants in this gene (PMIDs: 22883145; 25118024; 26092869); to: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag).

Independent reports of at least 3 unrelated cases with Joubert syndrome, presenting with ID, and different biallelic variants in this gene (PMIDs: 22883145; 25118024; 26092869)
Intellectual disability v3.759 TCTN3 Arina Puzriakova Classified gene: TCTN3 as Amber List (moderate evidence)
Intellectual disability v3.759 TCTN3 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag).

At least 3 unrelated cases with Joubert syndrome, presenting with ID, and biallelic variants in this gene (PMIDs: 22883145; 25118024; 26092869)
Intellectual disability v3.759 TCTN3 Arina Puzriakova Gene: tctn3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v2.288 PMPCB Ivone Leong Tag for-review was removed from gene: PMPCB.
Fetal anomalies v1.613 PRUNE1 Eleanor Williams Publications for gene: PRUNE1 were set to
Severe microcephaly v2.100 PRUNE1 Eleanor Williams Publications for gene: PRUNE1 were set to Brain 2017 awx014. doi: 10.1093/brain/awx014
Severe microcephaly v2.99 PRUNE1 Eleanor Williams Phenotypes for gene: PRUNE1 were changed from microcephaly, spasticity, developmental delay to microcephaly, spasticity, developmental delay; Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies OMIM:617481; neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MONDO:0060490
Severe microcephaly v2.98 PRUNE1 Eleanor Williams reviewed gene: PRUNE1: Rating: ; Mode of pathogenicity: None; Publications: 33105479; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.758 PRUNE1 Eleanor Williams Phenotypes for gene: PRUNE1 were changed from Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies, 617481; NMIHBA; Complex neurological syndrome to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies OMIM:617481; neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MONDO:0060490; NMIHBA; Complex neurological syndrome
Intellectual disability v3.757 PRUNE1 Eleanor Williams Publications for gene: PRUNE1 were set to 26539891; 28334956
Intellectual disability v3.756 PRUNE1 Eleanor Williams reviewed gene: PRUNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33105479; Phenotypes: Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies OMIM:617481, neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MONDO:0060490; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.756 TCTN3 Arina Puzriakova Tag for-review tag was added to gene: TCTN3.
Bilateral congenital or childhood onset cataracts v2.62 VPS4A Arina Puzriakova Added comment: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline.
Bilateral congenital or childhood onset cataracts v2.62 VPS4A Arina Puzriakova Mode of inheritance for gene: VPS4A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset dystonia, chorea or related movement disorder v1.83 VPS4A Arina Puzriakova Added comment: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline.
Childhood onset dystonia, chorea or related movement disorder v1.83 VPS4A Arina Puzriakova Mode of inheritance for gene: VPS4A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bilateral congenital or childhood onset cataracts v2.61 VPS4A Arina Puzriakova Classified gene: VPS4A as Amber List (moderate evidence)
Bilateral congenital or childhood onset cataracts v2.61 VPS4A Arina Puzriakova Added comment: Comment on list classification: At least 5 different variants reported in 10 unrelated individuals with a comparable phenotype, including congenital/early-onset cataracts in 6/10 cases. Pathogenicity is supported by functional data.

There are sufficient cases to promote this gene to Green at the next GMS panel update (added 'for-review' tag)
Bilateral congenital or childhood onset cataracts v2.61 VPS4A Arina Puzriakova Gene: vps4a has been classified as Amber List (Moderate Evidence).
Bilateral congenital or childhood onset cataracts v2.60 VPS4A Arina Puzriakova gene: VPS4A was added
gene: VPS4A was added to Cataracts. Sources: Expert Review
for-review tags were added to gene: VPS4A.
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to 33186545; 33186543; 33460484
Phenotypes for gene: VPS4A were set to CIMDAG syndrome
Review for gene: VPS4A was set to GREEN
Added comment: Gene currently not associated with any phenotype in OMIM (last edited: 20/12/2019) or Gene2Phenotype.

- PMID: 33186545 (2020) - Six unrelated individuals with de novo missense variants (c.850A>T, c.850A>G, c.616G>A) affecting the ATPase domain of VPS4A. Clinical features include severe DD and profound ID (6/6), hypotonia (5/6), microcephaly (6/6), dystonia (5/6), congenital cataracts (4/5), epilepsy (3/6), anaemia (3/6 - dyserythropoietic in 2), and structural brain abnormalities including cerebellar hypoplasia (5/6) or severe cerebral atrophy (1/6). Some functional data indicating a dominant-negative effect.

- PMID: 33186543 (2020) - Three unrelated individuals with congenital dyserythropoietic anaemia, severe neurodevelopmental delay, and dystonia. Two patients harboured different de novo variants (c.850A>T, c.608G>A) in the ATPase domain, while the third had a homozygous alteration (c.83C>T) occurring in the N-terminal microtubule interacting and trafficking domain of VPS4A. The first two individuals congenital microcephaly with brain MRI showing white matter and cerebral volume loss, thin corpus callosum, and ponto-cerebellar atrophy. One individual also displayed a seizure disorder and congenital cataracts. The case with the biallelic variant presented with a milder hematologic phenotype and had macrocephaly (rather than microcephaly) and delayed white matter myelination. Functional studies support pathogenicity.

- PMID: 33460484 (2021) - One child with a a severe neurodevelopmental disorder and congenital haemolytic anaemia but no overt sign of dyserythropoiesis, associated with a de novo variant (c.850A>T) in VPS4A. Other features include microcephaly (-2.5 SD), choreodystonic movements, and bilateral cataract. Brain MRI showed cerebral atrophy, thin dysplastic corpus callosum, basal ganglia atrophy, brainstem hypoplasia, cerebellar hypoplasia and dysplasia
Sources: Expert Review
Childhood onset dystonia, chorea or related movement disorder v1.82 VPS4A Arina Puzriakova Classified gene: VPS4A as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.82 VPS4A Arina Puzriakova Added comment: Comment on list classification: At least 5 different variants reported in 10 unrelated individuals with a comparable phenotype, including childhood onset dystonia in 9/10 cases. Pathogenicity is supported by functional data.

There is enough evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag)
Childhood onset dystonia, chorea or related movement disorder v1.82 VPS4A Arina Puzriakova Gene: vps4a has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.81 VPS4A Arina Puzriakova gene: VPS4A was added
gene: VPS4A was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert Review
for-review tags were added to gene: VPS4A.
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to 33186545; 33186543; 33460484
Phenotypes for gene: VPS4A were set to CIMDAG syndrome
Review for gene: VPS4A was set to GREEN
Added comment: Gene currently not associated with any phenotype in OMIM (last edited: 20/12/2019) or Gene2Phenotype.

- PMID: 33186545 (2020) - Six unrelated individuals with de novo missense variants (c.850A>T, c.850A>G, c.616G>A) affecting the ATPase domain of VPS4A. Clinical features include severe DD and profound ID (6/6), hypotonia (5/6), microcephaly (6/6), dystonia (5/6), congenital cataracts (4/5), epilepsy (3/6), anaemia (3/6 - dyserythropoietic in 2), and structural brain abnormalities including cerebellar hypoplasia (5/6) or severe cerebral atrophy (1/6). Some functional data indicating a dominant-negative effect.

- PMID: 33186543 (2020) - Three unrelated individuals with congenital dyserythropoietic anaemia, severe neurodevelopmental delay, and dystonia. Two patients harboured different de novo variants (c.850A>T, c.608G>A) in the ATPase domain, while the third had a homozygous alteration (c.83C>T) occurring in the N-terminal microtubule interacting and trafficking domain of VPS4A. The first two individuals congenital microcephaly with brain MRI showing white matter and cerebral volume loss, thin corpus callosum, and ponto-cerebellar atrophy. One individual also displayed a seizure disorder and congenital cataracts. The case with the biallelic variant presented with a milder hematologic phenotype and had macrocephaly (rather than microcephaly) and delayed white matter myelination. Functional studies support pathogenicity.

- PMID: 33460484 (2021) - One child with a a severe neurodevelopmental disorder and congenital haemolytic anaemia but no overt sign of dyserythropoiesis, associated with a de novo variant (c.850A>T) in VPS4A. Other features include microcephaly (-2.5 SD), choreodystonic movements, and bilateral cataract. Brain MRI showed cerebral atrophy, thin dysplastic corpus callosum, basal ganglia atrophy, brainstem hypoplasia, cerebellar hypoplasia and dysplasia
Sources: Expert Review
Rare anaemia v1.13 VPS4A Arina Puzriakova Classified gene: VPS4A as Amber List (moderate evidence)
Rare anaemia v1.13 VPS4A Arina Puzriakova Added comment: Comment on list classification: New gene added by Evan Reid (University of Cambridge). At least 5 different variants reported in 10 unrelated individuals with a comparable phenotype, including haemolytic anaemia in 7/10 cases. Pathogenicity is supported by functional data.

There is enough evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag)
Rare anaemia v1.13 VPS4A Arina Puzriakova Gene: vps4a has been classified as Amber List (Moderate Evidence).
Rare anaemia v1.12 VPS4A Arina Puzriakova Publications for gene: VPS4A were set to (PMID: 33186545; 33186543; 33460484)
Rare anaemia v1.11 VPS4A Arina Puzriakova Added comment: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline.
Rare anaemia v1.11 VPS4A Arina Puzriakova Mode of inheritance for gene: VPS4A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare anaemia v1.10 VPS4A Arina Puzriakova reviewed gene: VPS4A: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 33186545, 33186543, 33460484; Phenotypes: CIMDAG syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v3.756 VPS4A Arina Puzriakova edited their review of gene: VPS4A: Changed publications: 33186545, 33186543, 33460484
Intellectual disability v3.756 VPS4A Arina Puzriakova Classified gene: VPS4A as Amber List (moderate evidence)
Intellectual disability v3.756 VPS4A Arina Puzriakova Added comment: Comment on list classification: New gene added by Evan Reid (University of Cambridge). At least 5 different variants reported in 10 unrelated individuals with a comparable phenotype, including severe-to-profound ID/DD. Pathogenicity is supported by functional data.

There is enough evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag)
Intellectual disability v3.756 VPS4A Arina Puzriakova Gene: vps4a has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.755 VPS4A Arina Puzriakova Added comment: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline.
Intellectual disability v3.755 VPS4A Arina Puzriakova Mode of inheritance for gene: VPS4A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.754 VPS4A Arina Puzriakova reviewed gene: VPS4A: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 33186545, 33186543; Phenotypes: CIMDAG syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare anaemia v1.10 VPS4A Ivone Leong Tag for-review tag was added to gene: VPS4A.
Rare anaemia v1.10 VPS4A Ivone Leong Classified gene: VPS4A as Amber List (moderate evidence)
Rare anaemia v1.10 VPS4A Ivone Leong Gene: vps4a has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.754 VPS4A Ivone Leong Tag for-review tag was added to gene: VPS4A.
Intellectual disability v3.754 VPS4A Ivone Leong Classified gene: VPS4A as Amber List (moderate evidence)
Intellectual disability v3.754 VPS4A Ivone Leong Gene: vps4a has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.753 VPS4A Ivone Leong Publications for gene: VPS4A were set to (PMID: 33186545; 33186543; 33460484)
Haematological malignancies cancer susceptibility v2.15 CSF3R Arina Puzriakova Classified gene: CSF3R as Red List (low evidence)
Haematological malignancies cancer susceptibility v2.15 CSF3R Arina Puzriakova Added comment: Comment on list classification: New gene added by Kiran Tawana (Addenbrooke's Hospital, Cambridge). Rating Red as increased risk of AML due to CSF3R is associated with acquired rather than hereditary variants. One individual from PMID: 19620628 did develop a myelodysplastic syndrome, however this is not sufficient to promote this gene at present.
Haematological malignancies cancer susceptibility v2.15 CSF3R Arina Puzriakova Gene: csf3r has been classified as Red List (Low Evidence).
Haematological malignancies cancer susceptibility v2.14 CSF3R Arina Puzriakova Phenotypes for gene: CSF3R were changed from MDS; Myeloma; B-ALL to Acute myeloid leukaemia; Hereditary neutrophilia; Neutropenia, severe congenital, 7, autosomal recessive, OMIM:617014
Haematological malignancies cancer susceptibility v2.13 CSF3R Arina Puzriakova Publications for gene: CSF3R were set to PMID: 27939403
Haematological malignancies cancer susceptibility v2.12 CSF3R Arina Puzriakova Tag somatic tag was added to gene: CSF3R.
Haematological malignancies cancer susceptibility v2.12 CSF3R Arina Puzriakova reviewed gene: CSF3R: Rating: ; Mode of pathogenicity: None; Publications: 19620628, 12203110, 24753537, 26324699; Phenotypes: Acute myeloid leukaemia, Hereditary neutrophilia, Neutropenia, severe congenital, 7, autosomal recessive, OMIM:617014; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Haematological malignancies cancer susceptibility v2.12 MBD4 Arina Puzriakova Classified gene: MBD4 as Amber List (moderate evidence)
Haematological malignancies cancer susceptibility v2.12 MBD4 Arina Puzriakova Added comment: Comment on list classification: New gene added by Kiran Tawana (Addenbrooke's Hospital, Cambridge) with a Green expert review rating.

Studies indicate that while germline MBD4 deficiency alone does not drive malignant transformation, it may alter the mutational spectrum and in turn modify susceptibility and predisposition to cancers such as AML.

Therefore, rating this gene as Amber with the recommendation of review by the GMS team with regards to whether such alterations are within the scope of this panel (added 'for-review' tag)
Haematological malignancies cancer susceptibility v2.12 MBD4 Arina Puzriakova Gene: mbd4 has been classified as Amber List (Moderate Evidence).
Haematological malignancies cancer susceptibility v2.11 MBD4 Arina Puzriakova Tag for-review tag was added to gene: MBD4.
Haematological malignancies cancer susceptibility v2.11 MBD4 Arina Puzriakova reviewed gene: MBD4: Rating: ; Mode of pathogenicity: None; Publications: 30049810; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Haematological malignancies cancer susceptibility v2.11 IKZF1 Arina Puzriakova edited their review of gene: IKZF1: Changed publications: 26981933, 28096536, 29889099, 29681510
Haematological malignancies cancer susceptibility v2.11 IKZF1 Arina Puzriakova Publications for gene: IKZF1 were set to PMID: 29681510; PMID: 29889099; PMID: 27939403
Haematological malignancies cancer susceptibility v2.10 IKZF1 Arina Puzriakova Classified gene: IKZF1 as Amber List (moderate evidence)
Haematological malignancies cancer susceptibility v2.10 IKZF1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Kiran Tawana (Addenbrooke's Hospital, Cambridge). Several studies indicate that coding germline IKZF1 variants are a risk factor for genetic predisposition to ALL. Therefore, this gene may be promoted to Green at the next panel update following GMS review (added 'for-review' tag)
Haematological malignancies cancer susceptibility v2.10 IKZF1 Arina Puzriakova Gene: ikzf1 has been classified as Amber List (Moderate Evidence).
Haematological malignancies cancer susceptibility v2.9 IKZF1 Arina Puzriakova Tag for-review tag was added to gene: IKZF1.
Haematological malignancies cancer susceptibility v2.9 IKZF1 Arina Puzriakova reviewed gene: IKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26981933, 28096536, 29681510; Phenotypes: Acute lymphoblastic leukemia (ALL), Immunodeficiency, common variable, 13, OMIM:616873; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Respiratory ciliopathies including non-CF bronchiectasis v1.43 CFTR Matthew Edwards reviewed gene: CFTR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Haematological malignancies cancer susceptibility v2.9 IKZF1 Arina Puzriakova Phenotypes for gene: IKZF1 were changed from B-ALL; immunodeficiency, autoimmunity to Acute lymphoblastic leukaemia (ALL); Immunodeficiency, common variable, 13, OMIM:616873
Haematological malignancies cancer susceptibility v2.8 DNAJC21 Arina Puzriakova Tag for-review tag was added to gene: DNAJC21.
Haematological malignancies cancer susceptibility v2.8 DNAJC21 Arina Puzriakova Publications for gene: DNAJC21 were set to PMID: 27346687; PMID: 29700810
Haematological malignancies cancer susceptibility v2.7 DNAJC21 Arina Puzriakova Classified gene: DNAJC21 as Amber List (moderate evidence)
Haematological malignancies cancer susceptibility v2.7 DNAJC21 Arina Puzriakova Added comment: Comment on list classification: New gene added by Kiran Tawana (Addenbrooke's Hospital, Cambridge) with a Green expert review rating.

Biallelic variants in the DNAJC21 gene are associated with bone marrow failure syndrome-3 (MIM# 617052). At least 15 individuals reported in literature (PMIDs: 27346687; 28062395; 29146883; 29700810), of which only one developed acute myeloid leukaemia (AML-M7), at the age of 12 years (P3 in PMID: 27346687). However, it should be considered that the remaining cases were all children (14 mo - 14 yrs of age) and so the risk of malignancy later in life remains.

BMF syndromes can be associated with an increased cancer risk, and in parallel with the Green expert review, DNAJC21 will be flagged for GMS review to assess whether there is substantial evidence to rate this gene Green on this panel.
Haematological malignancies cancer susceptibility v2.7 DNAJC21 Arina Puzriakova Gene: dnajc21 has been classified as Amber List (Moderate Evidence).
Haematological malignancies cancer susceptibility v2.6 DNAJC21 Arina Puzriakova Phenotypes for gene: DNAJC21 were changed from bone marrow failure; AML; developmental delay; pancreatic insufficiency, overlap with SBDS to Bone marrow failure syndrome 3, OMIM:617052; Bone marrow failure syndrome 3, MONDO:0014887
Intellectual disability v3.752 ADAM22 Sarah Leigh Phenotypes for gene: ADAM22 were changed from to ?Epileptic encephalopathy, early infantile, 61 OMIM:617933; developmental and epileptic encephalopathy, 61 MONDO:0033370
Intellectual disability v3.751 ADAM22 Sarah Leigh Tag for-review tag was added to gene: ADAM22.
Intellectual disability v3.751 ADAM22 Sarah Leigh reviewed gene: ADAM22: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v2.288 ADAM22 Sarah Leigh Tag for-review tag was added to gene: ADAM22.
Early onset or syndromic epilepsy v2.288 ADAM22 Sarah Leigh reviewed gene: ADAM22: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v2.288 ADAM22 Sarah Leigh Phenotypes for gene: ADAM22 were changed from ?Epileptic encephalopathy, early infantile, 61 OMIM:617933 to ?Epileptic encephalopathy, early infantile, 61 OMIM:617933; developmental and epileptic encephalopathy, 61 MONDO:0033370
Early onset or syndromic epilepsy v2.287 ADAM22 Sarah Leigh Tag watchlist tag was added to gene: ADAM22.
Fetal anomalies v1.612 SUFU Arina Puzriakova changed review comment from: The patients described by Schroder et al 2020 (PMID: 33024317) display cerebellar abnormalities that were said to be within the milder range of the Joubert clinical spectrum. This gene will be flagged for review by the GMS team with regards to whether these features may conceivably be detected prenatally (added 'for-review' tag).

Note that these individuals harboured heterozygous truncating variants, and monoallelic variants in this gene have also previously been associated with Basal cell nevus syndrome and Medulloblastoma.; to: SUFU was reassessed in line with the recent expert review by Rhiannon Mellis (GOSH). The patients described by Schroder et al 2020 (PMID: 33024317) display cerebellar abnormalities that were said to be within the milder range of the Joubert clinical spectrum. However, it is unclear whether these features may conceivably be detected prenatally and therefore this gene will be flagged for review by the GMS team with regards to phenotypic fit for this panel (added 'for-review' tag).

Note that unlike the 2 Joubert syndrome families with biallelic variants reported by De Mori et al. (2017, PMID: 28965847), these individuals harboured heterozygous truncating variants in the SUFU gene. Monoallelic variants have previously been associated with basal cell nevus syndrome and medulloblastoma, and there was no evidence of tumours in any of the families described by Schroder et al.
Proteinuric renal disease v2.48 APOL1 Eleanor Williams Classified gene: APOL1 as Amber List (moderate evidence)
Proteinuric renal disease v2.48 APOL1 Eleanor Williams Added comment: Comment on list classification: Changing the rating from red to amber, following review and proposal for green by Natalie Forrester. It should be considered for green rating following GMS review.
Proteinuric renal disease v2.48 APOL1 Eleanor Williams Gene: apol1 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.47 APOL1 Eleanor Williams Phenotypes for gene: APOL1 were changed from Focal Segmental Glomerulosclerosis 4, Susceptibility to #612551 to {Focal Segmental Glomerulosclerosis 4, Susceptibility to} OMIM:612551; {End-stage renal disease, nondiabetic, susceptibility to} OMIM:612551
Proteinuric renal disease v2.46 APOL1 Eleanor Williams Mode of inheritance for gene: APOL1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.612 SUFU Arina Puzriakova commented on gene: SUFU
Early onset or syndromic epilepsy v2.287 GALNT2 Sarah Leigh changed review comment from: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, depending on the policy of inclusion of metabolic genes on this panel.; to: Comment on list classification:
For-review tag has been added to highlight that there is enough evidence for this gene to be rated GREEN at the next major review, depending on the policy of inclusion of metabolic genes on this panel.
Early onset or syndromic epilepsy v2.287 GALNT2 Sarah Leigh Deleted their comment
Early onset or syndromic epilepsy v2.287 GALNT2 Sarah Leigh commented on gene: GALNT2: For-review tag has been added to highlight whether this gene should be green on this panel due to the uncoupling of metabolic genes from Genetic epilepsy syndromes panel.
Proteinuric renal disease v2.45 APOL1 Eleanor Williams Publications for gene: APOL1 were set to 20647424
Early onset or syndromic epilepsy v2.287 ALG14 Sarah Leigh commented on gene: ALG14: For-review tag has been added to highlight whether this gene should be green on this panel due to the uncoupling of metabolic genes from Genetic epilepsy syndromes panel.
Proteinuric renal disease v2.44 APOL1 Eleanor Williams Tag for-review tag was added to gene: APOL1.
Fetal anomalies v1.612 SUFU Arina Puzriakova Tag for-review tag was added to gene: SUFU.
Fetal anomalies v1.612 SUFU Arina Puzriakova Phenotypes for gene: SUFU were changed from Joubert Syndrome with Cranio-facial and Skeletal Defects; Basal cell nevus syndrome 109400 to Joubert syndrome 32, OMIM: 617757; Joubert Syndrome with Cranio-facial and Skeletal Defects
Fetal anomalies v1.611 SUFU Arina Puzriakova Publications for gene: SUFU were set to 28965847
Fetal anomalies v1.610 SUFU Arina Puzriakova Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Rare anaemia v1.9 VPS4A Evan Reid gene: VPS4A was added
gene: VPS4A was added to Rare anaemia. Sources: Literature,Research
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to (PMID: 33186545; 33186543; 33460484)
Phenotypes for gene: VPS4A were set to developmental delay; intellectual disability; cerebellar hypoplasia; pontine hypoplasia; thin corpus callosum; microcephaly; growth retardation; congenital anaemia; dyserythropeoitic anaemia; dystonia; congenital cataracts; deafness
Penetrance for gene: VPS4A were set to Complete
Mode of pathogenicity for gene: VPS4A was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: VPS4A was set to GREEN
Added comment: Multiple families (now 10) described with a consistent phenotype (termed CIMDAG as an acronym for the major features). This includes congenital anaemia in most cases, in some cases this is of a dyserythropoeitic type. All have de novo heterozygous missense mutations of VPS4A, with a distinct mutational hotspot (R284) in many families. Mechanism is likely dominant negative. Haplo-insufficiency of VPS4A is tolerated and present in general population databases, so loss of function mutations likely do not cause this disease.
Sources: Literature, Research
Intellectual disability v3.751 VPS4A Evan Reid changed review comment from: Multiple families (now 10) described with a consistent phenotype (we have termed it CIMDAG as an acronym for the major features). All have de novo heterozygous missense mutations of VPS4A, with a distinct mutational hotspot (R284) in many families. Mechanism is likely dominant negative. Haplo-insufficiency of VPS4A is tolerated and present in general population databases, so loss of function mutations likely do not cause this disease.
Sources: Literature, Research; to: Multiple families (now 10) described with a consistent phenotype (termed CIMDAG as an acronym for the major features). All have de novo heterozygous missense mutations of VPS4A, with a distinct mutational hotspot (R284) in many families. Mechanism is likely dominant negative. Haplo-insufficiency of VPS4A is tolerated and present in general population databases, so loss of function mutations likely do not cause this disease.
Sources: Literature, Research
Intellectual disability v3.751 VPS4A Evan Reid gene: VPS4A was added
gene: VPS4A was added to Intellectual disability. Sources: Literature,Research
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to (PMID: 33186545; 33186543; 33460484)
Phenotypes for gene: VPS4A were set to developmental delay; intellectual disability; cerebellar hypoplasia; pontine hypoplasia; thin corpus callosum; microcephaly; growth retardation; congenital anaemia; dyserythropeoitic anaemia; dystonia; congenital cataracts; deafness
Penetrance for gene: VPS4A were set to Complete
Mode of pathogenicity for gene: VPS4A was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: VPS4A was set to GREEN
Added comment: Multiple families (now 10) described with a consistent phenotype (we have termed it CIMDAG as an acronym for the major features). All have de novo heterozygous missense mutations of VPS4A, with a distinct mutational hotspot (R284) in many families. Mechanism is likely dominant negative. Haplo-insufficiency of VPS4A is tolerated and present in general population databases, so loss of function mutations likely do not cause this disease.
Sources: Literature, Research
Severe microcephaly v2.98 COASY Sarah Leigh edited their review of gene: COASY: Changed rating: GREEN
Severe microcephaly v2.98 COASY Sarah Leigh Classified gene: COASY as Amber List (moderate evidence)
Severe microcephaly v2.98 COASY Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Severe microcephaly v2.98 COASY Sarah Leigh Gene: coasy has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.97 COASY Sarah Leigh Publications for gene: COASY were set to 30089828; 24360804
Severe microcephaly v2.96 COASY Sarah Leigh Tag for-review tag was added to gene: COASY.
Severe microcephaly v2.96 COASY Sarah Leigh commented on gene: COASY: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen (although it has a confirmed associated with Neurodegeneration with brain iron accumulation 6 OMIM:615643, PMID 24360804). At least two terminating variants have been reported in four cases of Pontocerebellar hypoplasia, type 12 OMIM:618266 in two unrelated families (PMID 30089828). Segregation and supportive functional studies were reported, together with a zebrafish morpholino knockdown, where the lack of COASY expression was rescued by addition of CoA to the water or by injection of CoA in the brain ventricle (PMID 27892483). It was proposed that the human fetuses survived gestation due to exposure to maternal CoA (PMID 30089828).
Severe microcephaly v2.96 COASY Sarah Leigh Added comment: Comment on phenotypes: Variants are also associated with Neurodegeneration with brain iron accumulation 6 OMIM:615643, but this phenotype is not relevant to the Severe microcephaly panel (PMID 24360804).
Severe microcephaly v2.96 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Pontocerebellar hypoplasia, type 12 OMIM:618266 to Pontocerebellar hypoplasia, type 12 OMIM:618266
Fetal anomalies v1.609 SMPD4 Arina Puzriakova Phenotypes for gene: SMPD4 were changed from Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies to Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, OMIM:618622; Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, MONDO:0032838
Fetal anomalies v1.608 SMPD4 Arina Puzriakova Publications for gene: SMPD4 were set to PMID: 31495489
Fetal anomalies v1.607 SLC29A3 Arina Puzriakova Phenotypes for gene: SLC29A3 were changed from Histiocytosis-lymphadenopathy plus syndrome to Histiocytosis-lymphadenopathy plus syndrome, OMIM:602782; H syndrome, MONDO:0011273
Fetal anomalies v1.606 SLC18A3 Arina Puzriakova Phenotypes for gene: SLC18A3 were changed from Myasthenic syndrome, congenital, 21, presynaptic to Myasthenic syndrome, congenital, 21, presynaptic, OMIM:617239; Congenital myasthenic syndrome 21, MONDO:0014983
Fetal anomalies v1.605 SLC18A3 Arina Puzriakova Publications for gene: SLC18A3 were set to PMID: 31059209
Fetal anomalies v1.604 SIX6 Arina Puzriakova Phenotypes for gene: SIX6 were changed from Optic disc anomalies with retinal and/or macular dystrophy to Optic disc anomalies with retinal and/or macular dystrophy, OMIM:212550; Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, MONDO:0008927
Fetal anomalies v1.603 SMPD4 Arina Puzriakova Classified gene: SMPD4 as Amber List (moderate evidence)
Fetal anomalies v1.603 SMPD4 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.603 SMPD4 Arina Puzriakova Gene: smpd4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.602 SMPD4 Arina Puzriakova Tag for-review tag was added to gene: SMPD4.
Fetal anomalies v1.602 SLC29A3 Arina Puzriakova Classified gene: SLC29A3 as Amber List (moderate evidence)
Fetal anomalies v1.602 SLC29A3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.602 SLC29A3 Arina Puzriakova Gene: slc29a3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.601 SLC29A3 Arina Puzriakova Tag for-review tag was added to gene: SLC29A3.
Fetal anomalies v1.601 SLC18A3 Arina Puzriakova Classified gene: SLC18A3 as Amber List (moderate evidence)
Fetal anomalies v1.601 SLC18A3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.601 SLC18A3 Arina Puzriakova Gene: slc18a3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.600 SLC18A3 Arina Puzriakova Tag for-review tag was added to gene: SLC18A3.
Fetal anomalies v1.600 SIX6 Arina Puzriakova Classified gene: SIX6 as Amber List (moderate evidence)
Fetal anomalies v1.600 SIX6 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.600 SIX6 Arina Puzriakova Gene: six6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.599 SIX6 Arina Puzriakova Tag for-review tag was added to gene: SIX6.
Fetal anomalies v1.599 SLC5A7 Arina Puzriakova Phenotypes for gene: SLC5A7 were changed from Congenital Myasthenic Syndrome with Episodic Apnea to Myasthenic syndrome, congenital, 20, presynaptic, OMIM:617143; Congenital myasthenic syndrome 20, MONDO:0014939
Fetal anomalies v1.598 TSFM Catherine Snow Publications for gene: TSFM were set to
Fetal anomalies v1.597 SLC5A7 Arina Puzriakova Publications for gene: SLC5A7 were set to
Fetal anomalies v1.596 SLC5A7 Arina Puzriakova Classified gene: SLC5A7 as Amber List (moderate evidence)
Fetal anomalies v1.596 SLC5A7 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.596 SLC5A7 Arina Puzriakova Gene: slc5a7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.595 SLC5A7 Arina Puzriakova Tag for-review tag was added to gene: SLC5A7.
Fetal anomalies v1.595 SMS Arina Puzriakova Phenotypes for gene: SMS were changed from SNYDER-ROBINSON SYNDROME to Mental retardation, X-linked, Snyder-Robinson type, OMIM:309583; Syndromic X-linked intellectual disability Snyder type, MONDO:0010664
Fetal anomalies v1.594 TSFM Catherine Snow Tag for-review tag was added to gene: TSFM.
Fetal anomalies v1.594 SLC25A19 Arina Puzriakova Phenotypes for gene: SLC25A19 were changed from AMISH LETHAL MICROCEPHALY to Microcephaly, Amish type, OMIM:607196; Amish lethal microcephaly, MONDO:0011790
Fetal anomalies v1.593 TSFM Catherine Snow Classified gene: TSFM as Amber List (moderate evidence)
Fetal anomalies v1.593 TSFM Catherine Snow Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.593 TSFM Catherine Snow Gene: tsfm has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.592 SMS Arina Puzriakova Classified gene: SMS as Amber List (moderate evidence)
Fetal anomalies v1.592 SMS Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.592 SMS Arina Puzriakova Gene: sms has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.591 TSEN34 Catherine Snow Tag for-review tag was added to gene: TSEN34.
Fetal anomalies v1.591 SMS Arina Puzriakova Tag for-review tag was added to gene: SMS.
Fetal anomalies v1.591 SLC25A19 Arina Puzriakova Classified gene: SLC25A19 as Amber List (moderate evidence)
Fetal anomalies v1.591 SLC25A19 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.591 SLC25A19 Arina Puzriakova Gene: slc25a19 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.590 TSEN34 Catherine Snow Classified gene: TSEN34 as Amber List (moderate evidence)
Fetal anomalies v1.590 TSEN34 Catherine Snow Added comment: Comment on list classification: Gene reviewed by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.590 TSEN34 Catherine Snow Gene: tsen34 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.589 SLC25A19 Arina Puzriakova Tag for-review tag was added to gene: SLC25A19.
Fetal anomalies v1.589 SHANK3 Arina Puzriakova Phenotypes for gene: SHANK3 were changed from PHELAN-MCDERMID SYNDROME to Phelan-McDermid syndrome, OMIM:606232; Phelan-McDermid syndrome, MONDO:0011652
Fetal anomalies v1.588 SHANK3 Arina Puzriakova Classified gene: SHANK3 as Amber List (moderate evidence)
Fetal anomalies v1.588 SHANK3 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.588 SHANK3 Arina Puzriakova Gene: shank3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.587 TSEN2 Catherine Snow Tag for-review tag was added to gene: TSEN2.
Fetal anomalies v1.587 SHANK3 Arina Puzriakova Tag for-review tag was added to gene: SHANK3.
Fetal anomalies v1.587 TSEN2 Catherine Snow Classified gene: TSEN2 as Amber List (moderate evidence)
Fetal anomalies v1.587 TSEN2 Catherine Snow Added comment: Comment on list classification: Gene reviewed by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.587 TSEN2 Catherine Snow Gene: tsen2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.586 SGCG Arina Puzriakova Phenotypes for gene: SGCG were changed from Muscular dystrophy, limb-girdle, autosomal recessive 5 to Muscular dystrophy, limb-girdle, autosomal recessive 5, OMIM:253700; Autosomal recessive limb-girdle muscular dystrophy type 2C, MONDO:0009677
Fetal anomalies v1.585 TRMT10A Catherine Snow Tag for-review tag was added to gene: TRMT10A.
Fetal anomalies v1.585 TRMT10A Catherine Snow Classified gene: TRMT10A as Amber List (moderate evidence)
Fetal anomalies v1.585 TRMT10A Catherine Snow Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.585 TRMT10A Catherine Snow Gene: trmt10a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.584 SERPINH1 Arina Puzriakova Phenotypes for gene: SERPINH1 were changed from Osteogenesis imperfecta, type X to Osteogenesis imperfecta, type X, OMIM:613848; Osteogenesis imperfecta type 10, MONDO:0013459
Fetal anomalies v1.583 TRAP1 Catherine Snow Tag for-review tag was added to gene: TRAP1.
Fetal anomalies v1.583 SERPINF1 Arina Puzriakova Phenotypes for gene: SERPINF1 were changed from Osteogenesis imperfecta, type VI to Osteogenesis imperfecta, type VI, OMIM:613982; Osteogenesis imperfecta type 6, MONDO:0013515
Fetal anomalies v1.582 TRAP1 Catherine Snow Publications for gene: TRAP1 were set to
Fetal anomalies v1.581 SGCG Arina Puzriakova Classified gene: SGCG as Amber List (moderate evidence)
Fetal anomalies v1.581 SGCG Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.581 SGCG Arina Puzriakova Gene: sgcg has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.580 SGCG Arina Puzriakova Tag for-review tag was added to gene: SGCG.
Fetal anomalies v1.580 SERPINH1 Arina Puzriakova Classified gene: SERPINH1 as Amber List (moderate evidence)
Fetal anomalies v1.580 SERPINH1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.580 SERPINH1 Arina Puzriakova Gene: serpinh1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.579 SERPINH1 Arina Puzriakova Tag for-review tag was added to gene: SERPINH1.
Fetal anomalies v1.579 SERPINF1 Arina Puzriakova Classified gene: SERPINF1 as Amber List (moderate evidence)
Fetal anomalies v1.579 SERPINF1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.579 SERPINF1 Arina Puzriakova Gene: serpinf1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.578 SERPINF1 Arina Puzriakova Tag for-review tag was added to gene: SERPINF1.
Fetal anomalies v1.578 TRAP1 Catherine Snow Classified gene: TRAP1 as Amber List (moderate evidence)
Fetal anomalies v1.578 TRAP1 Catherine Snow Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.578 TRAP1 Catherine Snow Gene: trap1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.577 TOE1 Arina Puzriakova Phenotypes for gene: TOE1 were changed from PONTOCEREBELLAR HYPOPLASIA to Pontocerebellar hypoplasia, type 7, OMIM:614969; Pontocerebellar hypoplasia type 7, MONDO:0013993
Fetal anomalies v1.576 TOE1 Arina Puzriakova Classified gene: TOE1 as Amber List (moderate evidence)
Fetal anomalies v1.576 TOE1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.576 TOE1 Arina Puzriakova Gene: toe1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.575 TOE1 Arina Puzriakova Tag for-review tag was added to gene: TOE1.
Fetal anomalies v1.575 TRAIP Catherine Snow Publications for gene: TRAIP were set to
Fetal anomalies v1.574 TRAIP Catherine Snow Classified gene: TRAIP as Amber List (moderate evidence)
Fetal anomalies v1.574 TRAIP Catherine Snow Added comment: Comment on list classification: Gene reviewed by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.574 TRAIP Catherine Snow Gene: traip has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.573 TRAIP Catherine Snow Tag for-review tag was added to gene: TRAIP.
Fetal anomalies v1.573 TRAIP Catherine Snow Phenotypes for gene: TRAIP were changed from PRIMORDIAL DWARFISM to Seckel syndrome 9
Fetal anomalies v1.572 TELO2 Arina Puzriakova Phenotypes for gene: TELO2 were changed from TELO2 Syndromic Intellectual Disability Disorder to You-Hoover-Fong syndrome, OMIM:616954; TELO2-related intellectual disability-neurodevelopmental disorder, MONDO:0014848
Fetal anomalies v1.571 TELO2 Arina Puzriakova Classified gene: TELO2 as Amber List (moderate evidence)
Fetal anomalies v1.571 TELO2 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.571 TELO2 Arina Puzriakova Gene: telo2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.570 TELO2 Arina Puzriakova Tag for-review tag was added to gene: TELO2.
Fetal anomalies v1.570 TRAF3IP1 Catherine Snow Tag for-review tag was added to gene: TRAF3IP1.
Fetal anomalies v1.570 TRAF3IP1 Catherine Snow Classified gene: TRAF3IP1 as Amber List (moderate evidence)
Fetal anomalies v1.570 TRAF3IP1 Catherine Snow Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.570 TRAF3IP1 Catherine Snow Gene: traf3ip1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.569 STIL Arina Puzriakova Phenotypes for gene: STIL were changed from MICROCEPHALY PRIMARY TYPE 7 to Microcephaly 7, primary, autosomal recessive, OMIM:612703; Microcephaly 7, primary, autosomal recessive, MONDO:0012989
Fetal anomalies v1.568 STIL Arina Puzriakova Publications for gene: STIL were set to
Fetal anomalies v1.567 STIL Arina Puzriakova Classified gene: STIL as Amber List (moderate evidence)
Fetal anomalies v1.567 STIL Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.567 STIL Arina Puzriakova Gene: stil has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.566 STIL Arina Puzriakova Tag for-review tag was added to gene: STIL.
Fetal anomalies v1.566 SPARC Arina Puzriakova Phenotypes for gene: SPARC were changed from OSTEOGENESIS IMPERFECTA, TYPE XVII to Osteogenesis imperfecta, type XVII, OMIM:616507; Osteogenesis imperfecta type 17, MONDO:0014672
Fetal anomalies v1.565 SPECC1L Arina Puzriakova Phenotypes for gene: SPECC1L were changed from FACIAL CLEFTING, OBLIQUE, 1 to ?Facial clefting, oblique, 1, OMIM:600251; Tessier number 4 facial cleft, MONDO:0010850; Hypertelorism, Teebi type, OMIM:145420; Hypertelorism, Teebi type, MONDO:0007780; Opitz GBBB syndrome, type II, OMIM:145410; Autosomal dominant Opitz G/BBB syndrome, MONDO:0007779
Fetal anomalies v1.564 ST14 Arina Puzriakova Phenotypes for gene: ST14 were changed from ICHTHYOSIS AUTOSOMAL RECESSIVE WITH HYPOTRICHOSIS to Ichthyosis, congenital, autosomal recessive 11, OMIM:602400; Autosomal recessive congenital ichthyosis 11, MONDO:0011218
Fetal anomalies v1.563 ST14 Arina Puzriakova Classified gene: ST14 as Amber List (moderate evidence)
Fetal anomalies v1.563 ST14 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.563 ST14 Arina Puzriakova Gene: st14 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.562 ST14 Arina Puzriakova Tag for-review tag was added to gene: ST14.
Fetal anomalies v1.562 SPECC1L Arina Puzriakova Classified gene: SPECC1L as Amber List (moderate evidence)
Fetal anomalies v1.562 SPECC1L Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.562 SPECC1L Arina Puzriakova Gene: specc1l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.561 SPECC1L Arina Puzriakova Tag for-review tag was added to gene: SPECC1L.
Fetal anomalies v1.561 SPARC Arina Puzriakova Classified gene: SPARC as Amber List (moderate evidence)
Fetal anomalies v1.561 SPARC Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.561 SPARC Arina Puzriakova Gene: sparc has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.560 SPARC Arina Puzriakova Tag for-review tag was added to gene: SPARC.
Severe microcephaly v2.95 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis to Pontocerebellar hypoplasia, type 12 OMIM:618266
Fetal anomalies v1.560 TUBB3 Catherine Snow Publications for gene: TUBB3 were set to
Fetal anomalies v1.559 TUBB3 Catherine Snow Tag for-review tag was added to gene: TUBB3.
Fetal anomalies v1.559 TUBB3 Catherine Snow Classified gene: TUBB3 as Amber List (moderate evidence)
Fetal anomalies v1.559 TUBB3 Catherine Snow Added comment: Comment on list classification: Gene reviewed by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.559 TUBB3 Catherine Snow Gene: tubb3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.558 TUBG1 Catherine Snow Tag for-review tag was added to gene: TUBG1.
Fetal anomalies v1.558 TBC1D32 Arina Puzriakova Classified gene: TBC1D32 as Amber List (moderate evidence)
Fetal anomalies v1.558 TBC1D32 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). There are sufficient unrelated cases with a fetally-relevant phenotype and biallelic variants in TBC1D32 to promoted this gene to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.558 TBC1D32 Arina Puzriakova Gene: tbc1d32 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.557 TUBG1 Catherine Snow Classified gene: TUBG1 as Amber List (moderate evidence)
Fetal anomalies v1.557 TUBG1 Catherine Snow Added comment: Comment on list classification: Gene reviewed by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.557 TUBG1 Catherine Snow Gene: tubg1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.556 TUBG1 Catherine Snow Publications for gene: TUBG1 were set to
Fetal anomalies v1.555 TBC1D32 Arina Puzriakova Publications for gene: TBC1D32 were set to PMID: 32573025; 31130284; 32060556
Fetal anomalies v1.554 TUBGCP4 Catherine Snow Publications for gene: TUBGCP4 were set to
Fetal anomalies v1.553 TBC1D32 Arina Puzriakova Tag for-review tag was added to gene: TBC1D32.
Fetal anomalies v1.553 TUBGCP4 Catherine Snow Tag for-review tag was added to gene: TUBGCP4.
Fetal anomalies v1.553 TUBGCP4 Catherine Snow Classified gene: TUBGCP4 as Amber List (moderate evidence)
Fetal anomalies v1.553 TUBGCP4 Catherine Snow Added comment: Comment on list classification: Gene reviewed by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.553 TUBGCP4 Catherine Snow Gene: tubgcp4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.552 TXNDC15 Catherine Snow Tag for-review tag was added to gene: TXNDC15.
Fetal anomalies v1.552 TXNDC15 Catherine Snow Publications for gene: TXNDC15 were set to
Fetal anomalies v1.551 TXNDC15 Catherine Snow Classified gene: TXNDC15 as Amber List (moderate evidence)
Fetal anomalies v1.551 TXNDC15 Catherine Snow Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.551 TXNDC15 Catherine Snow Gene: txndc15 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.550 UBE2T Catherine Snow Classified gene: UBE2T as Amber List (moderate evidence)
Fetal anomalies v1.550 UBE2T Catherine Snow Added comment: Comment on list classification: Gene reviewed by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.550 UBE2T Catherine Snow Gene: ube2t has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.549 UBE2T Catherine Snow Tag for-review tag was added to gene: UBE2T.
Fetal anomalies v1.549 UBE2T Catherine Snow Publications for gene: UBE2T were set to
Fetal anomalies v1.548 STRADA Arina Puzriakova Phenotypes for gene: STRADA were changed from Polyhydramnios, megalencephaly, and symptomatic epilepsy to Polyhydramnios, megalencephaly, and symptomatic epilepsy, OMIM:611087; Polyhydramnios, megalencephaly, and symptomatic epilepsy, MONDO:0012611
Fetal anomalies v1.547 STRADA Arina Puzriakova Classified gene: STRADA as Amber List (moderate evidence)
Fetal anomalies v1.547 STRADA Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.547 STRADA Arina Puzriakova Gene: strada has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.546 STRADA Arina Puzriakova Tag for-review tag was added to gene: STRADA.
Fetal anomalies v1.546 STAC3 Arina Puzriakova Publications for gene: STAC3 were set to PMID: 30168660
Fetal anomalies v1.545 STAC3 Arina Puzriakova Phenotypes for gene: STAC3 were changed from Myopathy, congenital, Baily-Bloch to Myopathy, congenital, Baily-Bloch, OMIM:255995; Bailey-Bloch congenital myopathy, MONDO:0009722
Fetal anomalies v1.544 STAC3 Arina Puzriakova Classified gene: STAC3 as Amber List (moderate evidence)
Fetal anomalies v1.544 STAC3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.544 STAC3 Arina Puzriakova Gene: stac3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.543 STAC3 Arina Puzriakova Tag for-review tag was added to gene: STAC3.
Fetal anomalies v1.543 SEC24D Ivone Leong commented on gene: SEC24D
Fetal anomalies v1.543 SEC24D Ivone Leong Tag for-review tag was added to gene: SEC24D.
Fetal anomalies v1.543 SP7 Arina Puzriakova Phenotypes for gene: SP7 were changed from Osteogenesis imperfecta, type XII to Osteogenesis imperfecta, type XII, OMIM:613849; Osteogenesis imperfecta type 12, MONDO:0013460
Fetal anomalies v1.542 SOX6 Arina Puzriakova Phenotypes for gene: SOX6 were changed from Tolchin-Le Caignec syndrome to Tolchin-Le Caignec syndrome, OMIM:618971; Tolchin-Le Caignec syndrome, MONDO:0033544
Fetal anomalies v1.541 SOX18 Arina Puzriakova Phenotypes for gene: SOX18 were changed from Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome; Hypotrichosis-lymphedema-telangiectasia syndrome to Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, OMIM:137940; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, MONDO:0019073; Hypotrichosis-lymphedema-telangiectasia syndrome, OMIM:607823; Hypotrichosis-lymphedema-telangiectasia syndrome, MONDO:0011914
Fetal anomalies v1.540 SNX10 Arina Puzriakova Phenotypes for gene: SNX10 were changed from Osteopetrosis, autosomal recessive 8 to Osteopetrosis, autosomal recessive 8, OMIM:615085; Autosomal recessive osteopetrosis 8, MONDO:0014040
Early onset or syndromic epilepsy v2.287 TET3 Sarah Leigh changed review comment from: Taking account the review of Helen Lord and Konstantinos Varvagiannis, there is not enough convincing evidence for this gene to be rated GREEN on the Genetic epilepsy syndromes panel. The "for-review" tag has been replaced with the "watchlist" tag to highlight that further cases with seizures are needed for this gene to be rated Green on this panel.; to: Taking account the review of Helen Lord and Konstantinos Varvagiannis, there is not enough convincing evidence for this gene to be rated GREEN on the Genetic epilepsy syndromes panel. The "for-review" tag has been removed. The "watchlist" tag will remain to highlight that further cases with seizures are needed for this gene to be rated Green on this panel.
Fetal anomalies v1.539 SP7 Arina Puzriakova Classified gene: SP7 as Amber List (moderate evidence)
Fetal anomalies v1.539 SP7 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.539 SP7 Arina Puzriakova Gene: sp7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.538 SP7 Arina Puzriakova Tag for-review tag was added to gene: SP7.
Fetal anomalies v1.538 SOX6 Arina Puzriakova Classified gene: SOX6 as Amber List (moderate evidence)
Fetal anomalies v1.538 SOX6 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.538 SOX6 Arina Puzriakova Gene: sox6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.537 SOX6 Arina Puzriakova Tag for-review tag was added to gene: SOX6.
Early onset or syndromic epilepsy v2.287 TET3 Sarah Leigh Tag for-review was removed from gene: TET3.
Fetal anomalies v1.537 SOX18 Arina Puzriakova Classified gene: SOX18 as Amber List (moderate evidence)
Fetal anomalies v1.537 SOX18 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.537 SOX18 Arina Puzriakova Gene: sox18 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.536 SOX18 Arina Puzriakova Tag for-review tag was added to gene: SOX18.
Early onset or syndromic epilepsy v2.287 TET3 Sarah Leigh changed review comment from: There is enough evidence for this gene to be rated GREEN at the next major review.; to: Taking account the review of Helen Lord and Konstantinos Varvagiannis, there is not enough convincing evidence for this gene to be rated GREEN on the Genetic epilepsy syndromes panel. The "for-review" tag has been replaced with the "watchlist" tag to highlight that further cases with seizures are needed for this gene to be rated Green on this panel.
Fetal anomalies v1.536 SNX10 Arina Puzriakova Classified gene: SNX10 as Amber List (moderate evidence)
Fetal anomalies v1.536 SNX10 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.536 SNX10 Arina Puzriakova Gene: snx10 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.535 SNX10 Arina Puzriakova Tag for-review tag was added to gene: SNX10.
Fetal anomalies v1.535 RPS24 Arina Puzriakova Phenotypes for gene: RPS24 were changed from Diamond-blackfan anemia 3 610629 to Diamond-blackfan anemia 3, OMIM:610629; Diamond-Blackfan anemia 3, MONDO:0012529
Fetal anomalies v1.534 RPL35A Arina Puzriakova Phenotypes for gene: RPL35A were changed from Diamond-Blackfan anemia 5 612528 to Diamond-Blackfan anemia 5, OMIM:612528; Diamond-Blackfan anemia 5, MONDO:0012925
Fetal anomalies v1.533 RPS24 Arina Puzriakova Classified gene: RPS24 as Amber List (moderate evidence)
Fetal anomalies v1.533 RPS24 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene has been upgraded from Red to Amber, but should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.533 RPS24 Arina Puzriakova Gene: rps24 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.532 RPS24 Arina Puzriakova Tag for-review tag was added to gene: RPS24.
Fetal anomalies v1.532 RPL35A Arina Puzriakova Classified gene: RPL35A as Amber List (moderate evidence)
Fetal anomalies v1.532 RPL35A Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene has been upgraded from Red to Amber, but should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.532 RPL35A Arina Puzriakova Gene: rpl35a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.531 RPL35A Arina Puzriakova Tag for-review tag was added to gene: RPL35A.
Fetal anomalies v1.531 SDR9C7 Ivone Leong Tag for-review tag was added to gene: SDR9C7.
Fetal anomalies v1.531 SDR9C7 Ivone Leong Classified gene: SDR9C7 as Amber List (moderate evidence)
Fetal anomalies v1.531 SDR9C7 Ivone Leong Added comment: Comment on list classification: New gene added by Rhiannon Mellis (Great Ormond Street Hospital).

Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag).
Fetal anomalies v1.531 SDR9C7 Ivone Leong Gene: sdr9c7 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.751 TET3 Sarah Leigh Phenotypes for gene: TET3 were changed from Beck-Fahrner syndrome 618798 to Beck-Fahrner syndrome OMIM:618798
Intellectual disability v3.751 TET3 Sarah Leigh Publications for gene: TET3 were set to https://doi.org/10.1016/j.ajhg.2019.12.007; 31928709
Fetal anomalies v1.530 SDR9C7 Ivone Leong Phenotypes for gene: SDR9C7 were changed from Ichthyosis, congenital, autosomal recessive 13 to Ichthyosis, congenital, autosomal recessive 13, OMIM:617574
Fetal anomalies v1.529 SCLT1 Ivone Leong Classified gene: SCLT1 as Amber List (moderate evidence)
Fetal anomalies v1.529 SCLT1 Ivone Leong Added comment: Comment on list classification: New gene added by Rhiannon Mellis (Great Ormond Street Hospital).

Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag).
Fetal anomalies v1.529 SCLT1 Ivone Leong Gene: sclt1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v2.287 TET3 Sarah Leigh Publications for gene: TET3 were set to https://doi.org/10.1016/j.ajhg.2019.12.007; 31928709
Fetal anomalies v1.528 SCLT1 Ivone Leong Publications for gene: SCLT1 were set to
Fetal anomalies v1.527 RFT1 Arina Puzriakova Phenotypes for gene: RFT1 were changed from CONGENITAL DISORDER OF GLYCOSYLATION TYPE 1N to Congenital disorder of glycosylation, type In, OMIM:612015; RFT1-CDG, MONDO:0012783
Fetal anomalies v1.526 RFT1 Arina Puzriakova Classified gene: RFT1 as Amber List (moderate evidence)
Fetal anomalies v1.526 RFT1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.526 RFT1 Arina Puzriakova Gene: rft1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.525 RSPH9 Ivone Leong Tag for-review tag was added to gene: RSPH9.
Fetal anomalies v1.525 RFT1 Arina Puzriakova Tag for-reivew tag was added to gene: RFT1.
Fetal anomalies v1.525 RSPH9 Ivone Leong Classified gene: RSPH9 as Amber List (moderate evidence)
Fetal anomalies v1.525 RSPH9 Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber.

Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag).
Fetal anomalies v1.525 RSPH9 Ivone Leong Gene: rsph9 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.524 RBM10 Arina Puzriakova Phenotypes for gene: RBM10 were changed from TARP SYNDROME to TARP syndrome, OMIM:311900; Tarp syndrome, MONDO:0010711
Fetal anomalies v1.523 RSPH4A Ivone Leong Classified gene: RSPH4A as Amber List (moderate evidence)
Fetal anomalies v1.523 RSPH4A Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber.

Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag).
Fetal anomalies v1.523 RSPH4A Ivone Leong Gene: rsph4a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.522 RBM10 Arina Puzriakova Classified gene: RBM10 as Amber List (moderate evidence)
Fetal anomalies v1.522 RBM10 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.522 RBM10 Arina Puzriakova Gene: rbm10 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.521 RSPH4A Ivone Leong Tag for-review tag was added to gene: RSPH4A.
Fetal anomalies v1.521 RBM10 Arina Puzriakova Tag for-review tag was added to gene: RBM10.
Fetal anomalies v1.521 PTPN14 Arina Puzriakova Phenotypes for gene: PTPN14 were changed from CHOANAL ATRESIA AND LYMPHEDEMA to Choanal atresia and lymphedema, OMIM:613611; Lymphedema-posterior choanal atresia syndrome, MONDO:0013324
Early onset or syndromic epilepsy v2.286 TET3 Sarah Leigh Phenotypes for gene: TET3 were changed from Beck-Fahrner syndrome 618798 to Beck-Fahrner syndrome OMIM:618798
Fetal anomalies v1.520 PTPN14 Arina Puzriakova Classified gene: PTPN14 as Amber List (moderate evidence)
Fetal anomalies v1.520 PTPN14 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.520 PTPN14 Arina Puzriakova Gene: ptpn14 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.519 PTPN14 Arina Puzriakova Tag for-review tag was added to gene: PTPN14.
Fetal anomalies v1.519 PSAT1 Arina Puzriakova Phenotypes for gene: PSAT1 were changed from Neu-Laxova syndrome 2, 616038; NEU-LAXOVA SYNDROME; PHOSPHOSERINE AMINOTRANSFERASE DEFICIENCY to Neu-Laxova syndrome 2, OMIM:616038; Neu-Laxova syndrome 2, MONDO:0014466
Fetal anomalies v1.518 PRUNE1 Arina Puzriakova Phenotypes for gene: PRUNE1 were changed from PEHO Like condition to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies, OMIM:617481; Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies, MONDO:0060490
Fetal anomalies v1.517 PRUNE1 Arina Puzriakova Classified gene: PRUNE1 as Amber List (moderate evidence)
Fetal anomalies v1.517 PRUNE1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.517 PRUNE1 Arina Puzriakova Gene: prune1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.516 PRUNE1 Arina Puzriakova Tag for-review tag was added to gene: PRUNE1.
Fetal anomalies v1.516 RPS7 Arina Puzriakova Phenotypes for gene: RPS7 were changed from Diamond-Blackfan anemia 8 to Diamond-Blackfan anemia 8, OMIM:612563; Diamond-Blackfan anemia 8, MONDO:0012939
Fetal anomalies v1.515 RPL10 Arina Puzriakova Phenotypes for gene: RPL10 were changed from Mental retardation, X-linked, syndromic, 35 to Mental retardation, X-linked, syndromic, 35, OMIM:300998; Intellectual disability, X-linked, syndromic, 35, MONDO:0030908
Pulmonary arterial hypertension v2.9 KDR Nicholas Morrell reviewed gene: KDR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33320693, PMID: 31980491; Phenotypes: Pulmonary arterial hypertension, low diffusion coefficient for carbon monoxide; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.514 ROBO3 Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag); to: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.514 ROBO3 Arina Puzriakova Phenotypes for gene: ROBO3 were changed from to Gaze palsy, familial horizontal, with progressive scoliosis, 1, OMIM:607313; Gaze palsy, familial horizontal, with progressive scoliosis 1, MONDO:0020790
Fetal anomalies v1.513 RBBP8 Arina Puzriakova Phenotypes for gene: RBBP8 were changed from Seckel syndrome 2 to Seckel syndrome 2, OMIM:606744; Seckel syndrome 2, MONDO:0011715
Fetal anomalies v1.512 RAB33B Arina Puzriakova Phenotypes for gene: RAB33B were changed from Smith-McCort dysplasia 2 to Smith-McCort dysplasia 2, OMIM:615222; Smith-McCort dysplasia 2, MONDO:0014087
Fetal anomalies v1.511 PYGM Arina Puzriakova Phenotypes for gene: PYGM were changed from McArdle disease to McArdle disease, OMIM:232600; Glycogen storage disease V, MONDO:0009293
Fetal anomalies v1.510 PRKAG2 Arina Puzriakova Phenotypes for gene: PRKAG2 were changed from Cardiomyopathy, hypertrophic 6; Glycogen storage disease of heart, lethal congenital to Cardiomyopathy, hypertrophic 6, OMIM:600858; Hypertrophic cardiomyopathy 6, MONDO:0010946; Glycogen storage disease of heart, lethal congenital, OMIM:261740; Lethal congenital glycogen storage disease of heart, MONDO:0009867
Fetal anomalies v1.509 POP1 Arina Puzriakova Phenotypes for gene: POP1 were changed from Anauxetic dysplasia 2 to Anauxetic dysplasia 2, OMIM:617396; Anauxetic dysplasia 2, MONDO:0054561
Fetal anomalies v1.508 POLG2 Arina Puzriakova Phenotypes for gene: POLG2 were changed from Mitochondrial DNA depletion syndrome 16 (hepatic type); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 to Mitochondrial DNA depletion syndrome 16 (hepatic type), OMIM:618528; Mitochondrial DNA depletion syndrome 16 (hepatic type), MONDO:0032799; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, OMIM:610131; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MONDO:0012415
Fetal anomalies v1.507 RRAS2 Arina Puzriakova Phenotypes for gene: RRAS2 were changed from Noonan syndrome 12 to Noonan syndrome 12, OMIM:618624; Noonan syndrome 12, MONDO:0032839
Fetal anomalies v1.506 RRAS2 Arina Puzriakova Classified gene: RRAS2 as Amber List (moderate evidence)
Fetal anomalies v1.506 RRAS2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.506 RRAS2 Arina Puzriakova Gene: rras2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.505 RRAS2 Arina Puzriakova Tag for-review tag was added to gene: RRAS2.
Fetal anomalies v1.505 RPS7 Arina Puzriakova Classified gene: RPS7 as Amber List (moderate evidence)
Fetal anomalies v1.505 RPS7 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.505 RPS7 Arina Puzriakova Gene: rps7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.504 RPS7 Arina Puzriakova Tag for-review tag was added to gene: RPS7.
Fetal anomalies v1.504 RPL10 Arina Puzriakova Classified gene: RPL10 as Amber List (moderate evidence)
Fetal anomalies v1.504 RPL10 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.504 RPL10 Arina Puzriakova Gene: rpl10 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.503 RPL10 Arina Puzriakova Tag for-review tag was added to gene: RPL10.
Fetal anomalies v1.503 ROBO3 Arina Puzriakova Mode of inheritance for gene: ROBO3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.502 ROBO3 Arina Puzriakova Classified gene: ROBO3 as Amber List (moderate evidence)
Fetal anomalies v1.502 ROBO3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.502 ROBO3 Arina Puzriakova Gene: robo3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.501 ROBO3 Arina Puzriakova Tag for-review tag was added to gene: ROBO3.
Fetal anomalies v1.501 RBBP8 Arina Puzriakova Classified gene: RBBP8 as Amber List (moderate evidence)
Fetal anomalies v1.501 RBBP8 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.501 RBBP8 Arina Puzriakova Gene: rbbp8 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.500 RBBP8 Arina Puzriakova Tag for-review tag was added to gene: RBBP8.
Fetal anomalies v1.500 RAB33B Arina Puzriakova Classified gene: RAB33B as Amber List (moderate evidence)
Fetal anomalies v1.500 RAB33B Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.500 RAB33B Arina Puzriakova Gene: rab33b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.499 RAB33B Arina Puzriakova Tag for-review tag was added to gene: RAB33B.
Fetal anomalies v1.499 PYGM Arina Puzriakova Classified gene: PYGM as Amber List (moderate evidence)
Fetal anomalies v1.499 PYGM Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.499 PYGM Arina Puzriakova Gene: pygm has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.498 PYGM Arina Puzriakova Tag for-review tag was added to gene: PYGM.
Fetal anomalies v1.498 PRKAG2 Arina Puzriakova Classified gene: PRKAG2 as Amber List (moderate evidence)
Fetal anomalies v1.498 PRKAG2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.498 PRKAG2 Arina Puzriakova Gene: prkag2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.497 PRKAG2 Arina Puzriakova Tag for-review tag was added to gene: PRKAG2.
Fetal anomalies v1.497 POP1 Arina Puzriakova Classified gene: POP1 as Amber List (moderate evidence)
Fetal anomalies v1.497 POP1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.497 POP1 Arina Puzriakova Gene: pop1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.496 POP1 Arina Puzriakova Tag for-review tag was added to gene: POP1.
Fetal anomalies v1.496 POLG2 Arina Puzriakova Classified gene: POLG2 as Amber List (moderate evidence)
Fetal anomalies v1.496 POLG2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.496 POLG2 Arina Puzriakova Gene: polg2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.495 POLG2 Arina Puzriakova Tag for-review tag was added to gene: POLG2.
Fetal anomalies v1.495 PNPLA1 Arina Puzriakova Phenotypes for gene: PNPLA1 were changed from CONGENITAL ICHTHYOSIS to Ichthyosis, congenital, autosomal recessive 10, OMIM:615024; Autosomal recessive congenital ichthyosis 10, MONDO:0014011
Fetal anomalies v1.494 POLR1A Arina Puzriakova Phenotypes for gene: POLR1A were changed from ACROFACIAL DYSOSTOSIS, CINCINNATI TYPE to Acrofacial dysostosis, Cincinnati type, OMIM:616462; Acrofacial dysostosis Cincinnati type, MONDO:0014651
Fetal anomalies v1.493 POLR1A Arina Puzriakova Classified gene: POLR1A as Amber List (moderate evidence)
Fetal anomalies v1.493 POLR1A Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.493 POLR1A Arina Puzriakova Gene: polr1a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.492 POLR1A Arina Puzriakova Tag for-review tag was added to gene: POLR1A.
Fetal anomalies v1.492 PNPLA1 Arina Puzriakova Classified gene: PNPLA1 as Amber List (moderate evidence)
Fetal anomalies v1.492 PNPLA1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.492 PNPLA1 Arina Puzriakova Gene: pnpla1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.491 PNPLA1 Arina Puzriakova Tag for-review tag was added to gene: PNPLA1.
Early onset or syndromic epilepsy v2.285 SNX27 Sarah Leigh Tag for-review was removed from gene: SNX27.
Tag watchlist tag was added to gene: SNX27.
Fetal anomalies v1.491 PITX1 Arina Puzriakova Phenotypes for gene: PITX1 were changed from CONGENITAL CLUBFOOT; HOMEOTIC ARM-TO-LEG TRANSFORMATION ASSOCIATED WITH GENOMIC REARRANGEMENTS AT THE PITX1 LOCUS to Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly, OMIM:119800; Clubfoot, MONDO:0007342; Liebenberg syndrome, OMIM:186550; Brachydactyly-elbow wrist dysplasia syndrome, MONDO:0008520
Early onset or syndromic epilepsy v2.285 SNX27 Sarah Leigh edited their review of gene: SNX27: Added comment: Taking account of Helen Lord's review that there is insufficient evidence that seizures are associated with variants in SNX27, the "for review" tag has been replaced with the "watchlist" tag. The rating of this gene will remain amber on the Genetic epilepsy syndromes panel.; Changed rating: AMBER
Fetal anomalies v1.490 PITX1 Arina Puzriakova Classified gene: PITX1 as Amber List (moderate evidence)
Fetal anomalies v1.490 PITX1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.490 PITX1 Arina Puzriakova Gene: pitx1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.489 PITX1 Arina Puzriakova Tag for-review tag was added to gene: PITX1.
Fetal anomalies v1.489 PIGN Arina Puzriakova Phenotypes for gene: PIGN were changed from MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME to Multiple congenital anomalies-hypotonia-seizures syndrome 1, OMIM:614080; Multiple congenital anomalies-hypotonia-seizures syndrome 1, MONDO:0013563
Fetal anomalies v1.488 PIGN Arina Puzriakova Classified gene: PIGN as Amber List (moderate evidence)
Fetal anomalies v1.488 PIGN Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.488 PIGN Arina Puzriakova Gene: pign has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.487 PIGN Arina Puzriakova Tag for-review tag was added to gene: PIGN.
Fetal anomalies v1.487 PGM3 Arina Puzriakova Publications for gene: PGM3 were set to
Fetal anomalies v1.486 PGM3 Arina Puzriakova Phenotypes for gene: PGM3 were changed from IMMUNODEFICIENCY 23 to Immunodeficiency 23, OMIM:615816; PGM3-CDG, MONDO:0014353
Possible mitochondrial disorder - nuclear genes v1.33 COX4I1 Ivone Leong commented on gene: COX4I1: This gene is associated with a relevant phenotype in OMIM and not Gene2Phenotype. Based on the fact that there are now 2 unrelated cases and functional studies there is enough evidence for this gene to be Green.
Possible mitochondrial disorder - nuclear genes v1.33 COX4I1 Ivone Leong Tag for-review tag was added to gene: COX4I1.
Mitochondrial disorder with complex IV deficiency v1.10 COX4I1 Ivone Leong commented on gene: COX4I1: This gene is associated with a relevant phenotype in OMIM and not Gene2Phenotype. Based on the fact that there are now 2 unrelated cases and functional studies there is enough evidence for this gene to be Green.
Fetal anomalies v1.485 PGM3 Arina Puzriakova Classified gene: PGM3 as Amber List (moderate evidence)
Fetal anomalies v1.485 PGM3 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene has been upgraded from Red to Amber, but should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.485 PGM3 Arina Puzriakova Gene: pgm3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.484 PGM3 Arina Puzriakova Tag for-review tag was added to gene: PGM3.
Mitochondrial disorder with complex IV deficiency v1.10 COX4I1 Ivone Leong Tag for-review tag was added to gene: COX4I1.
Fetal anomalies v1.484 P4HB Arina Puzriakova Phenotypes for gene: P4HB were changed from COLE-CARPENTER SYNDROME to Cole-Carpenter syndrome 1, OMIM:112240; Cole-Carpenter syndrome 1, MONDO:0007204
Fetal anomalies v1.483 OSGEP Arina Puzriakova Phenotypes for gene: OSGEP were changed from Nephrotic syndrome with primary microcephaly to Galloway-Mowat syndrome 3, OMIM:617729; Galloway-Mowat syndrome 3, MONDO:0033007
Fetal anomalies v1.482 P4HB Arina Puzriakova Classified gene: P4HB as Amber List (moderate evidence)
Fetal anomalies v1.482 P4HB Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.482 P4HB Arina Puzriakova Gene: p4hb has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.481 P4HB Arina Puzriakova Tag for-review tag was added to gene: P4HB.
Fetal anomalies v1.481 OSGEP Arina Puzriakova Classified gene: OSGEP as Amber List (moderate evidence)
Fetal anomalies v1.481 OSGEP Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.481 OSGEP Arina Puzriakova Gene: osgep has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v1.33 COX4I1 Ivone Leong Phenotypes for gene: COX4I1 were changed from No OMIM phenotype to Mitochondrial complex IV deficiency, nuclear type 16, OMIM:619060
Fetal anomalies v1.480 OSGEP Arina Puzriakova Tag for-review tag was added to gene: OSGEP.
Mitochondrial disorder with complex IV deficiency v1.10 COX4I1 Ivone Leong Phenotypes for gene: COX4I1 were changed from No OMIM phenotype to Mitochondrial complex IV deficiency, nuclear type 16, OMIM:619060
Fetal anomalies v1.480 NEK8 Arina Puzriakova Phenotypes for gene: NEK8 were changed from RENAL-HEPATIC-PANCREATIC DYSPLASIA 2; NEPHRONOPHTHISIS 9 to ?Nephronophthisis 9, OMIM:613824; Nephronophthisis 9, MONDO:0013444; Renal-hepatic-pancreatic dysplasia 2, OMIM:615415; Renal-hepatic-pancreatic dysplasia 2, MONDO:0014174
Mitochondrial disorder with complex IV deficiency v1.9 COX4I1 Ivone Leong Publications for gene: COX4I1 were set to 28766551
Possible mitochondrial disorder - nuclear genes v1.32 COX4I1 Ivone Leong Publications for gene: COX4I1 were set to 28766551
Fetal anomalies v1.479 NEK8 Arina Puzriakova Publications for gene: NEK8 were set to
Fetal anomalies v1.478 NEK8 Arina Puzriakova Classified gene: NEK8 as Amber List (moderate evidence)
Fetal anomalies v1.478 NEK8 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.478 NEK8 Arina Puzriakova Gene: nek8 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.477 NEK8 Arina Puzriakova Tag for-review tag was added to gene: NEK8.
Early onset or syndromic epilepsy v2.285 SLC5A6 Sarah Leigh changed review comment from: For review tag has been added, to allow for GMS discussion in relation to the metabolic role of this gene.; to: For review tag has been added, to allow for GMS discussion in relation to the metabolic role of this gene. There are insufficient cases with seizures to be green on the Genetic epilepsy syndromes panel.
Fetal anomalies v1.477 NEDD4L Arina Puzriakova Phenotypes for gene: NEDD4L were changed from Periventricular nodular heterotopia with ID, cleft palate and 2.3 toe syndactyly to Periventricular nodular heterotopia 7, OMIM:617201; Periventricular nodular heterotopia 7, MONDO:0014966
Fetal anomalies v1.476 NEDD4L Arina Puzriakova Classified gene: NEDD4L as Amber List (moderate evidence)
Fetal anomalies v1.476 NEDD4L Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.476 NEDD4L Arina Puzriakova Gene: nedd4l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.475 NEDD4L Arina Puzriakova Tag for-review tag was added to gene: NEDD4L.
Fetal anomalies v1.475 PLG Arina Puzriakova Phenotypes for gene: PLG were changed from Plasminogen deficiency, type I to Plasminogen deficiency, type I, OMIM:217090; Hypoplasminogenemia, MONDO:0009009
Fetal anomalies v1.474 PLAG1 Arina Puzriakova Phenotypes for gene: PLAG1 were changed from Silver-Russell syndrome 4 to Silver-Russell syndrome 4, OMIM:618907; Silver-russell syndrome 4, MONDO:0030118
Fetal anomalies v1.473 PIK3C2A Arina Puzriakova Phenotypes for gene: PIK3C2A were changed from Oculoskeletodental syndrome to Oculoskeletodental syndrome, OMIM:618440; Oculocerebrodental syndrome, MONDO:0034145
Fetal anomalies v1.472 PIH1D3 Arina Puzriakova Phenotypes for gene: PIH1D3 were changed from Ciliary dyskinesia, primary, 36, X-linked to Ciliary dyskinesia, primary, 36, X-linked, OMIM:300991; Ciliary dyskinesia, primary, 36, X-linked, MONDO:0010517
Fetal anomalies v1.471 PIBF1 Arina Puzriakova Phenotypes for gene: PIBF1 were changed from Joubert syndrome 33 to Joubert syndrome 33, OMIM:617767; Joubert syndrome 33, MONDO:0033311
Fetal anomalies v1.470 PLG Arina Puzriakova Classified gene: PLG as Amber List (moderate evidence)
Fetal anomalies v1.470 PLG Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.470 PLG Arina Puzriakova Gene: plg has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.469 PLG Arina Puzriakova Tag for-review tag was added to gene: PLG.
Fetal anomalies v1.469 PLAG1 Arina Puzriakova Classified gene: PLAG1 as Amber List (moderate evidence)
Fetal anomalies v1.469 PLAG1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.469 PLAG1 Arina Puzriakova Gene: plag1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.468 PLAG1 Arina Puzriakova Tag for-review tag was added to gene: PLAG1.
Fetal anomalies v1.468 PIH1D3 Arina Puzriakova Classified gene: PIH1D3 as Amber List (moderate evidence)
Fetal anomalies v1.468 PIH1D3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.468 PIH1D3 Arina Puzriakova Gene: pih1d3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.467 PIK3C2A Arina Puzriakova Classified gene: PIK3C2A as Amber List (moderate evidence)
Fetal anomalies v1.467 PIK3C2A Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.467 PIK3C2A Arina Puzriakova Gene: pik3c2a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.466 PIK3C2A Arina Puzriakova Tag for-review tag was added to gene: PIK3C2A.
Fetal anomalies v1.466 PIH1D3 Arina Puzriakova Tag for-review tag was added to gene: PIH1D3.
Fetal anomalies v1.466 PIBF1 Arina Puzriakova Classified gene: PIBF1 as Amber List (moderate evidence)
Fetal anomalies v1.466 PIBF1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.466 PIBF1 Arina Puzriakova Gene: pibf1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.465 PIBF1 Arina Puzriakova Tag for-review tag was added to gene: PIBF1.
Fetal anomalies v1.465 PFKM Arina Puzriakova Phenotypes for gene: PFKM were changed from Glycogen storage disease VII to Glycogen storage disease VII, OMIM:232800; Glycogen storage disease VII, MONDO:0009295
Fetal anomalies v1.464 PFKM Arina Puzriakova Classified gene: PFKM as Amber List (moderate evidence)
Fetal anomalies v1.464 PFKM Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.464 PFKM Arina Puzriakova Gene: pfkm has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.463 PFKM Arina Puzriakova Tag for-review tag was added to gene: PFKM.
Fetal anomalies v1.463 PBX1 Arina Puzriakova Phenotypes for gene: PBX1 were changed from Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM:617641; Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MONDO:0060549
Fetal anomalies v1.462 PBX1 Arina Puzriakova Classified gene: PBX1 as Amber List (moderate evidence)
Fetal anomalies v1.462 PBX1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.462 PBX1 Arina Puzriakova Gene: pbx1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.461 PBX1 Arina Puzriakova Tag for-review tag was added to gene: PBX1.
Fetal anomalies v1.461 PAX7 Arina Puzriakova Phenotypes for gene: PAX7 were changed from Myopathy, congenital, progressive, with scoliosis to Myopathy, congenital, progressive, with scoliosis, OMIM:618578; Myopathy, congenital, progressive, with scoliosis, MONDO:0032821
Fetal anomalies v1.460 PAX7 Arina Puzriakova Classified gene: PAX7 as Amber List (moderate evidence)
Fetal anomalies v1.460 PAX7 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.460 PAX7 Arina Puzriakova Gene: pax7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.459 PAX7 Arina Puzriakova Tag for-review tag was added to gene: PAX7.
Fetal anomalies v1.459 NXN Arina Puzriakova Phenotypes for gene: NXN were changed from Robinow syndrome, autosomal recessive 2 to Robinow syndrome, autosomal recessive 2, OMIM:618529; Robinow syndrome, autosomal recessive 2, MONDO:0032800
Fetal anomalies v1.458 NXN Arina Puzriakova Classified gene: NXN as Amber List (moderate evidence)
Fetal anomalies v1.458 NXN Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.458 NXN Arina Puzriakova Gene: nxn has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.457 NXN Arina Puzriakova Tag for-review tag was added to gene: NXN.
Fetal anomalies v1.457 NECTIN1 Arina Puzriakova Phenotypes for gene: NECTIN1 were changed from Cleft lip/palate-ectodermal dysplasia syndrome; Orofacial cleft 7 to Cleft lip/palate-ectodermal dysplasia syndrome, OMIM:225060; Orofacial cleft 7, OMIM:225060
Fetal anomalies v1.456 NIPAL4 Arina Puzriakova Phenotypes for gene: NIPAL4 were changed from Ichthyosis, congenital, autosomal recessive 6 to Ichthyosis, congenital, autosomal recessive 6, OMIM:612281; Autosomal recessive congenital ichthyosis 6, MONDO:0012847
Fetal anomalies v1.455 NIPAL4 Arina Puzriakova Classified gene: NIPAL4 as Amber List (moderate evidence)
Fetal anomalies v1.455 NIPAL4 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.455 NIPAL4 Arina Puzriakova Gene: nipal4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.454 NIPAL4 Arina Puzriakova Tag for-review tag was added to gene: NIPAL4.
Fetal anomalies v1.454 NECTIN1 Arina Puzriakova Classified gene: NECTIN1 as Amber List (moderate evidence)
Fetal anomalies v1.454 NECTIN1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.454 NECTIN1 Arina Puzriakova Gene: nectin1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.453 NECTIN1 Arina Puzriakova Tag for-review tag was added to gene: NECTIN1.
Fetal anomalies v1.453 NADSYN1 Arina Puzriakova Phenotypes for gene: NADSYN1 were changed from Vertebral, cardiac, renal, and limb defects syndrome 3 to Vertebral, cardiac, renal, and limb defects syndrome 3, OMIM:618845; Vertebral, cardiac, renal, and limb defects syndrome 3, MONDO:0030077
Fetal anomalies v1.452 NADSYN1 Arina Puzriakova Classified gene: NADSYN1 as Amber List (moderate evidence)
Fetal anomalies v1.452 NADSYN1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.452 NADSYN1 Arina Puzriakova Gene: nadsyn1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.451 NADSYN1 Arina Puzriakova Tag for-review tag was added to gene: NADSYN1.
Fetal anomalies v1.451 MYPN Arina Puzriakova Classified gene: MYPN as Amber List (moderate evidence)
Fetal anomalies v1.451 MYPN Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.451 MYPN Arina Puzriakova Gene: mypn has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.450 MYPN Arina Puzriakova Tag for-review tag was added to gene: MYPN.
Fetal anomalies v1.450 MOGS Arina Puzriakova Phenotypes for gene: MOGS were changed from CONGENITAL DISORDERS OF GLYCOSYLATION to Congenital disorder of glycosylation, type IIb, OMIM:606056; MOGS-CDG, MONDO:0011629
Fetal anomalies v1.449 MOGS Arina Puzriakova Classified gene: MOGS as Amber List (moderate evidence)
Fetal anomalies v1.449 MOGS Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.449 MOGS Arina Puzriakova Gene: mogs has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.448 MOGS Arina Puzriakova Tag for-review tag was added to gene: MOGS.
Fetal anomalies v1.448 MEOX1 Arina Puzriakova Phenotypes for gene: MEOX1 were changed from KLIPPEL-FEIL ANOMALY to Klippel-Feil syndrome 2, OMIM:214300; Klippel-Feil syndrome 2, autosomal recessive, MONDO:0008958
Fetal anomalies v1.447 MEOX1 Arina Puzriakova Classified gene: MEOX1 as Amber List (moderate evidence)
Fetal anomalies v1.447 MEOX1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.447 MEOX1 Arina Puzriakova Gene: meox1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.446 MEOX1 Arina Puzriakova Tag for-review tag was added to gene: MEOX1.
Fetal anomalies v1.446 MAP3K7 Arina Puzriakova Phenotypes for gene: MAP3K7 were changed from Cardiospondylocarpofacial syndrome; FRONTOMETAPHYSEAL DYSPLASIA to Cardiospondylocarpofacial syndrome, OMIM:157800; Cardiospondylocarpofacial syndrome, MONDO:0008005; Frontometaphyseal dysplasia 2, OMIM:617137; Frontometaphyseal dysplasia 2, MONDO:0014935
Fetal anomalies v1.445 MAP3K7 Arina Puzriakova Classified gene: MAP3K7 as Amber List (moderate evidence)
Fetal anomalies v1.445 MAP3K7 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.445 MAP3K7 Arina Puzriakova Gene: map3k7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.444 MAP3K7 Arina Puzriakova Tag for-review tag was added to gene: MAP3K7.
Fetal anomalies v1.444 LONP1 Arina Puzriakova Phenotypes for gene: LONP1 were changed from CODAS SYNDROME to CODAS syndrome, OMIM:600373; CODAS syndrome, MONDO:0010879
Fetal anomalies v1.443 LONP1 Arina Puzriakova Classified gene: LONP1 as Amber List (moderate evidence)
Fetal anomalies v1.443 LONP1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.443 LONP1 Arina Puzriakova Gene: lonp1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.442 LONP1 Arina Puzriakova Tag for-review tag was added to gene: LONP1.
Fetal anomalies v1.442 LAMB1 Arina Puzriakova Phenotypes for gene: LAMB1 were changed from COBBLESTONE BRAIN MALFORMATION WITHOUT MUSCULAR OR OCULAR ABNORMALITIES to Lissencephaly 5, OMIM:615191; Cobblestone lissencephaly without muscular or ocular involvement, MONDO:0014077
Fetal anomalies v1.441 LAMB1 Arina Puzriakova Classified gene: LAMB1 as Amber List (moderate evidence)
Fetal anomalies v1.441 LAMB1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.441 LAMB1 Arina Puzriakova Gene: lamb1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.440 LAMB1 Arina Puzriakova Tag for-review tag was added to gene: LAMB1.
Fetal anomalies v1.440 KLHL7 Arina Puzriakova Phenotypes for gene: KLHL7 were changed from Cold-induced sweating syndrome type 1 (CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa to PERCHING syndrome, OMIM:617055; PERCHING syndrome, MONDO:0014890
Fetal anomalies v1.439 KLHL7 Arina Puzriakova Classified gene: KLHL7 as Amber List (moderate evidence)
Fetal anomalies v1.439 KLHL7 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.439 KLHL7 Arina Puzriakova Gene: klhl7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.438 KLHL7 Arina Puzriakova Tag for-review tag was added to gene: KLHL7.
Fetal anomalies v1.438 KIF5C Arina Puzriakova Phenotypes for gene: KIF5C were changed from CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 2 to Cortical dysplasia, complex, with other brain malformations 2, OMIM:615282; Complex cortical dysplasia with other brain malformations 2, MONDO:0014116
Fetal anomalies v1.437 KIF5C Arina Puzriakova Classified gene: KIF5C as Amber List (moderate evidence)
Fetal anomalies v1.437 KIF5C Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.437 KIF5C Arina Puzriakova Gene: kif5c has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.436 KIF5C Arina Puzriakova Tag for-review tag was added to gene: KIF5C.
Fetal anomalies v1.436 USP9X Catherine Snow Classified gene: USP9X as Amber List (moderate evidence)
Fetal anomalies v1.436 USP9X Catherine Snow Added comment: Comment on list classification: Gene reviewed by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.436 USP9X Catherine Snow Gene: usp9x has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.435 HESX1 Arina Puzriakova Phenotypes for gene: HESX1 were changed from HESX1-RELATED COMBINED PITUITARY HORMONE DEFICIENCY; SEPTOOPTIC DYSPLASIA to Septooptic dysplasia, OMIM:182230; Septooptic dysplasia, MONDO:0008428
Fetal anomalies v1.434 USP9X Catherine Snow Tag for-review tag was added to gene: USP9X.
Fetal anomalies v1.434 VAMP1 Catherine Snow Classified gene: VAMP1 as Amber List (moderate evidence)
Fetal anomalies v1.434 VAMP1 Catherine Snow Gene: vamp1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.434 HIST1H1E Arina Puzriakova Phenotypes for gene: HIST1H1E were changed from Childhood overgrowth to Rahman syndrome, OMIM:617537; Rahman syndrome, MONDO:0044323
Fetal anomalies v1.433 KIF2A Arina Puzriakova Phenotypes for gene: KIF2A were changed from MALFORMATIONS OF CORTICAL DEVELOPMENT AND MICROCEPHALY. to Cortical dysplasia, complex, with other brain malformations 3, OMIM:615411; Complex cortical dysplasia with other brain malformations 3, MONDO:0014170
Fetal anomalies v1.432 KIF2A Arina Puzriakova Classified gene: KIF2A as Amber List (moderate evidence)
Fetal anomalies v1.432 KIF2A Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.432 KIF2A Arina Puzriakova Gene: kif2a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.431 KIF2A Arina Puzriakova Tag for-review tag was added to gene: KIF2A.
Fetal anomalies v1.431 ITGA8 Arina Puzriakova Phenotypes for gene: ITGA8 were changed from bilateral renal agenesis; anhydramnios; RENAL HYPODYSPLASIA/APLASIA 1; Renal hypodysplasia/aplasia 1, 191830 to Renal hypodysplasia/aplasia 1, OMIM:191830; Renal hypodysplasia/aplasia 1, MONDO:0024519
Fetal anomalies v1.430 VAMP1 Catherine Snow Tag for-review tag was added to gene: VAMP1.
Fetal anomalies v1.430 VAMP1 Catherine Snow Publications for gene: VAMP1 were set to
Fetal anomalies v1.429 VAMP1 Catherine Snow Classified gene: VAMP1 as Amber List (moderate evidence)
Fetal anomalies v1.429 VAMP1 Catherine Snow Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.429 VAMP1 Catherine Snow Gene: vamp1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.428 VEGFC Catherine Snow changed review comment from: Comment on list classification: Comment on list classification: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag); to: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Early onset or syndromic epilepsy v2.285 SEMA6B Sarah Leigh Phenotypes for gene: SEMA6B were changed from Epilepsy, progressive myoclonic, 11, 618876 to Epilepsy, progressive myoclonic, 11 OMIM:618876
Primary immunodeficiency or monogenic inflammatory bowel disease v2.401 STXBP3 Ivone Leong Classified gene: STXBP3 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.401 STXBP3 Ivone Leong Added comment: Comment on list classification: New gene added by Kelsey Jones (Great Ormond Street Hospital). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. Based on the available evidence this gene has been given an Amber rating.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.401 STXBP3 Ivone Leong Gene: stxbp3 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.400 SLC9A3 Ivone Leong Classified gene: SLC9A3 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.400 SLC9A3 Ivone Leong Added comment: Comment on list classification: New gene added by Kelsey Jones (Great Ormond Street Hospital). This gene is associated with a phenotype in OMIM and not Gene2Phenotype. Based on the expert review and available evidence this gene has been given an Amber rating.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.400 SLC9A3 Ivone Leong Gene: slc9a3 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.399 SLC9A3 Ivone Leong Phenotypes for gene: SLC9A3 were changed from Very Early Onset Inflammatory Bowel Disease; Congenital sodium diarrhoea to Very Early Onset Inflammatory Bowel Disease; Diarrhea 8, secretory sodium, congenital, OMIM:616868
Primary immunodeficiency or monogenic inflammatory bowel disease v2.398 NPC1 Ivone Leong Classified gene: NPC1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.398 NPC1 Ivone Leong Added comment: Comment on list classification: New gene added by Kelsey Jones (Great Ormond Street Hospital). This gene is associated with a phenotype in OMIM and Gene2Phenotype. Based on the expert review and available evidence, this gene is recommended to be Green at the next review.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.398 NPC1 Ivone Leong Gene: npc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.750 PIGK Sarah Leigh Phenotypes for gene: PIGK were changed from Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures OMIM:618879
Early onset or syndromic epilepsy v2.284 PIGK Sarah Leigh Phenotypes for gene: PIGK were changed from Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures 618879 to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures OMIM:618879
Primary immunodeficiency or monogenic inflammatory bowel disease v2.397 NPC1 Ivone Leong Tag for-review tag was added to gene: NPC1.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.397 STXBP3 Ivone Leong Publications for gene: STXBP3 were set to PMID: 33346580
Primary immunodeficiency or monogenic inflammatory bowel disease v2.396 SLC9A3 Ivone Leong Publications for gene: SLC9A3 were set to PMID: 26358773
Primary immunodeficiency or monogenic inflammatory bowel disease v2.395 NPC1 Ivone Leong Publications for gene: NPC1 were set to PMID: 26953272
Primary immunodeficiency or monogenic inflammatory bowel disease v2.394 COL7A1 Ivone Leong Classified gene: COL7A1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.394 COL7A1 Ivone Leong Added comment: Comment on list classification: New gene added by Kelsey Jones (Great Ormond Street Hospital). This gene is associated with a phenotype in OMIM and Gene2Phenotype. This gene has been given an Amber rating.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.394 COL7A1 Ivone Leong Gene: col7a1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.393 COL7A1 Ivone Leong Publications for gene: COL7A1 were set to PMID: 18363753
Fetal anomalies v1.428 ITGA8 Arina Puzriakova Classified gene: ITGA8 as Amber List (moderate evidence)
Fetal anomalies v1.428 ITGA8 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)

