Cytopenia - NOT Fanconi anaemia
Gene: RPA1

RPA1 (replication protein A1)
EnsemblGeneIds (GRCh38): ENSG00000132383
EnsemblGeneIds (GRCh37): ENSG00000132383
OMIM: 179835, Gene2Phenotype
RPA1 is in 2 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

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 imprinted' following NHS Genomic Medicine Service approval.
Created: 1 Feb 2023, 8:15 a.m. | Last Modified: 1 Feb 2023, 8:15 a.m.

Panel Version: 2.3

Created: 1 Feb 2023, 8:15 a.m.
Last Modified: 1 Feb 2023, 8:15 a.m.
Panel version: 2.3

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Despite the heterogenous phenotypes observed, there are sufficient cases (3) with hematopoietic manifestations to warrant a green rating on this panel at the next GMS review.
Created: 6 Apr 2022, 10:55 a.m. | Last Modified: 6 Apr 2022, 10:55 a.m.

Panel Version: 1.61

Sharma et al., 2022 (PMID: 34767620) report four unrelated individuals with three distinct heterozygous GOF variants in the RPA1 gene. Clinical presentation was variable but mainly affecting the hematopoietic or pulmonary systems. Patient 1 presented with pancytopenia, hypoplastic bone marrow, and the classic DKC triad; Patient 2 developed myelodysplastic syndrome (MDS) with excess blasts, as well as mildly restrictive lung disease which progressed to pulmonary fibrosis (PF) following several HSCT-related complications; Patient 3 had adult-onset idiopathic PF with a positive family history (although segregation analysis was not possible); Patient 4 presented at birth with T- and B-cell lymphopenia and hypogammaglobulinemia. All probands demonstrated short telomere lengths.
Created: 6 Apr 2022, 10:45 a.m. | Last Modified: 6 Apr 2022, 10:45 a.m.

Panel Version: 1.58

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, OMIM:619767

Publications

34767620

Created: 6 Apr 2022, 10:45 a.m.
Last Modified: 6 Apr 2022, 10:45 a.m.
Panel version: 1.58

Dmitrijs Rots (Children's Clinical University Hospital)

Green List (high evidence)

4 cases with gain of function mutations with "including bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopenia, pulmonary fibrosis, or skin manifestations." described in
https://doi.org/10.1182/blood.2021011980
Sources: Literature
Created: 12 Nov 2021, 7:21 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
bone marrow failure; T- and B-cell lymphopenia; pulmonary fibrosis; skin manifestations.

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Created: 12 Nov 2021, 7:21 p.m.

Panel version: 1.43

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

NHS GMS
Expert Review Green

Phenotypes

Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, OMIM:619767

OMIM

179835

Clinvar variants

Variants in RPA1

Penetrance

Incomplete

Publications

34767620

Mode of Pathogenicity

Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Panels with this gene

History Filter Activity

1 Feb 2023, Gel status: 3

Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_22_rating was removed from gene: RPA1.

1 Feb 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source Expert Review Green was added to RPA1. Source NHS GMS was added to RPA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

6 Apr 2022, Gel status: 2