rs776264780
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_001134407.3(GRIN2A):c.1224C>T(p.Ile408=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GRIN2A
NM_001134407.3 synonymous
NM_001134407.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.600
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 16-9849860-G-A is Benign according to our data. Variant chr16-9849860-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 532723.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.6 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIN2A | NM_001134407.3 | c.1224C>T | p.Ile408= | synonymous_variant | 5/13 | ENST00000330684.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2A | ENST00000330684.4 | c.1224C>T | p.Ile408= | synonymous_variant | 5/13 | 1 | NM_001134407.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 152086Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 genomes
?
AF:
AC:
1
AN:
152086
Hom.:
Cov.:
32
FAILED QC
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251284Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135800
GnomAD3 exomes
AF:
AC:
4
AN:
251284
Hom.:
AF XY:
AC XY:
3
AN XY:
135800
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461562Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11AN XY: 727096
GnomAD4 exome
AF:
AC:
14
AN:
1461562
Hom.:
Cov.:
33
AF XY:
AC XY:
11
AN XY:
727096
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74284
GnomAD4 genome
?
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
152086
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74284
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Landau-Kleffner syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 07, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at