16-10183567-GACACACACACACACACAC-GACACACACACACACACACACACACACAC

Variant names:

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

Variant summary

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

The ENST00000784515.1(ENSG00000302122):​n.209+1867_209+1868insACACACACAC 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 0.13 (1518 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 (EAS) allele frequency at 95% confidence interval = 0.249 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+1868insACACACACAC		intron_variant	Intron 1 of 2
ENSG00000302122	ENST00000784516.1	n.209+1867_209+1868insACACACACAC		intron_variant	Intron 1 of 1
ENSG00000302122	ENST00000784517.1	n.208+1867_208+1868insACACACACAC		intron_variant	Intron 1 of 2
GRIN2A	ENST00000675398.2	c.-1124_-1123insGTGTGTGTGT		upstream_gene_variant				ENSP00000502752.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 16477 AN: 125278 Hom.: 1517 Cov.: 0

Gnomad AFR AF: 0.0814

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.131 AC: 16481 AN: 125342 Hom.: 1518 Cov.: 0 AF XY: 0.136 AC XY: 8100 AN XY: 59348

African (AFR) AF: 0.0813 AC: 2635 AN: 32426

American (AMR) AF: 0.231 AC: 2947 AN: 12760

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 390 AN: 3190

East Asian (EAS) AF: 0.262 AC: 1058 AN: 4044

South Asian (SAS) AF: 0.228 AC: 748 AN: 3278

European-Finnish (FIN) AF: 0.120 AC: 836 AN: 6988

Middle Eastern (MID) AF: 0.193 AC: 46 AN: 238

European-Non Finnish (NFE) AF: 0.124 AC: 7423 AN: 59918

Other (OTH) AF: 0.166 AC: 282 AN: 1698

Alfa AF: 0.102 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; COSMIC: COSV58045670;