ITGA8 is also Green on the 'Unexplained paediatric onset end-stage renal disease v.1.2' GMS panel
Fetal anomalies v1.428 ITGA8 Arina Puzriakova Gene: itga8 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.427 ITGA8 Arina Puzriakova Tag for-review tag was added to gene: ITGA8.
Fetal anomalies v1.427 HIST1H1E Arina Puzriakova Classified gene: HIST1H1E as Amber List (moderate evidence)
Fetal anomalies v1.427 HIST1H1E Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.427 HIST1H1E Arina Puzriakova Gene: hist1h1e has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.426 HIST1H1E Arina Puzriakova Tag for-review tag was added to gene: HIST1H1E.
Fetal anomalies v1.426 HESX1 Arina Puzriakova Classified gene: HESX1 as Amber List (moderate evidence)
Fetal anomalies v1.426 HESX1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.426 HESX1 Arina Puzriakova Gene: hesx1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.425 HESX1 Arina Puzriakova Tag for-review tag was added to gene: HESX1.
Fetal anomalies v1.425 GZF1 Arina Puzriakova Phenotypes for gene: GZF1 were changed from LARSEN SYNDROME to Joint laxity, short stature, and myopia, OMIM:617662; Joint laxity, short stature, and myopia, MONDO:0060556
Fetal anomalies v1.424 GZF1 Arina Puzriakova Classified gene: GZF1 as Amber List (moderate evidence)
Fetal anomalies v1.424 GZF1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.424 GZF1 Arina Puzriakova Gene: gzf1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.423 GZF1 Arina Puzriakova Tag for-review tag was added to gene: GZF1.
Fetal anomalies v1.423 GPC6 Arina Puzriakova Phenotypes for gene: GPC6 were changed from OMODYSPLASIA TYPE 1 (OMOD1) [ to Omodysplasia 1, OMIM:258315; Autosomal recessive omodysplasia, MONDO:0009779
Fetal anomalies v1.422 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome to Meier-Gorlin syndrome 6, OMIM:616835; Meier-Gorlin syndrome 6, MONDO:0014794
Fetal anomalies v1.421 GPC6 Arina Puzriakova Classified gene: GPC6 as Amber List (moderate evidence)
Fetal anomalies v1.421 GPC6 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.421 GPC6 Arina Puzriakova Gene: gpc6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.420 GPC6 Arina Puzriakova Tag for-review tag was added to gene: GPC6.
Fetal anomalies v1.420 GMNN Arina Puzriakova Classified gene: GMNN as Amber List (moderate evidence)
Fetal anomalies v1.420 GMNN Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.420 GMNN Arina Puzriakova Gene: gmnn has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.419 GMNN Arina Puzriakova Tag for-review tag was added to gene: GMNN.
Fetal anomalies v1.419 HADHB Arina Puzriakova Phenotypes for gene: HADHB were changed from Trifunctional protein deficiency to Trifunctional protein deficiency, OMIM:609015; Mitochondrial trifunctional protein deficiency, MONDO:0012172
Fetal anomalies v1.418 GSC Arina Puzriakova Phenotypes for gene: GSC were changed from Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, OMIM:602471; Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome, MONDO:0011227
Fetal anomalies v1.417 HADHB Arina Puzriakova Classified gene: HADHB as Amber List (moderate evidence)
Fetal anomalies v1.417 HADHB Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.417 HADHB Arina Puzriakova Gene: hadhb has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.416 HADHB Arina Puzriakova Tag for-review tag was added to gene: HADHB.
Fetal anomalies v1.416 GSC Arina Puzriakova Classified gene: GSC as Amber List (moderate evidence)
Fetal anomalies v1.416 GSC Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.416 GSC Arina Puzriakova Gene: gsc has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.415 GSC Arina Puzriakova Tag for-review tag was added to gene: GSC.
Fetal anomalies v1.415 GLI1 Arina Puzriakova Phenotypes for gene: GLI1 were changed from Polydactyly, postaxial, type A8 618123; Polydactyly, preaxial I 174400 to Polydactyly, postaxial, type A8, OMIM:618123; Polydactyly, postaxial, type A8, MONDO:0029130; Polydactyly, preaxial I, OMIM:174400; Preaxial polydactyly of fingers, MONDO:0017425
Fetal anomalies v1.414 GFPT1 Arina Puzriakova Phenotypes for gene: GFPT1 were changed from Myasthenia, congenital, 12, with tubular aggregates to Myasthenia, congenital, 12, with tubular aggregates, OMIM:610542; Congenital myasthenic syndrome 12, MONDO:0012518
Fetal anomalies v1.413 GATA3 Arina Puzriakova Phenotypes for gene: GATA3 were changed from Hypoparathyroidism, sensorineural deafness, and renal dysplasia to Hypoparathyroidism, sensorineural deafness, and renal dysplasia, OMIM:146255; Hypoparathyroidism-deafness-renal disease syndrome, MONDO:0007797
Fetal anomalies v1.412 GANAB Arina Puzriakova Phenotypes for gene: GANAB were changed from Polycystic kidney disease 3 to Polycystic kidney disease 3, OMIM:600666; Polycystic kidney disease 3 with or without polycystic liver disease, MONDO:0010916
Fetal anomalies v1.411 FZD2 Arina Puzriakova Phenotypes for gene: FZD2 were changed from Omodysplasia 2 to Omodysplasia 2, OMIM:164745; Autosomal dominant omodysplasia, MONDO:0008123
Fetal anomalies v1.410 FUT8 Arina Puzriakova Phenotypes for gene: FUT8 were changed from Congenital disorder of glycosylation with defective fucosylation 1 to Congenital disorder of glycosylation with defective fucosylation 1, OMIM:618005; Congenital disorder of glycosylation with defective fucosylation 1, MONDO:0020775
Fetal anomalies v1.409 FKBP10 Arina Puzriakova Phenotypes for gene: FKBP10 were changed from Bruck syndrome 1; Osteogenesis imperfecta, type XI to Bruck syndrome 1, OMIM:259450; Bruck syndrome 1, MONDO:0009806; Osteogenesis imperfecta, type XI, OMIM:610968; Osteogenesis imperfecta type 11, MONDO:0012592
Fetal anomalies v1.408 GLI1 Arina Puzriakova Classified gene: GLI1 as Amber List (moderate evidence)
Fetal anomalies v1.408 GLI1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.408 GLI1 Arina Puzriakova Gene: gli1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.407 GLI1 Arina Puzriakova Tag for-review tag was added to gene: GLI1.
Fetal anomalies v1.407 GFPT1 Arina Puzriakova Classified gene: GFPT1 as Amber List (moderate evidence)
Fetal anomalies v1.407 GFPT1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.407 GFPT1 Arina Puzriakova Gene: gfpt1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.406 GFPT1 Arina Puzriakova Tag for-review tag was added to gene: GFPT1.
Fetal anomalies v1.406 GATA3 Arina Puzriakova Classified gene: GATA3 as Amber List (moderate evidence)
Fetal anomalies v1.406 GATA3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.406 GATA3 Arina Puzriakova Gene: gata3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.405 GATA3 Arina Puzriakova Tag for-review tag was added to gene: GATA3.
Fetal anomalies v1.405 GANAB Arina Puzriakova Classified gene: GANAB as Amber List (moderate evidence)
Fetal anomalies v1.405 GANAB Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.405 GANAB Arina Puzriakova Gene: ganab has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.404 GANAB Arina Puzriakova Tag for-review tag was added to gene: GANAB.
Fetal anomalies v1.404 FZD2 Arina Puzriakova Classified gene: FZD2 as Amber List (moderate evidence)
Fetal anomalies v1.404 FZD2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.404 FZD2 Arina Puzriakova Gene: fzd2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.403 FZD2 Arina Puzriakova Tag for-review tag was added to gene: FZD2.
Fetal anomalies v1.403 FUT8 Arina Puzriakova Classified gene: FUT8 as Amber List (moderate evidence)
Fetal anomalies v1.403 FUT8 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.403 FUT8 Arina Puzriakova Gene: fut8 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.402 FUT8 Arina Puzriakova Tag for-review tag was added to gene: FUT8.
Fetal anomalies v1.402 FKBP10 Arina Puzriakova Classified gene: FKBP10 as Amber List (moderate evidence)
Fetal anomalies v1.402 FKBP10 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.402 FKBP10 Arina Puzriakova Gene: fkbp10 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.401 FKBP10 Arina Puzriakova Tag for-review tag was added to gene: FKBP10.
Fetal anomalies v1.401 FAM46A Arina Puzriakova Phenotypes for gene: FAM46A were changed from Osteogenesis imperfecta, type XVIII to Osteogenesis imperfecta, type XVIII, OMIM:617952; Osteogenesis imperfecta, type 18, MONDO:0044329
Fetal anomalies v1.400 FAM46A Arina Puzriakova Classified gene: FAM46A as Amber List (moderate evidence)
Fetal anomalies v1.400 FAM46A Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.400 FAM46A Arina Puzriakova Gene: fam46a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.399 FAM46A Arina Puzriakova Tag for-review tag was added to gene: FAM46A.
Fetal anomalies v1.399 EMX2 Arina Puzriakova Classified gene: EMX2 as Amber List (moderate evidence)
Fetal anomalies v1.399 EMX2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.399 EMX2 Arina Puzriakova Gene: emx2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.398 EMX2 Arina Puzriakova Tag for-review tag was added to gene: EMX2.
Fetal anomalies v1.398 EML1 Arina Puzriakova Classified gene: EML1 as Amber List (moderate evidence)
Fetal anomalies v1.398 EML1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.398 EML1 Arina Puzriakova Gene: eml1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.397 EML1 Arina Puzriakova Tag for-review tag was added to gene: EML1.
Fetal anomalies v1.397 DZIP1L Arina Puzriakova Classified gene: DZIP1L as Amber List (moderate evidence)
Fetal anomalies v1.397 DZIP1L Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.397 DZIP1L Arina Puzriakova Gene: dzip1l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.396 DZIP1L Arina Puzriakova Tag for-review tag was added to gene: DZIP1L.
Fetal anomalies v1.396 GALNT2 Sarah Leigh Classified gene: GALNT2 as Amber List (moderate evidence)
Fetal anomalies v1.396 GALNT2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Fetal anomalies v1.396 GALNT2 Sarah Leigh Gene: galnt2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.395 GALNT2 Sarah Leigh Phenotypes for gene: GALNT2 were changed from Congenital disorder of glycosylation, type IIt to Congenital disorder of glycosylation, type IIt OMIM:618885
Early onset or syndromic epilepsy v2.283 GALNT2 Sarah Leigh Phenotypes for gene: GALNT2 were changed from Congenital disorder of glycosylation, type IIt 618885 to Congenital disorder of glycosylation, type IIt OMIM:618885
Fetal anomalies v1.394 GALNT2 Sarah Leigh Publications for gene: GALNT2 were set to
Fetal anomalies v1.393 GALNT2 Sarah Leigh reviewed gene: GALNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v1.393 GALNT2 Sarah Leigh Tag for-review tag was added to gene: GALNT2.
Fetal anomalies v1.393 VEGFC Catherine Snow Classified gene: VEGFC as Amber List (moderate evidence)
Fetal anomalies v1.393 VEGFC Catherine Snow Added comment: Comment on list classification: Comment on list classification: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.393 VEGFC Catherine Snow Gene: vegfc has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.392 VEGFC Catherine Snow Tag for-review tag was added to gene: VEGFC.
Fetal anomalies v1.392 DYNC2LI1 Arina Puzriakova Classified gene: DYNC2LI1 as Amber List (moderate evidence)
Fetal anomalies v1.392 DYNC2LI1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.392 DYNC2LI1 Arina Puzriakova Gene: dync2li1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.391 DYNC2LI1 Arina Puzriakova Tag for-review tag was added to gene: DYNC2LI1.
Fetal anomalies v1.391 VRK1 Catherine Snow Classified gene: VRK1 as Amber List (moderate evidence)
Fetal anomalies v1.391 VRK1 Catherine Snow Added comment: Comment on list classification: Comment on list classification: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.391 VRK1 Catherine Snow Gene: vrk1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.390 VRK1 Catherine Snow Tag for-review tag was added to gene: VRK1.
Early onset or syndromic epilepsy v2.282 GAD1 Sarah Leigh Publications for gene: GAD1 were set to 15571623; 26503795; 24896178; 26350204; https://doi-org.ezproxy.library.qmul.ac.uk/10.1093/brain/awaa085
Fetal anomalies v1.390 WDR73 Catherine Snow Tag for-review tag was added to gene: WDR73.
Fetal anomalies v1.390 WDR73 Catherine Snow Classified gene: WDR73 as Amber List (moderate evidence)
Fetal anomalies v1.390 WDR73 Catherine Snow Added comment: Comment on list classification: Comment on list classification: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.390 WDR73 Catherine Snow Gene: wdr73 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.389 FIG4 Arina Puzriakova Phenotypes for gene: FIG4 were changed from CLEIDOCRANIAL DYSPLASIA WITH MICROGNATHIA, ABSENT THUMBS, AND DISTAL APHALANGIA YUNIS-VARON SYNDROME; CHARCOT-MARIE-TOOTH DISEASE, TYPE 4J to Yunis-Varon syndrome, OMIM:216340; Yunis-Varon syndrome, MONDO:0008995; Charcot-Marie-Tooth disease, type 4J, OMIM:611228; Charcot-Marie-Tooth disease type 4J, MONDO:0012640; ?Polymicrogyria, bilateral temporooccipital, OMIM:612691; Bilateral parasagittal parieto-occipital polymicrogyria, MONDO:0012986
Fetal anomalies v1.388 XYLT2 Catherine Snow Classified gene: XYLT2 as Amber List (moderate evidence)
Fetal anomalies v1.388 XYLT2 Catherine Snow Added comment: Comment on list classification: Comment on list classification: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.388 XYLT2 Catherine Snow Gene: xylt2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.387 XYLT2 Catherine Snow Tag for-review tag was added to gene: XYLT2.
Fetal anomalies v1.387 FANCL Arina Puzriakova Phenotypes for gene: FANCL were changed from FANCL-RELATED FANCONI ANEMIA; FANCONI ANEMIA to Fanconi anemia, complementation group L, OMIM:614083; Fanconi anemia complementation group L, MONDO:0013566
Fetal anomalies v1.386 EIF2S3 Arina Puzriakova Phenotypes for gene: EIF2S3 were changed from Syndromic ID with severe microcephaly to MEHMO syndrome, OMIM:300148; MEHMO syndrome, MONDO:0010258
Fetal anomalies v1.385 EED Arina Puzriakova Phenotypes for gene: EED were changed from Weaver-like overgrowth syndrome to Cohen-Gibson syndrome, OMIM:617561; Cohen-Gibson syndrome, MONDO:0060510
Fetal anomalies v1.384 FIG4 Arina Puzriakova Classified gene: FIG4 as Amber List (moderate evidence)
Fetal anomalies v1.384 FIG4 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.384 FIG4 Arina Puzriakova Gene: fig4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.383 FIG4 Arina Puzriakova Tag for-review tag was added to gene: FIG4.
Fetal anomalies v1.383 FANCL Arina Puzriakova Classified gene: FANCL as Amber List (moderate evidence)
Fetal anomalies v1.383 FANCL Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.383 FANCL Arina Puzriakova Gene: fancl has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.382 FANCL Arina Puzriakova Tag for-review tag was added to gene: FANCL.
Fetal anomalies v1.382 EIF2S3 Arina Puzriakova Classified gene: EIF2S3 as Amber List (moderate evidence)
Fetal anomalies v1.382 EIF2S3 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.382 EIF2S3 Arina Puzriakova Gene: eif2s3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.381 EIF2S3 Arina Puzriakova Tag for-review tag was added to gene: EIF2S3.
Fetal anomalies v1.381 EED Arina Puzriakova Classified gene: EED as Amber List (moderate evidence)
Fetal anomalies v1.381 EED Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.381 EED Arina Puzriakova Gene: eed has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.380 EED Arina Puzriakova Tag for-review tag was added to gene: EED.
Fetal anomalies v1.380 DPM3 Arina Puzriakova Phenotypes for gene: DPM3 were changed from CONGENITAL DISORDER OF GLYCOSYLATION TYPE 1O to ?Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15, 618992; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15, 612937
Fetal anomalies v1.379 DPM3 Arina Puzriakova Classified gene: DPM3 as Amber List (moderate evidence)
Fetal anomalies v1.379 DPM3 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.379 DPM3 Arina Puzriakova Gene: dpm3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.378 DPM3 Arina Puzriakova Tag for-review tag was added to gene: DPM3.
Fetal anomalies v1.378 DDX59 Arina Puzriakova Phenotypes for gene: DDX59 were changed from OROFACIODIGITAL SYNDROME to Orofaciodigital syndrome V, OMIM:174300; Orofaciodigital syndrome V, MONDO:0008267
Fetal anomalies v1.377 DENND5A Arina Puzriakova Phenotypes for gene: DENND5A were changed from EPILEPTIC ENCEPHALOPATHY to Developmental and epileptic encephalopathy 49, OMIM:617281; Developmental and epileptic encephalopathy, 49, MONDO:0015002
Fetal anomalies v1.376 DNAAF5 Arina Puzriakova Phenotypes for gene: DNAAF5 were changed from CILIARY DYSKINESIA, PRIMARY, 18 to Ciliary dyskinesia, primary, 18, OMIM:614874; Primary ciliary dyskinesia 18, MONDO:0013940
Fetal anomalies v1.375 DNAAF5 Arina Puzriakova Classified gene: DNAAF5 as Amber List (moderate evidence)
Fetal anomalies v1.375 DNAAF5 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.375 DNAAF5 Arina Puzriakova Gene: dnaaf5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.374 DNAAF5 Arina Puzriakova Tag for-review tag was added to gene: DNAAF5.
Fetal anomalies v1.374 DENND5A Arina Puzriakova Classified gene: DENND5A as Amber List (moderate evidence)
Fetal anomalies v1.374 DENND5A Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.374 DENND5A Arina Puzriakova Gene: dennd5a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.373 DENND5A Arina Puzriakova Tag for-review tag was added to gene: DENND5A.
Fetal anomalies v1.373 DDX59 Arina Puzriakova Classified gene: DDX59 as Amber List (moderate evidence)
Fetal anomalies v1.373 DDX59 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.373 DDX59 Arina Puzriakova Gene: ddx59 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.372 DDX59 Arina Puzriakova Tag for-review tag was added to gene: DDX59.
Fetal anomalies v1.372 DPM2 Arina Puzriakova Classified gene: DPM2 as Amber List (moderate evidence)
Fetal anomalies v1.372 DPM2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.372 DPM2 Arina Puzriakova Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.371 DPM2 Arina Puzriakova Tag for-review tag was added to gene: DPM2.
Fetal anomalies v1.371 DONSON Arina Puzriakova Classified gene: DONSON as Amber List (moderate evidence)
Fetal anomalies v1.371 DONSON Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.371 DONSON Arina Puzriakova Gene: donson has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.370 DONSON Arina Puzriakova Tag for-review tag was added to gene: DONSON.
Fetal anomalies v1.370 ZMYND10 Catherine Snow Classified gene: ZMYND10 as Amber List (moderate evidence)
Fetal anomalies v1.370 ZMYND10 Catherine Snow Added comment: Comment on list classification: Comment on list classification: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.370 ZMYND10 Catherine Snow Gene: zmynd10 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.369 ZMYND10 Catherine Snow Tag for-review tag was added to gene: ZMYND10.
Fetal anomalies v1.369 DNM2 Arina Puzriakova Classified gene: DNM2 as Amber List (moderate evidence)
Fetal anomalies v1.369 DNM2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.369 DNM2 Arina Puzriakova Gene: dnm2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.368 DNM2 Arina Puzriakova Tag for-review tag was added to gene: DNM2.
Fetal anomalies v1.368 DNM1L Arina Puzriakova Classified gene: DNM1L as Amber List (moderate evidence)
Fetal anomalies v1.368 DNM1L Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.368 DNM1L Arina Puzriakova Gene: dnm1l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.367 DNM1L Arina Puzriakova Tag for-review tag was added to gene: DNM1L.
Fetal anomalies v1.367 DNAL1 Arina Puzriakova Classified gene: DNAL1 as Amber List (moderate evidence)
Fetal anomalies v1.367 DNAL1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.367 DNAL1 Arina Puzriakova Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.366 DNAL1 Arina Puzriakova Tag for-review tag was added to gene: DNAL1.
Fetal anomalies v1.366 DNAJB11 Arina Puzriakova Classified gene: DNAJB11 as Amber List (moderate evidence)
Fetal anomalies v1.366 DNAJB11 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.366 DNAJB11 Arina Puzriakova Gene: dnajb11 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.365 DNAJB11 Arina Puzriakova Tag for-review tag was added to gene: DNAJB11.
Fetal anomalies v1.365 DNAI2 Arina Puzriakova Classified gene: DNAI2 as Amber List (moderate evidence)
Fetal anomalies v1.365 DNAI2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.365 DNAI2 Arina Puzriakova Gene: dnai2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.364 DNAI2 Arina Puzriakova Tag for-review tag was added to gene: DNAI2.
Fetal anomalies v1.364 DNAAF2 Arina Puzriakova Classified gene: DNAAF2 as Amber List (moderate evidence)
Fetal anomalies v1.364 DNAAF2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.364 DNAAF2 Arina Puzriakova Gene: dnaaf2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.363 DNAAF2 Arina Puzriakova Tag for-review tag was added to gene: DNAAF2.
Fetal anomalies v1.363 DLX5 Arina Puzriakova Classified gene: DLX5 as Amber List (moderate evidence)
Fetal anomalies v1.363 DLX5 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.363 DLX5 Arina Puzriakova Gene: dlx5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.362 DLX5 Arina Puzriakova Tag for-review tag was added to gene: DLX5.
Fetal anomalies v1.362 DISP1 Arina Puzriakova Classified gene: DISP1 as Amber List (moderate evidence)
Fetal anomalies v1.362 DISP1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.362 DISP1 Arina Puzriakova Gene: disp1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.361 DISP1 Arina Puzriakova Tag for-review tag was added to gene: DISP1.
Fetal anomalies v1.361 DIAPH1 Arina Puzriakova Classified gene: DIAPH1 as Amber List (moderate evidence)
Fetal anomalies v1.361 DIAPH1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.361 DIAPH1 Arina Puzriakova Gene: diaph1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.360 DIAPH1 Arina Puzriakova Tag for-review tag was added to gene: DIAPH1.
Fetal anomalies v1.360 CYP4F22 Arina Puzriakova Classified gene: CYP4F22 as Amber List (moderate evidence)
Fetal anomalies v1.360 CYP4F22 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.360 CYP4F22 Arina Puzriakova Gene: cyp4f22 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.359 CYP4F22 Arina Puzriakova Tag for-review tag was added to gene: CYP4F22.
Fetal anomalies v1.359 CYP26B1 Arina Puzriakova Classified gene: CYP26B1 as Amber List (moderate evidence)
Fetal anomalies v1.359 CYP26B1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.359 CYP26B1 Arina Puzriakova Gene: cyp26b1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.358 CYP26B1 Arina Puzriakova Tag for-review tag was added to gene: CYP26B1.
Fetal anomalies v1.358 CTU2 Arina Puzriakova Classified gene: CTU2 as Amber List (moderate evidence)
Fetal anomalies v1.358 CTU2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.358 CTU2 Arina Puzriakova Gene: ctu2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.357 CTU2 Arina Puzriakova Tag for-review tag was added to gene: CTU2.
Fetal anomalies v1.357 CRIPT Arina Puzriakova Classified gene: CRIPT as Amber List (moderate evidence)
Fetal anomalies v1.357 CRIPT Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.357 CRIPT Arina Puzriakova Gene: cript has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.356 CRIPT Arina Puzriakova Tag for-review tag was added to gene: CRIPT.
Skeletal dysplasia v2.81 PKDCC Ivone Leong commented on gene: PKDCC
Skeletal dysplasia v2.81 PKDCC Ivone Leong Tag for-review tag was added to gene: PKDCC.
Fetal anomalies v1.356 ZSWIM6 Catherine Snow Tag for-review tag was added to gene: ZSWIM6.
Fetal anomalies v1.356 COLEC10 Arina Puzriakova Phenotypes for gene: COLEC10 were changed from 3MC to 3MC syndrome 3, OMIM:248340; 3MC syndrome 3, MONDO:0009554
Fetal anomalies v1.355 COL13A1 Arina Puzriakova Phenotypes for gene: COL13A1 were changed from Congenital Myasthenic Syndrome Type 19 to Myasthenic syndrome, congenital, 19, OMIM:616720; Congenital myasthenic syndrome 19, MONDO:0014745
Fetal anomalies v1.355 ZSWIM6 Catherine Snow Classified gene: ZSWIM6 as Amber List (moderate evidence)
Fetal anomalies v1.355 ZSWIM6 Catherine Snow Added comment: Comment on list classification: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.355 ZSWIM6 Catherine Snow Gene: zswim6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.354 COLEC10 Arina Puzriakova Classified gene: COLEC10 as Amber List (moderate evidence)
Fetal anomalies v1.354 COLEC10 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.354 COLEC10 Arina Puzriakova Gene: colec10 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.353 COLEC10 Arina Puzriakova Tag for-review tag was added to gene: COLEC10.
Fetal anomalies v1.353 COL13A1 Arina Puzriakova Classified gene: COL13A1 as Amber List (moderate evidence)
Fetal anomalies v1.353 COL13A1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.353 COL13A1 Arina Puzriakova Gene: col13a1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.352 COL13A1 Arina Puzriakova Tag for-review tag was added to gene: COL13A1.
Fetal anomalies v1.352 COG5 Arina Puzriakova Phenotypes for gene: COG5 were changed from COG5-CDG to Congenital disorder of glycosylation, type III, OMIM:613612; COG5-CDG, MONDO:0013325
Fetal anomalies v1.351 CLP1 Arina Puzriakova Phenotypes for gene: CLP1 were changed from PONTOCEREBELLAR HYPOPLASIA, TYPE 10 to Pontocerebellar hypoplasia, type 10, OMIM:615803; Pontocerebellar hypoplasia type 10, MONDO:0014349
Fetal anomalies v1.350 CIT Arina Puzriakova Phenotypes for gene: CIT were changed from PRIMARY MICROCEPHALY to Microcephaly 17, primary, autosomal recessive, OMIM:617090; Microcephaly 17, primary, autosomal recessive, MONDO:0014908
Fetal anomalies v1.349 COG5 Arina Puzriakova Classified gene: COG5 as Amber List (moderate evidence)
Fetal anomalies v1.349 COG5 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.349 COG5 Arina Puzriakova Gene: cog5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.348 COG5 Arina Puzriakova Tag for-review tag was added to gene: COG5.
Fetal anomalies v1.348 CLP1 Arina Puzriakova Classified gene: CLP1 as Amber List (moderate evidence)
Fetal anomalies v1.348 CLP1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.348 CLP1 Arina Puzriakova Gene: clp1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.347 CLP1 Arina Puzriakova Tag for-review tag was added to gene: CLP1.
Fetal anomalies v1.347 CIT Arina Puzriakova Classified gene: CIT as Amber List (moderate evidence)
Fetal anomalies v1.347 CIT Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.347 CIT Arina Puzriakova Gene: cit has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.346 CIT Arina Puzriakova Tag for-review tag was added to gene: CIT.
Skeletal dysplasia v2.81 SMAD6 Ivone Leong Classified gene: SMAD6 as Amber List (moderate evidence)
Skeletal dysplasia v2.81 SMAD6 Ivone Leong Added comment: Comment on list classification: New gene added by Tracy Lester (Genetics laboratory, Oxford UK). This gene is associated with a phenotype in OMIM and Gene2Phenotype.

