chr16-9753632-A-G
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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
NM_001134407.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.59
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 |
---|---|---|---|---|---|---|---|
GRIN2A | NM_001134407.3 | c.*9517T>C | 3_prime_UTR_variant | 13/13 | ENST00000330684.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2A | ENST00000330684.4 | c.*9517T>C | 3_prime_UTR_variant | 13/13 | 1 | NM_001134407.3 | P1 | ||
GRIN2A | ENST00000396573.6 | c.*9517T>C | 3_prime_UTR_variant | 14/14 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0117 AC: 1781AN: 152220Hom.: 22 Cov.: 32
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GnomAD4 exome AF: 0.00233 AC: 100AN: 42906Hom.: 0 Cov.: 0 AF XY: 0.00212 AC XY: 42AN XY: 19816
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GnomAD4 genome AF: 0.0117 AC: 1788AN: 152338Hom.: 22 Cov.: 32 AF XY: 0.0116 AC XY: 861AN XY: 74502
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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 submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at