NM_001510.4:c.87C>T
Variant names:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1
The NM_001510.4(GRID2):c.87C>T(p.Ile29Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000349 in 1,604,544 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
GRID2
NM_001510.4 splice_region, synonymous
NM_001510.4 splice_region, synonymous
Scores
2
Splicing: ADA: 0.004902
2
Clinical Significance
Conservation
PhyloP100: 1.32
Genes affected
GRID2 (HGNC:4576): (glutamate ionotropic receptor delta type subunit 2) The protein encoded by this gene is a member of the family of ionotropic glutamate receptors which are the predominant excitatory neurotransmitter receptors in the mammalian brain. The encoded protein is a multi-pass membrane protein that is expressed selectively in cerebellar Purkinje cells. A point mutation in the mouse ortholog, associated with the phenotype named 'lurcher', in the heterozygous state leads to ataxia resulting from selective, cell-autonomous apoptosis of cerebellar Purkinje cells during postnatal development. Mice homozygous for this mutation die shortly after birth from massive loss of mid- and hindbrain neurons during late embryogenesis. This protein also plays a role in synapse organization between parallel fibers and Purkinje cells. Alternate splicing results in multiple transcript variants encoding distinct isoforms. Mutations in this gene cause cerebellar ataxia in humans. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
Variant 4-92304743-C-T is Benign according to our data. Variant chr4-92304743-C-T is described in ClinVar as [Benign]. Clinvar id is 2064428.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-92304743-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.33 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00183 (278/152232) while in subpopulation AFR AF= 0.00635 (264/41550). AF 95% confidence interval is 0.00572. There are 0 homozygotes in gnomad4. There are 144 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GRID2 | ENST00000282020.9 | c.87C>T | p.Ile29Ile | splice_region_variant, synonymous_variant | Exon 1 of 16 | 1 | NM_001510.4 | ENSP00000282020.4 | ||
| GRID2 | ENST00000510992.5 | c.87C>T | p.Ile29Ile | splice_region_variant, synonymous_variant | Exon 1 of 15 | 1 | ENSP00000421257.1 | |||
| GRID2 | ENST00000505687.5 | n.259C>T | splice_region_variant, non_coding_transcript_exon_variant | Exon 1 of 6 | 1 |
Frequencies
GnomAD3 genomes 0.00182 AC: 277AN: 152114Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000522 AC: 130AN: 249074Hom.: 0 AF XY: 0.000430 AC XY: 58AN XY: 134848
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GnomAD4 exome AF: 0.000194 AC: 282AN: 1452312Hom.: 0 Cov.: 29 AF XY: 0.000176 AC XY: 127AN XY: 723174
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GnomAD4 genome 0.00183 AC: 278AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.00193 AC XY: 144AN XY: 74430
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Sep 16, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
GRID2-related disorder Benign:1
Apr 01, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at