NM_001134407.3(GRIN2A):c.2075_2116dup (p.Arg692_Met705dup) AND Landau-Kleffner syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 12, 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:: RCV002014111.6

Allele description [Variation Report for NM_001134407.3(GRIN2A):c.2075_2116dup (p.Arg692_Met705dup)]

NM_001134407.3(GRIN2A):c.2075_2116dup (p.Arg692_Met705dup)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

16p13.2

Genomic location:

Preferred name:

NM_001134407.3(GRIN2A):c.2075_2116dup (p.Arg692_Met705dup)

HGVS:

NC_000016.10:g.9822318_9822359dup
NG_011812.2:g.365398_365439dup
NM_000833.5:c.2075_2116dup
NM_001134407.3:c.2075_2116dupMANE SELECT
NM_001134408.2:c.2075_2116dup
NP_000824.1:p.Arg692_Met705dup
NP_001127879.1:p.Arg692_Met705dup
NP_001127880.1:p.Arg692_Met705dup
NC_000016.9:g.9916172_9916173insTCATGTACTGATGCATGTAGGGATAGTTATTCCGAATGTTTC
NC_000016.9:g.9916175_9916216dup

Links:

dbSNP: rs2141294782

NCBI 1000 Genomes Browser:

rs2141294782

Molecular consequence:

NM_000833.5:c.2075_2116dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001134407.3:c.2075_2116dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001134408.2:c.2075_2116dup - inframe_insertion - [Sequence Ontology: SO:0001821]

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
SCV002301869	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 12, 2022)	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

SCV002301869

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 12, 2022)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002301869.3

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: 1510767). This variant has been observed in individual(s) with GRIN2A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This variant, c.2075_2116dup, results in the insertion of 14 amino acid(s) of the GRIN2A protein (p.Arg692_Met705dup), but otherwise preserves the integrity of the reading frame.

#	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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