NM_000834.5(GRIN2B):c.895A>G (p.Ile299Val) AND multiple conditions

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 28, 2023
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:: RCV001270385.4

Allele description [Variation Report for NM_000834.5(GRIN2B):c.895A>G (p.Ile299Val)]

NM_000834.5(GRIN2B):c.895A>G (p.Ile299Val)

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.895A>G (p.Ile299Val)

HGVS:

NC_000012.12:g.13753432T>C
NG_031854.2:g.233581A>G
NM_000834.5:c.895A>GMANE SELECT
NP_000825.2:p.Ile299Val
NC_000012.11:g.13906366T>C
NM_000834.3:c.895A>G

Protein change:

I299V

Links:

Molecular consequence:

NM_000834.5:c.895A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Intellectual disability, autosomal dominant 6 (MRD6)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 6, WITH OR WITHOUT SEIZURES
Identifiers:: MONDO: MONDO:0013509; MedGen: C3151411; OMIM: 613970

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001450665	Service de Génétique Moléculaire, Hôpital Robert Debré	no assertion criteria provided	Likely pathogenic	de novo	clinical testing
SCV004604934	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2023)	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

SCV001450665

Service de Génétique Moléculaire, Hôpital Robert Debré

no assertion criteria provided

Likely pathogenic

de novo

clinical testing

SCV004604934

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2023)

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	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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 Service de Génétique Moléculaire, Hôpital Robert Debré, SCV001450665.1

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

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004604934.1

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

Description

This variant has not been reported in the literature in individuals affected with GRIN2B-related conditions. This variant is present in population databases (rs760488868, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 299 of the GRIN2B protein (p.Ile299Val). ClinVar contains an entry for this variant (Variation ID: 988725). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GRIN2B protein function. 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.

#	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

ClinVar

Relating variation to medicine