Based on the available evidence it is recommended that this gene be given Green status at the next review.
Skeletal dysplasia v2.81 SMAD6 Ivone Leong Gene: smad6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.346 CHMP1A Arina Puzriakova Phenotypes for gene: CHMP1A were changed from PONTOCEREBELLAR HYPOPLASIA AND MICROCEPHALY to Pontocerebellar hypoplasia, type 8, OMIM:614961; Pontocerebellar hypoplasia type 8, MONDO:0013990
Skeletal dysplasia v2.80 SMAD6 Ivone Leong Tag for-review tag was added to gene: SMAD6.
Fetal anomalies v1.345 CFL2 Arina Puzriakova Phenotypes for gene: CFL2 were changed from NEMALINE MYOPATHY 7 to Nemaline myopathy 7, autosomal recessive, OMIM:610687; Nemaline myopathy 7, MONDO:0012538
Fetal anomalies v1.344 CHMP1A Arina Puzriakova Classified gene: CHMP1A as Amber List (moderate evidence)
Fetal anomalies v1.344 CHMP1A Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.344 CHMP1A Arina Puzriakova Gene: chmp1a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.343 CHMP1A Arina Puzriakova Tag for-review tag was added to gene: CHMP1A.
Fetal anomalies v1.343 CFL2 Arina Puzriakova Classified gene: CFL2 as Amber List (moderate evidence)
Fetal anomalies v1.343 CFL2 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.343 CFL2 Arina Puzriakova Gene: cfl2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.342 CFL2 Arina Puzriakova Tag for-review tag was added to gene: CFL2.
Fetal anomalies v1.342 CEP63 Arina Puzriakova Phenotypes for gene: CEP63 were changed from SECKEL SYNDROME 6 to ?Seckel syndrome 6, OMIM:614728; Seckel syndrome 6, MONDO:0013871
Fetal anomalies v1.341 CEP63 Arina Puzriakova Classified gene: CEP63 as Amber List (moderate evidence)
Fetal anomalies v1.341 CEP63 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.341 CEP63 Arina Puzriakova Gene: cep63 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.340 CEP63 Arina Puzriakova Tag for-review tag was added to gene: CEP63.
Fetal anomalies v1.340 CEP135 Arina Puzriakova Phenotypes for gene: CEP135 were changed from PRIMARY MICROCEPHALY AND DISTURBED CENTROSOMAL FUNCTION to Microcephaly 8, primary, autosomal recessive, OMIM:614673; Microcephaly 8, primary, autosomal recessive, MONDO:0013849
Fetal anomalies v1.339 CEP135 Arina Puzriakova Classified gene: CEP135 as Amber List (moderate evidence)
Fetal anomalies v1.339 CEP135 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.339 CEP135 Arina Puzriakova Gene: cep135 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.338 CEP135 Arina Puzriakova Tag for-review tag was added to gene: CEP135.
Fetal anomalies v1.338 CDK5RAP2 Arina Puzriakova Phenotypes for gene: CDK5RAP2 were changed from PRIMARY AUTOSOMAL RECESSIVE MICROCEPHALY to Microcephaly 3, primary, autosomal recessive, OMIM:604804; Microcephaly 3, primary, autosomal recessive, MONDO:0011488
Fetal anomalies v1.337 CCDC88C Arina Puzriakova Phenotypes for gene: CCDC88C were changed from HYDROCEPHALUS, NONSYNDROMIC, AUTOSOMAL RECESSIVE to Hydrocephalus, congenital, 1, OMIM:236600; Hydrocephalus, nonsyndromic, autosomal recessive 1, MONDO:0009360
Fetal anomalies v1.336 CCDC8 Arina Puzriakova Phenotypes for gene: CCDC8 were changed from THREE M SYNDROME 3 to 3-M syndrome 3, OMIM:614205; 3M syndrome 3, MONDO:0013627
Fetal anomalies v1.335 CDK5RAP2 Arina Puzriakova Classified gene: CDK5RAP2 as Amber List (moderate evidence)
Fetal anomalies v1.335 CDK5RAP2 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.335 CDK5RAP2 Arina Puzriakova Gene: cdk5rap2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.334 CDK5RAP2 Arina Puzriakova Tag for-review tag was added to gene: CDK5RAP2.
Fetal anomalies v1.334 CCDC88C Arina Puzriakova Classified gene: CCDC88C as Amber List (moderate evidence)
Fetal anomalies v1.334 CCDC88C Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.334 CCDC88C Arina Puzriakova Gene: ccdc88c has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.333 CCDC88C Arina Puzriakova Tag for-review tag was added to gene: CCDC88C.
Fetal anomalies v1.333 CCDC8 Arina Puzriakova Classified gene: CCDC8 as Amber List (moderate evidence)
Fetal anomalies v1.333 CCDC8 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.333 CCDC8 Arina Puzriakova Gene: ccdc8 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.332 CCDC8 Arina Puzriakova Tag for-review tag was added to gene: CCDC8.
Fetal anomalies v1.332 CCDC151 Arina Puzriakova Phenotypes for gene: CCDC151 were changed from PRIMARY CILLARY DYSKINEASIA to Ciliary dyskinesia, primary, 30, OMIM:616037; Primary ciliary dyskinesia 30, MONDO:0014465
Fetal anomalies v1.331 CCDC151 Arina Puzriakova Classified gene: CCDC151 as Amber List (moderate evidence)
Fetal anomalies v1.331 CCDC151 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.331 CCDC151 Arina Puzriakova Gene: ccdc151 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.330 CCDC151 Arina Puzriakova Tag for-review tag was added to gene: CCDC151.
Fetal anomalies v1.330 C2CD3 Arina Puzriakova Phenotypes for gene: C2CD3 were changed from OROFACIODIGITAL SYNDROME XIV to Orofaciodigital syndrome XIV, OMIM:615948; Orofaciodigital syndrome type 14, MONDO:0014413
Fetal anomalies v1.329 C2CD3 Arina Puzriakova Classified gene: C2CD3 as Amber List (moderate evidence)
Fetal anomalies v1.329 C2CD3 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.329 C2CD3 Arina Puzriakova Gene: c2cd3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.328 C2CD3 Arina Puzriakova Tag for-review tag was added to gene: C2CD3.
Fetal anomalies v1.328 C21orf59 Arina Puzriakova Phenotypes for gene: C21orf59 were changed from PRIMARY CILIARY DYSKINESIA to Ciliary dyskinesia, primary, 26, OMIM:615500; Primary ciliary dyskinesia 26, MONDO:0014211
Fetal anomalies v1.327 C21orf59 Arina Puzriakova Classified gene: C21orf59 as Amber List (moderate evidence)
Fetal anomalies v1.327 C21orf59 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.327 C21orf59 Arina Puzriakova Gene: c21orf59 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.326 C21orf59 Arina Puzriakova Tag for-review tag was added to gene: C21orf59.
Fetal anomalies v1.326 B3GALNT2 Arina Puzriakova Phenotypes for gene: B3GALNT2 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 11 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11, OMIM:615181; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11, MONDO:0014071
Fetal anomalies v1.325 B3GALNT2 Arina Puzriakova Classified gene: B3GALNT2 as Amber List (moderate evidence)
Fetal anomalies v1.325 B3GALNT2 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.325 B3GALNT2 Arina Puzriakova Gene: b3galnt2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.324 B3GALNT2 Arina Puzriakova Tag for-review tag was added to gene: B3GALNT2.
Fetal anomalies v1.324 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from SECKEL SYNDROME TYPE 1 to Seckel syndrome 1, OMIM:210600; Seckel syndrome 1, MONDO:0008869
Fetal anomalies v1.323 ATR Arina Puzriakova Classified gene: ATR as Amber List (moderate evidence)
Fetal anomalies v1.323 ATR Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.323 ATR Arina Puzriakova Gene: atr has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.322 ATR Arina Puzriakova Tag for-review tag was added to gene: ATR.
Fetal anomalies v1.322 ARFGEF2 Arina Puzriakova Phenotypes for gene: ARFGEF2 were changed from PERIVENTRICULAR HETEROTOPIA WITH MICROCEPHALY to Periventricular heterotopia with microcephaly, OMIM:608097
Fetal anomalies v1.321 ARFGEF2 Arina Puzriakova Classified gene: ARFGEF2 as Amber List (moderate evidence)
Fetal anomalies v1.321 ARFGEF2 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.321 ARFGEF2 Arina Puzriakova Gene: arfgef2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.320 ARFGEF2 Arina Puzriakova Tag for-review tag was added to gene: ARFGEF2.
Fetal anomalies v1.320 ANTXR2 Arina Puzriakova Publications for gene: ANTXR2 were set to
Fetal anomalies v1.319 ANTXR2 Arina Puzriakova Classified gene: ANTXR2 as Amber List (moderate evidence)
Fetal anomalies v1.319 ANTXR2 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene has been upgraded from Red to Amber, but should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.319 ANTXR2 Arina Puzriakova Gene: antxr2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.318 ANTXR2 Arina Puzriakova Tag for-review tag was added to gene: ANTXR2.
Fetal anomalies v1.318 CREB3L1 Arina Puzriakova Classified gene: CREB3L1 as Amber List (moderate evidence)
Fetal anomalies v1.318 CREB3L1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.318 CREB3L1 Arina Puzriakova Gene: creb3l1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.317 CREB3L1 Arina Puzriakova Tag for-review tag was added to gene: CREB3L1.
Fetal anomalies v1.317 COLQ Arina Puzriakova Publications for gene: COLQ were set to PMID: 9689136; 11865139
Fetal anomalies v1.316 COLQ Arina Puzriakova Classified gene: COLQ as Amber List (moderate evidence)
Fetal anomalies v1.316 COLQ Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.316 COLQ Arina Puzriakova Gene: colq has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.315 COLQ Arina Puzriakova Tag for-review tag was added to gene: COLQ.
Fetal anomalies v1.315 COL12A1 Arina Puzriakova Classified gene: COL12A1 as Amber List (moderate evidence)
Fetal anomalies v1.315 COL12A1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.315 COL12A1 Arina Puzriakova Gene: col12a1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.314 COL12A1 Arina Puzriakova Tag for-review tag was added to gene: COL12A1.
Fetal anomalies v1.314 CNBP Arina Puzriakova Classified gene: CNBP as Amber List (moderate evidence)
Fetal anomalies v1.314 CNBP Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.314 CNBP Arina Puzriakova Gene: cnbp has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.313 COG6 Arina Puzriakova Classified gene: COG6 as Amber List (moderate evidence)
Fetal anomalies v1.313 COG6 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.313 COG6 Arina Puzriakova Gene: cog6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.312 COG6 Arina Puzriakova Tag for-review tag was added to gene: COG6.
Fetal anomalies v1.312 CNBP Arina Puzriakova Tag for-review tag was added to gene: CNBP.
Fetal anomalies v1.312 CHRNE Arina Puzriakova Classified gene: CHRNE as Amber List (moderate evidence)
Fetal anomalies v1.312 CHRNE Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.312 CHRNE Arina Puzriakova Gene: chrne has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.311 CHRNE Arina Puzriakova Tag for-review tag was added to gene: CHRNE.
Fetal anomalies v1.311 CHRNB1 Arina Puzriakova Classified gene: CHRNB1 as Amber List (moderate evidence)
Fetal anomalies v1.311 CHRNB1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.311 CHRNB1 Arina Puzriakova Gene: chrnb1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.310 CHRNB1 Arina Puzriakova Tag for-review tag was added to gene: CHRNB1.
Fetal anomalies v1.310 CHRNA3 Arina Puzriakova Classified gene: CHRNA3 as Amber List (moderate evidence)
Fetal anomalies v1.310 CHRNA3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.310 CHRNA3 Arina Puzriakova Gene: chrna3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.309 CHRNA3 Arina Puzriakova Tag for-review tag was added to gene: CHRNA3.
Intellectual disability v3.749 HIRA Zornitza Stark gene: HIRA was added
gene: HIRA was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: HIRA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIRA were set to 33417013; 28135719; 25363760
Phenotypes for gene: HIRA were set to Neurodevelopmental disorder
Review for gene: HIRA was set to GREEN
gene: HIRA was marked as current diagnostic
Added comment: Two unrelated patients with different de novo loss of function variants identified in PMID 33417013:

Individual 1: intragenic deletion, phenotype included psychomotor retardation, ID, growth retardation, microcephaly, and facial features reminiscent of 22q deletion syndrome.
Individual 2: canonical splice variant, phenotype mostly confined to ASD

Another two de novo variants were identified in the literature by the authors of that paper, one stop-gain (DDD study, PMID 28135719) and one missense (large autism cohort, PMID 25363760).

PMID 33417013 also showed that HIRA knockdown in mice results in neurodevelopmental abnormalities.

Rated Green due to 4 unrelated individuals (albeit 2 in large cohort studies) and a mouse model. NB: HIRA is within the common 22q deletion region.
Sources: Literature
Monogenic hearing loss v2.146 CLRN2 Zornitza Stark gene: CLRN2 was added
gene: CLRN2 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: CLRN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLRN2 were set to 33496845
Phenotypes for gene: CLRN2 were set to Non-syndromic hearing loss
Review for gene: CLRN2 was set to AMBER
Added comment: Missense variant segregates with non-syndromic hearing loss in 3 members of a consanguineous family, two from one nuclear family and one from another. The variant was also shown to result in some transcripts being abnormally spliced, resulting in a premature stop codon.

Functional studies in zebrafish and mice show the gene plays an essential role in normal organization and maintenance of the auditory hair bundles, and for hearing function.

Rated Amber due to supporting functional studies in mice.
Sources: Literature
Hereditary neuropathy or pain disorder v1.23 POLR3B Zornitza Stark gene: POLR3B was added
gene: POLR3B was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: POLR3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3B were set to 33417887
Phenotypes for gene: POLR3B were set to Ataxia, spasticity, and demyelinating neuropathy
Review for gene: POLR3B was set to GREEN
Added comment: Note biallelic variants cause a leukodystrophy.

New MOI and new phenotype reported in PMID: 33417887: Six unrelated individuals with de novo missense variants and ataxia, spasticity, variable intellectual disability and epilepsy, and predominantly demyelinating sensory motor peripheral neuropathy.
Protein modeling and proteomic analysis shows variants caused aberrant association of individual enzyme subunits rather than affecting overall enzyme assembly or stability.
Sources: Literature
Bleeding and platelet disorders v1.20 PTGS1 Ivone Leong commented on gene: PTGS1
Bleeding and platelet disorders v1.20 PTGS1 Ivone Leong Tag for-review tag was added to gene: PTGS1.
Primary ovarian insufficiency v1.19 C14orf39 Zornitza Stark gene: C14orf39 was added
gene: C14orf39 was added to Primary ovarian insufficiency. Sources: Literature
Mode of inheritance for gene: C14orf39 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C14orf39 were set to 33508233; 27796301
Phenotypes for gene: C14orf39 were set to Premature ovarian insufficiency
Review for gene: C14orf39 was set to AMBER
Added comment: PMID: 33508233
- 1 family with two males (azoospermia) and 1 female (premature ovarian insufficiency) with a homozygous PTC

PMID: 27796301
- Mouse K/O with ovarian failure
Sources: Literature
Fetal anomalies v1.309 CERS3 Arina Puzriakova Classified gene: CERS3 as Amber List (moderate evidence)
Fetal anomalies v1.309 CERS3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.309 CERS3 Arina Puzriakova Gene: cers3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.308 CERS3 Arina Puzriakova Tag for-review tag was added to gene: CERS3.
Intellectual disability v3.749 SATB1 Zornitza Stark changed review comment from: PMID: 33513338: 42 patients with SNVs. 28 de novo, 3 inherited from an affected parent.
Missense variants - more severe, profound ID
NMD PTCs - milder disease; to: PMID: 33513338: 42 patients with SNVs. 28 de novo, 3 inherited from an affected parent.
Missense variants - more severe, profound ID
NMD PTCs - milder disease

Consider adding to epilepsy and ataxia panels.
Intellectual disability v3.749 SATB1 Zornitza Stark edited their review of gene: SATB1: Added comment: PMID: 33513338: 42 patients with SNVs. 28 de novo, 3 inherited from an affected parent.
Missense variants - more severe, profound ID
NMD PTCs - milder disease; Changed rating: GREEN; Changed publications: 33057194, 33513338; Changed phenotypes: Neurodevelopmental disorder; Set current diagnostic: yes
Bilateral congenital or childhood onset cataracts v2.59 NSUN2 Zornitza Stark gene: NSUN2 was added
gene: NSUN2 was added to Cataracts. Sources: Literature
Mode of inheritance for gene: NSUN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSUN2 were set to 33084202
Phenotypes for gene: NSUN2 were set to Mental retardation, autosomal recessive 5, MIM# 611091; cataracts
Review for gene: NSUN2 was set to RED
Added comment: Two siblings compound het for two variants c.546_547insCT, p.Met183Leufs*13; c.1583del, p.Pro528Hisfs*19 and juvenile cataracts
Sources: Literature
Intellectual disability v3.749 METAP1 Zornitza Stark gene: METAP1 was added
gene: METAP1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: METAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: METAP1 were set to 32764695
Phenotypes for gene: METAP1 were set to Intellectual disability, aggression, neurodevelopmental delay
Review for gene: METAP1 was set to RED
Added comment: Biallelic nonsense (NMD-predicted) variant identified in 4 sibs in a consanguineous family with dev delay. One sib had bilateral clinodactyly of her toes and her left 3rd finger, other sibs were not dysmorphic. Rated red due to single consanguineous family.
Sources: Literature
Optic neuropathy v2.29 PDSS1 Zornitza Stark gene: PDSS1 was added
gene: PDSS1 was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: PDSS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDSS1 were set to 33285023
Phenotypes for gene: PDSS1 were set to Coenzyme Q10 deficiency, primary, 2, MIM# 614651
Review for gene: PDSS1 was set to AMBER
Added comment: Two families reported where optic atrophy and deafness are part of the phenotype.
Sources: Literature
Bleeding and platelet disorders v1.20 PTGS1 Ivone Leong Publications for gene: PTGS1 were set to 11442478; 27629384; 8562397; 28748566; 6103258
Fetal anomalies v1.308 CENPF Arina Puzriakova Classified gene: CENPF as Amber List (moderate evidence)
Fetal anomalies v1.308 CENPF Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.308 CENPF Arina Puzriakova Gene: cenpf has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.307 CENPF Arina Puzriakova Tag for-review tag was added to gene: CENPF.
Fetal anomalies v1.307 CELSR1 Arina Puzriakova Classified gene: CELSR1 as Amber List (moderate evidence)
Fetal anomalies v1.307 CELSR1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.307 CELSR1 Arina Puzriakova Gene: celsr1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.306 CELSR1 Arina Puzriakova Tag for-review tag was added to gene: CELSR1.
Fetal anomalies v1.306 CASR Arina Puzriakova Classified gene: CASR as Amber List (moderate evidence)
Fetal anomalies v1.306 CASR Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.306 CASR Arina Puzriakova Gene: casr has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.305 CANT1 Arina Puzriakova Classified gene: CANT1 as Amber List (moderate evidence)
Fetal anomalies v1.305 CANT1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.305 CANT1 Arina Puzriakova Gene: cant1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.304 CANT1 Arina Puzriakova Tag for-review tag was added to gene: CANT1.
Fetal anomalies v1.304 CACNA1G Arina Puzriakova Classified gene: CACNA1G as Amber List (moderate evidence)
Fetal anomalies v1.304 CACNA1G Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.304 CACNA1G Arina Puzriakova Gene: cacna1g has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.303 CACNA1G Arina Puzriakova Tag for-review tag was added to gene: CACNA1G.
Fetal anomalies v1.303 BNC2 Arina Puzriakova Classified gene: BNC2 as Amber List (moderate evidence)
Fetal anomalies v1.303 BNC2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.303 BNC2 Arina Puzriakova Gene: bnc2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.302 BNC2 Arina Puzriakova Tag for-review tag was added to gene: BNC2.
Fetal anomalies v1.302 B4GAT1 Arina Puzriakova Publications for gene: B4GAT1 were set to PMID: 23877401; 23359570
Fetal anomalies v1.301 B4GAT1 Arina Puzriakova Classified gene: B4GAT1 as Amber List (moderate evidence)
Fetal anomalies v1.301 B4GAT1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.301 B4GAT1 Arina Puzriakova Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.300 B4GAT1 Arina Puzriakova Tag for-review tag was added to gene: B4GAT1.
Fetal anomalies v1.300 ARHGAP29 Arina Puzriakova Classified gene: ARHGAP29 as Amber List (moderate evidence)
Fetal anomalies v1.300 ARHGAP29 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.300 ARHGAP29 Arina Puzriakova Gene: arhgap29 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.299 ARHGAP29 Arina Puzriakova Tag for-review tag was added to gene: ARHGAP29.
Fetal anomalies v1.299 ANKS6 Arina Puzriakova Classified gene: ANKS6 as Amber List (moderate evidence)
Fetal anomalies v1.299 ANKS6 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.299 ANKS6 Arina Puzriakova Gene: anks6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.298 ANKS6 Arina Puzriakova Tag for-review tag was added to gene: ANKS6.
Fetal anomalies v1.298 AMMECR1 Arina Puzriakova Classified gene: AMMECR1 as Amber List (moderate evidence)
Fetal anomalies v1.298 AMMECR1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.298 AMMECR1 Arina Puzriakova Gene: ammecr1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.297 AMMECR1 Arina Puzriakova Tag for-review tag was added to gene: AMMECR1.
Fetal anomalies v1.297 AMACR Arina Puzriakova Classified gene: AMACR as Amber List (moderate evidence)
Fetal anomalies v1.297 AMACR Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.297 AMACR Arina Puzriakova Gene: amacr has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.296 AMACR Arina Puzriakova Tag for-review tag was added to gene: AMACR.
Fetal anomalies v1.296 ALOXE3 Arina Puzriakova Classified gene: ALOXE3 as Amber List (moderate evidence)
Fetal anomalies v1.296 ALOXE3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.296 ALOXE3 Arina Puzriakova Gene: aloxe3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.295 ALOXE3 Arina Puzriakova Tag for-review tag was added to gene: ALOXE3.
Fetal anomalies v1.295 ALOX12B Arina Puzriakova Classified gene: ALOX12B as Amber List (moderate evidence)
Fetal anomalies v1.295 ALOX12B Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.295 ALOX12B Arina Puzriakova Gene: alox12b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.294 ALOX12B Arina Puzriakova Tag for-review tag was added to gene: ALOX12B.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.392 RHOG Boaz Palterer gene: RHOG was added
gene: RHOG was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: RHOG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RHOG were set to 33513601
Phenotypes for gene: RHOG were set to HLH; hemophagocytic lymphohistiocytosis
Penetrance for gene: RHOG were set to unknown
Review for gene: RHOG was set to RED
Added comment: One patient with HLH and impaired cytotoxic T lymphocyte and natural killer (NK) cell exocytosis functions, bearing biallelic deleterious mutations in the RhoG gene.
Experimental ablation of RHOG in a model cell line and primary CTLs confirmed that RhoG engages in a protein-protein interaction with Munc13-4, an exocytosis protein essential for cytotoxic granules fusion with the plasma membrane.
Sources: Literature
Fetal anomalies v1.294 ALG2 Arina Puzriakova Tag for-review tag was added to gene: ALG2.
Fetal anomalies v1.294 ALG2 Arina Puzriakova Classified gene: ALG2 as Amber List (moderate evidence)
Fetal anomalies v1.294 ALG2 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.294 ALG2 Arina Puzriakova Gene: alg2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.293 ABL1 Arina Puzriakova Phenotypes for gene: ABL1 were changed from Congenital heart defects and skeletal malformations to Congenital heart defects and skeletal malformations, OMIM:617602; Congenital heart defects and skeletal malformations syndrome, MONDO:0060532
Fetal anomalies v1.292 ABL1 Arina Puzriakova Classified gene: ABL1 as Amber List (moderate evidence)
Fetal anomalies v1.292 ABL1 Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.292 ABL1 Arina Puzriakova Gene: abl1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.291 ABL1 Arina Puzriakova Tag for-review tag was added to gene: ABL1.
Malformations of cortical development v2.44 ENO1 Zornitza Stark gene: ENO1 was added
gene: ENO1 was added to Malformations of cortical development. Sources: Literature
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
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 though note variants in RERE also cause a neurodevelopmental phenotype.
Sources: Literature
Intellectual disability v3.749 KCNN2 Zornitza Stark gene: KCNN2 was added
gene: KCNN2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: KCNN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNN2 were set to 33242881
Phenotypes for gene: KCNN2 were set to Intellectual disability; seizures; movement disorder
Review for gene: KCNN2 was set to GREEN
gene: KCNN2 was marked as current diagnostic
Added comment: - 11 probands all de novo except for 1 mother-daughter pair.
- a mix of null and missense variants
- 2/11 with microcephaly, 10/11 motor delay, 7/11 language delay (excluding 2 with regression), all with varying degrees of ID, 3/11 seizures, 7/11 movement disorder, 4/11 cerebellar ataxia, 6/11 MRI anomalies
Sources: Literature
Thoracic aortic aneurysm or dissection (GMS) v1.3 HEY2 Zornitza Stark gene: HEY2 was added
gene: HEY2 was added to Thoracic aortic aneurysm and dissection. Sources: Literature
Mode of inheritance for gene: HEY2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: HEY2 were set to 32820247
Phenotypes for gene: HEY2 were set to congenital heart defects and thoracic aortic aneurysms
Review for gene: HEY2 was set to RED
Added comment: A very large family affected by CHD and familial thoracic aortic aneurysms. Trio genome sequencing was carried out in an index patient with critical CHD, and family members had either exome or Sanger sequencing. Identified homozygous loss-of-function variant (c.318_319delAG, p.G108*) in HEY2 in 3 individuals in family with critical CHD, whereas the 20 heterozygous carriers show a spectrum of CVDs (CHD and FTAA, but varying expressivity and incomplete penetrance).

Other studies show that knockout of HEY2 in mice results in cardiovascular defects (CVDs), including septal defects, cardiomyopathy, a thin-walled aorta, and valve anomalies.
Sources: Literature
Skeletal dysplasia v2.80 FGF9 Zornitza Stark edited their review of gene: FGF9: Set current diagnostic: yes
Skeletal dysplasia v2.80 FGF9 Zornitza Stark reviewed gene: FGF9: Rating: GREEN; Mode of pathogenicity: None; Publications: 33140402, 28730625, 19589401, 33174625; Phenotypes: Multiple synostoses syndrome 3, OMIM # 612961; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v2.281 CCDC186 Zornitza Stark gene: CCDC186 was added
gene: CCDC186 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: CCDC186 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC186 were set to 33259146
Phenotypes for gene: CCDC186 were set to Epileptic encephalopathy
Review for gene: CCDC186 was set to RED
Added comment: One individual reported with bi-allelic truncating variant and EE.
Sources: Literature
Intellectual disability v3.749 OTUD5 Zornitza Stark gene: OTUD5 was added
gene: OTUD5 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: OTUD5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OTUD5 were set to 33131077
Phenotypes for gene: OTUD5 were set to X-linked severe neurodevelopmental delay, hydrocephalus, and early lethality
Review for gene: OTUD5 was set to RED
Added comment: 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with IUGR, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. WGS in four individuals identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals.
Sources: Literature
Proteinuric renal disease v2.44 NOS1AP Zornitza Stark gene: NOS1AP was added
gene: NOS1AP was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: NOS1AP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NOS1AP were set to Nephrotic syndrome, type 22, MIM# 619155
Review for gene: NOS1AP was set to GREEN
gene: NOS1AP was marked as current diagnostic
Added comment: Nephrotic syndrome type 22 (NPHS22) is an autosomal recessive renal disease characterized by onset of progressive kidney dysfunction in infancy. Affected individuals usually present with edema associated with hypoproteinemia, proteinuria, and microscopic hematuria. Renal biopsy shows effacement of the podocyte foot processes, glomerulosclerosis, and thickening of the glomerular basement membrane. The disease is steroid-resistant and progressive, resulting in end-stage renal disease usually necessitating kidney transplant. Two unrelated families and animal model.

