GeneBe

NM_001134407.3:c.*8361_*8362dupTT

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001134407.3(GRIN2A):​c.*8361_*8362dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 66,882 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

GRIN2A
NM_001134407.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRIN2ANM_001134407.3 linkc.*8361_*8362dupTT 3_prime_UTR_variant Exon 13 of 13 ENST00000330684.4 NP_001127879.1 Q12879-1Q547U9Q59EW6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRIN2AENST00000330684.4 linkc.*8361_*8362dupTT 3_prime_UTR_variant Exon 13 of 13 1 NM_001134407.3 ENSP00000332549.3 Q12879-1
GRIN2AENST00000396573.6 linkc.*8361_*8362dupTT 3_prime_UTR_variant Exon 14 of 14 1 ENSP00000379818.2 Q12879-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000150
AC:
1
AN:
66882
Hom.:
0
Cov.:
0
AF XY:
0.0000324
AC XY:
1
AN XY:
30870
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
3120
American (AMR)
AF:
0.00
AC:
0
AN:
2036
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
4286
East Asian (EAS)
AF:
0.00
AC:
0
AN:
9682
South Asian (SAS)
AF:
0.00
AC:
0
AN:
586
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
402
European-Non Finnish (NFE)
AF:
0.0000243
AC:
1
AN:
41104
Other (OTH)
AF:
0.00
AC:
0
AN:
5618
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.24

Splicing

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

Publications

Other links and lift over

dbSNP: rs544326150; hg19: chr16-9848643; API