Description
This panel is used for clinical indication 'R149 Severe early-onset obesity', and can also be applied as a virtual panel in the analysis of genome or exome data in the NHS Genomic Medicine Service.

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 'R149 Severe early-onset obesity'.

The content of this panel (version 2.2: https://panelapp.genomicsengland.co.uk/api/v1/panels/130/?version=2.2) was signed off under NHS Genomic Medicine Service governance on 18/02/2020).

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 version number. 

CNVs, STRs and genes encoded by the mitochondrial genome may not be routinely included in the analysis where the panel is NOT delivered by WGS. Please contact your Genomic Laboratory Hub for information regarding specific queries.

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

7 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • stephen o'rahilly (university of cambridge)

    Group: GeCIP domain
    Workplace: Research lab

  • alisdair mcneill (Sheffield childrens hospital)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Ayesha Ahmed (GEL)

    Group: Other
    Workplace: GEL

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Ivone Leong (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Ismaa Farooqi (University of Cambridge)

    Group: GeCIP domain
    Workplace: Research lab

42 Entities

42 reviewed, 29 green

List Entity Reviews Mode of inheritance Details
42 Entitiess
Green Green List (high evidence)
ALMS1
4 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Truncal obesity (onset in childhood)
  • Alstrom syndrome associated with obesity
  • Alstrom syndrome, 203800
Tags
Green Green List (high evidence)
ARL6
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 3, 600151
  • Bardet-Biedl syndrome 3
Tags
Green Green List (high evidence)
BBS1
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 1
  • Bardet-Biedl syndrome 1, 209900
Tags
Green Green List (high evidence)
BBS10
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • obesity
  • Bardet-Biedl syndrome 10
  • Bardet-Biedl syndrome 10, 615987
Tags
Green Green List (high evidence)
BBS12
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • obesity
  • Bardet-Biedl syndrome 12
  • Bardet-Biedl syndrome 12, 615989
Tags
Green Green List (high evidence)
BBS2
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 2
  • Bardet-Biedl syndrome 2, 615981
Tags
Green Green List (high evidence)
BBS4
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 4, 615982
  • Bardet-Biedl syndrome 4
Tags
Green Green List (high evidence)
BBS5
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 5, 615983
  • Bardet-Biedl syndrome 5
Tags
Green Green List (high evidence)
BBS7
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 7, 615984
  • Bardet-Biedl syndrome 7
Tags
Green Green List (high evidence)
BBS9
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 9, 615986
  • Bardet-Biedl syndrome 9
Tags
Green Green List (high evidence)
CEP19
5 reviews
3 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Morbid obesity and spermatogenic failure, 615703
Tags
Green Green List (high evidence)
GNAS
2 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Congenital Obesity
  • Pseudohypoparathyroidism Ia, 103580
  • Pseudohypoparathyroidism Ib, 603233
  • Pseudohypoparathyroidism Ic, 612462
Tags
Green Green List (high evidence)
15q11q13 recurrent (PWS/AS) region (BP1-BP3, Class 1) Loss
ISCA-37404-Loss
Region
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert list
  • Expert Review Green
Phenotypes
  • microcephaly
  • Developmental delay, muscle weakness
  • Mental retardation
  • Angelman syndrome
  • 176270
  • Prader-Willi syndrome
  • 105835
Tags
Green Green List (high evidence)
15q11q13 recurrent (PWS/AS) region (BP2-BP3, Class 2) Loss
ISCA-37478-Loss
Region
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert list
  • Expert Review Green
Phenotypes
  • microcephaly
  • Developmental delay, muscle weakness
  • Mental retardation
  • Angelman syndrome
  • 176270
  • Prader-Willi syndrome
  • 105830
Tags
Green Green List (high evidence)
16p11.2 recurrent region (includes SH2B1) (distal region) (BP2-BP3) Loss
ISCA-37486-Loss
Region
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert list
  • Expert Review Green
Phenotypes
  • developmental delay
  • 613444
  • obesity
Tags
Green Green List (high evidence)
LEP
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Obesity, morbid, due to leptin deficiency, 614962
  • Congenital Obesity
Tags
Green Green List (high evidence)
LEPR
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Obesity, morbid, due to leptin receptor deficiency, 614963
  • Congenital Obesity
Tags
Green Green List (high evidence)
MC4R
2 reviews
