NM_001134407.3(GRIN2A):c.2833_2834insTTCAG (p.Asp945fs) AND Landau-Kleffner syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 30, 2022
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:: RCV001380855.7

Allele description [Variation Report for NM_001134407.3(GRIN2A):c.2833_2834insTTCAG (p.Asp945fs)]

NM_001134407.3(GRIN2A):c.2833_2834insTTCAG (p.Asp945fs)

Gene:

GRIN2A:glutamate ionotropic receptor NMDA type subunit 2A [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

16p13.2

Genomic location:

Preferred name:

NM_001134407.3(GRIN2A):c.2833_2834insTTCAG (p.Asp945fs)

HGVS:

NC_000016.10:g.9764714_9764715insACTGA
NG_011812.2:g.423044_423045insTTCAG
NM_000833.5:c.2833_2834insTTCAG
NM_001134407.3:c.2833_2834insTTCAGMANE SELECT
NM_001134408.2:c.2833_2834insTTCAG
NP_000824.1:p.Asp945fs
NP_001127879.1:p.Asp945fs
NP_001127880.1:p.Asp945fs
NC_000016.9:g.9858567_9858568insCTGAA
NC_000016.9:g.9858571_9858572insACTGA

Protein change:

D945fs

Links:

dbSNP: rs2141136701

NCBI 1000 Genomes Browser:

rs2141136701

Molecular consequence:

NM_000833.5:c.2833_2834insTTCAG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001134407.3:c.2833_2834insTTCAG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001134408.2:c.2833_2834insTTCAG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Landau-Kleffner syndrome (FESD)
Synonyms:: Acquired aphasia with convulsive disorder; Acquired epileptiform aphasia; APHASIA, ACQUIRED, WITH EPILEPSY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009509; MedGen: C0282512; Orphanet: 1945; Orphanet: 725; Orphanet: 98818; OMIM: 245570

Recent activity

Clear Turn Off Turn On

Culicomorpha alanyl tRNA synthetase (AATS) gene, partial cds.
Culicomorpha alanyl tRNA synthetase (AATS) gene, partial cds.
PopSet: 1044327580

PopSet

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
SCV001579040	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 30, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29961510, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001579040

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 30, 2022)

germline

clinical testing

PubMed (2)
[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

A Novel Phenotype in a Previously Described Epilepsy-Aphasia Disorder.

Fine AL, Wong-Kisiel LC, Wirrell EC.

Semin Pediatr Neurol. 2018 Jul;26:21-24. doi: 10.1016/j.spen.2018.04.004.

PubMed [citation]

PMID:: 29961510

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001579040.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GRIN2A protein in which other variant(s) (p.Trp1271*) have been determined to be pathogenic (PMID: 29961510). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1069106). This variant has not been reported in the literature in individuals affected with GRIN2A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp945Valfs*18) in the GRIN2A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 520 amino acid(s) of the GRIN2A protein.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine