NM_000834.5(GRIN2B):c.2065G>A (p.Gly689Ser) AND Developmental and epileptic encephalopathy, 27

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 23, 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:: RCV001004753.4

Allele description [Variation Report for NM_000834.5(GRIN2B):c.2065G>A (p.Gly689Ser)]

NM_000834.5(GRIN2B):c.2065G>A (p.Gly689Ser)

Gene:

GRIN2B:glutamate ionotropic receptor NMDA type subunit 2B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.1

Genomic location:

Preferred name:

NM_000834.5(GRIN2B):c.2065G>A (p.Gly689Ser)

HGVS:

NC_000012.12:g.13571910C>T
NG_031854.2:g.415103G>A
NM_000834.5:c.2065G>AMANE SELECT
NP_000825.2:p.Gly689Ser
NC_000012.11:g.13724844C>T
NM_000834.3:c.2065G>A

Protein change:

G689S

Links:

Molecular consequence:

NM_000834.5:c.2065G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 27 (DEE27)
Synonyms:: Epileptic encephalopathy, early infantile, 27
Identifiers:: MONDO: MONDO:0014505; MedGen: C4015316; Orphanet: 3451; OMIM: 616139

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001164232	Génétique des Maladies du Développement, Hospices Civils de Lyon	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 3, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005201017	Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 23, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28377535, 30842224, 34212862, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001164232

Génétique des Maladies du Développement, Hospices Civils de Lyon

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 3, 2018)

unknown

clinical testing

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

SCV005201017

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 23, 2023)

germline

clinical testing

PubMed (4)
[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	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

GRIN2B encephalopathy: novel findings on phenotype, variant clustering, functional consequences and treatment aspects.

Platzer K, Yuan H, Schütz H, Winschel A, Chen W, Hu C, Kusumoto H, Heyne HO, Helbig KL, Tang S, Willing MC, Tinkle BT, Adams DJ, Depienne C, Keren B, Mignot C, Frengen E, Strømme P, Biskup S, Döcker D, Strom TM, Mefford HC, et al.

J Med Genet. 2017 Jul;54(7):460-470. doi: 10.1136/jmedgenet-2016-104509. Epub 2017 Apr 4.

PubMed [citation]

PMID:: 28377535
PMCID:: PMC5656050

Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing.

Iwama K, Mizuguchi T, Takeshita E, Nakagawa E, Okazaki T, Nomura Y, Iijima Y, Kajiura I, Sugai K, Saito T, Sasaki M, Yuge K, Saikusa T, Okamoto N, Takahashi S, Amamoto M, Tomita I, Kumada S, Anzai Y, Hoshino K, Fattal-Valevski A, Shiroma N, et al.

J Med Genet. 2019 Jun;56(6):396-407. doi: 10.1136/jmedgenet-2018-105775. Epub 2019 Mar 6.

PubMed [citation]

PMID:: 30842224

See all PubMed Citations (4)

Details of each submission

From Génétique des Maladies du Développement, Hospices Civils de Lyon, SCV001164232.1

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

#	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

From Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, SCV005201017.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	clinical testing	PubMed (4)

Description

PS3: In vitro functional studies showed this variant impacts protein function (PMID: 34212862). PS4 (applied as moderate) reported in various publications. PM1: Located in a mutational hot spot and/or critical and well-established functional domain (PMID: 28377535). PM2: Absent in the population databases. PM6: De novo without the confirmation of paternity and maternity PP2: GRIN2b has a low rate of benign missense variation (Z score: 7.34) PP3: In silico scores predict the variant to be damaging to the protein function. PP5: Reported as pathogenic variant in ClinVar.

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

Last Updated: Oct 20, 2024

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