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NM_000836.4(GRIN2D):c.2041A>G (p.Met681Val) AND Developmental and epileptic encephalopathy, 46

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 1, 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:
RCV005253793.2

Allele description [Variation Report for NM_000836.4(GRIN2D):c.2041A>G (p.Met681Val)]

NM_000836.4(GRIN2D):c.2041A>G (p.Met681Val)

Gene:
GRIN2D:glutamate ionotropic receptor NMDA type subunit 2D [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.33
Genomic location:
Preferred name:
NM_000836.4(GRIN2D):c.2041A>G (p.Met681Val)
HGVS:
  • NC_000019.10:g.48419764A>G
  • NG_052829.1:g.29890A>G
  • NM_000836.4:c.2041A>GMANE SELECT
  • NP_000827.2:p.Met681Val
  • NC_000019.9:g.48923021A>G
Protein change:
M681V
Links:
dbSNP: rs1555893359
NCBI 1000 Genomes Browser:
rs1555893359
Molecular consequence:
  • NM_000836.4:c.2041A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Developmental and epileptic encephalopathy, 46 (DEE46)
Synonyms:
Epileptic encephalopathy, early infantile, 46
Identifiers:
MONDO: MONDO:0014947; MedGen: C4310687; OMIM: 617162

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV0059056493billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Sep 1, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

GRIN2D variants in three cases of developmental and epileptic encephalopathy.

Tsuchida N, Hamada K, Shiina M, Kato M, Kobayashi Y, Tohyama J, Kimura K, Hoshino K, Ganesan V, Teik KW, Nakashima M, Mitsuhashi S, Mizuguchi T, Takata A, Miyake N, Saitsu H, Ogata K, Miyatake S, Matsumoto N.

Clin Genet. 2018 Dec;94(6):538-547. doi: 10.1111/cge.13454.

PubMed [citation]
PMID:
30280376

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 3billion, SCV005905649.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product [3Cnet: 0.97 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV001013174). A different missense change at the same codon (p.Met681Ile) has been reported to be associated with GRIN2D related disorder (ClinVar ID: VCV000599388 /PMID: 30280376). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 22, 2025