chr16-9841209-T-G

Position:

• chr16-9841209-T-G

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.1329-105A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 986,132 control chromosomes in the GnomAD database, including 67,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11685 hom., cov: 32)
  • Exomes 𝑓: 0.35 (56201 hom.)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.328

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=-0.83).
• BP6: Variant 16-9841209-T-G is Benign according to our data. Variant chr16-9841209-T-G is described in ClinVar as [Benign]. Clinvar id is 674884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2A	NM_001134407.3	c.1329-105A>C		intron_variant		ENST00000330684.4	NP_001127879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2A	ENST00000330684.4	c.1329-105A>C		intron_variant		1	NM_001134407.3	ENSP00000332549	P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58134 AN: 151866 Hom.: 11672 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.0742

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.355 AC: 296095 AN: 834146 Hom.: 56201 AF XY: 0.350 AC XY: 152890 AN XY: 436370

Gnomad4 AFR exome AF: 0.473

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.0665

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.389

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.383 AC: 58170 AN: 151986 Hom.: 11685 Cov.: 32 AF XY: 0.372 AC XY: 27595 AN XY: 74266

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.0743

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.381

Alfa AF: 0.386 Hom.: 14892

Bravo AF: 0.385

Asia WGS AF: 0.171 AC: 599 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 19, 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	-0.83
CADD	Benign	2.8
DANN	Benign	0.54

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: rs6497540; hg19: chr16-9935066; COSMIC: COSV58043190;