chr16-9753632-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001134407.3(GRIN2A):​c.*9517T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00967 in 195,244 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 22 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 0 hom. )

Consequence

GRIN2A
NM_001134407.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.59
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 16-9753632-A-G is Benign according to our data. Variant chr16-9753632-A-G is described in ClinVar as [Benign]. Clinvar id is 321460.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 (1788/152338) while in subpopulation AFR AF= 0.0403 (1675/41580). AF 95% confidence interval is 0.0387. There are 22 homozygotes in gnomad4. There are 861 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1788 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIN2ANM_001134407.3 linkuse as main transcriptc.*9517T>C 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.*9517T>C 3_prime_UTR_variant 13/131 NM_001134407.3 P1Q12879-1
GRIN2AENST00000396573.6 linkuse as main transcriptc.*9517T>C 3_prime_UTR_variant 14/141 P1Q12879-1

Frequencies

GnomAD3 genomes
AF:
0.0117
AC:
1781
AN:
152220
Hom.:
22
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0402
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:
0.00764
GnomAD4 exome
AF:
0.00233
AC:
100
AN:
42906
Hom.:
0
Cov.:
0
AF XY:
0.00212
AC XY:
42
AN XY:
19816
show subpopulations
Gnomad4 AFR exome
AF:
0.0395
Gnomad4 AMR exome
AF:
0.00840
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:
0.000117
Gnomad4 OTH exome
AF:
0.00482
GnomAD4 genome
AF:
0.0117
AC:
1788
AN:
152338
Hom.:
22
Cov.:
32
AF XY:
0.0116
AC XY:
861
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.0403
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:
0.00756
Alfa
AF:
0.00999
Hom.:
8
Bravo
AF:
0.0138
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Landau-Kleffner syndrome Benign:1
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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
17
DANN
Benign
0.86

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: rs16966242; hg19: chr16-9847489; API