16-9891116-G-C

Variant names:

• chr16-9891116-G-C
• rs9932916
• NM_001134407.3:c.1008-16C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001134407.3(GRIN2A):​c.1008-16C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00622 in 1,480,722 control chromosomes in the GnomAD database, including 470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (276 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (194 hom.)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.612

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 16-9891116-G-C is Benign according to our data. Variant chr16-9891116-G-C is described in ClinVar as [Benign]. Clinvar id is 137507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-9891116-G-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2A	NM_001134407.3	c.1008-16C>G		intron_variant	Intron 3 of 12	ENST00000330684.4	NP_001127879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2A	ENST00000330684.4	c.1008-16C>G		intron_variant	Intron 3 of 12	1	NM_001134407.3	ENSP00000332549.3

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4805 AN: 152146 Hom.: 275 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.00803 AC: 2014 AN: 250850 Hom.: 100 AF XY: 0.00606 AC XY: 821 AN XY: 135564

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.00597

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000309

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00330 AC: 4385 AN: 1328458 Hom.: 194 Cov.: 21 AF XY: 0.00283 AC XY: 1891 AN XY: 668340

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.00674

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000455

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000194

Gnomad4 OTH exome AF: 0.00745

GnomAD4 genome AF: 0.0317 AC: 4829 AN: 152264 Hom.: 276 Cov.: 32 AF XY: 0.0312 AC XY: 2325 AN XY: 74468

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.00245 Hom.: 2

Bravo AF: 0.0355

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Oct 31, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Landau-Kleffner syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.7
DANN	Benign	0.38

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: rs9932916; hg19: chr16-9984973;