No PMID yet: https://advances.sciencemag.org/content/7/1/eabe1386
Sources: Literature
Early onset or syndromic epilepsy v2.281 TET3 Helen Lord reviewed gene: TET3: Rating: AMBER; Mode of pathogenicity: None; Publications: 31928709; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v2.281 SNX27 Helen Lord reviewed gene: SNX27: Rating: AMBER; Mode of pathogenicity: None; Publications: 31721175; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v2.281 SLC5A6 Helen Lord reviewed gene: SLC5A6: Rating: RED; Mode of pathogenicity: None; Publications: 31754459, 27904971; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v2.281 SEMA6B Helen Lord reviewed gene: SEMA6B: Rating: AMBER; Mode of pathogenicity: None; Publications: 32169168; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v2.281 RALGAPA1 Helen Lord reviewed gene: RALGAPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32004447; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and platelet disorders v1.19 PTGS1 Carl Fratter edited their review of gene: PTGS1: Added comment: There now appears to be sufficient evidence for green rating (PMID: 32299908;24008976) for biallelic inheritance and there is also one report of monoallelic inheritance (PMID: 33326144).; Changed publications: PMID: 32299908, 24008976, 33326144, 32584621; Changed phenotypes: Platelet dysfunction and bleeding; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 TONSL Michael Oldridge reviewed gene: TONSL: Rating: GREEN; Mode of pathogenicity: None; Publications: 30773277, 30773278; Phenotypes: SPONASTRIME dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v1.80 HYAL2 Eleanor Williams Classified gene: HYAL2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.80 HYAL2 Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team the recommendation is that this gene be rated green based on two unrelated families both which contain individuals with a cardiac phenotype, and a mouse model in which the cardiac phenotype is also noted.
Paediatric disorders - additional genes v1.80 HYAL2 Eleanor Williams Gene: hyal2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.79 HYAL2 Eleanor Williams Tag for-review tag was added to gene: HYAL2.
Familial non syndromic congenital heart disease v1.57 HYAL2 Eleanor Williams Classified gene: HYAL2 as Green List (high evidence)
Familial non syndromic congenital heart disease v1.57 HYAL2 Eleanor Williams Added comment: Comment on list classification: Promoting to green after further consultation with the Genomics England clinical team. 2 cases which both report a cardiac phenotype, and mouse model which also re-capitulates the cardiac phenotype, so should be rated green.
Familial non syndromic congenital heart disease v1.57 HYAL2 Eleanor Williams Gene: hyal2 has been classified as Green List (High Evidence).
Bleeding and platelet disorders v1.19 PRKACG Kate Downes reviewed gene: PRKACG: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 25061177; Phenotypes: Macrothrombocytopenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v2.51 STT3A Zornitza Stark reviewed gene: STT3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23842455, 30701557, 28424003; Phenotypes: Congenital disorder of glycosylation, type Iw, OMIM #615596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Likely inborn error of metabolism v2.51 TTC37 Zornitza Stark reviewed gene: TTC37: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v2.80 SMAD6 Tracy Lester gene: SMAD6 was added
gene: SMAD6 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD6 were set to 31138930
Phenotypes for gene: SMAD6 were set to Radioulnar synostosis
Penetrance for gene: SMAD6 were set to Incomplete
Review for gene: SMAD6 was set to GREEN
Added comment: SMAD6 is frequently mutated in non-syndromic radioulnar synostosis.Using exome seq the authors found 16 LOF and 6 rare missense variants in sporadic cases, which was a highly significant association. The findings were replicated in a different cohort. Four cases had de novo variants and others were inherited in a dominant fashion.
SMAD6 LOF variants have also been shown to be enriched in mid-line craniosynostosis and in certain cardiac disorders. It isn't yet clear if a variant can cause different phenotypes in the same family or combinations of these phenotypes in the same individual. Genotype-phenotype correlation is not understood.
This gene is currently tested diagnostically in cases of mid-line craniosynostosis and is green on panel R100.
Sources: NHS GMS
Skeletal dysplasia v2.80 POLR1B Michael Oldridge reviewed gene: POLR1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31649276; Phenotypes: TCS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.80 PKDCC Michael Oldridge reviewed gene: PKDCC: Rating: GREEN; Mode of pathogenicity: None; Publications: 30478137; Phenotypes: rhizomelic limb shortening, facial dysmorphism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 NXN Michael Oldridge changed review comment from: 2 unrelated families with recessive Robinow syndrome (RRS), one hom and one comp het for variants, segregation fits with recessive inheritance. Mouse model has overlapping clinical features to RRS . Gene expressed in limb bud of mice and acts in the Wnt/PCP pathway, as do the DVL genes, WNT5A and ROR2, genes also associated with the very specific RRS phenotype.; to: 2 unrelated families with recessive Robinow syndrome (RRS), one hom and one comp het for variants, segregation fits with recessive inheritance. Mouse model has overlapping clinical features to RRS . Gene expressed in limb bud of mice and acts in the Wnt/PCP pathway, as do the DVL genes, WNT5A, FZD2 and ROR2, genes also associated with the very specific RRS phenotype.
Skeletal dysplasia v2.80 NXN Michael Oldridge changed review comment from: 2 unrelated families with recessive Robinow syndrome (RRS), one hom and one comp het for variants, segregation fits with recessive inheritance. Mouse model has overlapping clinical features to RRS . Gene expressed in limb bud of mice and acts in the Wnt/PCP pathway, as do the DVL genes and ROR2, genes also associated with the very specific RRS phenotype.; to: 2 unrelated families with recessive Robinow syndrome (RRS), one hom and one comp het for variants, segregation fits with recessive inheritance. Mouse model has overlapping clinical features to RRS . Gene expressed in limb bud of mice and acts in the Wnt/PCP pathway, as do the DVL genes, WNT5A and ROR2, genes also associated with the very specific RRS phenotype.
Skeletal dysplasia v2.80 NXN Michael Oldridge reviewed gene: NXN: Rating: GREEN; Mode of pathogenicity: None; Publications: 29276006; Phenotypes: recessive Robinow syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 KIAA1217 Michael Oldridge reviewed gene: KIAA1217: Rating: RED; Mode of pathogenicity: None; Publications: 32369272; Phenotypes: vertebral malformations; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.80 HS2ST1 Michael Oldridge reviewed gene: HS2ST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33159882; Phenotypes: ID, facial dysmorphism, skeletal abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 GNPNAT1 Michael Oldridge reviewed gene: GNPNAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32591345; Phenotypes: rhizomelic short stature; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.80 CSGALNACT1 Michael Oldridge reviewed gene: CSGALNACT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31705726, 27599773, 31325655; Phenotypes: Skeletal dysplasia, mild, with joint laxity and advanced bone age , MIM618870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.44 APOL1 Natalie Forrester reviewed gene: APOL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 23766536; Phenotypes: chronic kidney disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v2.392 SLC9A3 Kelsey Jones gene: SLC9A3 was added
gene: SLC9A3 was added to Primary immunodeficiency. Sources: Expert Review
Mode of inheritance for gene: SLC9A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC9A3 were set to PMID: 26358773
Phenotypes for gene: SLC9A3 were set to Very Early Onset Inflammatory Bowel Disease; Congenital sodium diarrhoea
Penetrance for gene: SLC9A3 were set to Incomplete
Review for gene: SLC9A3 was set to AMBER
Added comment: Described as a monogenic cause of VEOIBD (recognised criteria for the R15 panel). 2 patients from unrelated families in a series of 9 cases with SLC9A3-related congenital sodium diarrhoea developed intestinal inflammation/IBD (PMID: 26358773). GWAS have indicated a strong association between SLC9A3 and IBD, and there are supportive mouse models (reviewed in PMID: 26358773).Included on a monogenic IBD gene panel proposed by The Paediatric IBD Porto Group of ESPGHAN (PMID: 33346580).
Sources: Expert Review
Fetal anomalies v1.291 WDR81 Arina Puzriakova Publications for gene: WDR81 were set to
Fetal anomalies v1.290 WDR81 Arina Puzriakova Phenotypes for gene: WDR81 were changed from Hydrocephalus, congenital, 3, with brain anomalies to Hydrocephalus, congenital, 3, with brain anomalies, OMIM:617967; Hydrocephalus, congenital, 3, with brain anomalies, MONDO:0054794
Fetal anomalies v1.289 WDR81 Arina Puzriakova Classified gene: WDR81 as Amber List (moderate evidence)
Fetal anomalies v1.289 WDR81 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.289 WDR81 Arina Puzriakova Gene: wdr81 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.288 WDR81 Arina Puzriakova Tag for-review tag was added to gene: WDR81.
CAKUT v1.158 MYOCD Arina Puzriakova Phenotypes for gene: MYOCD were changed from Megabladder, congenital 618719 to Megabladder, congenital, OMIM:618719; Megabladder, congenital, MONDO:0032879
Fetal anomalies v1.288 MYOCD Arina Puzriakova Mode of inheritance for gene: MYOCD was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.287 MYOCD Arina Puzriakova Publications for gene: MYOCD were set to
Paediatric disorders - additional genes v1.79 MYOCD Arina Puzriakova Phenotypes for gene: MYOCD were changed from Megabladder, congenital 618719 to Megabladder, congenital, OMIM:618719; Megabladder, congenital, MONDO:0032879
Fetal anomalies v1.286 MYOCD Arina Puzriakova Phenotypes for gene: MYOCD were changed from Megabladder, congenital to Megabladder, congenital, OMIM:618719; Megabladder, congenital, MONDO:0032879
Fetal anomalies v1.285 MYOCD Arina Puzriakova Classified gene: MYOCD as Amber List (moderate evidence)
Fetal anomalies v1.285 MYOCD Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.285 MYOCD Arina Puzriakova Gene: myocd has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.284 MYOCD Arina Puzriakova Tag for-review tag was added to gene: MYOCD.
Arthrogryposis v3.64 MYO9A Arina Puzriakova Phenotypes for gene: MYO9A were changed from Arthrogryposis; OrphaNet: ORPHA109007 to Myasthenic syndrome, congenital, 24, presynaptic, OMIM:618198; Myasthenic syndrome, congenital, 24, presynaptic, MONDO:0032597
Fetal anomalies v1.284 MYO9A Arina Puzriakova Publications for gene: MYO9A were set to
Primary immunodeficiency or monogenic inflammatory bowel disease v2.392 STXBP3 Kelsey Jones gene: STXBP3 was added
gene: STXBP3 was added to Primary immunodeficiency. Sources: Expert Review
Mode of inheritance for gene: STXBP3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: STXBP3 were set to PMID: 33346580
Phenotypes for gene: STXBP3 were set to Very Early Onset Inflammatory Bowel Disease; Sensorineural hearing loss
Penetrance for gene: STXBP3 were set to unknown
Review for gene: STXBP3 was set to AMBER
Added comment: Described as a monogenic cause of VEOIBD (recognised criteria for the R15 panel) in a report published in abstract form (DOI: https://doi.org/10.1053/j.gastro.2017.11.120). 8 patients from 4 unrelated families with defects in STXBP3 reportedly associated with VEO-IBD, bilateral sensorineural hearing loss, and impaired cytotoxic T-lymphocyte function (granule release, stimulated CD107a upregulation). Included on a monogenic IBD gene panel proposed by The Paediatric IBD Porto Group of ESPGHAN (PMID: 33346580).
Sources: Expert Review
Congenital myaesthenic syndrome v2.8 MYO9A Arina Puzriakova Phenotypes for gene: MYO9A were changed from congenital myasthenic syndrome 24, presynaptic 618198; CMS to Myasthenic syndrome, congenital, 24, presynaptic, OMIM:618198; Myasthenic syndrome, congenital, 24, presynaptic, MONDO:0032597
Fetal anomalies v1.283 MYO9A Arina Puzriakova Phenotypes for gene: MYO9A were changed from Myasthenic syndrome, congenital, 24, presynaptic to Myasthenic syndrome, congenital, 24, presynaptic, OMIM:618198; Myasthenic syndrome, congenital, 24, presynaptic, MONDO:0032597
Fetal anomalies v1.282 MYO9A Arina Puzriakova Classified gene: MYO9A as Amber List (moderate evidence)
Fetal anomalies v1.282 MYO9A Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.282 MYO9A Arina Puzriakova Gene: myo9a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.281 MYO9A Arina Puzriakova Tag for-review tag was added to gene: MYO9A.
Fetal anomalies v1.281 MYO18B Arina Puzriakova Publications for gene: MYO18B were set to
Congenital myopathy v2.28 MYO18B Arina Puzriakova Phenotypes for gene: MYO18B were changed from KLIPPEL-FEIL SYNDROME 4, AUTOSOMAL RECESSIVE, WITH NEMALINE MYOPATHY AND FACIAL DYSMORPHISM to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, OMIM:616549; Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome, MONDO:0014689
Fetal anomalies v1.280 MYO18B Arina Puzriakova Phenotypes for gene: MYO18B were changed from Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism, OMIM:616549; Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome, MONDO:0014689
Fetal anomalies v1.279 MYO18B Arina Puzriakova Classified gene: MYO18B as Amber List (moderate evidence)
Fetal anomalies v1.279 MYO18B Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.279 MYO18B Arina Puzriakova Gene: myo18b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.278 MYO18B Arina Puzriakova Tag for-review tag was added to gene: MYO18B.
Fetal anomalies v1.278 MYMK Arina Puzriakova Publications for gene: MYMK were set to
Clefting v2.24 MYMK Arina Puzriakova Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome 254940 to Carey-Fineman-Ziter syndrome, OMIM:254940; Carey-Fineman-Ziter syndrome, MONDO:0009700
Congenital myopathy v2.27 MYMK Arina Puzriakova Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome 254940 to Carey-Fineman-Ziter syndrome, OMIM:254940; Carey-Fineman-Ziter syndrome, MONDO:0009700
Arthrogryposis v3.63 MYMK Arina Puzriakova Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome 254940 to Carey-Fineman-Ziter syndrome, OMIM:254940; Carey-Fineman-Ziter syndrome, MONDO:0009700
Congenital muscular dystrophy v2.6 MYMK Arina Puzriakova Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome, 254940 to Carey-Fineman-Ziter syndrome, OMIM:254940; Carey-Fineman-Ziter syndrome, MONDO:0009700
Hydrocephalus v2.7 MYMK Arina Puzriakova Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome 254940 to Carey-Fineman-Ziter syndrome, OMIM:254940; Carey-Fineman-Ziter syndrome, MONDO:0009700
Fetal anomalies v1.277 MYMK Arina Puzriakova Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome to Carey-Fineman-Ziter syndrome, OMIM:254940; Carey-Fineman-Ziter syndrome, MONDO:0009700
Fetal anomalies v1.276 MYMK Arina Puzriakova Classified gene: MYMK as Amber List (moderate evidence)
Fetal anomalies v1.276 MYMK Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.276 MYMK Arina Puzriakova Gene: mymk has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.275 MYMK Arina Puzriakova Tag for-review tag was added to gene: MYMK.
Congenital myopathy v2.26 MYL1 Arina Puzriakova Phenotypes for gene: MYL1 were changed from congenital myopathy; Myopathy, congenital, with fast-twitch (type II) fiber atrophy, 618414 to Myopathy, congenital, with fast-twitch (type II) fiber atrophy, OMIM:618414; Congenital myopathy with reduced type 2 muscle fibers, MONDO:0034109
Arthrogryposis v3.62 MYL1 Arina Puzriakova Phenotypes for gene: MYL1 were changed from congenital myopathy to Myopathy, congenital, with fast-twitch (type II) fiber atrophy, OMIM:618414; Congenital myopathy with reduced type 2 muscle fibers, MONDO:0034109
Fetal anomalies v1.275 MYL1 Arina Puzriakova Phenotypes for gene: MYL1 were changed from Myopathy, congenital, with fast-twitch (type II) fiber atrophy to Myopathy, congenital, with fast-twitch (type II) fiber atrophy, OMIM:618414; Congenital myopathy with reduced type 2 muscle fibers, MONDO:0034109
Fetal anomalies v1.274 MYL1 Arina Puzriakova Publications for gene: MYL1 were set to PMID: 30215711
Fetal anomalies v1.273 MYL1 Arina Puzriakova Classified gene: MYL1 as Amber List (moderate evidence)
Fetal anomalies v1.273 MYL1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.273 MYL1 Arina Puzriakova Gene: myl1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.272 MYL1 Arina Puzriakova Tag for-review tag was added to gene: MYL1.
Fetal anomalies v1.272 MYH7 Arina Puzriakova Phenotypes for gene: MYH7 were changed from Cardiomyopathy, dilated, 1S; Cardiomyopathy, hypertrophic, 1; Laing distal myopathy; Left ventricular noncompaction 5 to Laing distal myopathy, OMIM:160500; Laing early-onset distal myopathy, MONDO:0008050; Cardiomyopathy, hypertrophic, 1, OMIM:192600; Hypertrophic cardiomyopathy 1, MONDO:0008647; Cardiomyopathy, dilated, 1S, OMIM:613426; Dilated cardiomyopathy 1S, MONDO:0013262; Left ventricular noncompaction 5, OMIM:613426
Fetal anomalies v1.271 MYH7 Arina Puzriakova Publications for gene: MYH7 were set to PMID: 22859017; 25547560; 26337809
Fetal anomalies v1.270 MYH7 Arina Puzriakova Classified gene: MYH7 as Amber List (moderate evidence)
Fetal anomalies v1.270 MYH7 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.270 MYH7 Arina Puzriakova Gene: myh7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.269 MYH7 Arina Puzriakova Tag for-review tag was added to gene: MYH7.
Arthrogryposis v3.61 MYH2 Arina Puzriakova Tag for-review tag was added to gene: MYH2.
Arthrogryposis v3.61 MYH2 Arina Puzriakova Publications for gene: MYH2 were set to 23489661; 24193343,20418530
Arthrogryposis v3.60 MYH2 Arina Puzriakova Publications for gene: MYH2 were set to PMC18967; 24193343,
Arthrogryposis v3.59 MYH2 Arina Puzriakova Added comment: Comment on mode of inheritance: Independent reports of both biallelic (PMIDs: 20418530; 24193343) and monoallelic cases (PMIDs: 23489661) with joint contractures. MOI should therefore be changed from 'Monoallelic' to 'Both monoallelic and biallelic' at the next GMS panel update (added 'for-review' tag)
Arthrogryposis v3.59 MYH2 Arina Puzriakova Mode of inheritance for gene: MYH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.269 MYH2 Arina Puzriakova Publications for gene: MYH2 were set to
Congenital myopathy v2.25 MYH2 Arina Puzriakova Publications for gene: MYH2 were set to
Congenital myopathy v2.24 MYH2 Arina Puzriakova Tag for-review tag was added to gene: MYH2.
Congenital myopathy v2.24 MYH2 Arina Puzriakova Added comment: Comment on mode of inheritance: Multiple independent reports of both biallelic (PMIDs: 15548556; 23388406; 20418530; 24193343) and monoallelic cases (PMIDs: 11114175; 23489661). MOI should therefore be changed from 'Monoallelic' to 'Both monoallelic and biallelic' at the next GMS panel update (added 'for-review' tag)
Congenital myopathy v2.24 MYH2 Arina Puzriakova Mode of inheritance for gene: MYH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v2.281 PIGK Helen Lord reviewed gene: PIGK: Rating: GREEN; Mode of pathogenicity: None; Publications: 32220290; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v2.23 MYH2 Arina Puzriakova Phenotypes for gene: MYH2 were changed from Proximal myopathy and ophthalmoplegia 605637 to Proximal myopathy and ophthalmoplegia, OMIM:605637; Myopathy, proximal, and ophthalmoplegia, MONDO:0011577
Arthrogryposis v3.58 MYH2 Arina Puzriakova Phenotypes for gene: MYH2 were changed from Proximal myopathy and ophthalmoplegia 605637 to Proximal myopathy and ophthalmoplegia, OMIM:605637; Myopathy, proximal, and ophthalmoplegia, MONDO:0011577
Skeletal dysplasia v2.80 COG4 Michael Oldridge reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 30290151; Phenotypes: Saul-Wilson syndrome, OMIM:618150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.268 MYH2 Arina Puzriakova Phenotypes for gene: MYH2 were changed from Proximal myopathy and ophthalmoplegia to Proximal myopathy and ophthalmoplegia, OMIM:605637; Myopathy, proximal, and ophthalmoplegia, MONDO:0011577
Early onset or syndromic epilepsy v2.281 LMBRD2 Helen Lord reviewed gene: LMBRD2: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 32820033; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.267 MYH2 Arina Puzriakova Mode of inheritance for gene: MYH2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v2.392 COL7A1 Kelsey Jones changed review comment from: Important monogenic cause of VEOIBD (recognised criteria for the R15 panel). In a retrospective case series, 9 of 57 (16%) children with recessive DEBP had diarrhoea with macroscopic/microscopic features of colitis (PMID: 18363753). Included on a monogenic IBD gene panel proposed by The Paediatric IBD Porto Group of ESPGHAN (PMID: 33346580). Not a recognised cause of immunodeficiency.
Sources: Expert Review; to: Important monogenic cause of VEOIBD (recognised criteria for the R15 panel). In a retrospective case series, 9 of 57 (16%) children with recessive DEBP had diarrhoea with macroscopic/microscopic features of colitis (PMID: 18363753). There is additionally a recognised association between Epidermolysis Bullosa Acquisita (an autoimmune condition directed against Type VII Collagen (the COL7A1 protein product) (PMID: 23517353). Included on a monogenic IBD gene panel proposed by The Paediatric IBD Porto Group of ESPGHAN (PMID: 33346580). Not a recognised cause of immunodeficiency.
Sources: Expert Review
Primary immunodeficiency or monogenic inflammatory bowel disease v2.392 COL7A1 Kelsey Jones gene: COL7A1 was added
gene: COL7A1 was added to Primary immunodeficiency. Sources: Expert Review
Mode of inheritance for gene: COL7A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL7A1 were set to PMID: 18363753
Phenotypes for gene: COL7A1 were set to Very Early Onset Inflammatory Bowel Disease; Dystrophic Epidermolysis Bullosa Pruriginosa
Penetrance for gene: COL7A1 were set to Incomplete
Review for gene: COL7A1 was set to AMBER
Added comment: Important monogenic cause of VEOIBD (recognised criteria for the R15 panel). In a retrospective case series, 9 of 57 (16%) children with recessive DEBP had diarrhoea with macroscopic/microscopic features of colitis (PMID: 18363753). Included on a monogenic IBD gene panel proposed by The Paediatric IBD Porto Group of ESPGHAN (PMID: 33346580). Not a recognised cause of immunodeficiency.
Sources: Expert Review
Fetal anomalies v1.266 MYH2 Arina Puzriakova Classified gene: MYH2 as Amber List (moderate evidence)
Fetal anomalies v1.266 MYH2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.266 MYH2 Arina Puzriakova Gene: myh2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.265 MYH2 Arina Puzriakova Tag for-review tag was added to gene: MYH2.
Skeletal dysplasia v2.80 C16orf62 Michael Oldridge reviewed gene: C16orf62: Rating: AMBER; Mode of pathogenicity: None; Publications: 31712251; Phenotypes: 3C/Ritscher-Schinzel-like syndrome, MIM619135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.265 MSTO1 Arina Puzriakova Publications for gene: MSTO1 were set to
Fetal anomalies v1.264 MSTO1 Arina Puzriakova Phenotypes for gene: MSTO1 were changed from Myopathy, mitochondrial, and ataxia to Myopathy, mitochondrial, and ataxia, OMIM:617675; Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome, MONDO:0044714
Fetal anomalies v1.263 MSTO1 Arina Puzriakova Classified gene: MSTO1 as Amber List (moderate evidence)
Fetal anomalies v1.263 MSTO1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.263 MSTO1 Arina Puzriakova Gene: msto1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.262 MSTO1 Arina Puzriakova Tag for-review tag was added to gene: MSTO1.
Fetal anomalies v1.262 MSMO1 Arina Puzriakova Publications for gene: MSMO1 were set to
Childhood onset dystonia, chorea or related movement disorder v1.80 MSMO1 Arina Puzriakova Mode of inheritance for gene: MSMO1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.749 MSMO1 Arina Puzriakova Phenotypes for gene: MSMO1 were changed from Microcephaly, congenital cataract, and psoriasiform dermatitis, 616834 to Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793
Likely inborn error of metabolism v2.51 MSMO1 Arina Puzriakova Phenotypes for gene: MSMO1 were changed from Sterol-C4-methyl oxidase deficiency (Disorders of sterol biosynthesis); (SC4MOL DEFICIENCY); Microcephaly, congenital cataract, and psoriasiform dermatitis, 616834 to Sterol-C4-methyl oxidase deficiency (Disorders of sterol biosynthesis); Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793
Undiagnosed metabolic disorders v1.441 MSMO1 Arina Puzriakova Phenotypes for gene: MSMO1 were changed from Sterol-C4-methyl oxidase deficiency (Disorders of sterol biosynthesis); Microcephaly, congenital cataract, and psoriasiform dermatitis, 616834; (SC4MOL DEFICIENCY) to Sterol-C4-methyl oxidase deficiency (Disorders of sterol biosynthesis); Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793
Severe microcephaly v2.94 MSMO1 Arina Puzriakova Phenotypes for gene: MSMO1 were changed from Microcephaly, congenital cataract, and psoriasiform dermatitis, 616834 to Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793
Bilateral congenital or childhood onset cataracts v2.59 MSMO1 Arina Puzriakova Phenotypes for gene: MSMO1 were changed from Microcephaly, congenital cataract, and psoriasiform dermatitis, 616834 to Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793
Generalised pustular psoriasis v1.9 MSMO1 Arina Puzriakova Phenotypes for gene: MSMO1 were changed from Microcephaly, congenital cataract, and psoriasiform dermatitis 616834 to Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793
Ichthyosis and erythrokeratoderma v1.6 MSMO1 Arina Puzriakova Phenotypes for gene: MSMO1 were changed from to Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793
Fetal anomalies v1.261 MSMO1 Arina Puzriakova Phenotypes for gene: MSMO1 were changed from Microcephaly, congenital cataract, and psoriasiform dermatitis to Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793
Fetal anomalies v1.260 MSMO1 Arina Puzriakova Classified gene: MSMO1 as Amber List (moderate evidence)
Fetal anomalies v1.260 MSMO1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.260 MSMO1 Arina Puzriakova Gene: msmo1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.259 MSMO1 Arina Puzriakova Tag for-review tag was added to gene: MSMO1.
Fetal anomalies v1.259 MRAS Arina Puzriakova Classified gene: MRAS as Amber List (moderate evidence)
Fetal anomalies v1.259 MRAS Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.259 MRAS Arina Puzriakova Gene: mras has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.258 MRAS Arina Puzriakova Tag for-review tag was added to gene: MRAS.
Fetal anomalies v1.258 MRAS Arina Puzriakova Publications for gene: MRAS were set to
Paediatric or syndromic cardiomyopathy v1.19 MRAS Arina Puzriakova Phenotypes for gene: MRAS were changed from Noonan syndrome, 618499 to Noonan syndrome 11, OMIM:618499; Noonan syndrome 11, MONDO:0032786
RASopathies v1.75 MRAS Arina Puzriakova Phenotypes for gene: MRAS were changed from Noonan syndrome 11, 618499 to Noonan syndrome 11, OMIM:618499; Noonan syndrome 11, MONDO:0032786
Fetal anomalies v1.257 MRAS Arina Puzriakova Phenotypes for gene: MRAS were changed from Noonan syndrome 11 to Noonan syndrome 11, OMIM:618499; Noonan syndrome 11, MONDO:0032786
Fetal anomalies v1.256 MESD Arina Puzriakova Publications for gene: MESD were set to
Osteogenesis imperfecta v2.13 MESD Arina Puzriakova Phenotypes for gene: MESD were changed from Osteogenesis imperfecta, type XX, 618644 to Osteogenesis imperfecta, type XX, OMIM:618644; Osteogenesis imperfecta, type 20, MONDO:0032846
Fetal anomalies v1.255 MESD Arina Puzriakova Phenotypes for gene: MESD were changed from Osteogenesis imperfecta, type XX to Osteogenesis imperfecta, type XX, OMIM:618644; Osteogenesis imperfecta, type 20, MONDO:0032846
Fetal anomalies v1.254 MESD Arina Puzriakova Classified gene: MESD as Amber List (moderate evidence)
Fetal anomalies v1.254 MESD Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.254 MESD Arina Puzriakova Gene: mesd has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.80 ANAPC1 Michael Oldridge reviewed gene: ANAPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31303264; Phenotypes: Rothmund Thomson syndrome type 1, OMIM:618625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.253 MESD Arina Puzriakova Tag for-review tag was added to gene: MESD.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.392 NPC1 Kelsey Jones changed review comment from: Important monogenic cause of VEOIBD (recognised criteria for the R15 panel). 14 patients with defects in NPC1 presenting with severe Crohn's-like intestinal inflammation described in PMID: 26953272. Mechanism suggested to involve defective bacterial handling by macrophages. Estimated 3-7% penetrance of intestinal inflammation in patients with Niemann-Pick type C disease (same reference). Included on a monogenic IBD gene panel proposed by The Paediatric IBD Porto Group of ESPGHAN (PMID: 33346580). Not a recognised cause of immunodeficiency.
Sources: Expert list; to: Important monogenic cause of VEOIBD (recognised criteria for the R15 panel). 14 patients with defects in NPC1 presenting with severe Crohn's-like intestinal inflammation described in PMID: 26953272. Mechanism suggested to involve defective bacterial handling by macrophages. Estimated 3-7% penetrance of intestinal inflammation in patients with Niemann-Pick type C disease (same reference). Included on a monogenic IBD gene panel proposed by The Paediatric IBD Porto Group of ESPGHAN (PMID: 33346580). Not a recognised cause of immunodeficiency.
Sources: Expert list
Intellectual disability v3.748 MEIS2 Arina Puzriakova Phenotypes for gene: MEIS2 were changed from Cleft palate, cardiac defects, and mental retardation; Oral cleft; Abnormal heart morphology; Intellectual disability; Cleft palate, cardiac defects, and mental retardation, 600987 to Cleft palate, cardiac defects, and mental retardation, OMIM:600987; Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies, MONDO:0010970
Clefting v2.23 MEIS2 Arina Puzriakova Phenotypes for gene: MEIS2 were changed from Orofacial clefting; cardiac defects; intellectual disability; Cleft palate to Cleft palate, cardiac defects, and mental retardation, OMIM:600987; Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies, MONDO:0010970
Fetal anomalies v1.253 MEIS2 Arina Puzriakova Phenotypes for gene: MEIS2 were changed from Cleft palate, cardiac defects, and mental retardation to Cleft palate, cardiac defects, and mental retardation, OMIM:600987; Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies, MONDO:0010970
Fetal anomalies v1.252 MEIS2 Arina Puzriakova Publications for gene: MEIS2 were set to
Fetal anomalies v1.251 MEIS2 Arina Puzriakova Classified gene: MEIS2 as Amber List (moderate evidence)
Fetal anomalies v1.251 MEIS2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.251 MEIS2 Arina Puzriakova Gene: meis2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.250 MEIS2 Arina Puzriakova Tag for-review tag was added to gene: MEIS2.
Fetal anomalies v1.250 MAP3K20 Arina Puzriakova Publications for gene: MAP3K20 were set to
Fetal anomalies v1.249 MAP3K20 Arina Puzriakova Phenotypes for gene: MAP3K20 were changed from Split-foot malformation with mesoaxial polydactyly; Centronuclear myopathy 6 with fiber-type disproportion to Centronuclear myopathy 6 with fiber-type disproportion, OMIM:617760; Myopathy, centronuclear, 6, with fiber-type disproportion, MONDO:0054695; Split-foot malformation with mesoaxial polydactyly, OMIM:616890; Split-foot malformation-mesoaxial polydactyly syndrome, MONDO:0014816
Congenital myopathy v2.22 MAP3K20 Arina Puzriakova Phenotypes for gene: MAP3K20 were changed from congenital myopathy with fibre type disproportion to Centronuclear myopathy 6 with fiber-type disproportion, OMIM:617760; Myopathy, centronuclear, 6, with fiber-type disproportion, MONDO:0054695
Fetal anomalies v1.248 MAP3K20 Arina Puzriakova Classified gene: MAP3K20 as Amber List (moderate evidence)
Fetal anomalies v1.248 MAP3K20 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.248 MAP3K20 Arina Puzriakova Gene: map3k20 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.247 MAP3K20 Arina Puzriakova Tag for-review tag was added to gene: MAP3K20.
Fetal anomalies v1.247 MACF1 Arina Puzriakova Publications for gene: MACF1 were set to
Fetal anomalies v1.246 MACF1 Arina Puzriakova Phenotypes for gene: MACF1 were changed from Lissencephaly 9 with complex brainstem malformation to Lissencephaly 9 with complex brainstem malformation, OMIM:618325; Lissencephaly 9 with complex brainstem malformation, MONDO:0032677
Fetal anomalies v1.245 MACF1 Arina Puzriakova Classified gene: MACF1 as Amber List (moderate evidence)
Fetal anomalies v1.245 MACF1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.245 MACF1 Arina Puzriakova Gene: macf1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.244 MACF1 Arina Puzriakova Tag for-review tag was added to gene: MACF1.
Fetal anomalies v1.244 LRRC56 Arina Puzriakova Publications for gene: LRRC56 were set to
Laterality disorders and isomerism v1.21 LRRC56 Arina Puzriakova Phenotypes for gene: LRRC56 were changed from Ciliary dyskinesia, primary, 39, 618254; Mucociliary Clearance and Laterality Defect to Ciliary dyskinesia, primary, 39, OMIM:618254; Ciliary dyskinesia, primary, 39, MONDO:0032637; Mucociliary Clearance and Laterality Defect
Respiratory ciliopathies including non-CF bronchiectasis v1.43 LRRC56 Arina Puzriakova Phenotypes for gene: LRRC56 were changed from Ciliopathies to Ciliary dyskinesia, primary, 39, OMIM:618254; Ciliary dyskinesia, primary, 39, MONDO:0032637
Primary immunodeficiency or monogenic inflammatory bowel disease v2.392 NPC1 Kelsey Jones gene: NPC1 was added
gene: NPC1 was added to Primary immunodeficiency. Sources: Expert list
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to PMID: 26953272
Phenotypes for gene: NPC1 were set to Very Early Onset Inflammatory Bowel Disease
Penetrance for gene: NPC1 were set to Incomplete
Review for gene: NPC1 was set to GREEN
Added comment: Important monogenic cause of VEOIBD (recognised criteria for the R15 panel). 14 patients with defects in NPC1 presenting with severe Crohn's-like intestinal inflammation described in PMID: 26953272. Mechanism suggested to involve defective bacterial handling by macrophages. Estimated 3-7% penetrance of intestinal inflammation in patients with Niemann-Pick type C disease (same reference). Included on a monogenic IBD gene panel proposed by The Paediatric IBD Porto Group of ESPGHAN (PMID: 33346580). Not a recognised cause of immunodeficiency.
Sources: Expert list
Early onset or syndromic epilepsy v2.281 GALNT2 Helen Lord reviewed gene: GALNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32293671, 27508872; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.243 LRRC56 Arina Puzriakova Phenotypes for gene: LRRC56 were changed from Ciliary dyskinesia, primary, 39 to Ciliary dyskinesia, primary, 39, OMIM:618254; Ciliary dyskinesia, primary, 39, MONDO:0032637
Fetal anomalies v1.242 LRRC56 Arina Puzriakova Classified gene: LRRC56 as Amber List (moderate evidence)
Fetal anomalies v1.242 LRRC56 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.242 LRRC56 Arina Puzriakova Gene: lrrc56 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.241 LRRC56 Arina Puzriakova Tag for-review tag was added to gene: LRRC56.
Fetal anomalies v1.241 KNL1 Arina Puzriakova Publications for gene: KNL1 were set to
Intellectual disability v3.747 KNL1 Arina Puzriakova Phenotypes for gene: KNL1 were changed from Microcephaly 4, primary, autosomal recessive 604321 to Microcephaly 4, primary, autosomal recessive, OMIM:604321; Microcephaly 4, primary, autosomal recessive, MONDO:0011437
Severe microcephaly v2.93 KNL1 Arina Puzriakova Phenotypes for gene: KNL1 were changed from MCPH; primary microcephaly; Primary Microcephaly, Recessive; Microcephaly 4, primary, autosomal recessive, 604321; Microcephaly 4, Primary, Autosomal Recessive to Microcephaly 4, primary, autosomal recessive, OMIM:604321; Microcephaly 4, primary, autosomal recessive, MONDO:0011437
Fetal anomalies v1.240 KNL1 Arina Puzriakova Phenotypes for gene: KNL1 were changed from Microcephaly 4, primary, autosomal recessive to Microcephaly 4, primary, autosomal recessive, OMIM:604321; Microcephaly 4, primary, autosomal recessive, MONDO:0011437
Fetal anomalies v1.239 KNL1 Arina Puzriakova Classified gene: KNL1 as Amber List (moderate evidence)
Fetal anomalies v1.239 KNL1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.239 KNL1 Arina Puzriakova Gene: knl1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.238 KNL1 Arina Puzriakova Tag for-review tag was added to gene: KNL1.
Fetal anomalies v1.238 KIAA0753 Arina Puzriakova Classified gene: KIAA0753 as Amber List (moderate evidence)
Fetal anomalies v1.238 KIAA0753 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.238 KIAA0753 Arina Puzriakova Gene: kiaa0753 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.237 KIAA0753 Arina Puzriakova Publications for gene: KIAA0753 were set to
Fetal anomalies v1.236 KIAA0753 Arina Puzriakova Phenotypes for gene: KIAA0753 were changed from ?Orofaciodigital syndrome XV to ?Orofaciodigital syndrome XV, OMIM:617127; Orofaciodigital syndrome XV, MONDO:0014932
Fetal anomalies v1.235 KIAA0753 Arina Puzriakova Tag for-review tag was added to gene: KIAA0753.
Fetal anomalies v1.235 KATNB1 Arina Puzriakova Publications for gene: KATNB1 were set to
Intellectual disability v3.746 KATNB1 Arina Puzriakova Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly, MIM 616212 to Lissencephaly 6, with microcephaly, OMIM:616212, MONDO:0014534
Early onset or syndromic epilepsy v2.281 GAD1 Helen Lord reviewed gene: GAD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 320705143, 32282878; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v2.281 KATNB1 Arina Puzriakova Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly, 616212; seizures to Lissencephaly 6, with microcephaly, OMIM:616212, MONDO:0014534
Malformations of cortical development v2.44 KATNB1 Arina Puzriakova Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly 616212 to Lissencephaly 6, with microcephaly, OMIM:616212, MONDO:0014534
Fetal anomalies v1.234 KATNB1 Arina Puzriakova Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly to Lissencephaly 6, with microcephaly, OMIM:616212, MONDO:0014534
Fetal anomalies v1.233 KATNB1 Arina Puzriakova Classified gene: KATNB1 as Amber List (moderate evidence)
Fetal anomalies v1.233 KATNB1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.233 KATNB1 Arina Puzriakova Gene: katnb1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.232 KATNB1 Arina Puzriakova Tag for-review tag was added to gene: KATNB1.
Fetal anomalies v1.232 IFT81 Arina Puzriakova Publications for gene: IFT81 were set to
Fetal anomalies v1.231 IFT81 Arina Puzriakova Phenotypes for gene: IFT81 were changed from Short-rib thoracic dysplasia 19 with or without polydactyly to Short-rib thoracic dysplasia 19 with or without polydactyly, OMIM:617895; Short-rib thoracic dysplasia 19 with or without polydactyly, MONDO:0033485
Fetal anomalies v1.230 IFT81 Arina Puzriakova Classified gene: IFT81 as Amber List (moderate evidence)
Fetal anomalies v1.230 IFT81 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.230 IFT81 Arina Puzriakova Gene: ift81 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.229 IFT81 Arina Puzriakova Tag for-review tag was added to gene: IFT81.
Early onset or syndromic epilepsy v2.280 DHX16 Helen Lord reviewed gene: DHX16: Rating: AMBER; Mode of pathogenicity: None; Publications: 31256877; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.229 MYPN Rhiannon Mellis gene: MYPN was added
gene: MYPN was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MYPN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MYPN were set to Nemaline myopathy 11, autosomal recessive, 617336
Review for gene: MYPN was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Fetal anomalies v1.229 ALG2 Rhiannon Mellis reviewed gene: ALG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myasthenic syndrome, congenital, 14, with tubular aggregates, 616228, ?Congenital disorder of glycosylation, type Ii, 607906; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 ALG9 Rhiannon Mellis reviewed gene: ALG9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Il, 608776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 ALOX12B Rhiannon Mellis gene: ALOX12B was added
gene: ALOX12B was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ALOX12B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALOX12B were set to Ichthyosis, congenital, autosomal recessive 2, 242100
Review for gene: ALOX12B was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Autosomal recessive congenital ichthyosis
Sources: Expert list
Fetal anomalies v1.229 ALOXE3 Rhiannon Mellis gene: ALOXE3 was added
gene: ALOXE3 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ALOXE3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALOXE3 were set to Ichthyosis, congenital, autosomal recessive 3, 606545
Review for gene: ALOXE3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Autosomal recessive congenital ichthyosis
Sources: Expert list
Fetal anomalies v1.229 AMACR Rhiannon Mellis gene: AMACR was added
gene: AMACR was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: AMACR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AMACR were set to Alpha-methylacyl-CoA racemase deficiency, 614307
Review for gene: AMACR was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Peroxisomal disorders
Sources: Expert list
Fetal anomalies v1.229 AMMECR1 Rhiannon Mellis gene: AMMECR1 was added
gene: AMMECR1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: AMMECR1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: AMMECR1 were set to Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis, 300990
Review for gene: AMMECR1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): IUGR and IGF abnormalities
Sources: Expert list
Fetal anomalies v1.229 ANKS6 Rhiannon Mellis gene: ANKS6 was added
gene: ANKS6 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ANKS6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ANKS6 were set to Nephronophthisis 16, 615382
Review for gene: ANKS6 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cystic renal disease (super panel); Rare multisystem ciliopathy Super panel
Sources: Expert list
Fetal anomalies v1.229 ANTXR2 Rhiannon Mellis reviewed gene: ANTXR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30176098, 14508707, 20301698; Phenotypes: Hyaline fibromatosis syndrome, 228600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 ARFGEF2 Rhiannon Mellis reviewed gene: ARFGEF2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Periventricular heterotopia with microcephaly, 608097; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 ARHGAP29 Rhiannon Mellis gene: ARHGAP29 was added
gene: ARHGAP29 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ARHGAP29 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ARHGAP29 were set to cleft lip with or without cleft palate; Cleft palate
Review for gene: ARHGAP29 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Clefting
Sources: Expert list
Fetal anomalies v1.229 ATR Rhiannon Mellis reviewed gene: ATR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Seckel syndrome 1, 210600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 B3GALNT2 Rhiannon Mellis reviewed gene: B3GALNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23453667; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11, 615181; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 B4GAT1 Rhiannon Mellis gene: B4GAT1 was added
gene: B4GAT1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: B4GAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GAT1 were set to PMID: 23877401; 23359570
Phenotypes for gene: B4GAT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13, 615287
Review for gene: B4GAT1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis; Neuromuscular disorders

Additional comment: Severe structural brain phenotype and dysplastic kidneys, reported onset in utero. PMID: 23877401; PMID: 23359570
Sources: Expert list
Fetal anomalies v1.229 BNC2 Rhiannon Mellis gene: BNC2 was added
gene: BNC2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: BNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: BNC2 were set to Lower urinary tract obstruction, congenital, 618612
Review for gene: BNC2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): CAKUT
Sources: Expert list
Fetal anomalies v1.229 C21orf59 Rhiannon Mellis reviewed gene: C21orf59: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 26, 615500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 C2CD3 Rhiannon Mellis reviewed gene: C2CD3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome XIV, 615948; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CACNA1G Rhiannon Mellis gene: CACNA1G was added
gene: CACNA1G was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CACNA1G was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CACNA1G were set to Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits, 618087
Review for gene: CACNA1G was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cerebellar hypoplasia
Sources: Expert list
Fetal anomalies v1.229 CANT1 Rhiannon Mellis gene: CANT1 was added
gene: CANT1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CANT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CANT1 were set to Epiphyseal dysplasia, multiple, 7, 617719; Desbuquois dysplasia 1, 251450
Review for gene: CANT1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.229 CASR Rhiannon Mellis gene: CASR was added
gene: CASR was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CASR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: CASR were set to Hypocalcemia, autosomal dominant, 601198; Hypocalciuric hypercalcemia, type I, 145980; Hyperparathyroidism, neonatal, 239200; Hypocalcemia, autosomal dominant, with Bartter syndrome, 601198
Review for gene: CASR was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Osteogenesis imperfecta; Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.229 CCDC151 Rhiannon Mellis reviewed gene: CCDC151: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 30, 616037; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CCDC8 Rhiannon Mellis reviewed gene: CCDC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-M syndrome 3, 614205; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CCDC88C Rhiannon Mellis reviewed gene: CCDC88C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrocephalus, congenital, 1, 236600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CDK5RAP2 Rhiannon Mellis reviewed gene: CDK5RAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly 3, primary, autosomal recessive, 604804; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CELSR1 Rhiannon Mellis gene: CELSR1 was added
gene: CELSR1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CELSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CELSR1 were set to hereditary lymphedema
Review for gene: CELSR1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Primary lymphoedema
Sources: Expert list
Fetal anomalies v1.229 CENPF Rhiannon Mellis gene: CENPF was added
gene: CENPF was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPF were set to PMID: 26820108; 25564561
Phenotypes for gene: CENPF were set to Stromme syndrome, 243605
Review for gene: CENPF was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cystic renal disease (super panel); Hydrocephalus; Limb disorders; Rare multisystem ciliopathy Super panel; Severe microcephaly

Additional comment: Fetal phenotype (ciliopathy) reported in PMID: 26820108 and PMID: 25564561
Sources: Expert list
Haematological malignancies cancer susceptibility v2.5 DNAJC21 Kiran Tawana gene: DNAJC21 was added
gene: DNAJC21 was added to Haematological malignancies cancer susceptibility. Sources: Literature
Mode of inheritance for gene: DNAJC21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC21 were set to PMID: 27346687; PMID: 29700810
Phenotypes for gene: DNAJC21 were set to bone marrow failure; AML; developmental delay; pancreatic insufficiency, overlap with SBDS
Penetrance for gene: DNAJC21 were set to Complete
Review for gene: DNAJC21 was set to GREEN
Added comment: Sources: Literature
Fetal anomalies v1.229 CEP135 Rhiannon Mellis reviewed gene: CEP135: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly 8, primary, autosomal recessive, 614673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CEP55 Rhiannon Mellis reviewed gene: CEP55: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, 236500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Haematological malignancies cancer susceptibility v2.5 MBD4 Kiran Tawana gene: MBD4 was added
gene: MBD4 was added to Haematological malignancies cancer susceptibility. Sources: Literature
Mode of inheritance for gene: MBD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MBD4 were set to PMID: 30049810; PMID: 29760383; PMID: 32239153
Phenotypes for gene: MBD4 were set to AML, colonic polyps, uveal melanoma, glioblastoma
Penetrance for gene: MBD4 were set to Complete
Review for gene: MBD4 was set to GREEN
Added comment: Sources: Literature
Fetal anomalies v1.229 CEP63 Rhiannon Mellis reviewed gene: CEP63: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Seckel syndrome 6, 614728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CERS3 Rhiannon Mellis gene: CERS3 was added
gene: CERS3 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CERS3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CERS3 were set to Ichthyosis, congenital, autosomal recessive 9, 615023
Review for gene: CERS3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Autosomal recessive congenital ichthyosis
Sources: Expert list
Fetal anomalies v1.229 CFL2 Rhiannon Mellis reviewed gene: CFL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nemaline myopathy 7, autosomal recessive, 610687; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CHMP1A Rhiannon Mellis reviewed gene: CHMP1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia, type 8, 614961; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CHRNA3 Rhiannon Mellis gene: CHRNA3 was added
gene: CHRNA3 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CHRNA3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHRNA3 were set to Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, 191800
Review for gene: CHRNA3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): CAKUT
Sources: Expert list
Fetal anomalies v1.229 CHRNB1 Rhiannon Mellis gene: CHRNB1 was added
gene: CHRNB1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CHRNB1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: CHRNB1 were set to Myasthenic syndrome, congenital, 2A, slow-channel, 616313; ?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314
Review for gene: CHRNB1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis; Neuromuscular disorders
Sources: Expert list
Fetal anomalies v1.229 CHRNE Rhiannon Mellis gene: CHRNE was added
gene: CHRNE was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CHRNE was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: CHRNE were set to Myasthenic syndrome, congenital, 4A, slow-channel, 605809; Myasthenic syndrome, congenital, 4B, fast-channel, 616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931
Review for gene: CHRNE was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis; Neuromuscular disorders

Additional comment: Phenotype on OMIM reported as including arthrogryposis multiplex in severe cases. Decreased fetal movements in some cases.
Sources: Expert list
Fetal anomalies v1.229 CIT Rhiannon Mellis reviewed gene: CIT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly 17, primary, autosomal recessive, 617090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CLP1 Rhiannon Mellis reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia, type 10, 615803; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 CNBP Rhiannon Mellis gene: CNBP was added
gene: CNBP was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CNBP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CNBP were set to Myotonic dystrophy 2, 602668
Review for gene: CNBP was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Fetal anomalies v1.229 COG5 Rhiannon Mellis reviewed gene: COG5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IIi, 613612; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.229 COG6 Rhiannon Mellis gene: COG6 was added
gene: COG6 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: COG6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COG6 were set to Congenital disorder of glycosylation, type IIl, 614576; Shaheen syndrome, 615328
Review for gene: COG6 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Congenital disorders of glycosylation
Sources: Expert list
Fetal anomalies v1.229 IFT52 Arina Puzriakova Publications for gene: IFT52 were set to
Fetal anomalies v1.228 COL12A1 Rhiannon Mellis gene: COL12A1 was added
gene: COL12A1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: COL12A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: COL12A1 were set to Bethlem myopathy 2, 616471; ?Ullrich congenital muscular dystrophy 2, 616470
Review for gene: COL12A1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis

Additional comment: At least three affected families with Bethlem myopathy which is associated with early contractures (?congenital) as well as two brothers with Ulrich congenital muscular dystrophy which is associated with arthrogryposis
Sources: Expert list
Fetal anomalies v1.228 COL13A1 Rhiannon Mellis reviewed gene: COL13A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myasthenic syndrome, congenital, 19, 616720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.228 COLEC10 Rhiannon Mellis reviewed gene: COLEC10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3MC syndrome 3, 248340; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.228 COLQ Rhiannon Mellis gene: COLQ was added
gene: COLQ was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: COLQ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLQ were set to PMID: 9689136; 11865139
Phenotypes for gene: COLQ were set to Myasthenic syndrome, congenital, 5, 603034
Review for gene: COLQ was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis

Additional comment: I can’t see any reported cases specifically with arthrogryposis, but some cases presented at birth with hypotonia/weakness/fatigability. PMID: 9689136; 11865139. Therefore included on basis of severe neonatal phenotype that may conceivably also present prenatally.
Sources: Expert list
Fetal anomalies v1.228 CREB3L1 Rhiannon Mellis gene: CREB3L1 was added
gene: CREB3L1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CREB3L1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CREB3L1 were set to Osteogenesis imperfecta, type XVI, 616229
Review for gene: CREB3L1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Osteogenesis imperfecta; Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.228 CRIPT Rhiannon Mellis gene: CRIPT was added
gene: CRIPT was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CRIPT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CRIPT were set to Short stature with microcephaly and distinctive facies, 615789
Review for gene: CRIPT was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): IUGR and IGF abnormalities
Sources: Expert list
Fetal anomalies v1.228 CTU2 Rhiannon Mellis gene: CTU2 was added
gene: CTU2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, 618142
Review for gene: CTU2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): CAKUT
Sources: Expert list
Haematological malignancies cancer susceptibility v2.5 CSF3R Kiran Tawana reviewed gene: CSF3R: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 27939403; Phenotypes: MDS, Myeloma, B-ALL; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Childhood onset dystonia, chorea or related movement disorder v1.79 IFT52 Arina Puzriakova Mode of inheritance for gene: IFT52 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal ciliopathies v1.10 IFT52 Arina Puzriakova Phenotypes for gene: IFT52 were changed from Short-rib thoracic dysplasia 16 with or without polydactyly, 617102 to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Rare multisystem ciliopathy disorders v1.139 IFT52 Arina Puzriakova Phenotypes for gene: IFT52 were changed from Short-rib thoracic dysplasia 16 with or without polydactyly, 617102 to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Fetal anomalies v1.228 CYP26B1 Rhiannon Mellis gene: CYP26B1 was added
gene: CYP26B1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CYP26B1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP26B1 were set to Craniosynostosis with radiohumeral fusions and other skeletal and craniofacial anomalies, 614416
Review for gene: CYP26B1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Craniosynostosis
Sources: Expert list
Clefting v2.22 IFT52 Arina Puzriakova Phenotypes for gene: IFT52 were changed from SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY; SRTD16 to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Skeletal dysplasia v2.80 IFT52 Arina Puzriakova Phenotypes for gene: IFT52 were changed from SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY, SRTD16 #617102 to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Ductal plate malformation v1.16 IFT52 Arina Puzriakova Phenotypes for gene: IFT52 were changed from Short-rib thoracic dysplasia 16 with or without polydactyly (617102) to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Fetal anomalies v1.228 CYP4F22 Rhiannon Mellis gene: CYP4F22 was added
gene: CYP4F22 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: CYP4F22 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP4F22 were set to Ichthyosis, congenital, autosomal recessive 5, 604777
Review for gene: CYP4F22 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Autosomal recessive congenital ichthyosis
Sources: Expert list
Limb disorders v2.35 IFT52 Arina Puzriakova Phenotypes for gene: IFT52 were changed from Short-rib thoracic dysplasia 16 with or without polydactyly, 617102; Polydactyly to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Thoracic dystrophies v1.12 IFT52 Arina Puzriakova Phenotypes for gene: IFT52 were changed from SHORT-RIB THORACIC DYSPLASIA 16 WITH OR WITHOUT POLYDACTYLY, SRTD16 #617102 to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Fetal anomalies v1.228 DDX59 Rhiannon Mellis reviewed gene: DDX59: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome V, 174300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.228 IFT52 Arina Puzriakova Phenotypes for gene: IFT52 were changed from Short-rib thoracic dysplasia 16 with or without polydactyly to Short-rib thoracic dysplasia 16 with or without polydactyly, OMIM:617102; Short-rib thoracic dysplasia 16 with or without polydactyly, MONDO:0014915
Fetal anomalies v1.227 DENND5A Rhiannon Mellis reviewed gene: DENND5A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 49, 617281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.227 IFT52 Arina Puzriakova Classified gene: IFT52 as Amber List (moderate evidence)
Fetal anomalies v1.227 IFT52 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.227 IFT52 Arina Puzriakova Gene: ift52 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.226 IFT52 Arina Puzriakova Tag for-review tag was added to gene: IFT52.
Fetal anomalies v1.226 DIAPH1 Rhiannon Mellis gene: DIAPH1 was added
gene: DIAPH1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DIAPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DIAPH1 were set to Seizures, cortical blindness, microcephaly syndrome, 616632
Review for gene: DIAPH1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Severe microcephaly
Sources: Expert list
Fetal anomalies v1.226 DISP1 Rhiannon Mellis gene: DISP1 was added
gene: DISP1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DISP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DISP1 were set to 27363716
Phenotypes for gene: DISP1 were set to Holoprosencephaly
Review for gene: DISP1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cerebral malformations; Holoprosencephaly
Sources: Expert list
Fetal anomalies v1.226 IDH1 Arina Puzriakova Classified gene: IDH1 as Amber List (moderate evidence)
Fetal anomalies v1.226 IDH1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.226 IDH1 Arina Puzriakova Gene: idh1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.225 IDH1 Arina Puzriakova Tag for-review tag was added to gene: IDH1.
Haematological malignancies cancer susceptibility v2.5 CSF3R Kiran Tawana Deleted their review
Fetal anomalies v1.225 DLX5 Rhiannon Mellis gene: DLX5 was added
gene: DLX5 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DLX5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: DLX5 were set to ?Split-hand/foot malformation 1 with sensorineural hearing loss, 220600; Split-hand/foot malformation 1, 183600
Review for gene: DLX5 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Limb disorders; Skeletal dysplasia
Sources: Expert list
Haematological malignancies cancer susceptibility v2.5 CSF3R Kiran Tawana gene: CSF3R was added
gene: CSF3R was added to Haematological malignancies cancer susceptibility. Sources: Literature
Mode of inheritance for gene: CSF3R was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CSF3R were set to PMID: 27939403
Phenotypes for gene: CSF3R were set to MDS; Myeloma; B-ALL
Penetrance for gene: CSF3R were set to unknown
Review for gene: CSF3R was set to RED
Added comment: Sources: Literature
Fetal anomalies v1.225 DNAAF2 Rhiannon Mellis gene: DNAAF2 was added
gene: DNAAF2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DNAAF2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAAF2 were set to Ciliary dyskinesia, primary, 10, 612518
Review for gene: DNAAF2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Primary ciliary disorders
Sources: Expert list
Fetal anomalies v1.225 DNAAF5 Rhiannon Mellis reviewed gene: DNAAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 18,614874; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.225 DNAI2 Rhiannon Mellis gene: DNAI2 was added
gene: DNAI2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DNAI2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAI2 were set to Ciliary dyskinesia, primary, 9, with or without situs inversus,612444
Review for gene: DNAI2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Laterality disorders and isomerism; Primary ciliary disorders
Sources: Expert list
Fetal anomalies v1.225 DNAJB11 Rhiannon Mellis gene: DNAJB11 was added
gene: DNAJB11 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DNAJB11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: DNAJB11 were set to Polycystic kidney disease 6 with or without polycystic liver disease, 618061
Review for gene: DNAJB11 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cystic renal disease (super panel); Polycystic liver disease
Sources: Expert list
Fetal anomalies v1.225 DNAL1 Rhiannon Mellis gene: DNAL1 was added
gene: DNAL1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DNAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAL1 were set to Ciliary dyskinesia, primary, 16, 614017
Review for gene: DNAL1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Primary ciliary disorders

Additional comment: causes situs inversus
Sources: Expert list
Fetal anomalies v1.225 DNM1L Rhiannon Mellis gene: DNM1L was added
gene: DNM1L was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DNM1L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: DNM1L were set to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, 614388
Review for gene: DNM1L was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Peroxisomal disorders
Sources: Expert list
Fetal anomalies v1.225 ICK Arina Puzriakova Publications for gene: ICK were set to
Skeletal ciliopathies v1.9 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from short-rib thoracic dysplasia with polydactyly (SRTD); Endocrine-cerebroosteodysplasia, 612651; ECO to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Childhood onset dystonia, chorea or related movement disorder v1.78 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia, 612651; ECO; short-rib thoracic dysplasia with polydactyly (SRTD) to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Osteogenesis imperfecta v2.12 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Disproportionate Short Stature to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Thoracic dystrophies v1.11 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia 612651; ORPHA:199332 Endocrine-cerebro-osteodysplasia syndrome to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Limb disorders v2.34 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from ECO; Short-rib thoracic dysplasia with polydactyly; Rhizomelia; Polydactyly; SRTD; Mesomelia; Endocrine-cerebroosteodysplasia, 612651 to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Renal ciliopathies v1.40 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from short-rib thoracic dysplasia with polydactyly (SRTD); Endocrine-cerebroosteodysplasia, 612651; ECO to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Neurological ciliopathies v1.15 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from short-rib thoracic dysplasia with polydactyly (SRTD); Endocrine-cerebroosteodysplasia, 612651; ECO to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Rare multisystem ciliopathy disorders v1.138 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia, 612651; ECO; short-rib thoracic dysplasia with polydactyly (SRTD) to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Clefting v2.21 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia, 612651 (includes cleft lip, cleft palate); ECO to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Hydrocephalus v2.6 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia 612651 to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Unexplained young onset end-stage renal disease v1.13 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia, 612651; ECO; short-rib thoracic dysplasia with polydactyly (SRTD) to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Skeletal dysplasia v2.79 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia 612651 to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Fetal anomalies v1.224 ICK Arina Puzriakova commented on gene: ICK: Added new-gene-name tag, new approved HGNC gene symbol for ICK is CILK1
Fetal anomalies v1.224 ICK Arina Puzriakova Tag new-gene-name tag was added to gene: ICK.
Fetal anomalies v1.224 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Fetal anomalies v1.223 ICK Arina Puzriakova Classified gene: ICK as Amber List (moderate evidence)
Fetal anomalies v1.223 ICK Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.223 ICK Arina Puzriakova Gene: ick has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.222 ICK Arina Puzriakova Tag for-review tag was added to gene: ICK.
Haematological malignancies cancer susceptibility v2.5 IKZF1 Kiran Tawana gene: IKZF1 was added
gene: IKZF1 was added to Haematological malignancies cancer susceptibility. Sources: Literature
Mode of inheritance for gene: IKZF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF1 were set to PMID: 29681510; PMID: 29889099; PMID: 27939403
Phenotypes for gene: IKZF1 were set to B-ALL; immunodeficiency, autoimmunity
Penetrance for gene: IKZF1 were set to unknown
Review for gene: IKZF1 was set to GREEN
Added comment: Sources: Literature
Fetal anomalies v1.222 HMGA2 Arina Puzriakova Publications for gene: HMGA2 were set to
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.13 CDKN2C Ivone Leong Classified gene: CDKN2C as Amber List (moderate evidence)
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.13 CDKN2C Ivone Leong Added comment: Comment on list classification: This gene has been proposed to have Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is not associated with any phenotypes in OMIM or Gene2Phenotype.

