1. Panels
  2. Holoprosencephaly - NOT chromosomal
The latest signed off version for the GMS is v5.1. The current version, shown here, may differ from the signed-off version.

Holoprosencephaly - NOT chromosomal (Version 5.11)

Level 2: Neurology

Relevant disorders: Rhombencephalosynapsis, Holoprosencephaly, R85
Panel types: Rare Disease 100K, GMS Rare Disease Virtual, Component Of Super Panel, GMS signed-off
Latest signed off version: v5.1 (30 Oct 2024)
Previously signed off versions: v5.0, v4.4, v4.0, v3.0, v2.3
Previous code: 568e87e022c1fc1c79ca1754
Description
This panel is used as a virtual panel to analyse genome or exome data in the NHS Genomic Medicine Service; the panel will routinely be applied for clinical indication 'R85 Holoprosencephaly - NOT chromosomal' but can also be used as part of the analysis for a broader clinical presentation, where relevant.

Further information on the testing criteria and any overlapping clinical indications can be found within (https://www.england.nhs.uk/publication/national-genomic-test-directories/) under 'R85 Holoprosencephaly - NOT chromosomal'.

A version of this panel has been signed off under NHS Genomic Medicine Service governance (see 'Latest signed off version' in the panel header information).

This panel will continue to be curated based on external reviews and Genomics England curation. New changes will be reflected in an increase to the minor version of the panel and details of these can be viewed in the 'Panel Activity' page. Periodically, these changes will be reviewed by a NHS Genomic Medicine Service evaluation process.  The content that is agreed for the GMS panels will be reflected in an updated signed off version number.

This panel was originally developed for the 100,000 Genomes Project and is still being used for participants in the project. For the rare disease eligibility criteria refer to: https://www.genomicsengland.co.uk/rarediseasecriteria100K

This panel is also a constituent panel of super panel 'Cerebral malformation'. Changes made to this panel will automatically be updated in the relevant super panel(s).
Panel Activity

15 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Richard Scott (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Helen Brittain (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Lara Menzies (Great Ormond Street Hospital )

    Group: NHS Genomic Medicine Centre
    Workplace: NHS diagnostic lab

  • Eleanor Williams (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Zornitza Stark (Australian Genomics)

    Group: Other
    Workplace: Other clinical service

  • Ivone Leong (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Shane Mckee (Belfast HSC Trust)

    Group: Other NHS organisation
    Workplace: NHS clinical service

  • Arina Puzriakova (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Nour Elkhateeb (Cambridge University Hospitals NHS Foundation Trust)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Achchuthan Shanmugasundram (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Ida Ertmanska (Genomics England Curator)

