chr16-9754612-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001134407.3(GRIN2A):​c.*8536_*8537insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00896 in 216,630 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 22 hom., cov: 32)
Exomes 𝑓: 0.0025 ( 3 hom. )

Consequence

GRIN2A
NM_001134407.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.762
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 16-9754612-T-TG is Benign according to our data. Variant chr16-9754612-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 321470.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1784/152256) while in subpopulation AFR AF= 0.0402 (1671/41552). AF 95% confidence interval is 0.0386. There are 22 homozygotes in gnomad4. There are 862 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1784 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIN2ANM_001134407.3 linkuse as main transcriptc.*8536_*8537insC 3_prime_UTR_variant 13/13 ENST00000330684.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIN2AENST00000330684.4 linkuse as main transcriptc.*8536_*8537insC 3_prime_UTR_variant 13/131 NM_001134407.3 P1Q12879-1
GRIN2AENST00000396573.6 linkuse as main transcriptc.*8536_*8537insC 3_prime_UTR_variant 14/141 P1Q12879-1

Frequencies

GnomAD3 genomes
AF:
0.0117
AC:
1777
AN:
152138
Hom.:
22
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0401
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00544
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00766
GnomAD4 exome
AF:
0.00245
AC:
158
AN:
64374
Hom.:
3
Cov.:
0
AF XY:
0.00201
AC XY:
60
AN XY:
29778
show subpopulations
Gnomad4 AFR exome
AF:
0.0387
Gnomad4 AMR exome
AF:
0.00715
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000504
Gnomad4 OTH exome
AF:
0.00497
GnomAD4 genome
AF:
0.0117
AC:
1784
AN:
152256
Hom.:
22
Cov.:
32
AF XY:
0.0116
AC XY:
862
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0402
Gnomad4 AMR
AF:
0.00536
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00758
Alfa
AF:
0.0102
Hom.:
8
Bravo
AF:
0.0138
Asia WGS
AF:
0.00202
AC:
7
AN:
3476

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 submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

LitVar

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

Other links and lift over

dbSNP: rs59371229; hg19: chr16-9848469; API