Based on the currently available information there does not appear to be enough evidence to support a gene-disease association. Until more evidence is available this gene has been promoted from Red to Amber.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.13 CDKN2C Ivone Leong Gene: cdkn2c has been classified as Amber List (Moderate Evidence).
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.12 CDKN2C Ivone Leong Tag watchlist tag was added to gene: CDKN2C.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.12 CDKN2C Ivone Leong Added comment: Comment on publications: PMID: 19141585 is study looking at cases of MEN1 or related states for germline mutations in all cyclin-dependent kinase inhibitor (CDKI) genes. 196 cases were tested. 1 case had CDKN2C V31L, who had primary HPT with a family history of HPT.

PMID: 23715670. 85 parathyroid adenomas from 85 cases were screened. 2 adenomas had CDKN2C variants (c.62 T>A, Leu21His and c.494C>T, Thr165Ile). Both cases have no family history of primary hyperparathyroidism (one germline case and one somatic case).

PMID: 30536424. 121 patients were screened. No variants were found in CDKN2C.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.12 CDKN2C Ivone Leong Publications for gene: CDKN2C were set to 19141585
Silver Russell syndrome v1.11 HMGA2 Arina Puzriakova Phenotypes for gene: HMGA2 were changed from SRS; Silver-Russell syndrome to Silver-Russell syndrome 5, OMIM:618908; Silver-Russell syndrome 5, MONDO:0020795
Fetal anomalies v1.221 HMGA2 Arina Puzriakova Phenotypes for gene: HMGA2 were changed from Silver-Russell syndrome 5 to Silver-Russell syndrome 5, OMIM:618908; Silver-Russell syndrome 5, MONDO:0020795
Fetal anomalies v1.220 HMGA2 Arina Puzriakova Tag for-review tag was added to gene: HMGA2.
Fetal anomalies v1.220 HMGA2 Arina Puzriakova Classified gene: HMGA2 as Amber List (moderate evidence)
Fetal anomalies v1.220 HMGA2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.220 HMGA2 Arina Puzriakova Gene: hmga2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.219 GDF2 Arina Puzriakova Classified gene: GDF2 as Red List (low evidence)
Fetal anomalies v1.219 GDF2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Single family with 2 sibs affected by lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis. Homozygous truncating variant in GDF2 was detected which segregated with the disorder (PMID:32618121).

Rating Red as additional cases/functional evidence required to corroborate this gene-disease association.
Fetal anomalies v1.219 GDF2 Arina Puzriakova Gene: gdf2 has been classified as Red List (Low Evidence).
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.11 CDKN2B Ivone Leong Classified gene: CDKN2B as Amber List (moderate evidence)
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.11 CDKN2B Ivone Leong Added comment: Comment on list classification: This gene has been proposed to have Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is not associated with any phenotypes in OMIM or Gene2Phenotype.

Based on the currently available information there does not appear to be enough evidence to support a gene-disease association. Until more evidence is available this gene has been promoted from Red to Amber.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.11 CDKN2B Ivone Leong Gene: cdkn2b has been classified as Amber List (Moderate Evidence).
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.10 CDKN2B Ivone Leong Tag watchlist tag was added to gene: CDKN2B.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.10 CDKN2B Ivone Leong Publications for gene: CDKN2B were set to 19141585
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.9 CDKN2B Ivone Leong Added comment: Comment on publications: PMID: 19141585 is study looking at cases of MEN1 or related states for germline mutations in all cyclin-dependent kinase inhibitor (CDKI) genes. 196 cases were tested. 2 case had CDKN2B N41D and L64R. Both cases had primary HPT and there is no family history of the phenotype.

PMID: 23715670. 85 parathyroid adenomas from 85 cases were screened. 1 adenoma had a CDKN2B variant (c.256G>A, Asp86Asn). There was no family history of primary hyperparathyroidism and variant was confirmed in the germline.

PMID: 30536424. 121 patients were screened. No variants were found in CDKN2B.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.9 CDKN2B Ivone Leong Publications for gene: CDKN2B were set to 19141585
Fetal anomalies v1.218 AKT2 Arina Puzriakova Publications for gene: AKT2 were set to
Neurological segmental overgrowth v1.8 AKT2 Arina Puzriakova Phenotypes for gene: AKT2 were changed from HIHGHH; Hypoinsulinemic hypoglycemia with hemihypertrophy; Hypoinsulinemic hypoglycemia with hemihypertrophy,240900; Hypoinsulinemic hypoglycemia with hemihypertrophy, 240900 to Hypoinsulinemic hypoglycemia with hemihypertrophy, OMIM:240900; Hypoinsulinemic hypoglycemia and body hemihypertrophy, MONDO:0009416
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.103 AKT2 Arina Puzriakova Phenotypes for gene: AKT2 were changed from Segmental overgrowth disorders to Hypoinsulinemic hypoglycemia with hemihypertrophy, OMIM:240900; Hypoinsulinemic hypoglycemia and body hemihypertrophy, MONDO:0009416
Monogenic diabetes v2.4 AKT2 Arina Puzriakova Phenotypes for gene: AKT2 were changed from Diabetes mellitus, type II, 125853; Severe insulin resistance, partial lipodystrophy and diabetes to Diabetes mellitus, type II, OMIM:125853; Type 2 diabetes mellitus, MONDO:0005148
Lipodystrophy - childhood onset v2.9 AKT2 Arina Puzriakova Phenotypes for gene: AKT2 were changed from Diabetes mellitus, type II, 125853; Hypoinsulinemic hypoglycemia with hemihypertrophy, 240900; Partial lipodystrophy to Diabetes mellitus, type II, OMIM:125853; Type 2 diabetes mellitus, MONDO:0005148; Hypoinsulinemic hypoglycemia with hemihypertrophy, OMIM:240900; Hypoinsulinemic hypoglycemia and body hemihypertrophy, MONDO:0009416; Partial lipodystrophy
Familial diabetes v1.39 AKT2 Arina Puzriakova Phenotypes for gene: AKT2 were changed from Diabetes mellitus, type II,125853; Hypoinsulinemic hypoglycemia with hemihypertrophy, 240900 to Diabetes mellitus, type II, OMIM:125853; Type 2 diabetes mellitus, MONDO:0005148
Congenital hyperinsulinism v2.5 AKT2 Arina Puzriakova Phenotypes for gene: AKT2 were changed from hypoinsulinemic hypoketotic hypoglycemia, 240900; Autosomal dominant fasting hypoglycaemia and asymmetrical overgrowth to Hypoinsulinemic hypoglycemia with hemihypertrophy, OMIM:240900; Hypoinsulinemic hypoglycemia and body hemihypertrophy, MONDO:0009416
Insulin resistance (including lipodystrophy) v1.12 AKT2 Arina Puzriakova Phenotypes for gene: AKT2 were changed from Diabetes mellitus, type II 125853 to Diabetes mellitus, type II, OMIM:125853; Type 2 diabetes mellitus, MONDO:0005148
Segmental overgrowth disorders - Deep sequencing v2.10 AKT2 Arina Puzriakova Phenotypes for gene: AKT2 were changed from Hypoinsulinemic hypoglycemia with hemihypertrophy,240900; Hypoinsulinemic hypoglycemia with hemihypertrophy; HIHGHH; Hypoinsulinemic hypoglycemia with hemihypertrophy, 240900 to Hypoinsulinemic hypoglycemia with hemihypertrophy, OMIM:240900; Hypoinsulinemic hypoglycemia and body hemihypertrophy, MONDO:0009416
Fetal anomalies v1.217 AKT2 Arina Puzriakova Phenotypes for gene: AKT2 were changed from Hypoinsulinemic hypoglycemia with hemihypertrophy to Hypoinsulinemic hypoglycemia with hemihypertrophy, OMIM:240900; Hypoinsulinemic hypoglycemia and body hemihypertrophy, MONDO:0009416
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.8 CDKN1A Ivone Leong changed review comment from: Comment on list classification: This gene has been proposed to have Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

Based on the currently available information there does not appear to be enough evidence to support a gene-disease association. Until more evidence is available this gene has been promoted from Red to Amber.; to: Comment on list classification: This gene has been proposed to have Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is not associated with any phenotypes in OMIM or Gene2Phenotype. Based on the currently available information there does not appear to be enough evidence to support a gene-disease association. Until more evidence is available this gene has been promoted from Red to Amber.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.8 CDKN1A Ivone Leong Tag watchlist tag was added to gene: CDKN1A.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.8 CDKN1A Ivone Leong Classified gene: CDKN1A as Amber List (moderate evidence)
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.8 CDKN1A Ivone Leong Added comment: Comment on list classification: This gene has been proposed to have Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

Based on the currently available information there does not appear to be enough evidence to support a gene-disease association. Until more evidence is available this gene has been promoted from Red to Amber.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.8 CDKN1A Ivone Leong Gene: cdkn1a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.216 AKT2 Arina Puzriakova Classified gene: AKT2 as Amber List (moderate evidence)
Fetal anomalies v1.216 AKT2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.216 AKT2 Arina Puzriakova Gene: akt2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.215 AKT2 Arina Puzriakova Tag for-review tag was added to gene: AKT2.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.7 CDKN1A Ivone Leong Added comment: Comment on publications: PMID: 19141585 is study looking at cases of MEN1 or related states for germline mutations in all cyclin-dependent kinase inhibitor (CDKI) genes. 196 cases were tested. 1 case had CDKN1A R67L, who had primary HPT with a family history of HPT.

PMID: 23715670. 85 parathyroid adenomas from 85 cases were screened. 2 adenomas had CDKN1A variants (c.350G>A p.C117Y and c.26G>A p.R9H). Both cases have no family history of primary hyperparathyroidism (one germline and one of undetermined germline status).

PMID: 30536424. 121 patients were screened. A single CKDN1A VUS was identified (c.350G > A p.(Cys117Tyr)). The authors have deemed this variant likely benign based on gnomAD frequency of near 1 in 500 and reported as a VUS on ClinVar. This variant was also identified in PMID: 23715670.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.7 CDKN1A Ivone Leong Publications for gene: CDKN1A were set to 19141585
Fetal anomalies v1.215 DNM2 Rhiannon Mellis gene: DNM2 was added
gene: DNM2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DNM2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: DNM2 were set to PMID: 30208955
Phenotypes for gene: DNM2 were set to Lethal congenital contracture syndrome 5, 615368
Review for gene: DNM2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis

Additional comment: AR Phenotype = lethal congenital contracture syndrome – definite prenatal phenotype with arthrogryposis, decreased fetal movements, polyhydramnios. Mutations only identified in three siblings although supported by animal models --> Moderate evidence for arthrogryposis --> Made green on arthrogryposis panel after internal discussion (Jan 2017)

NB in 2018 a further report of 3 unrelated cases with heterozygous DNM2 pathogenic variants with a more severe phenotype than usual for the AD disease (centronuclear myopathy) – all 3 had severe hypotonia and respiratory distress from birth. 1 had reduced fetal movements, polyhydramnios, distal contractures at birth (born at 29/40). 1 had micrognathia and clenched fists prenatally, multiple contractures at birth. All 3 were ventilator-dependent and died within first few months of life. (i.e. some overlap with the lethal congenital contracture phenotype despite heterozygous variants). PMID: 30208955
Sources: Expert list
Fetal anomalies v1.215 DONSON Rhiannon Mellis gene: DONSON was added
gene: DONSON was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DONSON was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DONSON were set to Microcephaly-micromelia syndrome, 251230; Microcephaly, short stature, and limb abnormalities, 617604
Review for gene: DONSON was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Severe microcephaly
Sources: Expert list
Fetal anomalies v1.215 DPM2 Rhiannon Mellis gene: DPM2 was added
gene: DPM2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DPM2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DPM2 were set to Congenital disorder of glycosylation, type Iu, 615042
Review for gene: DPM2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Fetal anomalies v1.215 DPM3 Rhiannon Mellis reviewed gene: DPM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15, 618992, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15, 612937; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.215 DYNC2LI1 Rhiannon Mellis gene: DYNC2LI1 was added
gene: DYNC2LI1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DYNC2LI1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DYNC2LI1 were set to Short-rib thoracic dysplasia 15 with polydactyly, 617088
Review for gene: DYNC2LI1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Clefting; Rare multisystem ciliopathy Super panel; Skeletal dysplasia; Thoracic dystrophies
Sources: Expert list
Fetal anomalies v1.215 DZIP1L Rhiannon Mellis gene: DZIP1L was added
gene: DZIP1L was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DZIP1L was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DZIP1L were set to Polycystic kidney disease 5, 617610
Review for gene: DZIP1L was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cystic renal disease (super panel)
Sources: Expert list
Fetal anomalies v1.215 EED Rhiannon Mellis reviewed gene: EED: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cohen-Gibson syndrome, 617561; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.215 EIF2S3 Rhiannon Mellis reviewed gene: EIF2S3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MEHMO syndrome, 300148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.215 EML1 Rhiannon Mellis gene: EML1 was added
gene: EML1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: EML1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EML1 were set to Band heterotopia, 600348
Review for gene: EML1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Hydrocephalus
Sources: Expert list
Fetal anomalies v1.215 EMX2 Rhiannon Mellis gene: EMX2 was added
gene: EMX2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: EMX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: EMX2 were set to Schizencephaly, 269160
Review for gene: EMX2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cerebral malformations; Malformations of cortical development
Sources: Expert list
Fetal anomalies v1.215 FAM46A Rhiannon Mellis gene: FAM46A was added
gene: FAM46A was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: FAM46A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FAM46A were set to Osteogenesis imperfecta, type XVIII
Review for gene: FAM46A was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Osteogenesis imperfecta; Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.215 FANCL Rhiannon Mellis reviewed gene: FANCL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group L; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.215 FIG4 Rhiannon Mellis reviewed gene: FIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Yunis-Varon syndrome, Charcot-Marie-Tooth disease, type 4J, ?Polymicrogyria, bilateral temporooccipital; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.215 FKBP10 Rhiannon Mellis gene: FKBP10 was added
gene: FKBP10 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: FKBP10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FKBP10 were set to Bruck syndrome 1; Osteogenesis imperfecta, type XI
Review for gene: FKBP10 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis; Osteogenesis imperfecta; Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.215 FUT8 Rhiannon Mellis gene: FUT8 was added
gene: FUT8 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: FUT8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FUT8 were set to Congenital disorder of glycosylation with defective fucosylation 1
Review for gene: FUT8 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Congenital disorders of glycosylation
Sources: Expert list
Fetal anomalies v1.215 FZD2 Rhiannon Mellis gene: FZD2 was added
gene: FZD2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: FZD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FZD2 were set to Omodysplasia 2
Review for gene: FZD2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Limb disorders; Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.215 GALNT2 Rhiannon Mellis gene: GALNT2 was added
gene: GALNT2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALNT2 were set to Congenital disorder of glycosylation, type IIt
Review for gene: GALNT2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Congenital disorders of glycosylation
Sources: Expert list
Fetal anomalies v1.215 GANAB Rhiannon Mellis gene: GANAB was added
gene: GANAB was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: GANAB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GANAB were set to Polycystic kidney disease 3
Review for gene: GANAB was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cystic renal disease (super panel); Polycystic liver disease
Sources: Expert list
Fetal anomalies v1.215 GATA3 Rhiannon Mellis gene: GATA3 was added
gene: GATA3 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: GATA3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GATA3 were set to Hypoparathyroidism, sensorineural deafness, and renal dysplasia
Review for gene: GATA3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): CAKUT
Sources: Expert list
Fetal anomalies v1.215 GFPT1 Rhiannon Mellis gene: GFPT1 was added
gene: GFPT1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: GFPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GFPT1 were set to Myasthenia, congenital, 12, with tubular aggregates
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Congenital disorders of glycosylation
Sources: Expert list
Fetal anomalies v1.215 GFRA1 Arina Puzriakova Classified gene: GFRA1 as Amber List (moderate evidence)
Fetal anomalies v1.215 GFRA1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Two unrelated families with non-syndromic bilateral renal agenesis, detected during the prenatal period, and distinct homozygous LoF variants in GFRA1. Animal models support a role in renal morphogenesis (PMID:33020172).

Rating Amber awaiting further cases/clinical evidence prior to inclusion as diagnositc-grade.
Fetal anomalies v1.215 GFRA1 Arina Puzriakova Gene: gfra1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.214 GLI1 Rhiannon Mellis gene: GLI1 was added
gene: GLI1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: GLI1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GLI1 were set to Polydactyly, postaxial, type A8 618123; Polydactyly, preaxial I 174400
Review for gene: GLI1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Limb disorders
Sources: Expert list
Fetal anomalies v1.214 GMNN Rhiannon Mellis reviewed gene: GMNN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Meier-Gorlin syndrome 6 OMIM 616835; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.214 GPC6 Rhiannon Mellis reviewed gene: GPC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Omodysplasia 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 GREB1L Rhiannon Mellis changed review comment from: Further cases of renal agenesis with GREBL1 pathogenic variants reported by Herlin et al, 2019 and Jacquinet et al 2020 (see below). However I note this gene has recently been changed from Green to Amber at NHSE request.

PMID: 31424080: One family including a preterm infant with bilateral renal agenesis and Potters sequence.
PMID: 32378186: Four families including fetuses with uterovaginal aplasia and bilateral renal agenesis.; to: Further cases of renal agenesis with GREBL1 pathogenic variants reported by Herlin et al, 2019 and Jacquinet et al 2020 (see below).

PMID: 31424080: One family including a preterm infant with bilateral renal agenesis and Potters sequence.
PMID: 32378186: Four families including fetuses with uterovaginal aplasia and bilateral renal agenesis.
Fetal anomalies v1.214 GSC Rhiannon Mellis gene: GSC was added
gene: GSC was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: GSC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GSC were set to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities
Review for gene: GSC was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.214 GZF1 Rhiannon Mellis reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Joint laxity, short stature, and myopia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 HADHB Rhiannon Mellis gene: HADHB was added
gene: HADHB was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: HADHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HADHB were set to Trifunctional protein deficiency
Review for gene: HADHB was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders

Additional comment: Different clinical forms, including rapidly progressive neonatal onset with early death - associated with hydrops prenatally
Sources: Expert list
Clefting v2.20 PLCB4 Zornitza Stark reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23315542; Phenotypes: Auriculocondylar syndrome 2, MIM# 614669; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.214 HESX1 Rhiannon Mellis reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Septooptic dysplasia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.214 HIST1H1E Rhiannon Mellis reviewed gene: HIST1H1E: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rahman syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.214 HMGA2 Rhiannon Mellis gene: HMGA2 was added
gene: HMGA2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: HMGA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: HMGA2 were set to Silver-Russell syndrome 5
Review for gene: HMGA2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Silver Russell syndrome
Sources: Expert list
Fetal anomalies v1.214 ICK Rhiannon Mellis gene: ICK was added
gene: ICK was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ICK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ICK were set to Endocrine-cerebroosteodysplasia
Review for gene: ICK was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Clefting; Cystic renal disease (super panel); Rare multisystem ciliopathy Super panel; Skeletal dysplasia; Thoracic dystrophies
Sources: Expert list
Fetal anomalies v1.214 IDH1 Rhiannon Mellis gene: IDH1 was added
gene: IDH1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: IDH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IDH1 were set to 22025298; 22057236; 22057234; 24049096
Phenotypes for gene: IDH1 were set to Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria 614875; Maffucci syndrome 614569; Ollier disease/ Dyschondroplasia 166000
Review for gene: IDH1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Skeletal dysplasia

Copied from skeletal dysplasias panel: Lysosomal storage diseases with skeletal involvement (dysostosis multiplex gp of SD), disorganized development of skeletal components gp of SD - Somatic mosaicism seen in at least 3 cases with enchondromatosis (various types)/ metaphyseal chondromatosis. amber/green -Somatic mosaic missense variants in enchondromas. Listed in Bonafe (MetaphysealchondromatosiswithD-2-hydroxyglutaric aciduria).
Sources: Expert list
Fetal anomalies v1.214 IFT52 Rhiannon Mellis gene: IFT52 was added
gene: IFT52 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: IFT52 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFT52 were set to Short-rib thoracic dysplasia 16 with or without polydactyly
Review for gene: IFT52 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Rare multisystem ciliopathy Super panel; Skeletal dysplasia; Thoracic dystrophies
Sources: Expert list
Fetal anomalies v1.214 IFT81 Rhiannon Mellis gene: IFT81 was added
gene: IFT81 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: IFT81 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFT81 were set to Short-rib thoracic dysplasia 19 with or without polydactyly
Review for gene: IFT81 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Rare multisystem ciliopathy Super panel; Skeletal dysplasia; Thoracic dystrophies
Sources: Expert list
Fetal anomalies v1.214 ITGA8 Rhiannon Mellis reviewed gene: ITGA8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal hypodysplasia/aplasia 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 KATNB1 Rhiannon Mellis gene: KATNB1 was added
gene: KATNB1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: KATNB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KATNB1 were set to Lissencephaly 6, with microcephaly
Review for gene: KATNB1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cerebral malformations; Malformations of cortical development
Sources: Expert list
Fetal anomalies v1.214 KIAA0753 Rhiannon Mellis gene: KIAA0753 was added
gene: KIAA0753 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: KIAA0753 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KIAA0753 were set to ?Orofaciodigital syndrome XV
Review for gene: KIAA0753 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cystic renal disease (super panel); Rare multisystem ciliopathy Super panel; Skeletal dysplasia
Sources: Expert list
Congenital myopathy v2.21 HNRNPA2B1 Sarah Leigh changed review comment from: Comment on list classification: De novo terminating variants clustered in the C-terminus of the protein have been reported in six unrelated families all with a distinct class of dominantly-acting heterozygous variants in hnRNPA2B1 with a unique clinical phenotype of early childhood-onset progressive muscle weakness, ophthalmoplegia, ptosis, dysphagia, and variable degrees of respiratory insufficiency but no dementia (https://www.nmd-journal.com/article/S0960-8966(20)30203-0/fulltext). This source is a meeting abstract an there is no peer reviewed source at this time.; to: Comment on list classification: De novo terminating variants clustered in the C-terminus of the protein have been reported in six unrelated families all with a distinct class of dominantly-acting heterozygous variants in hnRNPA2B1 with a unique clinical phenotype of early childhood-onset progressive muscle weakness, ophthalmoplegia, ptosis, dysphagia, and variable degrees of respiratory insufficiency but no dementia (https://www.nmd-journal.com/article/S0960-8966(20)30203-0/fulltext). This source is a meeting abstract an there is no peer reviewed source at this time.

There is enough evidence for this gene to be green, but GMS opinion is required to confirm this.
Fetal anomalies v1.214 KIF2A Rhiannon Mellis reviewed gene: KIF2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 3; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.214 KIF5C Rhiannon Mellis reviewed gene: KIF5C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital muscular dystrophy v2.5 HNRNPA2B1 Sarah Leigh changed review comment from: Comment on list classification: De novo terminating variants clustered in the C-terminus of the protein have been reported in six unrelated families all with a distinct class of dominantly-acting heterozygous variants in hnRNPA2B1 with a unique clinical phenotype of early childhood-onset progressive muscle weakness, ophthalmoplegia, ptosis, dysphagia, and variable degrees of respiratory insufficiency but no dementia (https://www.nmd-journal.com/article/S0960-8966(20)30203-0/fulltext).
This source is a meeting abstract an there is no peer reviewed source at this time.; to: Comment on list classification: De novo terminating variants clustered in the C-terminus of the protein have been reported in six unrelated families all with a distinct class of dominantly-acting heterozygous variants in hnRNPA2B1 with a unique clinical phenotype of early childhood-onset progressive muscle weakness, ophthalmoplegia, ptosis, dysphagia, and variable degrees of respiratory insufficiency but no dementia (https://www.nmd-journal.com/article/S0960-8966(20)30203-0/fulltext).
This source is a meeting abstract an there is no peer reviewed source at this time.

There is enough evidence for this gene to be green, but GMS opinion is required to confirm this.
Intellectual disability v3.745 TOR1A Arina Puzriakova Classified gene: TOR1A as Amber List (moderate evidence)
Intellectual disability v3.745 TOR1A Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber, but there is sufficient evidence linking biallelic variants to a relevant phenotype to rate this gene Green at the next GMS panel update (added 'for-review' tag)
Intellectual disability v3.745 TOR1A Arina Puzriakova Gene: tor1a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.214 KLHL7 Rhiannon Mellis reviewed gene: KLHL7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PERCHING syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.744 TOR1A Arina Puzriakova reviewed gene: TOR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30244176, 29053766, 28516161; Phenotypes: Arthrogryposis multiplex congenita 5, OMIM:618947, Arthrogryposis multiplex congenita 5, MONDO:0100218; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 KNL1 Rhiannon Mellis gene: KNL1 was added
gene: KNL1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: KNL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KNL1 were set to Microcephaly 4, primary, autosomal recessive
Review for gene: KNL1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Severe microcephaly
Sources: Expert list
Fetal anomalies v1.214 LAMB1 Rhiannon Mellis reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 5; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 LONP1 Rhiannon Mellis reviewed gene: LONP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CODAS syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 LRRC56 Rhiannon Mellis gene: LRRC56 was added
gene: LRRC56 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39
Review for gene: LRRC56 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Laterality disorders and isomerism
Sources: Expert list
Fetal anomalies v1.214 MACF1 Rhiannon Mellis gene: MACF1 was added
gene: MACF1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MACF1 were set to Lissencephaly 9 with complex brainstem malformation
Review for gene: MACF1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Cerebellar hypoplasia; Cerebral malformations; Malformations of cortical development
Sources: Expert list
Fetal anomalies v1.214 MAP3K20 Rhiannon Mellis gene: MAP3K20 was added
gene: MAP3K20 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MAP3K20 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MAP3K20 were set to Split-foot malformation with mesoaxial polydactyly; Centronuclear myopathy 6 with fiber-type disproportion
Review for gene: MAP3K20 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Fetal anomalies v1.214 MAP3K7 Rhiannon Mellis reviewed gene: MAP3K7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Frontometaphyseal dysplasia 2, Cardiospondylocarpofacial syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.214 MEIS2 Rhiannon Mellis gene: MEIS2 was added
gene: MEIS2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MEIS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MEIS2 were set to Cleft palate, cardiac defects, and mental retardation
Review for gene: MEIS2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Clefting
Sources: Expert list
Fetal anomalies v1.214 MEOX1 Rhiannon Mellis reviewed gene: MEOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Klippel-Feil syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 MESD Rhiannon Mellis gene: MESD was added
gene: MESD was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MESD were set to Osteogenesis imperfecta, type XX
Review for gene: MESD was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Osteogenesis imperfecta
Sources: Expert list
Fetal anomalies v1.214 MOGS Rhiannon Mellis reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IIb; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 MRAS Rhiannon Mellis gene: MRAS was added
gene: MRAS was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MRAS were set to Noonan syndrome 11
Review for gene: MRAS was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): RASopathies
Sources: Expert list
Fetal anomalies v1.214 MSMO1 Rhiannon Mellis gene: MSMO1 was added
gene: MSMO1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MSMO1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MSMO1 were set to Microcephaly, congenital cataract, and psoriasiform dermatitis
Review for gene: MSMO1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Severe microcephaly
Sources: Expert list
Intellectual disability v3.744 TOR1A Arina Puzriakova Tag for-review tag was added to gene: TOR1A.
Intellectual disability v3.744 TOR1A Arina Puzriakova Publications for gene: TOR1A were set to 24896178
Fetal anomalies v1.214 MSTO1 Rhiannon Mellis gene: MSTO1 was added
gene: MSTO1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MSTO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia
Review for gene: MSTO1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Intellectual disability v3.743 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Dystonia-1, torsion, 128100; Dystonia, early-onset atypical, with myoclonic features; {Dystonia-1, modifier of} to Arthrogryposis multiplex congenita 5, OMIM:618947; Arthrogryposis multiplex congenita 5, MONDO:0100218
Intellectual disability v3.743 TOR1A Arina Puzriakova Mode of inheritance for gene: TOR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 MYH2 Rhiannon Mellis gene: MYH2 was added
gene: MYH2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MYH2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MYH2 were set to Proximal myopathy and ophthalmoplegia
Review for gene: MYH2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis; Neuromuscular disorders

Additional comments: Congenital contractures in some which improve with time - Contractures at birth are described (in some cases) so could be detected prenatally.
Sources: Expert list
Fetal anomalies v1.214 MYH7 Rhiannon Mellis gene: MYH7 was added
gene: MYH7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MYH7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYH7 were set to PMID: 22859017; 25547560; 26337809
Phenotypes for gene: MYH7 were set to Cardiomyopathy, dilated, 1S; Cardiomyopathy, hypertrophic, 1; Laing distal myopathy; Left ventricular noncompaction 5
Review for gene: MYH7 was set to GREEN
Added comment: Currently Green on arthrogryposis panel but no clear association with arthrogryposis in literature, it seems to be a more a slowly progressive myopathy phenotype.