    Group: Other
    Workplace: Other

26 Entities

26 reviewed, 17 green

List Entity Reviews Mode of inheritance Details
26 Entitiess
Green List (high evidence)
CDON
3 reviews
 MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • NHS GMS
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Holoprosencephaly 11, 614226
  • Holoprosencephaly
Tags
Green List (high evidence)
CNOT1
3 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Literature
  • NHS GMS
Phenotypes
  • Holoprosencephaly 12, with or without pancreatic agenesis, OMIM:618500
  • holoprosencephaly 12 with or without pancreatic agenesis, MONDO:0032787
Tags
Green List (high evidence)
DHCR7
1 review
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Smith-Lemli-Opitz syndrome, 270400
  • alobar holoprosencephaly (HPE)
Tags
Green List (high evidence)
DISP1
11 reviews
2 green 		BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Holoprosencephaly 10, OMIM:621143
  • holoprosencephaly 10, MONDO:0976262
Tags
Green List (high evidence)
FGF8
4 reviews
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Holoprosencephaly
Tags
Green List (high evidence)
FGFR1
5 reviews
2 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Hypogonadotropic hypogonadism 2 with or without anosmia, OMIM:147950
  • Hartsfield syndrome, OMIM:615465
Tags
  • Q1_26_MOI
Green List (high evidence)
GLI2
4 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • NHS GMS
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Holoprosencephaly-9
  • Holoprosencephaly
  • Holoprosencephaly 9, 610829
Tags
Green List (high evidence)
Xq25 region (includes STAG2) Loss
ISCA-46743-Loss
Region
1 review
1 green 		X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • ClinGen
  • Expert Review Green
Tags
Green List (high evidence)
KMT2D
3 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Kabuki syndrome 1, OMIM:147920
Tags
Green List (high evidence)
PTCH1
4 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • NHS GMS
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Holoprosencephaly 7, OMIM:610828
Tags
Green List (high evidence)
RAD21
3 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Cornelia de Lange syndrome 4, OMIM:614701
  • Holoprosencephaly with or without CdLS features
  • Septo-optic dysplasia
Tags
Green List (high evidence)
SHH
4 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • NHS GMS
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Holoprosencephaly-3
  • Holoprosencephaly
  • Holoprosencephaly 3, 142945
Tags
Green List (high evidence)
SIX3
4 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • NHS GMS
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Holoprosencephaly-2
  • Holoprosencephaly
  • Holoprosencephaly 2, 157170
Tags
Green List (high evidence)
SMC1A
3 reviews
1 green 		X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Developmental and epileptic encephalopathy 85, with midline brain defects, OMIM:301044
  • Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771
Tags
Green List (high evidence)
STAG2
2 reviews
2 green 		X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Holoprosencephaly 13, X-linked OMIM:301043
Tags
Green List (high evidence)
TGIF1
4 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • NHS GMS
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Holoprosencephaly-4
  • Holoprosencephaly
  • Holoprosencephaly 4, 142946
Tags
Green List (high evidence)
ZIC2
4 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • NHS GMS
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Holoprosencephaly-5
  • Holoprosencephaly
  • Holoprosencephaly 5, 609637
Tags
Amber List (moderate evidence)
DLL1
4 reviews
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
  • NHS GMS
Tags
  • watchlist
Amber List (moderate evidence)
HS2ST1
1 review
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Intellectual disability
  • dysmorphic features
  • congenital anomalies
Tags
  • watchlist
Amber List (moderate evidence)
PLCH1
1 review
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Severe developmental delay
  • Brain malformations
  • Holoprosencephaly spectrum
Tags
Amber List (moderate evidence)
PPP1R12A
2 reviews
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
  • Expert Review Amber
Phenotypes
  • Genitourinary and/or/brain malformation syndrome, 618820
Tags
  • watchlist
Amber List (moderate evidence)
SUFU
4 reviews
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • Basal cell nevus syndrome, OMIM:109400
Tags
  • watchlist
Red List (low evidence)
FOXH1
3 reviews
 MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • Illumina TruGenome Clinical Sequencing Services
  • NHS GMS
Phenotypes
  • Holoprosencephaly
Tags
Red List (low evidence)
GCM2
4 reviews
1 red 		MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • NHS GMS
  • Other
  • UKGTN
Phenotypes
  • Hypoparathyroidism, familial isolated (AD)
Tags
Red List (low evidence)
NODAL
3 reviews
 MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • Illumina TruGenome Clinical Sequencing Services
  • NHS GMS
Phenotypes
  • Holoprosencephaly
Tags
Red List (low evidence)
SMAD2
3 reviews
1 red 		Unknown
Sources
  • Expert Review Red
  • NHS GMS
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Unknown
Tags

Major version comments

  • 2024-08-07 16:04 Achchuthan Shanmugasundram (Genomics England Curator) promoted panel to 5.0
    The content of this panel has been updated in accordance with changes agreed with the NHS Genomic Medicine Service. The panel was promoted to the next major version (5.0) following this.

    2023-03-22 15:06 Arina Puzriakova (Genomics England Curator) promoted panel to 4.0
    The content of this panel has been updated in accordance with changes agreed with the NHS Genomic Medicine Service. The panel was promoted to the next major version (4.0) following this.

    2022-11-30 14:16 Eleanor Williams (Genomics England Curator) promoted panel to 3.0
    The content of this panel has been updated in accordance with changes agreed with the NHS Genomic Medicine Service. The panel was promoted to the next major version (3.0) following this.

    2019-10-18 15:50 Louise Daugherty (Genomics England Curator) promoted panel to 2.0
    The content of this panel (version 1.22 was signed off under NHS Genomic Medicine Service governance on (18/October/2019). The panel was promoted to the next major version (version 2.0) as a result of this.

    Promoted to version one after review within the genomics England curation team.

Downloads

Download lists

  • Whole panel
  • Green list (high evidence)
  • Green and Amber Genes
  • Amber Genes
  • Red list (low evidence)

Download Version