ENST00000784515.1:n.209+1867_209+1868insACAC

Variant names:

• chr16-10183567-G-GACAC
• rs3219790
• ENST00000784515.1:n.209+1867_209+1868insACAC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000784515.1(ENSG00000302122):​n.209+1867_209+1868insACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (627 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000302122 ENST00000784515.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 9 publications found

Genes affected

ENSG00000302122 (HGNC:):

GRIN2A (HGNC:4585): (glutamate ionotropic receptor NMDA type subunit 2A) This gene encodes a member of the glutamate-gated ion channel protein family. The encoded protein is an N-methyl-D-aspartate (NMDA) receptor subunit. NMDA receptors are both ligand-gated and voltage-dependent, and are involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. These receptors are permeable to calcium ions, and activation results in a calcium influx into post-synaptic cells, which results in the activation of several signaling cascades. Disruption of this gene is associated with focal epilepsy and speech disorder with or without cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

GRIN2A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Landau-Kleffner syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• continuous spikes and waves during sleep

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• rolandic epilepsy-speech dyspraxia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• self-limited epilepsy with centrotemporal spikes

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000302122	ENST00000784515.1	n.209+1867_209+1868insACAC		intron_variant	Intron 1 of 2
ENSG00000302122	ENST00000784516.1	n.209+1867_209+1868insACAC		intron_variant	Intron 1 of 1
ENSG00000302122	ENST00000784517.1	n.208+1867_208+1868insACAC		intron_variant	Intron 1 of 2
GRIN2A	ENST00000675398.2	c.-1124_-1123insGTGT		upstream_gene_variant				ENSP00000502752.1

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 7939 AN: 125404 Hom.: 627 Cov.: 0

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0715

Gnomad SAS AF: 0.0524

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.0116

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0531

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0634 AC: 7949 AN: 125468 Hom.: 627 Cov.: 0 AF XY: 0.0639 AC XY: 3798 AN XY: 59414

African (AFR) AF: 0.177 AC: 5735 AN: 32430

American (AMR) AF: 0.0383 AC: 489 AN: 12774

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 80 AN: 3190

East Asian (EAS) AF: 0.0710 AC: 287 AN: 4042

South Asian (SAS) AF: 0.0520 AC: 171 AN: 3288

European-Finnish (FIN) AF: 0.0201 AC: 141 AN: 7014

Middle Eastern (MID) AF: 0.0126 AC: 3 AN: 238

European-Non Finnish (NFE) AF: 0.0159 AC: 954 AN: 59990

Other (OTH) AF: 0.0524 AC: 89 AN: 1698

Alfa AF: 0.00 Hom.: 154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3219790; hg19: chr16-10277424;