NM_001134407.3(GRIN2A):c.3268G>A (p.Val1090Met) AND Landau-Kleffner syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 8, 2019
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:: RCV001059006.6

Allele description [Variation Report for NM_001134407.3(GRIN2A):c.3268G>A (p.Val1090Met)]

NM_001134407.3(GRIN2A):c.3268G>A (p.Val1090Met)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.2

Genomic location:

Preferred name:

NM_001134407.3(GRIN2A):c.3268G>A (p.Val1090Met)

HGVS:

NC_000016.10:g.9764276C>T
NG_011812.2:g.423479G>A
NM_000833.5:c.3268G>A
NM_001134407.3:c.3268G>AMANE SELECT
NM_001134408.2:c.3268G>A
NP_000824.1:p.Val1090Met
NP_001127879.1:p.Val1090Met
NP_001127880.1:p.Val1090Met
NC_000016.9:g.9858133C>T
NG_011812.1:g.423479G>A
NM_000833.3:c.3268G>A
NM_000833.4:c.3268G>A

Protein change:

V1090M

Links:

dbSNP: rs1320797353

NCBI 1000 Genomes Browser:

rs1320797353

Molecular consequence:

NM_000833.5:c.3268G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001134407.3:c.3268G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001134408.2:c.3268G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001223609	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 8, 2019)	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

SCV001223609

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 8, 2019)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001223609.5

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GRIN2A-related conditions. 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. This sequence change replaces valine with methionine at codon 1090 of the GRIN2A protein (p.Val1090Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine.

#	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 28, 2024

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