rs368110989

Variant names:

• chr16-9829413-G-A
• rs368110989
• NM_001134407.3:c.2007+10C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-9829413-G-A
• chr16-9829413-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_001134407.3(GRIN2A):​c.2007+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,587,278 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.578
• Publications: 0 publications found

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]

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 16-9829413-G-A is Benign according to our data. Variant chr16-9829413-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 321612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000118 (169/1435116) while in subpopulation NFE AF = 0.000127 (138/1088146). AF 95% confidence interval is 0.00011. There are 1 homozygotes in GnomAdExome4. There are 99 alleles in the male GnomAdExome4 subpopulation. Median coverage is 28. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2A	NM_001134407.3	c.2007+10C>T		intron_variant	Intron 9 of 12	ENST00000330684.4	NP_001127879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2A	ENST00000330684.4	c.2007+10C>T		intron_variant	Intron 9 of 12	1	NM_001134407.3	ENSP00000332549.3

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000128 AC: 32 AN: 250618 AF XY: 0.000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000118 AC: 169 AN: 1435116 Hom.: 1 Cov.: 28 AF XY: 0.000138 AC XY: 99 AN XY: 715744

African (AFR) AF: 0.00 AC: 0 AN: 32984

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.000770 AC: 20 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39468

South Asian (SAS) AF: 0.00 AC: 0 AN: 85684

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5404

European-Non Finnish (NFE) AF: 0.000127 AC: 138 AN: 1088146

Other (OTH) AF: 0.000118 AC: 7 AN: 59420

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000274 Hom.: 0

Bravo AF: 0.0000756

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Landau-Kleffner syndrome Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 16, 2017

GeneDx

Significance: Likely 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs368110989; hg19: chr16-9923270;