chr16-10183567-GACAC-G

Variant names:

• chr16-10183567-GACAC-G
• rs3219790
• ENST00000784515.1:n.209+1868_209+1871delACAC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000784515.1(ENSG00000302122):​n.209+1868_209+1871delACAC 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 0.0044 (6 hom., cov: 0)
• Consequence: ENSG00000302122 ENST00000784515.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 6 gene

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+1868_209+1871delACAC		intron_variant	Intron 1 of 2
ENSG00000302122	ENST00000784516.1	n.209+1868_209+1871delACAC		intron_variant	Intron 1 of 1
ENSG00000302122	ENST00000784517.1	n.208+1868_208+1871delACAC		intron_variant	Intron 1 of 2
GRIN2A	ENST00000675398.2	c.-1127_-1124delGTGT		upstream_gene_variant				ENSP00000502752.1

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 552 AN: 125448 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.00525

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00110

Gnomad ASJ AF: 0.000313

Gnomad EAS AF: 0.00148

Gnomad SAS AF: 0.00363

Gnomad FIN AF: 0.00271

Gnomad MID AF: 0.00775

Gnomad NFE AF: 0.00528

Gnomad OTH AF: 0.00656

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

GnomAD4 genome AF: 0.00439 AC: 551 AN: 125512 Hom.: 6 Cov.: 0 AF XY: 0.00444 AC XY: 264 AN XY: 59424

African (AFR) AF: 0.00524 AC: 170 AN: 32462

American (AMR) AF: 0.00110 AC: 14 AN: 12782

Ashkenazi Jewish (ASJ) AF: 0.000313 AC: 1 AN: 3190

East Asian (EAS) AF: 0.00148 AC: 6 AN: 4048

South Asian (SAS) AF: 0.00335 AC: 11 AN: 3288

European-Finnish (FIN) AF: 0.00271 AC: 19 AN: 7004

Middle Eastern (MID) AF: 0.00840 AC: 2 AN: 238

European-Non Finnish (NFE) AF: 0.00528 AC: 317 AN: 59998

Other (OTH) AF: 0.00648 AC: 11 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		3.4

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;