However, there are four reported cases of fetal cardiomyopathy related to MYH7, detectable on ultrasound. PMID: 22859017, PMID: 25547560, PMID: 26337809
Sources: Literature
Fetal anomalies v1.214 MYL1 Rhiannon Mellis gene: MYL1 was added
gene: MYL1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL1 were set to PMID: 30215711
Phenotypes for gene: MYL1 were set to Myopathy, congenital, with fast-twitch (type II) fiber atrophy
Review for gene: MYL1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis; Neuromuscular disorders

Additional comment: Predominant phenotype is severe hypotonia and respiratory failure from birth. 2 patients are reported: one had polyhydramnios and normal fetal movements, with mild flexion contractures at birth. The other had normal liquor volume, reduced fetal movements, no contractures. (PMID: 30215711). But severe neonatal phenotype so include as relevant.
Sources: Expert list
Fetal anomalies v1.214 MYMK Rhiannon Mellis gene: MYMK was added
gene: MYMK was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MYMK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MYMK were set to Carey-Fineman-Ziter syndrome
Review for gene: MYMK was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis; Clefting; Hydrocephalus; Neuromuscular disorders

Additional comment: Phenotype includes congenital contractures, talipes, Pierre-Robin sequence, clefts, reduced fetal movements.
Sources: Expert list
Fetal anomalies v1.214 MYO18B Rhiannon Mellis gene: MYO18B was added
gene: MYO18B was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MYO18B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MYO18B were set to Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism
Review for gene: MYO18B was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Early onset or syndromic epilepsy v2.280 ADAM22 Sarah Leigh Phenotypes for gene: ADAM22 were changed from ?Epileptic encephalopathy, early infantile, 61, 617933 to ?Epileptic encephalopathy, early infantile, 61 OMIM:617933
Fetal anomalies v1.214 MYO9A Rhiannon Mellis gene: MYO9A was added
gene: MYO9A was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MYO9A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MYO9A were set to Myasthenic syndrome, congenital, 24, presynaptic
Review for gene: MYO9A was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Childhood onset dystonia, chorea or related movement disorder v1.77 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Autosomal dominant or sporadic dystonia (DYT1); Early-Onset Primary Dystonia; Dystonia-1, torsion, 128100 to Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441
Adult onset dystonia, chorea or related movement disorder v1.17 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Dystonia-1, torsion, 128100; Early-Onset Primary Dystonia; Autosomal dominant or sporadic dystonia (DYT1) to Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441
Fetal anomalies v1.214 MYOCD Rhiannon Mellis gene: MYOCD was added
gene: MYOCD was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MYOCD was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MYOCD were set to Megabladder, congenital
Review for gene: MYOCD was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): CAKUT
Sources: Expert list
Adult onset neurodegenerative disorder v2.39 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from primary torsion dystonia (DYT1), early-onset isolated dystonia; Dystonia-1, torsion, 128100; Autosomal dominant or sporadic dystonia (DYT1); Early-Onset Primary Dystonia to Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441
Arthrogryposis v3.57 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from arthrogryposis with developmental delay, strabismus and tremor; Dystonia-1, torsion, 128100 to Arthrogryposis multiplex congenita 5, OMIM:618947; Arthrogryposis multiplex congenita 5, MONDO:0100218; Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441
Structural basal ganglia disorders v1.18 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Dystonia-1, torsion 128100 to Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441
Early onset dystonia v1.86 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Early-Onset Primary Dystonia; Dystonia-1, torsion, 128100; Autosomal dominant or sporadic dystonia (DYT1) to Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441
Parkinson Disease and Complex Parkinsonism v1.69 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Early-Onset Primary Dystonia; Dystonia-1, torsion, 128100; Autosomal dominant or sporadic dystonia (DYT1); primary torsion dystonia (DYT1), early-onset isolated dystonia to Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441
Fetal anomalies v1.214 NADSYN1 Rhiannon Mellis gene: NADSYN1 was added
gene: NADSYN1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: NADSYN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NADSYN1 were set to Vertebral, cardiac, renal, and limb defects syndrome 3
Review for gene: NADSYN1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): CAKUT
Sources: Expert list
Fetal anomalies v1.214 NECTIN1 Rhiannon Mellis gene: NECTIN1 was added
gene: NECTIN1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: NECTIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NECTIN1 were set to Cleft lip/palate-ectodermal dysplasia syndrome; Orofacial cleft 7
Review for gene: NECTIN1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Clefting
Sources: Expert list
Fetal anomalies v1.214 NEDD4L Rhiannon Mellis reviewed gene: NEDD4L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Periventricular nodular heterotopia 7; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.214 NEK8 Rhiannon Mellis reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 18199800, 23418306, 26967905, 26697755, 26862157; Phenotypes: NEPHRONOPHTHISIS 9, RENAL-HEPATIC-PANCREATIC DYSPLASIA 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.214 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Arthrogryposis multiplex congenita 5 to Arthrogryposis multiplex congenita 5, OMIM:618947; Arthrogryposis multiplex congenita 5, MONDO:0100218
Fetal anomalies v1.213 NIPAL4 Rhiannon Mellis gene: NIPAL4 was added
gene: NIPAL4 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: NIPAL4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NIPAL4 were set to Ichthyosis, congenital, autosomal recessive 6
Review for gene: NIPAL4 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Autosomal recessive congenital ichthyosis
Sources: Expert list
Fetal anomalies v1.213 NXN Rhiannon Mellis gene: NXN was added
gene: NXN was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: NXN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NXN were set to Robinow syndrome, autosomal recessive 2
Review for gene: NXN was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.213 TOR1A Arina Puzriakova Classified gene: TOR1A as Amber List (moderate evidence)
Fetal anomalies v1.213 TOR1A Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.213 TOR1A Arina Puzriakova Gene: tor1a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.212 TOR1A Arina Puzriakova Tag for-review tag was added to gene: TOR1A.
Fetal anomalies v1.212 TNNT3 Arina Puzriakova Tag for-review tag was added to gene: TNNT3.
Fetal anomalies v1.212 TNNT3 Arina Puzriakova Classified gene: TNNT3 as Amber List (moderate evidence)
Fetal anomalies v1.212 TNNT3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.212 TNNT3 Arina Puzriakova Gene: tnnt3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.211 OSGEP Rhiannon Mellis reviewed gene: OSGEP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Galloway-Mowat syndrome 3; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v2.16 TNNT3 Arina Puzriakova Phenotypes for gene: TNNT3 were changed from Arthrogryposis, distal, type 2B, 601680; Arthrogryposis to Arthrogryposis, distal, type 2B2, OMIM:618435; Arthrogryposis, distal, type 2B2, MONDO:0032750
Congenital myopathy v2.21 TNNT3 Arina Puzriakova Phenotypes for gene: TNNT3 were changed from Arthyrogryposis, distal, type 2B, 601680 to Arthrogryposis, distal, type 2B2, OMIM:618435; Arthrogryposis, distal, type 2B2, MONDO:0032750
Arthrogryposis v3.56 TNNT3 Arina Puzriakova Phenotypes for gene: TNNT3 were changed from Arthrogryposis Multiplex Congenita; Distal Arthrogryposis Multiplex Congenita; Distal Arthrogryposis Type 1; Distal Arthrogryposis Type 2B to Arthrogryposis, distal, type 2B2, OMIM:618435; Arthrogryposis, distal, type 2B2, MONDO:0032750
Fetal anomalies v1.211 P4HB Rhiannon Mellis reviewed gene: P4HB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cole-Carpenter syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.211 TNNT3 Arina Puzriakova Phenotypes for gene: TNNT3 were changed from Arthrogryposis, distal, type 2B2 to Arthrogryposis, distal, type 2B2, OMIM:618435; Arthrogryposis, distal, type 2B2, MONDO:0032750
Fetal anomalies v1.210 TNNT3 Arina Puzriakova Publications for gene: TNNT3 were set to 32779773
Fetal anomalies v1.209 PAX7 Rhiannon Mellis gene: PAX7 was added
gene: PAX7 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PAX7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PAX7 were set to Myopathy, congenital, progressive, with scoliosis
Review for gene: PAX7 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Fetal anomalies v1.209 PBX1 Rhiannon Mellis gene: PBX1 was added
gene: PBX1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
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
Review for gene: PBX1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): CAKUT
Sources: Expert list
Fetal anomalies v1.209 PFKM Rhiannon Mellis gene: PFKM was added
gene: PFKM was added to Fetal anomalies. Sources: Expert list,Literature
Mode of inheritance for gene: PFKM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PFKM were set to Glycogen storage disease VII
Review for gene: PFKM was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Arthrogryposis; Neuromuscular disorders

Additional comment: literature supports arthrogryposis in severe infantile form
Sources: Expert list, Literature
Fetal anomalies v1.209 PGM3 Rhiannon Mellis reviewed gene: PGM3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28543917, PMID: 24931394; Phenotypes: Immunodeficiency 23; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.209 PIBF1 Rhiannon Mellis gene: PIBF1 was added
gene: PIBF1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIBF1 were set to Joubert syndrome 33
Review for gene: PIBF1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Rare multisystem ciliopathy Super panel
Sources: Expert list
Fetal anomalies v1.209 PIGN Rhiannon Mellis reviewed gene: PIGN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.209 TMX2 Arina Puzriakova Publications for gene: TMX2 were set to
Intellectual disability v3.742 TMX2 Arina Puzriakova Phenotypes for gene: TMX2 were changed from Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormal cortical gyration; Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, 618730 to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, OMIM:618730; Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, MONDO:0032887
Early onset or syndromic epilepsy v2.279 TMX2 Arina Puzriakova Phenotypes for gene: TMX2 were changed from Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, 618730; seizures; Primary microcephaly, cortical malformation and epileptic encephalopathy to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, OMIM:618730; Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, MONDO:0032887
Severe microcephaly v2.92 TMX2 Arina Puzriakova Phenotypes for gene: TMX2 were changed from Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity 618730 to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, OMIM:618730; Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, MONDO:0032887
Malformations of cortical development v2.43 TMX2 Arina Puzriakova Phenotypes for gene: TMX2 were changed from Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity 618730 to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, OMIM:618730; Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, MONDO:0032887
Fetal anomalies v1.208 TMX2 Arina Puzriakova Phenotypes for gene: TMX2 were changed from Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, OMIM:618730; Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, MONDO:0032887
Fetal anomalies v1.207 TMX2 Arina Puzriakova Classified gene: TMX2 as Amber List (moderate evidence)
Fetal anomalies v1.207 TMX2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.207 TMX2 Arina Puzriakova Gene: tmx2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.206 TMX2 Arina Puzriakova Tag for-review tag was added to gene: TMX2.
Fetal anomalies v1.206 TMEM98 Arina Puzriakova Publications for gene: TMEM98 were set to
Fetal anomalies v1.205 PIH1D3 Rhiannon Mellis changed review comment from: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Laterality disorders and isomerism; Primary ciliary disorders
Sources: Expert list; to: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Laterality disorders and isomerism; Primary ciliary disorders
Sources: Expert list

Situs inversus in ~50%
Fetal anomalies v1.205 PIH1D3 Rhiannon Mellis gene: PIH1D3 was added
gene: PIH1D3 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PIH1D3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PIH1D3 were set to Ciliary dyskinesia, primary, 36, X-linked
Review for gene: PIH1D3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Laterality disorders and isomerism; Primary ciliary disorders
Sources: Expert list
Fetal anomalies v1.205 PIK3C2A Rhiannon Mellis gene: PIK3C2A was added
gene: PIK3C2A was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome
Review for gene: PIK3C2A was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Rare multisystem ciliopathy Super panel; Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.205 PITX1 Rhiannon Mellis reviewed gene: PITX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly, Liebenberg syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.205 PLAG1 Rhiannon Mellis gene: PLAG1 was added
gene: PLAG1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PLAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PLAG1 were set to Silver-Russell syndrome 4
Review for gene: PLAG1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Silver Russell syndrome
Sources: Expert list
Fetal anomalies v1.205 PLG Rhiannon Mellis gene: PLG was added
gene: PLG was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PLG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PLG were set to Plasminogen deficiency, type I
Review for gene: PLG was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Hydrocephalus

Additional comment: structural features detectable prenatally = -Occlusive hydrocephalus, congenital; Dandy-Walker malformation; Cerebellar hypoplasia
Sources: Expert list
Fetal anomalies v1.205 PNPLA1 Rhiannon Mellis reviewed gene: PNPLA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 10; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v2.278 ANKRD11 Sarah Leigh reviewed gene: ANKRD11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v1.205 POLG2 Rhiannon Mellis gene: POLG2 was added
gene: POLG2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: POLG2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: POLG2 were set to Mitochondrial DNA depletion syndrome 16 (hepatic type); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4
Review for gene: POLG2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Fetal anomalies v1.205 POLR1A Rhiannon Mellis reviewed gene: POLR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Acrofacial dysostosis, Cincinnati type; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.205 POP1 Rhiannon Mellis gene: POP1 was added
gene: POP1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: POP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POP1 were set to Anauxetic dysplasia 2
Review for gene: POP1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Skeletal dysplasia
Sources: Expert list
Anophthalmia or microphthalmia v1.38 TMEM98 Arina Puzriakova Phenotypes for gene: TMEM98 were changed from Nanophthalmos 4, 615972; NNO4 to Nanophthalmos 4, OMIM:615972; Nanophthalmos 4, MONDO:0014426
Fetal anomalies v1.205 PRKAG2 Rhiannon Mellis gene: PRKAG2 was added
gene: PRKAG2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PRKAG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PRKAG2 were set to Cardiomyopathy, hypertrophic 6; Glycogen storage disease of heart, lethal congenital
Review for gene: PRKAG2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Structural eye disease v1.44 TMEM98 Arina Puzriakova Phenotypes for gene: TMEM98 were changed from NNO4 Nanophthalmos 4, 615972 to Nanophthalmos 4, OMIM:615972; Nanophthalmos 4, MONDO:0014426
Fetal anomalies v1.205 TMEM98 Arina Puzriakova Phenotypes for gene: TMEM98 were changed from Nanophthalmos 4 to Nanophthalmos 4, OMIM:615972; Nanophthalmos 4, MONDO:0014426
Fetal anomalies v1.204 TMEM98 Arina Puzriakova Classified gene: TMEM98 as Amber List (moderate evidence)
Fetal anomalies v1.204 TMEM98 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.204 TMEM98 Arina Puzriakova Gene: tmem98 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.203 PRUNE1 Rhiannon Mellis reviewed gene: PRUNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.203 TMEM98 Arina Puzriakova Tag for-review tag was added to gene: TMEM98.
Fetal anomalies v1.203 PSAT1 Rhiannon Mellis reviewed gene: PSAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neu-Laxova syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.203 TMEM38B Arina Puzriakova Publications for gene: TMEM38B were set to
Fetal anomalies v1.202 PTPN14 Rhiannon Mellis reviewed gene: PTPN14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Choanal atresia and lymphedema; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.202 PYGM Rhiannon Mellis gene: PYGM was added
gene: PYGM was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PYGM were set to McArdle disease
Review for gene: PYGM was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Osteogenesis imperfecta v2.11 TMEM38B Arina Puzriakova Phenotypes for gene: TMEM38B were changed from Osteogenesis imperfecta, type XIV, 615066; osteogenesis imperfecta to Osteogenesis imperfecta, type XIV, OMIM:615066; Osteogenesis imperfecta type 14, MONDO:0014029
Skeletal dysplasia v2.78 TMEM38B Arina Puzriakova Phenotypes for gene: TMEM38B were changed from Osteogenesis imperfecta, type XIV 615066; Osteogenesis imperfecta, type XIV 615066; osteogenesis imperfecta; Osteogenesis imperfecta, type XIV, 615066 to Osteogenesis imperfecta, type XIV, OMIM:615066; Osteogenesis imperfecta type 14, MONDO:0014029
Fetal anomalies v1.202 TMEM38B Arina Puzriakova Phenotypes for gene: TMEM38B were changed from Osteogenesis imperfecta, type XIV to Osteogenesis imperfecta, type XIV, OMIM:615066; Osteogenesis imperfecta type 14, MONDO:0014029
Fetal anomalies v1.201 RAB33B Rhiannon Mellis gene: RAB33B was added
gene: RAB33B was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: RAB33B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RAB33B were set to Smith-McCort dysplasia 2
Review for gene: RAB33B was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.201 RBBP8 Rhiannon Mellis gene: RBBP8 was added
gene: RBBP8 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: RBBP8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RBBP8 were set to Seckel syndrome 2
Review for gene: RBBP8 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): IUGR and IGF abnormalities; Severe microcephaly
Sources: Expert list
Early onset or syndromic epilepsy v2.278 SCN9A Sarah Leigh edited their review of gene: SCN9A: Added comment: This gene should remain Red on this panel.; Changed rating: RED
Fetal anomalies v1.201 RBM10 Rhiannon Mellis reviewed gene: RBM10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: TARP syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.201 RFT1 Rhiannon Mellis reviewed gene: RFT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type In; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.201 ROBO3 Rhiannon Mellis reviewed gene: ROBO3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.201 TMEM38B Arina Puzriakova Classified gene: TMEM38B as Amber List (moderate evidence)
Fetal anomalies v1.201 TMEM38B Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.201 TMEM38B Arina Puzriakova Gene: tmem38b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.200 TMEM38B Arina Puzriakova Tag for-review tag was added to gene: TMEM38B.
Fetal anomalies v1.200 RPL10 Rhiannon Mellis gene: RPL10 was added
gene: RPL10 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: RPL10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: RPL10 were set to Mental retardation, X-linked, syndromic, 35
Review for gene: RPL10 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): IUGR and IGF abnormalities; Severe microcephaly
Sources: Expert list
Anophthalmia or microphthalmia v1.37 TENM3 Arina Puzriakova Publications for gene: TENM3 were set to
Structural eye disease v1.43 TENM3 Arina Puzriakova Phenotypes for gene: TENM3 were changed from Microphthalmia, isolated, with coloboma 9, 615145 to Microphthalmia, syndromic 15, OMIM:615145; ?Microphthalmia, isolated, with coloboma 9, OMIM:615145; Microphthalmia, isolated, with coloboma 9, MONDO:0014059
Intellectual disability v3.741 TENM3 Arina Puzriakova Phenotypes for gene: TENM3 were changed from Microphthalmia, syndromic 15, MIM#615145; coloboma to Microphthalmia, syndromic 15, OMIM:615145; ?Microphthalmia, isolated, with coloboma 9, OMIM:615145; Microphthalmia, isolated, with coloboma 9, MONDO:0014059
Anophthalmia or microphthalmia v1.36 TENM3 Arina Puzriakova Phenotypes for gene: TENM3 were changed from Microphthalmia, syndromic 15, 615145; ?Microphthalmia, isolated, with coloboma 9, 615145 to Microphthalmia, syndromic 15, OMIM:615145; ?Microphthalmia, isolated, with coloboma 9, OMIM:615145; Microphthalmia, isolated, with coloboma 9, MONDO:0014059
Childhood onset dystonia, chorea or related movement disorder v1.76 CACNB4 Sarah Leigh Tag for-review tag was added to gene: CACNB4.
Childhood onset dystonia, chorea or related movement disorder v1.76 CACNB4 Sarah Leigh edited their review of gene: CACNB4: Added comment: PMID 10762541 reports monoallelic variants associated with Idiopathic Generalized Epilepsy and Episodic Ataxia and PMID 32176688 reports biallelic variants associated with severe neurodevelopmental disorder and impairs channel and non-channel functions. Therefore recommend the MOI be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.200 TENM3 Arina Puzriakova Publications for gene: TENM3 were set to
Ocular coloboma v1.42 TENM3 Arina Puzriakova Phenotypes for gene: TENM3 were changed from Microphthalmia, isolated, with coloboma 9, 615145 to Microphthalmia, syndromic 15, OMIM:615145; ?Microphthalmia, isolated, with coloboma 9, OMIM:615145; Microphthalmia, isolated, with coloboma 9, MONDO:0014059
Fetal anomalies v1.199 TENM3 Arina Puzriakova Phenotypes for gene: TENM3 were changed from Microphthalmia, syndromic 15; ?Microphthalmia, isolated, with coloboma 9 to Microphthalmia, syndromic 15, OMIM:615145; ?Microphthalmia, isolated, with coloboma 9, OMIM:615145; Microphthalmia, isolated, with coloboma 9, MONDO:0014059
Fetal anomalies v1.198 RPL35A Rhiannon Mellis reviewed gene: RPL35A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diamond-Blackfan anemia 5; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.198 TENM3 Arina Puzriakova Classified gene: TENM3 as Amber List (moderate evidence)
Fetal anomalies v1.198 TENM3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.198 TENM3 Arina Puzriakova Gene: tenm3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.197 TENM3 Arina Puzriakova Tag for-review tag was added to gene: TENM3.
Fetal anomalies v1.197 RPS24 Rhiannon Mellis reviewed gene: RPS24: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diamond-blackfan anemia 3; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.197 TCTEX1D2 Arina Puzriakova Publications for gene: TCTEX1D2 were set to
Early onset or syndromic epilepsy v2.278 CACNB4 Sarah Leigh Phenotypes for gene: CACNB4 were changed from {Epilepsy, idiopathic generalized, susceptibility to, 9}, 607682; {Epilepsy, juvenile myoclonic, susceptibility to, 6}, 607682; Episodic ataxia, type 5, 613855; Intellectual disability to {Epilepsy, idiopathic generalized, susceptibility to, 9} OMIM:607682; {Epilepsy, juvenile myoclonic, susceptibility to, 6} OMIM:607682; Episodic ataxia, type 5 OMIM:613855; Intellectual disability
Fetal anomalies v1.196 RPS7 Rhiannon Mellis gene: RPS7 was added
gene: RPS7 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: RPS7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RPS7 were set to Diamond-Blackfan anemia 8
Review for gene: RPS7 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Limb disorders; Radial dysplasia
Sources: Expert list
Thoracic dystrophies v1.10 TCTEX1D2 Arina Puzriakova Phenotypes for gene: TCTEX1D2 were changed from Short-rib thoracic dysplasia 17 with or without polydactyly, 617405; Jeune Asphyxiating Thoracic Dystrophy to Short-rib thoracic dysplasia 17 with or without polydactyly, OMIM:617405; Short-rib thoracic dysplasia 17 with or without polydactyly, MONDO:0054565; Jeune asphyxiating thoracic dystrophy; JATD
Childhood onset dystonia, chorea or related movement disorder v1.76 TCTEX1D2 Arina Puzriakova Mode of inheritance for gene: TCTEX1D2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Rare multisystem ciliopathy disorders v1.137 TCTEX1D2 Arina Puzriakova Phenotypes for gene: TCTEX1D2 were changed from Short-rib thoracic dysplasia 17 with or without polydactyly, 617405; Jeune asphyxiating thoracic dystrophy; JATD to Short-rib thoracic dysplasia 17 with or without polydactyly, OMIM:617405; Short-rib thoracic dysplasia 17 with or without polydactyly, MONDO:0054565; Jeune asphyxiating thoracic dystrophy; JATD
Skeletal ciliopathies v1.8 TCTEX1D2 Arina Puzriakova Phenotypes for gene: TCTEX1D2 were changed from Short-rib thoracic dysplasia 17 with or without polydactyly, 617405; JATD; Jeune asphyxiating thoracic dystrophy to Short-rib thoracic dysplasia 17 with or without polydactyly, OMIM:617405; Short-rib thoracic dysplasia 17 with or without polydactyly, MONDO:0054565; Jeune asphyxiating thoracic dystrophy; JATD
Fetal anomalies v1.196 RRAS2 Rhiannon Mellis gene: RRAS2 was added
gene: RRAS2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: RRAS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RRAS2 were set to Noonan syndrome 12
Review for gene: RRAS2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): RASopathies
Sources: Expert list
Fetal anomalies v1.196 TCTEX1D2 Arina Puzriakova Phenotypes for gene: TCTEX1D2 were changed from Short-rib thoracic dysplasia 17 with or without polydactyly, OMIM:617405; Short-rib thoracic dysplasia 17 with or without polydactyly, MONDO:0054565 to Short-rib thoracic dysplasia 17 with or without polydactyly, OMIM:617405; Short-rib thoracic dysplasia 17 with or without polydactyly, MONDO:0054565; Jeune asphyxiating thoracic dystrophy; JATD
Ductal plate malformation v1.15 TCTEX1D2 Arina Puzriakova Phenotypes for gene: TCTEX1D2 were changed from Short-rib thoracic dysplasia 17 with or without polydactyly (617405) to Short-rib thoracic dysplasia 17 with or without polydactyly, OMIM:617405; Short-rib thoracic dysplasia 17 with or without polydactyly, MONDO:0054565
Skeletal dysplasia v2.77 TCTEX1D2 Arina Puzriakova Phenotypes for gene: TCTEX1D2 were changed from Short-rib thoracic dysplasia 17 with or without polydactyly, 617405; Short-rib thoracic dysplasia 17 with or without polydactyly, 617405 to Short-rib thoracic dysplasia 17 with or without polydactyly, OMIM:617405; Short-rib thoracic dysplasia 17 with or without polydactyly, MONDO:0054565
Fetal anomalies v1.195 RSPH4A Rhiannon Mellis reviewed gene: RSPH4A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 11; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.75 CACNB4 Sarah Leigh Publications for gene: CACNB4 were set to 10762541
Fetal anomalies v1.195 RSPH9 Rhiannon Mellis reviewed gene: RSPH9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 12; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v2.33 TCTEX1D2 Arina Puzriakova Phenotypes for gene: TCTEX1D2 were changed from Polydactyly; Short-rib thoracic dysplasia 17 with or without polydactyly, 617405; Brachydactyly to Short-rib thoracic dysplasia 17 with or without polydactyly, OMIM:617405; Short-rib thoracic dysplasia 17 with or without polydactyly, MONDO:0054565; Polydactyly; Brachydactyly
Childhood onset dystonia, chorea or related movement disorder v1.74 CACNB4 Sarah Leigh commented on gene: CACNB4: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 3 variants reported in at least 3 unrelated cases, together with supportive functional data.
Limb disorders v2.32 TCTEX1D2 Arina Puzriakova Tag watchlist was removed from gene: TCTEX1D2.
Limb disorders v2.32 TCTEX1D2 Arina Puzriakova commented on gene: TCTEX1D2
Childhood onset dystonia, chorea or related movement disorder v1.74 CACNB4 Sarah Leigh reviewed gene: CACNB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 32176688; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v1.195 SCLT1 Rhiannon Mellis gene: SCLT1 was added
gene: SCLT1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SCLT1 were set to No OMIM phenotype; Oro-facio-digital syndrome type IX; Senior-Løken Syndrome
Review for gene: SCLT1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Rare multisystem ciliopathy Super panel


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

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

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

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

= 3 cases plus a mouse model and functional evidence that the protein is a ciliary protein.
Sources: Literature
Fetal anomalies v1.195 TCTEX1D2 Arina Puzriakova Phenotypes for gene: TCTEX1D2 were changed from Short-rib thoracic dysplasia 17 with or without polydactyly to Short-rib thoracic dysplasia 17 with or without polydactyly, OMIM:617405; Short-rib thoracic dysplasia 17 with or without polydactyly, MONDO:0054565
Fetal anomalies v1.194 SDR9C7 Rhiannon Mellis gene: SDR9C7 was added
gene: SDR9C7 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: SDR9C7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SDR9C7 were set to Ichthyosis, congenital, autosomal recessive 13
Review for gene: SDR9C7 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Autosomal recessive congenital ichthyosis
Sources: Expert list
Fetal anomalies v1.194 TCTEX1D2 Arina Puzriakova Classified gene: TCTEX1D2 as Amber List (moderate evidence)
Fetal anomalies v1.194 TCTEX1D2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.194 TCTEX1D2 Arina Puzriakova Gene: tctex1d2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.193 SEC24D Rhiannon Mellis reviewed gene: SEC24D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25683121; Phenotypes: Cole-Carpenter syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.193 TCTEX1D2 Arina Puzriakova Tag for-review tag was added to gene: TCTEX1D2.
Fetal anomalies v1.193 SERPINF1 Rhiannon Mellis gene: SERPINF1 was added
gene: SERPINF1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: SERPINF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SERPINF1 were set to Osteogenesis imperfecta, type VI
Review for gene: SERPINF1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Osteogenesis imperfecta; Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.193 SERPINH1 Rhiannon Mellis gene: SERPINH1 was added
gene: SERPINH1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: SERPINH1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SERPINH1 were set to Osteogenesis imperfecta, type X
Review for gene: SERPINH1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Green on related panel(s): Osteogenesis imperfecta; Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.193 SGCG Rhiannon Mellis gene: SGCG was added
gene: SGCG was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: SGCG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SGCG were set to Muscular dystrophy, limb-girdle, autosomal recessive 5
Review for gene: SGCG was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Green on related panel(s): Neuromuscular disorders
Sources: Expert list
Autosomal recessive congenital ichthyosis v1.10 SULT2B1 Arina Puzriakova Phenotypes for gene: SULT2B1 were changed from Ichthyosis, congenital, autosomal recessive 14 617571 to Ichthyosis, congenital, autosomal recessive 14, OMIM:617571; Ichthyosis, congenital, autosomal recessive 14, MONDO:0033091
Fetal anomalies v1.193 SULT2B1 Arina Puzriakova Publications for gene: SULT2B1 were set to
Early onset or syndromic epilepsy v2.277 CPA6 Sarah Leigh Tag for-review tag was added to gene: CPA6.
Early onset or syndromic epilepsy v2.277 CPA6 Sarah Leigh commented on gene: CPA6: After consultation Helen Lord, recommend change of MOI to BIALLELIC, autosomal or pseudosomal
Fetal anomalies v1.192 SHANK3 Rhiannon Mellis reviewed gene: SHANK3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PHELAN-MCDERMID SYNDROME; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v2.277 CPA6 Sarah Leigh edited their review of gene: CPA6: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.192 SIX6 Rhiannon Mellis gene: SIX6 was added
gene: SIX6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SIX6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SIX6 were set to Optic disc anomalies with retinal and/or macular dystrophy
Review for gene: SIX6 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Green on related panel(s): Anophthalmia and microphthalmia
Sources: Literature
Palmoplantar keratodermas v1.7 SULT2B1 Arina Puzriakova Phenotypes for gene: SULT2B1 were changed from Ichthyosis, congenital, autosomal recessive 14; 617571 to Ichthyosis, congenital, autosomal recessive 14, OMIM:617571; Ichthyosis, congenital, autosomal recessive 14, MONDO:0033091
Ichthyosis and erythrokeratoderma v1.5 SULT2B1 Arina Puzriakova Phenotypes for gene: SULT2B1 were changed from Ichthyosis, congenital, autosomal recessive 14 617571 to Ichthyosis, congenital, autosomal recessive 14, OMIM:617571; Ichthyosis, congenital, autosomal recessive 14, MONDO:0033091
Fetal anomalies v1.192 SLC18A3 Rhiannon Mellis gene: SLC18A3 was added
gene: SLC18A3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SLC18A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC18A3 were set to PMID: 31059209
Phenotypes for gene: SLC18A3 were set to Myasthenic syndrome, congenital, 21, presynaptic
Review for gene: SLC18A3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Green on related panel(s): Neuromuscular disorders
Sources: Literature
Fetal anomalies v1.192 SULT2B1 Arina Puzriakova Phenotypes for gene: SULT2B1 were changed from Ichthyosis, congenital, autosomal recessive 14 to Ichthyosis, congenital, autosomal recessive 14, OMIM:617571; Ichthyosis, congenital, autosomal recessive 14, MONDO:0033091
Fetal anomalies v1.191 SULT2B1 Arina Puzriakova Classified gene: SULT2B1 as Amber List (moderate evidence)
Fetal anomalies v1.191 SULT2B1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.191 SULT2B1 Arina Puzriakova Gene: sult2b1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.190 SULT2B1 Arina Puzriakova Tag for-review tag was added to gene: SULT2B1.
Fetal anomalies v1.190 SLC25A19 Rhiannon Mellis reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly, Amish type, 607196; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary lymphoedema v2.8 ADAMTS3 Arina Puzriakova Phenotypes for gene: ADAMTS3 were changed from Hennekam syndrome; Hennekam lymphangiectasia-lymphedema syndrome 3 to Hennekam lymphangiectasia-lymphedema syndrome 3, OMIM:618154; Hennekam lymphangiectasia-lymphedema syndrome 3, MONDO:0032564
Fetal anomalies v1.190 ADAMTS3 Arina Puzriakova Publications for gene: ADAMTS3 were set to
Fetal anomalies v1.189 SLC29A3 Rhiannon Mellis gene: SLC29A3 was added
gene: SLC29A3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SLC29A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC29A3 were set to Histiocytosis-lymphadenopathy plus syndrome
Review for gene: SLC29A3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Green on related panel(s): Skeletal dysplasia
Sources: Literature
Fetal anomalies v1.189 SLC5A7 Rhiannon Mellis reviewed gene: SLC5A7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27569547, 31299140; Phenotypes: Myasthenic syndrome, congenital, 20, presynaptic; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.189 ADAMTS3 Arina Puzriakova Phenotypes for gene: ADAMTS3 were changed from Hennekam lymphangiectasia-lymphedema syndrome 3 to Hennekam lymphangiectasia-lymphedema syndrome 3, OMIM:618154; Hennekam lymphangiectasia-lymphedema syndrome 3, MONDO:0032564
Fetal anomalies v1.188 ADAMTS3 Arina Puzriakova Tag for-review tag was added to gene: ADAMTS3.
Fetal anomalies v1.188 ADAMTS3 Arina Puzriakova Classified gene: ADAMTS3 as Amber List (moderate evidence)
Fetal anomalies v1.188 ADAMTS3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Fetal anomalies v1.188 ADAMTS3 Arina Puzriakova Gene: adamts3 has been classified as Amber List (Moderate Evidence).
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.11 DLST Ivone Leong Classified gene: DLST as Amber List (moderate evidence)
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.11 DLST Ivone Leong Gene: dlst has been classified as Amber List (Moderate Evidence).
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.10 DLST Ivone Leong gene: DLST was added
gene: DLST was added to Inherited phaeochromocytoma and paraganglioma excluding NF1. Sources: Expert Review
for-review tags were added to gene: DLST.
Mode of inheritance for gene: DLST was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLST were set to 30929736; 33180916
Phenotypes for gene: DLST were set to Paragangliomas 7, OMIM:618475
Review for gene: DLST was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. Therefore, this gene should be rated Green at the next review.

This gene was suggested to be added and given a Green rating by Ruth Casey (Cambridge University Hospital). Sources: Expert Review
Sources: Expert Review
Fetal anomalies v1.187 SMPD4 Rhiannon Mellis gene: SMPD4 was added
gene: SMPD4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SMPD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMPD4 were set to PMID: 31495489
Phenotypes for gene: SMPD4 were set to Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
Review for gene: SMPD4 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Green on related panel(s): Arthrogryposis; Cerebellar hypoplasia

Additional comment: Documented fetal phenotype with IUGR, microcephaly, arthrogryposis, and structural brain anomalies in some. (32 reported cases from 12 families) PMID: 31495489
Sources: Literature
Fetal anomalies v1.187 SMS Rhiannon Mellis reviewed gene: SMS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: SNYDER-ROBINSON SYNDROME; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.187 SNX10 Rhiannon Mellis gene: SNX10 was added
gene: SNX10 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: SNX10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SNX10 were set to Osteopetrosis, autosomal recessive 8
Review for gene: SNX10 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Green on related panel(s): Hydrocephalus; Osteopetrosis; Skeletal dysplasia
Sources: Expert list
Fetal anomalies v1.187 SOX18 Rhiannon Mellis gene: SOX18 was added
gene: SOX18 was added to Fetal anomalies. Sources: Literature,Expert list
Mode of inheritance for gene: SOX18 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SOX18 were set to Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome; Hypotrichosis-lymphedema-telangiectasia syndrome
Review for gene: SOX18 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Green on related panel(s): Primary lymphoedema
Sources: Literature, Expert list
Fetal anomalies v1.187 SOX6 Rhiannon Mellis gene: SOX6 was added
gene: SOX6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOX6 were set to Tolchin-Le Caignec syndrome
Review for gene: SOX6 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Green on related panel(s): Craniosynostosis
Sources: Literature
Fetal anomalies v1.187 SP7 Rhiannon Mellis gene: SP7 was added
gene: SP7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SP7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SP7 were set to Osteogenesis imperfecta, type XII
Review for gene: SP7 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Green on related panel(s): Osteogenesis imperfecta; Skeletal dysplasia
Sources: Literature
Fetal anomalies v1.187 SPARC Rhiannon Mellis reviewed gene: SPARC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type XVII; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.187 SPECC1L Rhiannon Mellis reviewed gene: SPECC1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Facial clefting, oblique, 1, Hypertelorism, Teebi type, Opitz GBBB syndrome, type II; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.187 ST14 Rhiannon Mellis reviewed gene: ST14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 11; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.187 STAC3 Rhiannon Mellis gene: STAC3 was added
gene: STAC3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: STAC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAC3 were set to PMID: 30168660
Phenotypes for gene: STAC3 were set to Myopathy, congenital, Baily-Bloch
Review for gene: STAC3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Additional comment: Documented arthrogryposis, also cleft palate, polyhydramnios and reduced fetal movements. PMID: 30168660
Sources: Literature
Fetal anomalies v1.187 STIL Rhiannon Mellis reviewed gene: STIL: Rating: GREEN; Mode of pathogenicity: None; Publications: 29230157; Phenotypes: Microcephaly 7, primary, autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.187 STRADA Rhiannon Mellis gene: STRADA was added
gene: STRADA was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: STRADA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STRADA were set to Polyhydramnios, megalencephaly, and symptomatic epilepsy
Review for gene: STRADA was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Hydrocephalus). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.9 SLC25A11 Ivone Leong Classified gene: SLC25A11 as Amber List (moderate evidence)
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.9 SLC25A11 Ivone Leong Gene: slc25a11 has been classified as Amber List (Moderate Evidence).
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.8 SLC25A11 Ivone Leong gene: SLC25A11 was added
gene: SLC25A11 was added to Inherited phaeochromocytoma and paraganglioma excluding NF1. Sources: Expert Review
for-review tags were added to gene: SLC25A11.
Mode of inheritance for gene: SLC25A11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC25A11 were set to 29431636
Phenotypes for gene: SLC25A11 were set to Paragangliomas 6, OMIM:618464
Review for gene: SLC25A11 was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM but not on Gene2Phenotype. There are >3 unrelated cases and therefore, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.

This gene was suggested to be added and given a Green rating by Ruth Casey (Cambridge University Hospital).
Sources: Expert Review
Fetal anomalies v1.187 SUFU Rhiannon Mellis reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: 33024317, 21289193; Phenotypes: Joubert syndrome 32; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early onset or syndromic epilepsy v2.277 CPA6 Helen Lord reviewed gene: CPA6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v2.277 ALG14 Sarah Leigh edited their review of gene: ALG14: Changed rating: GREEN
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.7 MDH2 Ivone Leong Classified gene: MDH2 as Amber List (moderate evidence)
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.7 MDH2 Ivone Leong Gene: mdh2 has been classified as Amber List (Moderate Evidence).
Inherited phaeochromocytoma and paraganglioma excluding NF1 v1.6 MDH2 Ivone Leong gene: MDH2 was added
gene: MDH2 was added to Inherited phaeochromocytoma and paraganglioma excluding NF1. Sources: Expert Review
for-review tags were added to gene: MDH2.
Mode of inheritance for gene: MDH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDH2 were set to 30008476; 25766404
Phenotypes for gene: MDH2 were set to PPGL
Review for gene: MDH2 was set to GREEN
Added comment: This gene is associated with a phenotype in OMIM and Gene2Phenotype. There are >3 cases and therefore, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.

This gene was suggested to be added and given a Green rating by Ruth Casey (Cambridge University Hospital).
Sources: Expert Review
Congenital adrenal hypoplasia v2.6 POLE Ivone Leong Classified gene: POLE as Amber List (moderate evidence)
Congenital adrenal hypoplasia v2.6 POLE Ivone Leong Gene: pole has been classified as Amber List (Moderate Evidence).
Congenital adrenal hypoplasia v2.5 POLE Ivone Leong gene: POLE was added
gene: POLE was added to Congenital adrenal hypoplasia. Sources: Expert Review
for-review tags were added to gene: POLE.
Mode of inheritance for gene: POLE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLE were set to 14760276; 30503519
Phenotypes for gene: POLE were set to IMAGE-I syndrome, OMIM:618336
Review for gene: POLE was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There are >3 unrelated cases and therefore, enough evidence to support a gene-disease association. This gene should be Green at the next review.

This gene was also proposed to be added and given Green status by Soo-Mi Park (East Anglian Medical Genetics Service).
Sources: Expert Review
Respiratory ciliopathies including non-CF bronchiectasis v1.42 RPGR Gabrielle Wheway changed review comment from: Although few cases of PCD associated with RPGR variants have been published, the PCD diagnostic centre at University Hospital Southampton has diagnosed 5 cases of PCD where RPGR missense variants have been judged to be the cause of disease. 4 cases have stop gains in RPGR, 3 of whom had PCD diagnosed before eye disease and 1 of whom is an adult whose wet cough and rhinitis started in very early childhood before eye symptoms, but was diagnosed with RP before PCD (due to late referral for PCD rather than lack of symptoms). i.e. in all cases lung disease preceded eye disease. 1 case has a pathogenic missense mutation and is an adult who only has PCD, no eye disease. I am submitting this review as a researcher who works closely with the diagnostic service at UHS and Wessex Clinical Genetics Lab. The fact that RPGR has been downgraded to Amber was raised at our recent PCD genetics MDT and Prof Jane Lucas, who leads the diagnostic service at UHS asked me to submit a review to provide support for this gene being a 'Green' gene.
; to: Although few cases of PCD associated with RPGR variants have been published, the PCD diagnostic centre at University Hospital Southampton has diagnosed 5 cases of PCD where RPGR variants have been judged to be the cause of disease. 4 cases have stop gains in RPGR, 3 of whom had PCD diagnosed before eye disease and 1 of whom is an adult whose wet cough and rhinitis started in very early childhood before eye symptoms, but was diagnosed with RP before PCD (due to late referral for PCD rather than lack of symptoms). i.e. in all cases lung disease preceded eye disease. 1 case has a pathogenic missense mutation and is an adult who only has PCD, no eye disease. I am submitting this review as a researcher who works closely with the diagnostic service at UHS and Wessex Clinical Genetics Lab. The fact that RPGR has been downgraded to Amber was raised at our recent PCD genetics MDT and Prof Jane Lucas, who leads the diagnostic service at UHS asked me to submit a review to provide support for this gene being a 'Green' gene.
Respiratory ciliopathies including non-CF bronchiectasis v1.42 RPGR Gabrielle Wheway changed review comment from: Although few cases of PCD have been reported associated with RPGR variants, the PCD diagnostic centre at University Hospital Southampton has diagnosed a number of PCD cases where RPGR missense variants have been judged to be the cause of disease. At least one of these cases is isolated PCD, with no evidence of RP (the patient has been seen by the eye clinic). I am submitting this review as a researcher who works closely with the diagnostic service at UHS and Wessex Clinical Genetics Lab. The fact that RPGR has been downgraded to Amber was raised at our recent PCD genetics MDT and Prof Jane Lucas, who leads the diagnostic service at UHS asked me to submit a review to provide support for this gene being a 'Green' gene. Prof Lucas will register as a PanelApp reviewer to add additional detail.; to: Although few cases of PCD associated with RPGR variants have been published, the PCD diagnostic centre at University Hospital Southampton has diagnosed 5 cases of PCD where RPGR missense variants have been judged to be the cause of disease. 4 cases have stop gains in RPGR, 3 of whom had PCD diagnosed before eye disease and 1 of whom is an adult whose wet cough and rhinitis started in very early childhood before eye symptoms, but was diagnosed with RP before PCD (due to late referral for PCD rather than lack of symptoms). i.e. in all cases lung disease preceded eye disease. 1 case has a pathogenic missense mutation and is an adult who only has PCD, no eye disease. I am submitting this review as a researcher who works closely with the diagnostic service at UHS and Wessex Clinical Genetics Lab. The fact that RPGR has been downgraded to Amber was raised at our recent PCD genetics MDT and Prof Jane Lucas, who leads the diagnostic service at UHS asked me to submit a review to provide support for this gene being a 'Green' gene.
Fetal anomalies v1.187 ERCC5 Arina Puzriakova Publications for gene: ERCC5 were set to
Fetal anomalies v1.186 ERCC5 Arina Puzriakova Phenotypes for gene: ERCC5 were changed from XERODERMA PIGMENTOSUM COMPLEMENTATION GROUP G to Cerebrooculofacioskeletal syndrome 3, OMIM:616570; Cerebrooculofacioskeletal syndrome 3, MONDO:0014696
Severe microcephaly v2.91 ERCC5 Arina Puzriakova Publications for gene: ERCC5 were set to 24700531; 9096355 (Retracted)
Fetal anomalies v1.185 SULT2B1 Rhiannon Mellis gene: SULT2B1 was added
gene: SULT2B1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SULT2B1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SULT2B1 were set to Ichthyosis, congenital, autosomal recessive 14
Review for gene: SULT2B1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Autosomal recessive congenital ichthyosis). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Severe microcephaly v2.90 ERCC5 Arina Puzriakova Classified gene: ERCC5 as Amber List (moderate evidence)
Severe microcephaly v2.90 ERCC5 Arina Puzriakova Added comment: Comment on list classification: Gene reassessed in view of recent expert review. Upgraded from Red to Amber as there are at least 9 fetuses from 4 unrelated families with cerebrooculofacioskeletal syndrome due to biallelic variants in this gene (PMIDs: 24700531; 32052936; 32557569). Microcephaly is reported in all affected cases; however, as extent of this presentation is not specified ERCC5 cannot be promoted to Green on this panel at present.

