Hereditary haemorrhagic telangiectasia

Gene: RASA1

Red List (low evidence)

RASA1 (RAS p21 protein activator 1)
EnsemblGeneIds (GRCh38): ENSG00000145715
EnsemblGeneIds (GRCh37): ENSG00000145715
OMIM: 139150, Gene2Phenotype
RASA1 is in 11 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: This gene will be flagged for review at the date of next GMS panel update (added 'for-review' tag).

Given the phenotypic overlap with HHT, these patients are likely to benefit from inclusion of RASA1 on a HHT panel, aiding detection rate and accurate diagnosis. Therefore, a rating upgrade from Red to Green should be considered.
Created: 2 Oct 2020, 2:49 p.m. | Last Modified: 2 Oct 2020, 2:49 p.m.
Panel Version: 2.5
PMID: 27081547 (2015) - In two individuals who were clinically suspected to have HHT due to epistaxis and dermal lesions such as telangiectases, sequencing revealed different heterozygous variants in RASA1. One variant was said to segregate in two additional family members, but no information regarding segregation of the other variant is provided.

PMID: 29891884 (2018) - At least six individuals with a RASA1 variant who were initially suspected for HHT - at least three of whom were genetically tested for this clinical indication but yielded negative results.

PMID: 32900839 (2020) - Two unrelated cases of RASA1-related capillary malformation-arteriovenous malformation syndrome mimicking hereditary haemorrhagic telangiectasia. Features that are typically characteristic of HHT included cerebral AVMs, epistaxi, and mucocutaneous and hepatic vascular lesions in a 28-year-old male; and cyanosis, mucocutaneous telangiectasias, pulmonary and hepatic AVMs in a 9-year-old girl. Both were suspected for HHT but genetic testing did not detect any variants in HHT-related genes, and instead revealed LoF variants in RASA1. Segregation analysis confirmed de novo occurrence in the male; however, the variant found in the female was also identified in three non-symptomatic relatives.
Created: 2 Oct 2020, 2:39 p.m. | Last Modified: 2 Oct 2020, 2:39 p.m.
Panel Version: 2.4

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

Phenotypes
Capillary malformation-arteriovenous malformation 1, 608354

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Consider upgrading due to possible phenotypic overlap along similar lines to EPHB4.
Created: 27 Jul 2020, 4:33 a.m. | Last Modified: 27 Jul 2020, 4:33 a.m.
Panel Version: 2.4

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Demoted to red due to expert input regarding the phenotype not being relevant to this panel.
Created: 14 Dec 2016, 9:56 a.m.

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Phenotypes not relevant to this panel according to expert reviewer Claire Shovlin (Imperial College London)
Created: 13 Dec 2016, 2:08 p.m.
Comment on phenotypes: Also associated with Parkes Weber syndrome, 608355; Basal cell carcinoma, somatic, 605462
Created: 13 Dec 2016, 2:07 p.m.
Comment on phenotypes: Also associated with Parkes Weber syndrome 608355 and Basal cell carcinoma, somatic 605462
Created: 13 Dec 2016, 2:04 p.m.
Comment when marking as ready: Associated with phenotypes in OMIM and as a confirmed Developmental Disorder Gene / G2P. At least three variants reported in Capillary malformation-arteriovenous malformation 608354
Created: 13 Dec 2016, 2:01 p.m.
Comment on phenotypes: Also associated with Basal cell carcinoma, somatic 605462
Created: 12 Dec 2016, 4:23 p.m.

Claire Shovlin (Imperial College London)

Red List (low evidence)

To the best of my knowledge, at present the RASA1 phenotypic spectrum is distinct from the HHT spectrum, displaying different types of telangiectasia and different patterns of arteriovenous malformations (PMID: 18446851) but this may change in the future.
Created: 13 Nov 2016, 11:17 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
Phenotypes
  • Capillary malformation-arteriovenous malformation 608354
Tags
for-review
OMIM
139150
Clinvar variants
Variants in RASA1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Oct 2020, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: RASA1.

2 Oct 2020, Gel status: 1

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: RASA1 were set to 18446851; 27081547

2 Oct 2020, Gel status: 1

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: rasa1 has been classified as Red List (Low Evidence).

13 Dec 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

13 Dec 2016, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for RASA1 were set to Capillary malformation-arteriovenous malformation 608354

13 Dec 2016, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for RASA1 were set to Hereditary hemorrhagic telangiectasia (HHT)

13 Dec 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

12 Dec 2016, Gel status: 4

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted to V1 (12th December 2016)

12 Dec 2016, Gel status: 4

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for RASA1 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

12 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

12 Dec 2016, Gel status: 3

Upload gene information

Sarah Leigh (Genomics England Curator)

RASA1 was added to Hereditary haemorrhagic telangiectasiapanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services

12 Dec 2016, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for RASA1 were set to Parkes Weber syndrome 608355; Hereditary hemorrhagic telangiectasia (HHT)

12 Dec 2016, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for RASA1 were set to 18446851; 27081547

12 Dec 2016, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for RASA1 were set to 18446851

30 Oct 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

RASA1 was added to Hereditary haemorrhagic telangiectasiapanel. Sources: Emory Genetics Laboratory

30 Oct 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

RASA1 was created by ellenmcdonagh