NM_001134407.3(GRIN2A):c.2793del (p.Met932fs) AND Landau-Kleffner syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 28, 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:: RCV000822453.7

Allele description [Variation Report for NM_001134407.3(GRIN2A):c.2793del (p.Met932fs)]

NM_001134407.3(GRIN2A):c.2793del (p.Met932fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

16p13.2

Genomic location:

Preferred name:

NM_001134407.3(GRIN2A):c.2793del (p.Met932fs)

HGVS:

NC_000016.10:g.9764751del
NG_011812.2:g.423004del
NM_000833.5:c.2793del
NM_001134407.3:c.2793delMANE SELECT
NM_001134408.2:c.2793del
NP_000824.1:p.Met932fs
NP_001127879.1:p.Met932fs
NP_001127880.1:p.Met932fs
NC_000016.9:g.9858608del
NG_011812.1:g.423004del
NM_000833.4:c.2793delC

Protein change:

M932fs

Links:

dbSNP: rs1596377439

NCBI 1000 Genomes Browser:

rs1596377439

Molecular consequence:

NM_000833.5:c.2793del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001134407.3:c.2793del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001134408.2:c.2793del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000963255	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 28, 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

SCV000963255

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 28, 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, SCV000963255.4

#	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. ClinVar contains an entry for this variant (Variation ID: 664368). 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.Met932Trpfs*10) in the GRIN2A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 533 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

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