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

10 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

  • David Hunt (Wessex Clinical Genetics Service)

    Group: Other NHS organisation
    Workplace: NHS clinical service

  • Zornitza Stark (Australian Genomics)

    Group: Other
    Workplace: Other clinical service

  • Ivone Leong (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Ismaa Farooqi (University of Cambridge)

    Group: GeCIP domain
    Workplace: Research lab

  • Arina Puzriakova (Genomics England Curator)

    Group: Other
    Workplace: Other

45 Entities

45 reviewed, 29 green

List Entity Reviews Mode of inheritance Details
45 Entitiess
Green Green List (high evidence)
ALMS1
5 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Alstrom syndrome, OMIM: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, OMIM:600151
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
  • Bardet-Biedl syndrome 1 OMIM:209900
  • Bardet-Biedl syndrome 1 MONDO:0008854
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, OMIM: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, OMIM: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, OMIM: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, OMIM:615982
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, OMIM:615983
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, OMIM:615984
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, OMIM:615986
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, OMIM: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, OMIM:103580
  • Pseudohypoparathyroidism Ib, OMIM:603233
  • Pseudohypoparathyroidism Ic, OMIM: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, OMIM:614962
Tags
Green Green List (high evidence)
LEPR
3 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, OMIM:614963
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
  • Obesity (BMIQ20), OMIM:618406
  • {Obesity, resistence to (BMIQ20)}, OMIM:618306
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, OMIM: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, OMIM:615990
Tags
Green Green List (high evidence)
MYT1L
4 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
  • Expert Review Green
  • Literature
Phenotypes
  • obesity
  • Mental retardation, autosomal dominant 39, OMIM:616521
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, OMIM:613886
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}, OMIM:612362
  • Obesity with impaired prohormone processing, 600955
  • {Obesity, susceptibility to, BMIQ12}, OMIM:612362
Tags
Green Green List (high evidence)
PHF6
5 reviews
2 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Borjeson-Forssman-Lehmann syndrome, OMIM:301900
Tags
  • Q4_21_MOI
Green Green List (high evidence)
POMC
3 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}, OMIM:601665
  • Obesity, adrenal insufficiency, and red hair due to POMC deficiency, OMIM:609734
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, OMIM: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
  • 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, OMIM:615985
Tags
Green Green List (high evidence)
VPS13B
4 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert list
  • Expert Review Green
Phenotypes
  • Obesity
  • Cohen syndrome, OMIM:216550
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, OMIM:615991
Tags
Amber Amber List (moderate evidence)
CPE
4 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Amber
Phenotypes
  • Intellectual developmental disorder and hypogonadotropic hypogonadism, OMIM:619326
Tags
  • Q3_21_rating
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, OMIM:610156
Tags
Amber Amber List (moderate evidence)
KIDINS220
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Spastic paraplegia, intellectual disability, nystagmus, and obesity, OMIM:617296
Tags
  • Q4_21_rating
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)
PGM2L1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Neurodevelopmental disorder
Tags
  • Q3_21_rating
Amber Amber List (moderate evidence)
PHIP
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Obesity
  • global developmental delay
  • intellectual disability
  • behavioral abnormality
  • dysmorphic facies
Tags
  • Q3_21_NHS_review
  • Q3_21_rating
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, MONDO:0017994
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, OMIM: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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