U.S. flag

An official website of the United States government

NM_002072.5(GNAQ):c.626A>G (p.Gln209Arg) AND Sturge-Weber syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 3, 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:
RCV003458165.1

Allele description [Variation Report for NM_002072.5(GNAQ):c.626A>G (p.Gln209Arg)]

NM_002072.5(GNAQ):c.626A>G (p.Gln209Arg)

Gene:
GNAQ:G protein subunit alpha q [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q21.2
Genomic location:
Preferred name:
NM_002072.5(GNAQ):c.626A>G (p.Gln209Arg)
HGVS:
  • NC_000009.12:g.77794572T>C
  • NG_027904.2:g.241732A>G
  • NM_002072.5:c.626A>GMANE SELECT
  • NP_002063.2:p.Gln209Arg
  • LRG_1110t1:c.626A>G
  • LRG_1110:g.241732A>G
  • LRG_1110p1:p.Gln209Arg
  • NC_000009.11:g.80409488T>C
  • NM_002072.4:c.626A>G
Protein change:
Q209R
Links:
dbSNP: rs121913492
NCBI 1000 Genomes Browser:
rs121913492
Molecular consequence:
  • NM_002072.5:c.626A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Sturge-Weber syndrome (SWS)
Synonyms:
Encephalotrigeminal angiomatosis; Fourth phacomatosis; Meningeal capillary angiomatosis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008501; MedGen: C0038505; Orphanet: 3205; OMIM: 185300

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004176949Clinical Genomics Laboratory, Washington University in St. Louis
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Nov 3, 2023)
somaticclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedsomaticyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Clinical Genomics Laboratory, Washington University in St. Louis, SCV004176949.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

A GNAQ c.626A>G (p.Gln209Arg) variant was identified at an allelic fraction consistent with somatic origin. The GNAQ c.626A>G (p.Gln209Arg) variant has been described in numerous patients affected with Sturge-Weber syndrome, choroidal hemangioma, non-syndromic capillary malformations, and cherry angiomas (Francis JH et al., PMID: 30537484; Le Guin CHD et al., PMID: 31336681; Galeffi F et al., PMID: 35635655; Klebanov N et al., PMID: 30601876). This variant has been reported in eleven cases in the cancer database COSMIC (Genomic Mutation ID: COSV54108414) and is absent from the general population (gnomAD v.3.1.2), indicating it is not a common variant. It lies within the GTP-binding site of the ras-like domain of GNAQ, which is defined as a critical functional domain (Markby DW et al., PMID: 8266082; Van Raamsdonk CD et al., PMID: 19078957). Computational predictors indicate that the GNAQ c.626A>G (p.Gln209Arg) variant is damaging, evidence that correlates with impact on GNAQ function. In support of this prediction, functional studies show increased activation of mitogen-activated protein kinase (MAPK) signaling pathways and associated downstream transcriptional programs in microvascular endothelial cells (Galeffi F et al., PMID: 35635655). The GNAQ gene is a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease. Other variants in the same codon, p.Gln209His, p.Gln209Leu and p.Gln209Pro, have been reported in multiple individuals and are considered pathogenic (Van Raamsdonk CD et al., PMID: 19078957; ClinVar IDs: 1172602, 1172601, 375955, 375957). Based on an internally-developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868), the GNAQ c.626A>G (p.Gln209Arg) variant is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1somaticyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 30, 2023