rs11866328

chr16-9768699-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001134407.3(GRIN2A):c.2595+152C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 753,224 control chromosomes in the GnomAD database, including 54,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11361 hom., cov: 33)
  • Exomes 𝑓: 0.37 (42760 hom.)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.601

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-9768699-G-T is Benign according to our data. Variant chr16-9768699-G-T is described in ClinVar as [Benign]. Clinvar id is 681804.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2A	NM_001134407.3	c.2595+152C>A		intron_variant		ENST00000330684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2A	ENST00000330684.4	c.2595+152C>A		intron_variant		1	NM_001134407.3	P1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57901 AN: 151928 Hom.: 11356 Cov.: 33

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.368 AC: 221270 AN: 601178 Hom.: 42760 AF XY: 0.365 AC XY: 119366 AN XY: 327310

Gnomad4 AFR exome AF: 0.399

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.380

GnomAD4 genome AF: 0.381 AC: 57940 AN: 152046 Hom.: 11361 Cov.: 33 AF XY: 0.369 AC XY: 27446 AN XY: 74322

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.381

Alfa AF: 0.406 Hom.: 13007

Bravo AF: 0.386

Asia WGS AF: 0.244 AC: 853 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.48
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11866328; hg19: chr16-9862556; COSMIC: COSV58033400;