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Intellectual disability

Gene: HMGCL

Green List (high evidence)

HMGCL (3-hydroxymethyl-3-methylglutaryl-CoA lyase)
EnsemblGeneIds (GRCh38): ENSG00000117305
EnsemblGeneIds (GRCh37): ENSG00000117305
OMIM: 613898, Gene2Phenotype
HMGCL is in 10 panels

6 reviews

Arianna Tucci (Genomics England Curator)

Comment when marking as ready: Marked as green as ID is part of the phenotype
Created: 18 Dec 2017, 11:45 p.m.

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: promoted red to green- there is enough evidence to support ID phenotype
Created: 8 May 2018, 3:48 p.m.
Comment on phenotypes: added intellectual disability to phenotype
Created: 18 Dec 2017, 4:03 p.m.
Promoted from Amber to Green due to clinical feedback. Although ID is not a primary phenotype it s likely to present earlier with respect to metabolic decompensation, so worth including as Green rated gene on the the ID panel
Created: 18 Dec 2017, 4:02 p.m.
Confirmed disease gene in Developmental Disorders Genotype-Phenotype Database (DDG2P) for 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency. Grunert (2017) PMID: 28583327 reviewed the clinical presentation and outcome in a series of 37 patients with HMGCLD. 10 had no further metabolic decompensations after diagnosis, and 22 had at least one more metabolic crisis, most often associated with infections, especially gastroenteritis or respiratory tract infections. Half of the patients had normal cognitive development, and the remainder had psychomotor deficits of variable severity.
Created: 18 Dec 2017, 3:36 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HMG-CoA lyase deficiency, 246450; 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency; HMGCLD; intellectual disability

Publications

Caroline Wright (Sanger)

I don't know

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
3-HYDROXY-3-METHYLGLUTARYL-COENZYME A LYASE DEFICIENCY

Publications

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 6:35 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; Nijmegen_ID_candidates; GEL_ID_red_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 12:37 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Lu Raymond (university of cambridge )

I don't know

Richard Scott (Genomics England Curator)

Comment on list classification: Primary presentation not ID
Created: 7 Feb 2016, 9:06 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • HMG-CoA lyase deficiency, 246450
  • 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
  • HMGCLD
  • Intellectual disability
OMIM
613898
Clinvar variants
Variants in HMGCL
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

8 May 2018, Gel status: 3

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

5 Apr 2018, Gel status: 1

Clear Sources

Louise Daugherty (Genomics England Curator)

HMGCL Source: Expert Review Green was removed from gene: HMGCL

12 Mar 2018, Gel status: 4

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

4 Jan 2018, Gel status: 4

Added New Source, Set publications

Sarah Leigh (Genomics England Curator)

Expert Review Green was added to HMGCL. Panel: Intellectual disability Publications for gene HMGCL was set to ['28583327', '8617516', '9463337', '11129331']

7 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

7 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

HMGCL was created by ellenmcdonagh

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

HMGCL was added to Intellectual disabilitypanel. Sources: Expert Review Amber