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

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000784515.1(ENSG00000302122):​n.209+1867_209+1868insACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.085 (748 hom., cov: 0)
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

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+1868insACACACACACACACAC		intron_variant	Intron 1 of 2
ENSG00000302122	ENST00000784516.1	n.209+1867_209+1868insACACACACACACACAC		intron_variant	Intron 1 of 1
ENSG00000302122	ENST00000784517.1	n.208+1867_208+1868insACACACACACACACAC		intron_variant	Intron 1 of 2
GRIN2A	ENST00000675398.2	c.-1124_-1123insGTGTGTGTGTGTGTGT		upstream_gene_variant				ENSP00000502752.1

Frequencies

GnomAD3 genomes AF: 0.0845 AC: 10581 AN: 125212 Hom.: 749 Cov.: 0

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.0481

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0698

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0612

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

GnomAD4 genome AF: 0.0845 AC: 10588 AN: 125278 Hom.: 748 Cov.: 0 AF XY: 0.0809 AC XY: 4797 AN XY: 59318

African (AFR) AF: 0.0491 AC: 1591 AN: 32430

American (AMR) AF: 0.0706 AC: 901 AN: 12760

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 265 AN: 3186

East Asian (EAS) AF: 0.0483 AC: 195 AN: 4040

South Asian (SAS) AF: 0.0828 AC: 272 AN: 3286

European-Finnish (FIN) AF: 0.121 AC: 838 AN: 6942

Middle Eastern (MID) AF: 0.0672 AC: 16 AN: 238

European-Non Finnish (NFE) AF: 0.106 AC: 6339 AN: 59908

Other (OTH) AF: 0.0628 AC: 106 AN: 1688

Alfa AF: 0.0854 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;