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

Variant names:

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

Variant summary

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

The ENST00000784515.1(ENSG00000302122):​n.209+1867_209+1868insACACACACACACAC 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 0.10 (975 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 (SAS) allele frequency at 95% confidence interval = 0.15 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+1868insACACACACACACAC		intron_variant	Intron 1 of 2
ENSG00000302122	ENST00000784516.1	n.209+1867_209+1868insACACACACACACAC		intron_variant	Intron 1 of 1
ENSG00000302122	ENST00000784517.1	n.208+1867_208+1868insACACACACACACAC		intron_variant	Intron 1 of 2
GRIN2A	ENST00000675398.2	c.-1124_-1123insGTGTGTGTGTGTGT		upstream_gene_variant				ENSP00000502752.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 12886 AN: 125226 Hom.: 976 Cov.: 0

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.145

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.103 AC: 12881 AN: 125290 Hom.: 975 Cov.: 0 AF XY: 0.104 AC XY: 6146 AN XY: 59330

African (AFR) AF: 0.0522 AC: 1692 AN: 32434

American (AMR) AF: 0.0915 AC: 1166 AN: 12750

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 419 AN: 3182

East Asian (EAS) AF: 0.110 AC: 445 AN: 4042

South Asian (SAS) AF: 0.161 AC: 529 AN: 3280

European-Finnish (FIN) AF: 0.112 AC: 782 AN: 6966

Middle Eastern (MID) AF: 0.144 AC: 34 AN: 236

European-Non Finnish (NFE) AF: 0.125 AC: 7493 AN: 59912

Other (OTH) AF: 0.103 AC: 174 AN: 1688

Alfa AF: 0.0895 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;