NM_001134407.3(GRIN2A):c.2084G>A (p.Arg695Gln) AND Landau-Kleffner syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 20, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001253314.5

Allele description [Variation Report for NM_001134407.3(GRIN2A):c.2084G>A (p.Arg695Gln)]

NM_001134407.3(GRIN2A):c.2084G>A (p.Arg695Gln)

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.2084G>A (p.Arg695Gln)

HGVS:

NC_000016.10:g.9822348C>T
NG_011812.2:g.365407G>A
NM_000833.5:c.2084G>A
NM_001134407.3:c.2084G>AMANE SELECT
NM_001134408.2:c.2084G>A
NP_000824.1:p.Arg695Gln
NP_001127879.1:p.Arg695Gln
NP_001127880.1:p.Arg695Gln
NC_000016.9:g.9916205C>T
NG_011812.1:g.365407G>A
NM_000833.3:c.2084G>A
NM_000833.4:c.2084G>A

Protein change:

R695Q

Links:

dbSNP: rs1555491654

NCBI 1000 Genomes Browser:

rs1555491654

Molecular consequence:

NM_000833.5:c.2084G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001134407.3:c.2084G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001134408.2:c.2084G>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

Recent activity

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aspartyl/asparaginyl beta-hydroxylase-like isoform X1 [Caretta caretta]
aspartyl/asparaginyl beta-hydroxylase-like isoform X1 [Caretta caretta]
gi|2263235961|ref|XP_048696722.1|

Protein
Zebrafish DNA sequence from clone DKEY-11B8 in linkage group 20, complete sequen...
Zebrafish DNA sequence from clone DKEY-11B8 in linkage group 20, complete sequence
gi|31074660|emb|BX255905.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001428966	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 20, 2023)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003841626	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30544257, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001428966

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 20, 2023)

de novo

clinical testing

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

SCV003841626

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 23, 2023)

unknown

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	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Strehlow V, Heyne HO, Vlaskamp DRM, Marwick KFM, Rudolf G, de Bellescize J, Biskup S, Brilstra EH, Brouwer OF, Callenbach PMC, Hentschel J, Hirsch E, Kind PC, Mignot C, Platzer K, Rump P, Skehel PA, Wyllie DJA, Hardingham GE, van Ravenswaaij-Arts CMA, Lesca G, Lemke JR; et al.

Brain. 2019 Jan 1;142(1):80-92. doi: 10.1093/brain/awy304.

PubMed [citation]

PMID:: 30544257
PMCID:: PMC6308310

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001428966.4

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

Description

This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PS2, PS3_MOD, PS4_MOD, PM1_SUP, PM2_SUP

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV003841626.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000205689). The variant has been previously reported as de novo in a similarly affected individual (PMID: 30544257). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 5, 2023

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