NM_002890.3(RASA1):c.3007G>A (p.Val1003Met) AND Capillary malformation-arteriovenous malformation syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 19, 2023
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:: RCV003760388.3

Allele description [Variation Report for NM_002890.3(RASA1):c.3007G>A (p.Val1003Met)]

NM_002890.3(RASA1):c.3007G>A (p.Val1003Met)

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.3007G>A (p.Val1003Met)

HGVS:

NC_000005.10:g.87389474G>A
NG_011650.1:g.126141G>A
NM_001364075.2:c.933+5570C>T
NM_002890.3:c.3007G>AMANE SELECT
NM_022650.3:c.2476G>A
NP_002881.1:p.Val1003Met
NP_072179.1:p.Val826Met
NC_000005.9:g.86685291G>A

Protein change:

V1003M

Molecular consequence:

NM_001364075.2:c.933+5570C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_002890.3:c.3007G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022650.3:c.2476G>A - missense variant - [Sequence Ontology: SO:0001583]

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

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
SCV004532010	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30120215, 35209959, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004532010

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 2023)

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

Perturbations of BMP/TGF-β and VEGF/VEGFR signalling pathways in non-syndromic sporadic brain arteriovenous malformations (BAVM).

Wang K, Zhao S, Liu B, Zhang Q, Li Y, Liu J, Shen Y, Ding X, Lin J, Wu Y, Yan Z, Chen J, Li X, Song X, Niu Y, Liu J, Chen W, Ming Y, Du R, Chen C, Long B, Zhang Y, et al.

J Med Genet. 2018 Oct;55(10):675-684. doi: 10.1136/jmedgenet-2017-105224. Epub 2018 Aug 17.

PubMed [citation]

PMID:: 30120215
PMCID:: PMC6161649

Mutational spectrum of syndromic genes in sporadic brain arteriovenous malformation.

Wang K, Zhang M, Zhao S, Xie Z, Zhang Y, Liu J, Zhang Y, Yang X, Wu N.

Chin Neurosurg J. 2022 Feb 24;8(1):4. doi: 10.1186/s41016-022-00270-8.

PubMed [citation]

PMID:: 35209959
PMCID:: PMC8867132

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004532010.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. This missense change has been observed in individual(s) with clinical features of RASA1-related conditions (PMID: 30120215, 35209959). This variant is present in population databases (rs758894954, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1003 of the RASA1 protein (p.Val1003Met).

#	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: Nov 10, 2024

ClinVar

Relating variation to medicine