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Intellectual disability

Gene: ADAM22

Amber List (moderate evidence)

ADAM22 (ADAM metallopeptidase domain 22)
EnsemblGeneIds (GRCh38): ENSG00000008277
EnsemblGeneIds (GRCh37): ENSG00000008277
OMIM: 603709, Gene2Phenotype
ADAM22 is in 2 panels

2 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

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.
Created: 11 Feb 2021, 10:19 a.m. | Last Modified: 11 Feb 2021, 10:19 a.m.
Panel Version: 3.778
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least two variants reported, in two unrelated cases with biallelic variants together with a knock-in mouse model (Adam22 ΔC5/ΔC5), which has lethal epilepsy, together with other supportive functional studies.
Created: 2 Feb 2021, 12:46 p.m. | Last Modified: 2 Feb 2021, 12:46 p.m.
Panel Version: 3.751

Rebecca Foulger (Genomics England curator)

Comment on list classification: Set rating as Amber: 2 unrelated families with ID as part of the phenotype (PMID:27066583 and 30237576).
Created: 4 May 2020, 4:28 p.m. | Last Modified: 4 May 2020, 4:28 p.m.
Panel Version: 3.35
PMID:27066583. Muona et al., 2016 report a Finnish proband-parent-trio with intractable seizures and ID. Compound het variants c.1202G>A, p.Cys401Tyr and c.2396delG, p.Ser799IlefsTer96 were found in ADAM22. Functional assays showed that mutant proteins failed to form the LGI1-ADAM22 ligand-receptor complex. The variants are unlikely to be full LOF.
Created: 4 May 2020, 4:27 p.m. | Last Modified: 4 May 2020, 4:27 p.m.
Panel Version: 3.34
PMID:30237576 (Maddirevula et al., 2019) searched their database of clinical exomes for homozygous variants and report an 18 year old male with Arg860* variant and recurrent seizures (Supplementary Table). His development was normal until 5 months when he had a slower gain of milestones. He has ID with severely delayed speech. Family history revealed ID and epilepsy in his old brother and in wider family.
Created: 4 May 2020, 4:27 p.m. | Last Modified: 4 May 2020, 4:27 p.m.
Panel Version: 3.34
Added ADAM22 to ID panel based on literature curation for Epilepsy phenotype. Patients in PMID:27066583 (Finnish trio with compound het ADAM22 variants in the proband) and PMID:30237576 (18 year old male with Arg860* variant) both report ID alongside epilepsy.
Sources: Literature
Created: 4 May 2020, 4:23 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • ?Epileptic encephalopathy, early infantile, 61 OMIM:617933
  • developmental and epileptic encephalopathy, 61 MONDO:0033370
Tags
for-review
OMIM
603709
Clinvar variants
Variants in ADAM22
Penetrance
None
Publications
Panels with this gene

History Filter Activity

11 Feb 2021, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: adam22 has been classified as Amber List (Moderate Evidence).

2 Feb 2021, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: ADAM22 were changed from to ?Epileptic encephalopathy, early infantile, 61 OMIM:617933; developmental and epileptic encephalopathy, 61 MONDO:0033370

2 Feb 2021, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

Tag for-review tag was added to gene: ADAM22.

4 May 2020, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: adam22 has been classified as Amber List (Moderate Evidence).

4 May 2020, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications

Rebecca Foulger (Genomics England curator)

gene: ADAM22 was added gene: ADAM22 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAM22 were set to 27066583; 30237576