2 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Congenital Obesity
  • Obesity (BMIQ20), 618406
  • {Obesity, resistence to (BMIQ20)}, 618306
  • Obesity, autosomal dominant, 601665
Tags
Green Green List (high evidence)
MKKS
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 6
  • Bardet-Biedl syndrome 6, 605231
Tags
Green Green List (high evidence)
MKS1
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 13, 615990
  • Bardet-Biedl syndrome 13
Tags
Green Green List (high evidence)
MYT1L
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
  • Expert Review Green
  • Literature
Phenotypes
  • obesity
  • Mental retardation, autosomal dominant 39, 616521
  • intellectual disability
Tags
Green Green List (high evidence)
NTRK2
5 reviews
3 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Obesity, hyperphagia, and developmental delay, 613886
  • Congenital Obesity
Tags
Green Green List (high evidence)
PCSK1
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • {Obesity, susceptibility to, BMIQ12}, 612362
  • Congenital Obesity
  • Obesity with impaired prohormone processing, 600955
  • {Obesity, susceptibility to, BMIQ12}, 612362
Tags
Green Green List (high evidence)
PHF6
4 reviews
2 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Borjeson-Forssman-Lehmann syndrome, 301900
  • Borjeson-Forssman-Lehmann syndrome
Tags
Green Green List (high evidence)
POMC
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • {Obesity, early-onset, susceptibility to}, 601665
  • Obesity, adrenal insufficiency, and red hair due to POMC deficiency, 609734
  • Congenital Obesity
  • {Obesity, early-onset, susceptibility to}, 601665
Tags
Green Green List (high evidence)
SDCCAG8
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 16
  • Bardet-Biedl syndrome 16, 615993
Tags
Green Green List (high evidence)
SIM1
5 reviews
3 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Obesity, severe, 601665
  • obesity
  • Congenital Obesity
Tags
Green Green List (high evidence)
TTC8
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Bardet-Biedl syndrome 8, 615985
  • Bardet-Biedl syndrome 8
Tags
Green Green List (high evidence)
VPS13B
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Cohen syndrome, 216550
  • Cohen syndrome
  • Truncal obesity developing in mid-childhood
Tags
Amber Amber List (moderate evidence)
CEP290
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Amber
Phenotypes
  • Congenital Obesity
  • ?Bardet-Biedl syndrome 14, 615991
Tags
Amber Amber List (moderate evidence)
CPE
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Amber
Phenotypes
  • obesity
Tags
Amber Amber List (moderate evidence)
INPP5E
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Mental retardation, truncal obesity, retinal dystrophy, and micropenis, 610156
  • Joubert syndrome 1, 213300
Tags
Amber Amber List (moderate evidence)
KSR2
3 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review
  • Expert Review Amber
Phenotypes
  • obesity
Tags
Amber Amber List (moderate evidence)
SH2B1
3 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
  • Expert Review Amber
Phenotypes
  • obesity
  • Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency
Tags
Amber Amber List (moderate evidence)
TUB
4 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • ?Retinal dystrophy and obesity, 616188
Tags
Red Red List (low evidence)
AKR1C2
3 reviews
2 red
Not set
Sources
  • Expert list
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Obesity, hyperphagia, and developmental delay
Tags
Red Red List (low evidence)
MAGEL2
1 review
1 red
Not set
Sources
  • Emory Genetics Laboratory
  • Expert list
Phenotypes
  • Congenital Obesity
Tags
Red Red List (low evidence)
MRAP2
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
  • Expert Review
  • Expert Review Red
Phenotypes
  • obesity
  • {?Obesity, susceptibility to, BMIQ18}
  • Prader-Willi syndrome
Tags
Red Red List (low evidence)
NR0B2
3 reviews
2 red
Not set
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Obesity, mild, early-onset, 601665
  • Congenital Obesity
Tags
Red Red List (low evidence)
PPARG
3 reviews
2 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert list
  • Expert Review Red
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Obesity, severe, 601665
  • [Obesity, resistance to]
  • Insulin resistance, severe, digenic, 604367
  • Lipodystrophy, familial partial, type 3, 604367
  • Carotid intimal medial thickness 1, 609338
  • {Diabetes, type 2}, 125853
Tags
Red Red List (low evidence)
TRIM32
4 reviews
1 green 1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Red
Phenotypes
  • ?Bardet-Biedl syndrome 11
  • 615988
Tags
Red Red List (low evidence)
WDPCP
3 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Red
Phenotypes
  • Congenital Obesity
Tags

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