rs7193290

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001134407.3(GRIN2A):​c.1329-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,610,818 control chromosomes in the GnomAD database, including 174 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 90 hom., cov: 31)
Exomes 𝑓: 0.0019 ( 84 hom. )

Consequence

GRIN2A
NM_001134407.3 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0003008
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0180
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 16-9841112-G-A is Benign according to our data. Variant chr16-9841112-G-A is described in ClinVar as [Benign]. Clinvar id is 129191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-9841112-G-A is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GRIN2ANM_001134407.3 linkuse as main transcriptc.1329-8C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000330684.4 NP_001127879.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GRIN2AENST00000330684.4 linkuse as main transcriptc.1329-8C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_001134407.3 ENSP00000332549 P1Q12879-1

Frequencies

GnomAD3 genomes
AF:
0.0183
AC:
2777
AN:
152070
Hom.:
90
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0629
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00832
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00460
AC:
1151
AN:
250368
Hom.:
43
AF XY:
0.00321
AC XY:
434
AN XY:
135364
show subpopulations
Gnomad AFR exome
AF:
0.0633
Gnomad AMR exome
AF:
0.00296
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.00197
GnomAD4 exome
AF:
0.00185
AC:
2700
AN:
1458630
Hom.:
84
Cov.:
33
AF XY:
0.00158
AC XY:
1149
AN XY:
725948
show subpopulations
Gnomad4 AFR exome
AF:
0.0649
Gnomad4 AMR exome
AF:
0.00298
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000938
Gnomad4 OTH exome
AF:
0.00445
GnomAD4 genome
AF:
0.0183
AC:
2789
AN:
152188
Hom.:
90
Cov.:
31
AF XY:
0.0179
AC XY:
1330
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.0630
Gnomad4 AMR
AF:
0.00831
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00815
Hom.:
23
Bravo
AF:
0.0210
Asia WGS
AF:
0.00433
AC:
15
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitterclinical testingGeneDxNov 05, 2013This 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. -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Landau-Kleffner syndrome Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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. -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsJun 07, 2019- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
5.4
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00030
dbscSNV1_RF
Benign
0.034
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7193290; hg19: chr16-9934969; API