Nonetheless, we would expect this phenotype to be picked up via the Fetal anomalies panel, for which this gene is already Green (v.1.92).
Severe microcephaly v2.90 ERCC5 Arina Puzriakova Gene: ercc5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.185 TBC1D32 Rhiannon Mellis gene: TBC1D32 was added
gene: TBC1D32 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TBC1D32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D32 were set to PMID: 32573025; 31130284; 32060556
Phenotypes for gene: TBC1D32 were set to OFD IX
Review for gene: TBC1D32 was set to GREEN
Added comment: Now 5 families reported:

The same group who reported the first individual with a ciliopathy phenotype (Adly et al 2014) now report two further unrelated fetal cases (Alsahan 2020, Monies et al 2019) with OFD/ciliopathy phenotype:

- One had polyhydramnios, hydrocephaly with enlarged biparietal diameter and dilated lateral ventricles, single nostril, anophthalmia, short long bones and echogenic lungs
- The other had holoprosencephaly, cyclops, cleft lip, ventricular septal defect, agenesis of corpus callosum, and club feet

- There are also two sib pairs (one Finnish, one Pakistani) reported by Hietamaki et al 2020 with TBC1D32 variants and a variable phenotype of pituitary hypoplasia +/- other midline defects, hydrocephalus, short limbs, polydactyly
Sources: Literature
Fetal anomalies v1.185 TCTEX1D2 Rhiannon Mellis gene: TCTEX1D2 was added
gene: TCTEX1D2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TCTEX1D2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TCTEX1D2 were set to Short-rib thoracic dysplasia 17 with or without polydactyly
Review for gene: TCTEX1D2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Rare multisystem ciliopathy Super panel; Skeletal dysplasia; Thoracic dystrophies). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Arthrogryposis v3.55 ERCC5 Arina Puzriakova Phenotypes for gene: ERCC5 were changed from Cerebrooculofacioskeletal syndrome 3, 616570 to Cerebrooculofacioskeletal syndrome 3, OMIM:616570; Cerebrooculofacioskeletal syndrome 3, MONDO:0014696
Arthrogryposis v3.54 ERCC5 Arina Puzriakova Publications for gene: ERCC5 were set to 9096355; 24700531
Arthrogryposis v3.53 ERCC5 Arina Puzriakova Classified gene: ERCC5 as Amber List (moderate evidence)
Arthrogryposis v3.53 ERCC5 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag) - sufficient unrelated families (4) with multiple fetuses affected by COFS3, including arthrogryposis.
Arthrogryposis v3.53 ERCC5 Arina Puzriakova Gene: ercc5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.185 TELO2 Rhiannon Mellis reviewed gene: TELO2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: You-Hoover-Fong syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v3.52 ERCC5 Arina Puzriakova Tag for-review tag was added to gene: ERCC5.
Fetal anomalies v1.185 TENM3 Rhiannon Mellis gene: TENM3 was added
gene: TENM3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TENM3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TENM3 were set to Microphthalmia, syndromic 15; ?Microphthalmia, isolated, with coloboma 9
Review for gene: TENM3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Anophthalmia and microphthalmia). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Arthrogryposis v3.52 ERCC5 Arina Puzriakova reviewed gene: ERCC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24700531, 32052936, 32557569; Phenotypes: Cerebrooculofacioskeletal syndrome 3, OMIM:616570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.185 TMEM38B Rhiannon Mellis gene: TMEM38B was added
gene: TMEM38B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TMEM38B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM38B were set to Osteogenesis imperfecta, type XIV
Review for gene: TMEM38B was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Osteogenesis imperfecta; Skeletal dysplasia). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Fetal anomalies v1.185 TMEM98 Rhiannon Mellis gene: TMEM98 was added
gene: TMEM98 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TMEM98 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TMEM98 were set to Nanophthalmos 4
Review for gene: TMEM98 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Anophthalmia and microphthalmia). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Fetal anomalies v1.185 TMX2 Rhiannon Mellis gene: TMX2 was added
gene: TMX2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TMX2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMX2 were set to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity
Review for gene: TMX2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Cerebral malformations; Malformations of cortical development; Severe microcephaly). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Fetal anomalies v1.185 TNNT3 Rhiannon Mellis gene: TNNT3 was added
gene: TNNT3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TNNT3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNNT3 were set to 32779773
Phenotypes for gene: TNNT3 were set to Arthrogryposis, distal, type 2B2
Mode of pathogenicity for gene: TNNT3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: TNNT3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Additional comment: Clearly documented phenotype of distal arthrogryposis. Also, recent paper in Prenatal Diagnosis reporting a het pathogenic variant in TNNT3 in a fetus with FADS; that variant has previously only been described in a family with much milder distal arthrogryposis phenotype. PMID: 32779773

(copied from OMIM): In in vitro studies, Robinson et al. (2007) demonstrated that the TNNI2 R174Q (191043.0001) and R156X (191043.0002) mutations and the TNNT3 mutation R63H (600692.0001) resulted in a gain of function with increased ATPase activity in actin-activated myosin ATPase assays, reflecting increased calcium sensitivity and consistent with increased contractility. In patients, Robinson et al. (2007) concluded that the mutation would cause increased tension in developing muscles, thus resulting in contractures and limb deformities via an active process rather than a passive process. These findings implicated disturbed muscle function as the pathogenic mechanism underlying DA2B.
Sources: Literature
Fetal anomalies v1.185 TOE1 Rhiannon Mellis changed review comment from: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.; to: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (cerebellar hypoplasia). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Fetal anomalies v1.185 TOE1 Rhiannon Mellis reviewed gene: TOE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia, type 7; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.185 TOR1A Rhiannon Mellis gene: TOR1A was added
gene: TOR1A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TOR1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1A were set to 30244176; 29053766; 28516161
Phenotypes for gene: TOR1A were set to Arthrogryposis multiplex congenita 5
Review for gene: TOR1A was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Additional comment: documented phenotype of severe arthrogryposis multiplex congenital with prenatal onset
Sources: Literature
Fetal anomalies v1.185 TRAF3IP1 Rhiannon Mellis gene: TRAF3IP1 was added
gene: TRAF3IP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TRAF3IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRAF3IP1 were set to Senior-Loken syndrome 9
Review for gene: TRAF3IP1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Cystic renal disease (super panel); Rare multisystem ciliopathy Super panel). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Fetal anomalies v1.185 TRAIP Rhiannon Mellis reviewed gene: TRAIP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Seckel syndrome 9; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.185 TRAP1 Rhiannon Mellis gene: TRAP1 was added
gene: TRAP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TRAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRAP1 were set to CAKUT; VACTERL
Review for gene: TRAP1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Early onset or syndromic epilepsy v2.277 ADAM22 Sarah Leigh Publications for gene: ADAM22 were set to 27066583; 30237576; 15876356
Early onset or syndromic epilepsy v2.276 SCN9A Sarah Leigh Classified gene: SCN9A as Red List (low evidence)
Early onset or syndromic epilepsy v2.276 SCN9A Sarah Leigh Added comment: Comment on list classification: Evidence presented by PMID 33216760 disputes the association between SCN9A and epilepsy, inparticular the serendipitous identification of the SCN9A p.(Asn641Tyr) variant within the Wisconsin Amish community with no epilepsy in their phenotypes. The authors report this lack of gene disease association was also evident in the UK Biobank.
Early onset or syndromic epilepsy v2.276 SCN9A Sarah Leigh Gene: scn9a has been classified as Red List (Low Evidence).
Fetal anomalies v1.185 TRMT10A Rhiannon Mellis gene: TRMT10A was added
gene: TRMT10A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TRMT10A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRMT10A were set to Microcephaly, short stature, and impaired glucose metabolism 1
Review for gene: TRMT10A was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Severe microcephaly). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Fetal anomalies v1.185 TSEN2 Rhiannon Mellis reviewed gene: TSEN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia type 2B; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.185 TSEN34 Rhiannon Mellis reviewed gene: TSEN34: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia type 2C; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.185 TSFM Rhiannon Mellis gene: TSFM was added
gene: TSFM was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TSFM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSFM were set to Combined oxidative phosphorylation deficiency 3
Review for gene: TSFM was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Neuromuscular disorders). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Additional comment: IUGR, decreased fetal movements, reduced brain gyri
Sources: Literature
Fetal anomalies v1.185 TUBB3 Rhiannon Mellis reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.185 TUBG1 Rhiannon Mellis reviewed gene: TUBG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 4; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.185 TUBGCP4 Rhiannon Mellis reviewed gene: TUBGCP4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 3; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.185 TXNDC15 Rhiannon Mellis gene: TXNDC15 was added
gene: TXNDC15 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TXNDC15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TXNDC15 were set to Meckel Gruber syndrome
Review for gene: TXNDC15 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Cystic renal disease (super panel); Limb disorders; Rare multisystem ciliopathy Super panel). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Comment from copied from skeletal ciliopathies panel:
Shaheen et al. 2016 (PMID:27894351) report TXNDC15 variants in two consanguineous Saudi families that share the features of Meckel-Gruber syndrome (a ciliopathy phenotype). Phenotypes of both patients included polydactyly; one patients was still born, and one survived till 11 hours old. Furthermore, through an international collaboration, they were able to identify an additional Meckel-Gruber syndrome patient (Pakistani origin) with a homozygous truncating variant in this gene. The patient also had polydactyly, although a sibling presented similarly but with no polydactyl. Patient fibroblasts had aberrant ciliogenesis.
Sources: Other
Sources: Literature
Fetal anomalies v1.185 UBE2T Rhiannon Mellis reviewed gene: UBE2T: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group T; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.185 USP9X Rhiannon Mellis reviewed gene: USP9X: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MENTAL RETARDATION, X-LINKED 99, MRX99; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v2.275 SCN9A Sarah Leigh Publications for gene: SCN9A were set to 19763161; 29500686; 30834459; 23895530
Adult onset hereditary spastic paraplegia v1.16 AP4S1 Arina Puzriakova Tag for-review tag was added to gene: AP4S1.
Adult onset hereditary spastic paraplegia v1.16 AP4S1 Arina Puzriakova commented on gene: AP4S1
Fetal anomalies v1.185 VAMP1 Rhiannon Mellis changed review comment from: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature; to: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.

Additional comment: Phenotype = congenital myasthenic syndrome. Reported patients present with severe hypotonia from birth, some have contractures, unclear if present at birth but decreased fetal movements reported so could present prenatally. PubMed: 28600779, 28253535, 28168212

Sources: Literature
Endocrine neoplasia v1.10 VHL Ivone Leong changed review comment from: This gene was proposed to be added to this panel with Green by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review; to: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review
Endocrine neoplasia v1.10 TP53 Ivone Leong Classified gene: TP53 as Amber List (moderate evidence)
Endocrine neoplasia v1.10 TP53 Ivone Leong Gene: tp53 has been classified as Amber List (Moderate Evidence).
Endocrine neoplasia v1.9 PRKAR1A Ivone Leong changed review comment from: This gene was proposed to be added to this panel with Green by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review; to: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review
Endocrine neoplasia v1.9 TP53 Ivone Leong gene: TP53 was added
gene: TP53 was added to Endocrine neoplasms. Sources: Expert Review
for-review tags were added to gene: TP53.
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TP53 were set to Endocrine Cancer; Paragangliomas 1, with or without deafness, 168000; Pheochromocytoma, 171300; Carcinoid tumors, intestinal, 114900; Merkel cell carcinoma, somatic; Paraganglioma and gastric stromal sarcoma, 606864; Cowden syndrome 3, 615106
Review for gene: TP53 was set to AMBER
Added comment: This gene was proposed to be added to this panel with Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review
Fetal anomalies v1.185 VAMP1 Rhiannon Mellis gene: VAMP1 was added
gene: VAMP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: VAMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VAMP1 were set to Myasthenic syndrome, congenital, 25
Review for gene: VAMP1 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Endocrine neoplasia v1.8 VHL Ivone Leong Classified gene: VHL as Amber List (moderate evidence)
Endocrine neoplasia v1.8 VHL Ivone Leong Gene: vhl has been classified as Amber List (Moderate Evidence).
Endocrine neoplasia v1.7 VHL Ivone Leong gene: VHL was added
gene: VHL was added to Endocrine neoplasms. Sources: Expert Review
for-review tags were added to gene: VHL.
Mode of inheritance for gene: VHL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: VHL were set to Endocrine Cancer; Paragangliomas 1, with or without deafness, 168000; Pheochromocytoma, 171300; Carcinoid tumors, intestinal, 114900; Merkel cell carcinoma, somatic; Paraganglioma and gastric stromal sarcoma, 606864; Cowden syndrome 3, 615106
Review for gene: VHL was set to AMBER
Added comment: This gene was proposed to be added to this panel with Green by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review
Fetal anomalies v1.185 VEGFC Rhiannon Mellis gene: VEGFC was added
gene: VEGFC was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: VEGFC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: VEGFC were set to Lymphatic malformation 4
Review for gene: VEGFC was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Fetal anomalies v1.185 VRK1 Rhiannon Mellis reviewed gene: VRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia type 1A; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Endocrine neoplasia v1.6 PRKAR1A Ivone Leong Classified gene: PRKAR1A as Amber List (moderate evidence)
Endocrine neoplasia v1.6 PRKAR1A Ivone Leong Gene: prkar1a has been classified as Amber List (Moderate Evidence).
Endocrine neoplasia v1.5 PRKAR1A Ivone Leong Tag for-review tag was added to gene: PRKAR1A.
Endocrine neoplasia v1.5 PRKAR1A Ivone Leong gene: PRKAR1A was added
gene: PRKAR1A was added to Endocrine neoplasms. Sources: Expert Review
Mode of inheritance for gene: PRKAR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PRKAR1A were set to Endocrine Cancer
Review for gene: PRKAR1A was set to AMBER
Added comment: This gene was proposed to be added to this panel with Green by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is Green on the Multiple endocrine tumours (Version 1.9) panel.

This gene has been added as an Amber gene and will be given Green status pending decision by the GMS review panel.
Sources: Expert Review
Fetal anomalies v1.185 WDR73 Rhiannon Mellis reviewed gene: WDR73: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Galloway-Mowat syndrome 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.6 GCM2 Ivone Leong changed review comment from: PMID 31671402 is an additional paper report on the same variant that was detected previously by Guan et al 2016 and 2017. This gene is recommended to be promoted to Green at the next review.; to: Looking at the available evidence, there is an additional paper (PMID 31671402) reporting on the same variant that was detected previously by Guan et al 2016 and 2017. This gene is recommended to be promoted to Green at the next review.

This gene was proposed to be given Green status by Soo-Mi Park (East Anglian Medical Genetics Service).
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.6 GCM2 Ivone Leong Tag for-review tag was added to gene: GCM2.
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.6 GCM2 Ivone Leong edited their review of gene: GCM2: Added comment: PMID 31671402 is an additional paper report on the same variant that was detected previously by Guan et al 2016 and 2017. This gene is recommended to be promoted to Green at the next review.; Changed publications: 31671402
Fetal anomalies v1.185 WDR81 Rhiannon Mellis gene: WDR81 was added
gene: WDR81 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WDR81 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR81 were set to Hydrocephalus, congenital, 3, with brain anomalies
Review for gene: WDR81 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other PanelApp panel (Cerebellar hypoplasia). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.6 GCM2 Ivone Leong Publications for gene: GCM2 were set to 27745835; 29264504; 14715834; 29199197
Fetal anomalies v1.185 XYLT2 Rhiannon Mellis reviewed gene: XYLT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondyloocular syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.185 ZMYND10 Rhiannon Mellis reviewed gene: ZMYND10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 22; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.185 ZSWIM6 Rhiannon Mellis reviewed gene: ZSWIM6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Acromelic frontonasal dysostosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.185 AKT2 Rhiannon Mellis gene: AKT2 was added
gene: AKT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AKT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: AKT2 were set to Hypoinsulinemic hypoglycemia with hemihypertrophy
Review for gene: AKT2 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other PanelApp panel (BWS and Overgrowth panel). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Fetal anomalies v1.185 ADAMTS3 Rhiannon Mellis gene: ADAMTS3 was added
gene: ADAMTS3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3
Review for gene: ADAMTS3 was set to GREEN
Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Sources: Literature
Fetal anomalies v1.185 ABL1 Rhiannon Mellis reviewed gene: ABL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital heart defects and skeletal malformations syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v1.23 SORD Ivone Leong Tag for-review tag was added to gene: SORD.
Hereditary neuropathy or pain disorder v1.23 SORD Ivone Leong Classified gene: SORD as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v1.23 SORD Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics) and recommended to be Green by David Hunt (Wessex Clinical Genetics Service).

"Given that this is a potentially treatable neuropathy (https://www.ucl.ac.uk/ion/news/2020/may/sord-neuropathy-accelerated-journey-gene-identification-effective-treatment-patients), I think that SORD should be included in the ‘Hereditary neuropathy NOT PMP22 copy number’ gene panel."

There is enough evidence to support a gene-disease association and this gene should be Green at the next review.
Hereditary neuropathy or pain disorder v1.23 SORD Ivone Leong Gene: sord has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v1.22 SORD Ivone Leong Publications for gene: SORD were set to 32367058
Severe microcephaly v2.89 AP4S1 Arina Puzriakova Phenotypes for gene: AP4S1 were changed from Spastic paraplegia 52, autosomal recessive (MIM#614067) to Spastic paraplegia 52, autosomal recessive, OMIM:614067; Hereditary spastic paraplegia 52, MONDO:0013552
Early onset or syndromic epilepsy v2.274 CEP85L Helen Lord reviewed gene: CEP85L: Rating: GREEN; Mode of pathogenicity: None; Publications: 32097630; Phenotypes: Lissencephaly 10; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v2.88 AP4S1 Arina Puzriakova changed review comment from: Literature search revealed at least 23 individuals from 17 unrelated families reported in literature with biallelic variants in this gene (PMID: 21620353; 25552650; 27444738; 30283821; 32216065; 32979048). Microcephaly was observed in 15/21 cases but precise details regarding head circumference were mostly omitted or presentation was too mild relative to the scope of this panel. However, at least 2 individuals (2 families) did have microcephaly of relevant severity (OFC ≤ -3 SD) (see PMIDs: 21620353 and 25552650).

This disorder may be better represented by other panels (e.g. HSP, ID) for which this gene is already Green.; to: Literature search revealed at least 23 individuals from 17 unrelated families reported in literature with biallelic variants in this gene (PMID: 21620353; 25552650; 27444738; 30283821; 32216065; 32979048). Microcephaly was observed in 15/21 cases but precise details regarding head circumference were mostly omitted or presentation was too mild relative to the scope of this panel. However, at least 2 individuals (2 families) did have microcephaly of relevant severity (OFC ≤ -3 SD) (see PMIDs: 21620353 and 25552650).

This disorder may be better represented by other panels (e.g. HSP, ID) for which this gene is already Green.

- PMID: 32216065 (2020) - Zebrafish model recapitulates several human phenotypes, including decreased head size.
Early onset or syndromic epilepsy v2.274 CDK19 Helen Lord changed review comment from: Chung et al 2020 - 3 iunrealrted indicuduals with de novo missense variants in CDK19 - presented with hypotonia, global developmental delay, epileptic encephalopathy and dysmorphic features. Two patients had the Thr196Ala variant and the other Tyr32His - predicted to be likely pathogenic. Fuinctional work suggests dominant loss of function variants.; to: Chung et al 2020 - 3 unrelated indiviuduals with de novo missense variants in CDK19 - presented with hypotonia, global developmental delay, epileptic encephalopathy and dysmorphic features. Two patients had the Thr196Ala variant and the other Tyr32His - predicted to be likely pathogenic. Fuinctional work suggests dominant loss of function variants.
Early onset or syndromic epilepsy v2.274 CDK19 Helen Lord reviewed gene: CDK19: Rating: AMBER; Mode of pathogenicity: None; Publications: 32330417; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v2.88 AP4S1 Arina Puzriakova Classified gene: AP4S1 as Amber List (moderate evidence)
Severe microcephaly v2.88 AP4S1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Rating Amber with recommendation of review by the GMS team to assess whether there is sufficient evidence to support a Green rating (added 'for-review' tag)
Severe microcephaly v2.88 AP4S1 Arina Puzriakova Gene: ap4s1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.87 AP4S1 Arina Puzriakova Tag for-review tag was added to gene: AP4S1.
Severe microcephaly v2.87 AP4S1 Arina Puzriakova reviewed gene: AP4S1: Rating: ; Mode of pathogenicity: None; Publications: 21620353, 25552650, 27444738, 30283821, 32216065, 32979048; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v1.78 RINT1 Eleanor Williams Classified gene: RINT1 as Amber List (moderate evidence)
Cholestasis v1.78 RINT1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber, but with recommendation for green rating, pending review of whether the phenotype is within the scope of this panel.
Cholestasis v1.78 RINT1 Eleanor Williams Gene: rint1 has been classified as Amber List (Moderate Evidence).
Cholestasis v1.77 RINT1 Eleanor Williams Tag for-review tag was added to gene: RINT1.
Cholestasis v1.77 RINT1 Eleanor Williams gene: RINT1 was added
gene: RINT1 was added to Cholestasis. Sources: Literature
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to 31204009
Phenotypes for gene: RINT1 were set to Infantile liver failure syndrome 3 OMIM:618641; infantile liver failure syndrome 3 MONDO:0032844
Review for gene: RINT1 was set to GREEN
Added comment: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM. Probable association with Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities in Gene2Phenotype.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.
Sources: Literature
Retinal disorders v2.163 TUBGCP4 Ivone Leong commented on gene: TUBGCP4: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be promoted to Green at the next review.
Retinal disorders v2.163 TUBGCP4 Ivone Leong Tag for-review tag was added to gene: TUBGCP4.
Retinal disorders v2.163 TUBGCP4 Ivone Leong Added comment: Comment on publications: PMID: 33137195 extra case
Retinal disorders v2.163 TUBGCP4 Ivone Leong Publications for gene: TUBGCP4 were set to 25817018; 32270730
Paediatric disorders - additional genes v1.78 RINT1 Eleanor Williams Classified gene: RINT1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.78 RINT1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber, but with a recommendation for green rating following GMS review. Liver failure could lead to paediatric ITU admission and so thought appropriate for this panel.
Paediatric disorders - additional genes v1.78 RINT1 Eleanor Williams Gene: rint1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.77 RINT1 Eleanor Williams Tag for-review tag was added to gene: RINT1.
Paediatric disorders - additional genes v1.77 RINT1 Eleanor Williams gene: RINT1 was added
gene: RINT1 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to 31204009
Phenotypes for gene: RINT1 were set to Infantile liver failure syndrome 3 OMIM:618641; infantile liver failure syndrome 3 MONDO:0032844
Review for gene: RINT1 was set to GREEN
Added comment: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM. Probable association with Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities in Gene2Phenotype.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.
Sources: Literature
Skeletal dysplasia v2.76 RINT1 Eleanor Williams changed review comment from: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.; to: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM. Probable association with Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities in Gene2Phenotype.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.
Retinal disorders v2.162 TUBGCP4 Ivone Leong Phenotypes for gene: TUBGCP4 were changed from to Microcephaly and chorioretinopathy, autosomal recessive, 3, OMIM:616335
Retinal disorders v2.161 TUBGCP4 Ivone Leong Publications for gene: TUBGCP4 were set to
Retinal disorders v2.160 TUBGCP4 Ivone Leong Mode of inheritance for gene: TUBGCP4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v2.76 RINT1 Eleanor Williams changed review comment from: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF_ and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.; to: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.
Retinal disorders v2.159 TUBB4B Ivone Leong Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early-onset deafness MIM#617879 to Leber congenital amaurosis with early-onset deafness, OMIM:617879
Paediatric disorders - additional genes v1.76 HYAL2 Eleanor Williams Classified gene: HYAL2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.76 HYAL2 Eleanor Williams Gene: hyal2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.75 HYAL2 Eleanor Williams Classified gene: HYAL2 as Red List (low evidence)
Paediatric disorders - additional genes v1.75 HYAL2 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. Checking with Genomics England clinical team as to whether a green rating would be appropriate.
Paediatric disorders - additional genes v1.75 HYAL2 Eleanor Williams Gene: hyal2 has been classified as Red List (Low Evidence).
Paediatric disorders - additional genes v1.74 HYAL2 Eleanor Williams gene: HYAL2 was added
gene: HYAL2 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: HYAL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYAL2 were set to 28081210; 23172227; 26515055
Phenotypes for gene: HYAL2 were set to cor triatriatum; congenital cardiac malformations
Review for gene: HYAL2 was set to AMBER
Added comment: PMID: 28081210 (Muggenthaler et al 2017) report 2 unrelated consanguineous extended families (Amish and Arab) who have an orofacial clefting phenotype with cardiac anomalies are also reported.

In pedigree 1 (Amish) 5/5 analysed individuals had cleft lip and palate. 3/5 had congenital cardiac malformations including left cor triatriatum and dilated coronary sinus consistent with persistent left superior vena cava. All had a homzogyous c.443A>G, p.K148R variant which segregated with the disorder in the pedigree. It was found in a heterozygous state at a frequency of 0.013 in the Amish population, but was not found in 1000 Genomes or ExAC databases.

In pedigree 2 (Arab) 1/2 analysed individuals had cleft lip and palate and 1/2 had an abnormal mitral valve with accessory tissue. Both were found to have a homozygous c.749C>T; p.P250L variant following whole genome SNP mapping. This variant was found in 2 individuals in the ExAC database in heterozygous state. Transient expression of the patient variants in mouse embryonic fibroblasts showed a large decrease in protein levels compared to wild type.

They report that valvular thickening and atrial dilatation are found in all Hyal2-/- mice (PMID: 23172227) and that Cor triatriatum sinister has been detected in 50% of Hyal2-/- mice (PMID: 26515055).
Sources: Literature
Early onset or syndromic epilepsy v2.274 CACNB4 Helen Lord reviewed gene: CACNB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 32176688; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial non syndromic congenital heart disease v1.56 HYAL2 Eleanor Williams Classified gene: HYAL2 as Amber List (moderate evidence)
Familial non syndromic congenital heart disease v1.56 HYAL2 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. 2 cases reported with supporting data from mouse. Cardiac phenotype is not fully penetrant. Awaiting confirmation of further cases before promoting to green.
Familial non syndromic congenital heart disease v1.56 HYAL2 Eleanor Williams Gene: hyal2 has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.158 TRNT1 Ivone Leong commented on gene: TRNT1: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease assocation. This gene should be rated Green at the next review.
Familial non syndromic congenital heart disease v1.55 HYAL2 Eleanor Williams changed review comment from: PMID: 28081210 (Muggenthaler et al 2017) report 2 unrelated consanguineous extended families (Amish and Arab) who have an orofacial clefting phenotype but cardiac anomalies are also reported. In pedigree 1 (Amish) 5/5 analysed individuals had cleft lip and palate. 3/5 had congenital cardiac malformations including left cor triatriatum and dilated coronary sinus consistent with persistent left superior vena cava. All had a homzogyous c.443A>G, p.K148R variant which segregated with the disorder in the pedigree. It was found in a heterozygous state at a frequency of 0.013 in the Amish population, but was not found in 1000 Genomes or ExAC databases. In pedigree 2 (Arab) 1/2 analysed individuals had cleft lip and palate and 1/2 had an abnormal mitral valve with accessory tissue. Both were found to have a homozygous c.749C>T; p.P250L variant following whole genome SNP mapping. This variant was found in 2 individuals in the ExAC database in heterozygous state. Transient expression of the patient variants in mouse embryonic fibroblasts showed a large decrease in protein levels compared to wild type. They report that valvular thickening and atrial dilatation are found in all Hyal2-/- mice (PMID: 23172227) and that Cor triatriatum sinister has been detected in 50% of Hyal2-/- mice (PMID: 26515055).
Sources: Literature; to: PMID: 28081210 (Muggenthaler et al 2017) report 2 unrelated consanguineous extended families (Amish and Arab) who have an orofacial clefting phenotype with cardiac anomalies are also reported.

In pedigree 1 (Amish) 5/5 analysed individuals had cleft lip and palate. 3/5 had congenital cardiac malformations including left cor triatriatum and dilated coronary sinus consistent with persistent left superior vena cava. All had a homzogyous c.443A>G, p.K148R variant which segregated with the disorder in the pedigree. It was found in a heterozygous state at a frequency of 0.013 in the Amish population, but was not found in 1000 Genomes or ExAC databases.

In pedigree 2 (Arab) 1/2 analysed individuals had cleft lip and palate and 1/2 had an abnormal mitral valve with accessory tissue. Both were found to have a homozygous c.749C>T; p.P250L variant following whole genome SNP mapping. This variant was found in 2 individuals in the ExAC database in heterozygous state. Transient expression of the patient variants in mouse embryonic fibroblasts showed a large decrease in protein levels compared to wild type.

They report that valvular thickening and atrial dilatation are found in all Hyal2-/- mice (PMID: 23172227) and that Cor triatriatum sinister has been detected in 50% of Hyal2-/- mice (PMID: 26515055).
Sources: Literature
Familial non syndromic congenital heart disease v1.55 HYAL2 Eleanor Williams gene: HYAL2 was added
gene: HYAL2 was added to Familial non syndromic congenital heart disease. Sources: Literature
Mode of inheritance for gene: HYAL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYAL2 were set to 28081210; 23172227; 26515055
Phenotypes for gene: HYAL2 were set to cor triatriatum; congenital cardiac malformations
Review for gene: HYAL2 was set to AMBER
Added comment: PMID: 28081210 (Muggenthaler et al 2017) report 2 unrelated consanguineous extended families (Amish and Arab) who have an orofacial clefting phenotype but cardiac anomalies are also reported. In pedigree 1 (Amish) 5/5 analysed individuals had cleft lip and palate. 3/5 had congenital cardiac malformations including left cor triatriatum and dilated coronary sinus consistent with persistent left superior vena cava. All had a homzogyous c.443A>G, p.K148R variant which segregated with the disorder in the pedigree. It was found in a heterozygous state at a frequency of 0.013 in the Amish population, but was not found in 1000 Genomes or ExAC databases. In pedigree 2 (Arab) 1/2 analysed individuals had cleft lip and palate and 1/2 had an abnormal mitral valve with accessory tissue. Both were found to have a homozygous c.749C>T; p.P250L variant following whole genome SNP mapping. This variant was found in 2 individuals in the ExAC database in heterozygous state. Transient expression of the patient variants in mouse embryonic fibroblasts showed a large decrease in protein levels compared to wild type. They report that valvular thickening and atrial dilatation are found in all Hyal2-/- mice (PMID: 23172227) and that Cor triatriatum sinister has been detected in 50% of Hyal2-/- mice (PMID: 26515055).
Sources: Literature
Retinal disorders v2.158 TRNT1 Ivone Leong Tag for-review tag was added to gene: TRNT1.
Retinal disorders v2.158 TRNT1 Ivone Leong Mode of inheritance for gene: TRNT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v2.157 TRNT1 Ivone Leong Phenotypes for gene: TRNT1 were changed from to Retinitis pigmentosa and erythrocytic microcytosis, OMIM:616959; Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, OMIM:616084
Retinal disorders v2.156 TRNT1 Ivone Leong Publications for gene: TRNT1 were set to
Retinal disorders v2.155 TRIM32 Ivone Leong reviewed gene: TRIM32: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v2.274 SCN9A Helen Lord reviewed gene: SCN9A: Rating: RED; Mode of pathogenicity: None; Publications: 33216760; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v2.274 ANKRD11 Helen Lord reviewed gene: ANKRD11: Rating: GREEN; Mode of pathogenicity: None; Publications: 33476899; Phenotypes: KBG syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v2.155 TRIM32 Ivone Leong Tag for-review tag was added to gene: TRIM32.
Retinal disorders v2.155 TRIM32 Ivone Leong Phenotypes for gene: TRIM32 were changed from Eye Disorders to Bardet-Biedl syndrome 11, OMIM:615988
Retinal disorders v2.154 TRIM32 Ivone Leong Publications for gene: TRIM32 were set to
Retinal disorders v2.153 TREX1 Ivone Leong commented on gene: TREX1: This gene is associated with the relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support gene-disease association. This gene should be rated Green at the next review.
Retinal disorders v2.153 TREX1 Ivone Leong Tag for-review tag was added to gene: TREX1.
Early onset or syndromic epilepsy v2.274 ALG14 Helen Lord reviewed gene: ALG14: Rating: GREEN; Mode of pathogenicity: None; Publications: 28733338, 30221345; Phenotypes: epilepsy, behavioural problems, severe developmental delay, mild dysmorphic features, severe neurodegeneration with myopathic and myasthenic features; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v2.87 AP4E1 Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Zornitza Stark. Rating Amber but there is sufficient evidence to rate Green at the next GMS panel update (added 'for-review' tag)

At least 21 individuals from 11 unrelated families reported in literature with variants in this gene (PMID: 32979048). Microcephaly was observed in 14/16 cases but details regarding head circumference were mostly unavailable. At least 5 individuals (2 families) had microcephaly of relevant severity to this panel (OFC ≤ -3 SD) (see PMIDs: 21620353 and 20972249).; to: Comment on list classification: New gene added by Zornitza Stark. Rating Amber with recommendation of review by the GMS team to assess whether there is sufficient evidence to support a Green rating (added 'for-review' tag)

At least 21 individuals from 11 unrelated families reported in literature with variants in this gene (PMID: 32979048). Microcephaly was observed in 14/16 cases but precise details regarding head circumference were mostly omitted (no relevant info was provided for the remaining 5 patients). However, at least 5 individuals (2 families) had microcephaly of relevant severity to this panel (OFC ≤ -3 SD) (see PMIDs: 21620353 and 20972249).
Retinal disorders v2.153 TREX1 Ivone Leong Publications for gene: TREX1 were set to
Retinal disorders v2.152 TREX1 Ivone Leong Mode of inheritance for gene: TREX1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v2.151 TREX1 Ivone Leong Phenotypes for gene: TREX1 were changed from to Vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations, OMIM:192315
Early onset or syndromic epilepsy v2.274 ADAM22 Helen Lord reviewed gene: ADAM22: Rating: AMBER; Mode of pathogenicity: None; Publications: 31432233, 33397806; Phenotypes: Developmental and epileptic encephalopathy 61; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v2.150 TRAF3IP1 Ivone Leong Classified gene: TRAF3IP1 as Amber List (moderate evidence)
Retinal disorders v2.150 TRAF3IP1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be Green at the next review.
Retinal disorders v2.150 TRAF3IP1 Ivone Leong Gene: traf3ip1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.149 TRAF3IP1 Ivone Leong Tag for-review tag was added to gene: TRAF3IP1.
Retinal disorders v2.149 TRAF3IP1 Ivone Leong Phenotypes for gene: TRAF3IP1 were changed from Senior-Loken syndrome 9, MIM#616629 to Senior-Loken syndrome 9, OMIM:616629
Early onset or syndromic epilepsy v2.274 ABCA2 Helen Lord reviewed gene: ABCA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29302074, 31047799, 30237576; Phenotypes: intellectual delay, poor growth, ataxia, seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v1.16 AP4M1 Arina Puzriakova Tag for-review tag was added to gene: AP4M1.
Adult onset hereditary spastic paraplegia v1.16 AP4M1 Arina Puzriakova commented on gene: AP4M1
Retinal disorders v2.148 TMEM231 Ivone Leong Classified gene: TMEM231 as Amber List (moderate evidence)
Retinal disorders v2.148 TMEM231 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be Green at the next review.
Retinal disorders v2.148 TMEM231 Ivone Leong Gene: tmem231 has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.147 TMEM231 Ivone Leong Tag for-review tag was added to gene: TMEM231.
Retinal disorders v2.147 TMEM231 Ivone Leong Phenotypes for gene: TMEM231 were changed from Joubert syndrome 20 MIM#614970 to Joubert syndrome 20, OMIM:614970
Retinal disorders v2.146 TMEM216 Ivone Leong Classified gene: TMEM216 as Amber List (moderate evidence)
Retinal disorders v2.146 TMEM216 Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber. This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be promoted to Green status at the next review.
Retinal disorders v2.146 TMEM216 Ivone Leong Gene: tmem216 has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.145 TMEM216 Ivone Leong Tag for-review tag was added to gene: TMEM216.
Leber hereditary optic neuropathy v1.7 DNAJC30 Ivone Leong Phenotypes for gene: DNAJC30 were changed from Leber hereditary optic neuropathy to Leber hereditary optic neuropathy; LHON-like
Leber hereditary optic neuropathy v1.6 DNAJC30 Ivone Leong Publications for gene: DNAJC30 were set to
Severe microcephaly v2.87 AP4M1 Arina Puzriakova Phenotypes for gene: AP4M1 were changed from Spastic paraplegia 50, autosomal recessive (MIM#612936) to Spastic paraplegia 50, autosomal recessive, OMIM:612936; Hereditary spastic paraplegia 50, MONDO:0013048
Severe microcephaly v2.86 AP4M1 Arina Puzriakova Classified gene: AP4M1 as Amber List (moderate evidence)
Severe microcephaly v2.86 AP4M1 Arina Puzriakova Added comment: Comment on list classification: Microcephaly is a variable feature of the disease presentation - often too mild relative to the scope of this panel, or absent altogether. However, there are at least 3 unrelated cases with sufficiently severe microcephaly. Although the overall disorder may be better represented by other panels (e.g. HSP, ID) for which this gene is already Green, microcephaly can be an early manifestation that may be evident prior to other AP4M1-related phenotypes. Therefore, there may be value in inclusion on this panel.

Rating Amber, with recommendation of review by the GMS team to assess whether there is sufficient evidence to support a Green rating on this panel (added 'for-review' tag)
Severe microcephaly v2.86 AP4M1 Arina Puzriakova Gene: ap4m1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.85 AP4M1 Arina Puzriakova Tag for-review tag was added to gene: AP4M1.
Severe microcephaly v2.85 AP4M1 Arina Puzriakova reviewed gene: AP4M1: Rating: ; Mode of pathogenicity: None; Publications: 19559397, 21937992, 24700674, 25496299, 28464862, 29473051, 32337850; Phenotypes: Spastic paraplegia 50, autosomal recessive, OMIM:612936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v2.145 TMEM216 Ivone Leong Phenotypes for gene: TMEM216 were changed from Eye Disorders to Joubert syndrome 2, OMIM:608091, MONDO:0011963; Meckel syndrome 2, OMIM:603194, MONDO:0011296
Retinal disorders v2.144 SSBP1 Ivone Leong Classified gene: SSBP1 as Amber List (moderate evidence)
Retinal disorders v2.144 SSBP1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be reviewed by the GMS specialist group to see whether the phenotype is appropriate to be included in this panel.

This gene is Green on the Optic neuropathy panel (Version 2.29).
Retinal disorders v2.144 SSBP1 Ivone Leong Gene: ssbp1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.143 SSBP1 Ivone Leong Tag for-review tag was added to gene: SSBP1.
Severe microcephaly v2.85 ANKLE2 Arina Puzriakova Tag for-review tag was added to gene: ANKLE2.
Severe microcephaly v2.85 ANKLE2 Arina Puzriakova Phenotypes for gene: ANKLE2 were changed from ?Microcephaly 16, primary, autosomal recessive, 616681 to Microcephaly 16, primary, autosomal recessive, OMIM:616681; Microcephaly 16, primary, autosomal recessive, MONDO:0014730
Severe microcephaly v2.84 ANKLE2 Arina Puzriakova Publications for gene: ANKLE2 were set to 25259927
Severe microcephaly v2.83 ANKLE2 Arina Puzriakova Classified gene: ANKLE2 as Amber List (moderate evidence)
Severe microcephaly v2.83 ANKLE2 Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber, but there is enough evidence to rate Green at the next GMS panel update (added 'for-review' tag).

At least 5 individuals from 4 unrelated families with primary microcephaly (HC -4.33 to -16.30 SD) and biallelic variants in ANKLE2 (PMIDs: 25259927 and 30214071). Several lines of supporting evidence using Drosophila Ankle2 mutants, including reduced brain size which could be rescued by expression of wildtype human ANKLE2.

This gene-disease association is also listed in OMIM (MIM# 616681).
Severe microcephaly v2.83 ANKLE2 Arina Puzriakova Gene: ankle2 has been classified as Amber List (Moderate Evidence).
Leber hereditary optic neuropathy v1.5 DNAJC30 Neringa Jurkute reviewed gene: DNAJC30: Rating: RED; Mode of pathogenicity: Other; Publications: PMID: 33465056; Phenotypes: LHON-like; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v2.143 SSBP1 Ivone Leong Phenotypes for gene: SSBP1 were changed from Optic atrophy-13 with retinal and foveal abnormalities, MIM#165510 to Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510
Retinal disorders v2.142 RIMS2 Ivone Leong Tag for-review tag was added to gene: RIMS2.
Retinal disorders v2.142 RIMS2 Ivone Leong Classified gene: RIMS2 as Amber List (moderate evidence)