Cytopenia - NOT Fanconi anaemia

Gene: RAP1B

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.

Created: 6 Dec 2024, 12:24 p.m. | Last Modified: 6 Dec 2024, 12:25 p.m.

Panel Version: 3.36

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There are three unrelated cases with cytopenia and hence this gene can be promoted to green rating in the next GMS review.

This gene has been associated with relevant phenotype in Gene2Phenotype database (with 'limited' rating in the DD panel), but not yet been associated with phenotypes in OMIM.

Created: 6 Nov 2023, 4:30 p.m. | Last Modified: 6 Nov 2023, 4:30 p.m.

Panel Version: 3.10

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 32627184
• 35451551

Green List (high evidence)

New patient reported with mild intellectual disability, bicuspid aortic valve, dilation of aortic root and ascending aorta, hearing loss, and long‐standing thrombocytopenia with lymphopenia. Found to have a novel, missense mutation in RAP1B (p.Ala59Gly) - neighbouring amino acid to one of the previously reported variants.
Confirmed de novo and not in gnomAD

Created: 21 Aug 2023, 8:52 a.m. | Last Modified: 21 Aug 2023, 8:52 a.m.

Panel Version: 3.2

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Syndromic thrombocytopenia

Publications

• 35451551

I don't know

This gene is associated with a phenotype in Gene2Phenotype but not OMIM.

PMID: 32627184 describes 2 patients.
36 yo patient of non-consanguineous parents. Had unclear pancytopenia, multiple congenital malformations, mild intellectual disability, endocrine disorders (short stature with growth hormone deficiency), dysmorphism and other features. Parents and sibling unaffected.
13 yo of non-consanguineous parents with thrombocytopenia, multiple congenital anomalies and learning difficulties. He had normal developmental milestones, walk was achieved at 14 months and there was no speech delay. He attended mainstream school with auxiliary help because of learning difficulties with graphism, syntaxic comprehension, logical reasoning and attention deficit. Parents and siblings unaffected.

PMID: 26280580 describes another patient with variant in RAP1B. The clinical features can be found in supplementary table 2. The table lists ID, but doesn't say severity and lists a host of other features including short stature, facial dysmorphism and skeletal findings. Cytopenia is not a feature for this patient.

All 3 cases seem to have a very wide spectrum of differing phenotypes and therefore, this gene has been given an Amber rating until further evidence is available.
Sources: Literature

Created: 21 Dec 2020, 11:14 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Syndromic intellectual disability; cytopenia

Publications

• 32627184
• 26280580