NM_001353921.2(ARHGEF9):c.1536G>A (p.Trp512Ter) AND Developmental and epileptic encephalopathy, 8

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 5, 2021
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:: RCV000640877.6

Allele description [Variation Report for NM_001353921.2(ARHGEF9):c.1536G>A (p.Trp512Ter)]

NM_001353921.2(ARHGEF9):c.1536G>A (p.Trp512Ter)

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.1536G>A (p.Trp512Ter)

HGVS:

NC_000023.11:g.63638064C>T
NG_016975.1:g.152483G>A
NM_001173479.2:c.1356G>A
NM_001173480.2:c.1209G>A
NM_001330495.2:c.1452G>A
NM_001353921.2:c.1536G>AMANE SELECT
NM_001353922.2:c.1404G>A
NM_001353923.1:c.1554G>A
NM_001353924.2:c.1335G>A
NM_001353926.2:c.1335G>A
NM_001353927.2:c.1320G>A
NM_001353928.2:c.1383G>A
NM_001369030.1:c.1515G>A
NM_001369031.1:c.1515G>A
NM_001369032.1:c.1515G>A
NM_001369033.1:c.1452G>A
NM_001369034.1:c.1452G>A
NM_001369035.1:c.1452G>A
NM_001369036.1:c.1452G>A
NM_001369037.1:c.1452G>A
NM_001369038.1:c.1452G>A
NM_001369039.1:c.1335G>A
NM_001369040.1:c.1335G>A
NM_001369041.1:c.1320G>A
NM_001369042.1:c.1209G>A
NM_001369043.1:c.*173G>A
NM_001369044.1:c.*173G>A
NM_001369045.1:c.969G>A
NM_015185.3:c.1515G>A
NP_001166950.1:p.Trp452Ter
NP_001166951.1:p.Trp403Ter
NP_001317424.1:p.Trp484Ter
NP_001340850.1:p.Trp512Ter
NP_001340851.1:p.Trp468Ter
NP_001340852.1:p.Trp518Ter
NP_001340853.1:p.Trp445Ter
NP_001340855.1:p.Trp445Ter
NP_001340856.1:p.Trp440Ter
NP_001340857.1:p.Trp461Ter
NP_001355959.1:p.Trp505Ter
NP_001355960.1:p.Trp505Ter
NP_001355961.1:p.Trp505Ter
NP_001355962.1:p.Trp484Ter
NP_001355963.1:p.Trp484Ter
NP_001355964.1:p.Trp484Ter
NP_001355965.1:p.Trp484Ter
NP_001355966.1:p.Trp484Ter
NP_001355967.1:p.Trp484Ter
NP_001355968.1:p.Trp445Ter
NP_001355969.1:p.Trp445Ter
NP_001355970.1:p.Trp440Ter
NP_001355971.1:p.Trp403Ter
NP_001355974.1:p.Trp323Ter
NP_056000.1:p.Trp505Ter
NC_000023.10:g.62857944C>T
NM_015185.2:c.1515G>A

Protein change:

W323*

Links:

dbSNP: rs1556300769

NCBI 1000 Genomes Browser:

rs1556300769

Molecular consequence:

NM_001369043.1:c.*173G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369044.1:c.*173G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001173479.2:c.1356G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001173480.2:c.1209G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001330495.2:c.1452G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353921.2:c.1536G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353922.2:c.1404G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353923.1:c.1554G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353924.2:c.1335G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353926.2:c.1335G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353927.2:c.1320G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353928.2:c.1383G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369030.1:c.1515G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369031.1:c.1515G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369032.1:c.1515G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369033.1:c.1452G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369034.1:c.1452G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369035.1:c.1452G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369036.1:c.1452G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369037.1:c.1452G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369038.1:c.1452G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369039.1:c.1335G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369040.1:c.1335G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369041.1:c.1320G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369042.1:c.1209G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369045.1:c.969G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_015185.3:c.1515G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 8 (DEE8)
Synonyms:: HYPEREKPLEXIA AND EPILEPSY; Early infantile epileptic encephalopathy 8
Identifiers:: MONDO: MONDO:0010375; MedGen: C1845102; Orphanet: 163985; Orphanet: 2076; OMIM: 300607

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000762481	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000762481

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 5, 2021)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000762481.4

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

Description

This variant has not been reported in the literature in individuals with ARHGEF9-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the ARHGEF9 gene (p.Trp505*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 12 amino acids of the ARHGEF9 protein. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. 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.

#	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 20, 2024

ClinVar

Relating variation to medicine