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Intellectual disability

Gene: RAP1GDS1

Amber List (moderate evidence)

RAP1GDS1 (Rap1 GTPase-GDP dissociation stimulator 1)
EnsemblGeneIds (GRCh38): ENSG00000138698
EnsemblGeneIds (GRCh37): ENSG00000138698
OMIM: 179502, Gene2Phenotype
RAP1GDS1 is in 2 panels

4 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Promoting this gene from red to amber. There are now 4 families reported with the same splice site variant and a similar phenotype but intellectual disability is not seen in all probands. 2 of the families come from the same region. The ancestry of the other 2 families is not known. There is one additional case with a different 1bp deletion variant in RAP1GDS1 is also reported with ID as part of the phenotype. The expert reviewer proposes this gene should be green, and it also green on the PanelApp Australia Intellectual disability panel. Therefore the recommendation is for GREEN rating following GMS consideration and expert review.
Created: 10 Aug 2022, 11:21 a.m. | Last Modified: 10 Aug 2022, 11:21 a.m.
Panel Version: 3.1661
PMID: 33875846 - Bertoli-Avella et al 2021 - report 4 new patients with variants in RAP1GDS1 from 3 families. In two families the previously reported splice site variant c.1444-1G>A is found in a homozygous state. In one of these families the patient is reported to have motor delay and spastic paraplegia but no intellectual disability. In the other family, 2 siblings with this variant a phenotype that includes movement difficulties and hypotonia, and global developmental delay in one sibling. Exon 13 skipping was detected in blood mRNA from the patients. In the third family a different homozgyous variant (c.83delT, p.Leu28fs) and a phenotype that includes movement difficulties, hypotonia and global developmental delay. The ethnicity of the patients is not given.
Created: 10 Aug 2022, 11:14 a.m. | Last Modified: 10 Aug 2022, 11:14 a.m.
Panel Version: 3.1660

Dmitrijs Rots (RadboudUMC)

Green List (high evidence)

Additional cases (three with same splice variant, which segregates in one family) and one frameshift variant reported in PMID: 33875846. Cases seem to overlap those reported in PMID: 32431071.
Created: 30 Oct 2021, 11:54 a.m. | Last Modified: 30 Oct 2021, 11:56 a.m.
Panel Version: 3.1396

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability, developmental delay

Publications

Arina Puzriakova (Genomics England Curator)

Comment on list classification: The same variant identified in two families from the region, indicating a possible founder effect. Therefore rated Red as there is not currently enough evidence that other variants in the RAP1GDS1 gene are disease causing.
Created: 27 Aug 2020, 12:39 p.m. | Last Modified: 27 Aug 2020, 12:39 p.m.
Panel Version: 3.270
PMID: 32431071 (2020) - The same homozygous splice acceptor site variant was identified in four patients from two consanguineous Saudi families with ID, global DD, and hypotonia. The variant segregated with the disorder in both families and RT‐PCR analysis confirmed aberrant splicing and decreased mRNA expression, but no further functional studies were performed.
Created: 27 Aug 2020, 12:36 p.m. | Last Modified: 27 Aug 2020, 12:36 p.m.
Panel Version: 3.269

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; Global developmental delay; Hypotonia

Publications

Zornitza Stark (Australian Genomics)

I don't know

Four individuals from two consanguineous families, same homozygous splice site variant detected, borderline Red/Amber.
Sources: Literature
Created: 6 Jul 2020, 7:27 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; dysmorphic features

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Intellectual disability
  • dysmorphic features
Tags
founder-effect Q3_22_rating Q3_22_expert_review
OMIM
179502
Clinvar variants
Variants in RAP1GDS1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

10 Aug 2022, Gel status: 2

Added Tag, Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q3_22_rating tag was added to gene: RAP1GDS1. Tag Q3_22_expert_review tag was added to gene: RAP1GDS1.

10 Aug 2022, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).

27 Aug 2020, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag founder-effect tag was added to gene: RAP1GDS1.

27 Aug 2020, Gel status: 1

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: rap1gds1 has been classified as Red List (Low Evidence).

6 Jul 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: RAP1GDS1 was added gene: RAP1GDS1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RAP1GDS1 were set to 32431071 Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features Review for gene: RAP1GDS1 was set to AMBER