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NM_001353921.2(ARHGEF9):c.889C>T (p.Arg297Cys) AND Inborn genetic diseases

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 7, 2018
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:
RCV002447235.2

Allele description [Variation Report for NM_001353921.2(ARHGEF9):c.889C>T (p.Arg297Cys)]

NM_001353921.2(ARHGEF9):c.889C>T (p.Arg297Cys)

Gene:
ARHGEF9:Cdc42 guanine nucleotide exchange factor 9 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq11.1
Genomic location:
Preferred name:
NM_001353921.2(ARHGEF9):c.889C>T (p.Arg297Cys)
HGVS:
  • NC_000023.11:g.63674094G>A
  • NG_016975.1:g.116453C>T
  • NM_001173479.2:c.709C>T
  • NM_001173480.2:c.562C>T
  • NM_001330495.2:c.805C>T
  • NM_001353921.2:c.889C>TMANE SELECT
  • NM_001353922.2:c.889C>T
  • NM_001353923.1:c.907C>T
  • NM_001353924.2:c.688C>T
  • NM_001353926.2:c.688C>T
  • NM_001353927.2:c.805C>T
  • NM_001353928.2:c.868C>T
  • NM_001369030.1:c.868C>T
  • NM_001369031.1:c.868C>T
  • NM_001369032.1:c.868C>T
  • NM_001369033.1:c.805C>T
  • NM_001369034.1:c.805C>T
  • NM_001369035.1:c.805C>T
  • NM_001369036.1:c.805C>T
  • NM_001369037.1:c.805C>T
  • NM_001369038.1:c.805C>T
  • NM_001369039.1:c.688C>T
  • NM_001369040.1:c.688C>T
  • NM_001369041.1:c.805C>T
  • NM_001369042.1:c.562C>T
  • NM_001369043.1:c.805C>T
  • NM_001369044.1:c.805C>T
  • NM_001369045.1:c.454C>T
  • NM_015185.3:c.868C>T
  • NP_001166950.1:p.Arg237Cys
  • NP_001166951.1:p.Arg188Cys
  • NP_001317424.1:p.Arg269Cys
  • NP_001340850.1:p.Arg297Cys
  • NP_001340851.1:p.Arg297Cys
  • NP_001340852.1:p.Arg303Cys
  • NP_001340853.1:p.Arg230Cys
  • NP_001340855.1:p.Arg230Cys
  • NP_001340856.1:p.Arg269Cys
  • NP_001340857.1:p.Arg290Cys
  • NP_001355959.1:p.Arg290Cys
  • NP_001355960.1:p.Arg290Cys
  • NP_001355961.1:p.Arg290Cys
  • NP_001355962.1:p.Arg269Cys
  • NP_001355963.1:p.Arg269Cys
  • NP_001355964.1:p.Arg269Cys
  • NP_001355965.1:p.Arg269Cys
  • NP_001355966.1:p.Arg269Cys
  • NP_001355967.1:p.Arg269Cys
  • NP_001355968.1:p.Arg230Cys
  • NP_001355969.1:p.Arg230Cys
  • NP_001355970.1:p.Arg269Cys
  • NP_001355971.1:p.Arg188Cys
  • NP_001355972.1:p.Arg269Cys
  • NP_001355973.1:p.Arg269Cys
  • NP_001355974.1:p.Arg152Cys
  • NP_056000.1:p.Arg290Cys
  • NC_000023.10:g.62893974G>A
  • NC_000023.10:g.62893974G>A
  • NM_015185.2:c.868C>T
Protein change:
R152C
Links:
dbSNP: rs2050115619
NCBI 1000 Genomes Browser:
rs2050115619
Molecular consequence:
  • NM_001173479.2:c.709C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001173480.2:c.562C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330495.2:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353921.2:c.889C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353922.2:c.889C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353923.1:c.907C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353924.2:c.688C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353926.2:c.688C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353927.2:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353928.2:c.868C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369030.1:c.868C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369031.1:c.868C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369032.1:c.868C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369033.1:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369034.1:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369035.1:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369036.1:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369037.1:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369038.1:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369039.1:c.688C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369040.1:c.688C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369041.1:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369042.1:c.562C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369043.1:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369044.1:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369045.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015185.3:c.868C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002682177Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Mar 7, 2018) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

ARHGEF9 mutations in epileptic encephalopathy/intellectual disability: toward understanding the mechanism underlying phenotypic variation.

Wang JY, Zhou P, Wang J, Tang B, Su T, Liu XR, Li BM, Meng H, Shi YW, Yi YH, He N, Liao WP.

Neurogenetics. 2018 Jan;19(1):9-16. doi: 10.1007/s10048-017-0528-2. Epub 2017 Nov 13.

PubMed [citation]
PMID:
29130122

Details of each submission

From Ambry Genetics, SCV002682177.2

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

Description

The p.R290C variant (also known as c.868C>T), located in coding exon 6 of the ARHGEF9 gene, results from a C to T substitution at nucleotide position 868. The arginine at codon 290 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration co-segregated with disease in one family with four male siblings who all had refractory epileptic encephalopathy and carried this alteration. The alteration was determined to be inherited from the unaffected mother (Wang JY et al. Neurogenetics, 2018 Jan;19:9-16). Internal structural analysis indicates that this alteration is structurally deleterious (Ambry internal data; Xiang S et al. J. Mol. Biol., 2006 May;359:35-46). A different alteration located at the same position, p.R290H (c.869G>A), was identified in a male with seizures and intellectual disability (Lemke JR et al. Epilepsia, 2012 Aug;53:1387-98). The p.R290H variant was shown to impair proper function of the ARHGEF9 protein (Papadopoulos T et al. J. Biol. Chem., 2015 Mar;290:8256-70; Long P et al. Front Mol Neurosci, 2015 Jan;8:83). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024