chr16-9844123-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001134407.3(GRIN2A):​c.1329-3019A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,982 control chromosomes in the GnomAD database, including 7,773 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 7773 hom., cov: 32)

Consequence

GRIN2A
NM_001134407.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.239

Publications

6 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRIN2ANM_001134407.3 linkc.1329-3019A>G intron_variant Intron 5 of 12 ENST00000330684.4 NP_001127879.1 Q12879-1Q547U9Q59EW6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRIN2AENST00000330684.4 linkc.1329-3019A>G intron_variant Intron 5 of 12 1 NM_001134407.3 ENSP00000332549.3 Q12879-1

Frequencies

GnomAD3 genomes
AF:
0.315
AC:
47862
AN:
151862
Hom.:
7768
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.323
Gnomad AMI
AF:
0.355
Gnomad AMR
AF:
0.266
Gnomad ASJ
AF:
0.307
Gnomad EAS
AF:
0.123
Gnomad SAS
AF:
0.252
Gnomad FIN
AF:
0.319
Gnomad MID
AF:
0.220
Gnomad NFE
AF:
0.341
Gnomad OTH
AF:
0.307
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.315
AC:
47892
AN:
151982
Hom.:
7773
Cov.:
32
AF XY:
0.308
AC XY:
22901
AN XY:
74292
show subpopulations
African (AFR)
AF:
0.323
AC:
13381
AN:
41420
American (AMR)
AF:
0.265
AC:
4049
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.307
AC:
1065
AN:
3470
East Asian (EAS)
AF:
0.124
AC:
640
AN:
5176
South Asian (SAS)
AF:
0.250
AC:
1207
AN:
4820
European-Finnish (FIN)
AF:
0.319
AC:
3363
AN:
10550
Middle Eastern (MID)
AF:
0.229
AC:
67
AN:
292
European-Non Finnish (NFE)
AF:
0.341
AC:
23146
AN:
67974
Other (OTH)
AF:
0.309
AC:
651
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1645
3290
4934
6579
8224
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
478
956
1434
1912
2390
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.315
Hom.:
1476
Bravo
AF:
0.311
Asia WGS
AF:
0.204
AC:
713
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.71
DANN
Benign
0.51
PhyloP100
-0.24
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12920919; hg19: chr16-9937980; API