NM_002890.3(RASA1):c.1332+2T>G AND Capillary malformation-arteriovenous malformation syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 10, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001216670.16

Allele description [Variation Report for NM_002890.3(RASA1):c.1332+2T>G]

NM_002890.3(RASA1):c.1332+2T>G

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

5q14.3

Genomic location:

Preferred name:

NM_002890.3(RASA1):c.1332+2T>G

HGVS:

NC_000005.10:g.87353237T>G
NG_011650.1:g.89904T>G
NM_001364075.2:c.934-40442A>C
NM_002890.3:c.1332+2T>GMANE SELECT
NM_022650.3:c.801+2T>G
NC_000005.9:g.86649054T>G
NM_002890.2:c.1332+2T>G

Links:

dbSNP: rs1759410564

NCBI 1000 Genomes Browser:

rs1759410564

Molecular consequence:

NM_001364075.2:c.934-40442A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_002890.3:c.1332+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_022650.3:c.801+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Capillary malformation-arteriovenous malformation syndrome
Synonyms:: Capillary malformation-arteriovenous malformation
Identifiers:: MONDO: MONDO:0012016; MedGen: C1842180; OMIM: PS608354

Recent activity

Clear Turn Off Turn On

ribosomal protein L32, partial (chloroplast) [Saxifraga wahlenbergii]
ribosomal protein L32, partial (chloroplast) [Saxifraga wahlenbergii]
gi|2552397929|gb|WKV22649.1|

Protein
JGI_CABA3977.fwd NIH_XGC_tropKid1 Xenopus tropicalis cDNA clone IMAGE:7748653 5'...
JGI_CABA3977.fwd NIH_XGC_tropKid1 Xenopus tropicalis cDNA clone IMAGE:7748653 5', mRNA sequence
gi|59255208|gnl|dbEST|27759747|gb|D 17.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001388478	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 10, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 24038909, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001388478

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 10, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation.

Revencu N, Boon LM, Mendola A, Cordisco MR, Dubois J, Clapuyt P, Hammer F, Amor DJ, Irvine AD, Baselga E, Dompmartin A, Syed S, Martin-Santiago A, Ades L, Collins F, Smith J, Sandaradura S, Barrio VR, Burrows PE, Blei F, Cozzolino M, Brunetti-Pierri N, et al.

Hum Mutat. 2013 Dec;34(12):1632-41. doi: 10.1002/humu.22431. Epub 2013 Oct 10.

PubMed [citation]

PMID:: 24038909

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001388478.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RASA1 are known to be pathogenic (PMID: 24038909). This variant has been observed to be de novo in an individual affected with clinical features of RASA1-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 9 of the RASA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine