NM_002890.3(RASA1):c.475_476del (p.Leu159fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 30, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000200157.13

Allele description

NM_002890.3(RASA1):c.475_476del (p.Leu159fs)

Gene:

RASA1:RAS p21 protein activator 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

5q14.3

Genomic location:

Preferred name:

NM_002890.3(RASA1):c.475_476del (p.Leu159fs)

HGVS:

NC_000005.10:g.87268922CT[2]
NG_011650.1:g.5589CT[2]
NM_002890.2:c.475_476del
NM_002890.3:c.475_476delMANE SELECT
NP_002881.1:p.Leu159fs
NC_000005.9:g.86564739CT[2]
NC_000005.9:g.86564739_86564740del
NM_002890.2:c.475_476delCT
p.L159Gfs*20
p.Leu159fs

Protein change:

L159fs

Links:

OMIM: 139150.0004; dbSNP: rs797044451

NCBI 1000 Genomes Browser:

rs797044451

Molecular consequence:

NM_002890.3:c.475_476del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000250643	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 30, 2023)	germline	clinical testing	Citation Link,
SCV000884450	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Pathogenic (Jun 26, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000250643

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 30, 2023)

germline

clinical testing

Citation Link,

SCV000884450

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Pathogenic
(Jun 26, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000250643.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 14639529, 29891884, 31263281)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000884450.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The RASA1 c.475_476delCT; p.Leu159fs variant (rs797044451), is reported in the literature in one family and two individuals affected with capillary malformations and/or arteriovenous malformations (Eerola 2003 and Revencu 2013). This variant is classified as pathogenic in ClinVar (Variation ID: 15999), and it is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database). This variant causes a frameshift by deleting two nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Truncating, loss-of-function variants in RASA1 are an established mechanism of disease. Therefore, based on available information, this variant is considered pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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