rs6815704

Variant names:

• chr4-92553415-G-A
• rs6815704
• NM_001510.4:c.89-36716G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-92553415-G-A
• chr4-92553415-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001510.4(GRID2):​c.89-36716G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,930 control chromosomes in the GnomAD database, including 4,657 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4657 hom., cov: 32)
• Consequence: GRID2 NM_001510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 3 publications found

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]

GRID2 Gene-Disease associations (from GenCC):

• autosomal recessive spinocerebellar ataxia 18

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001510.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRID2	NM_001510.4	MANE Select	c.89-36716G>A		intron	N/A	NP_001501.2
	GRID2	NM_001440459.1		c.89-36716G>A		intron	N/A	NP_001427388.1
	GRID2	NM_001286838.1		c.89-36716G>A		intron	N/A	NP_001273767.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRID2	ENST00000282020.9	TSL:1 MANE Select	c.89-36716G>A		intron	N/A	ENSP00000282020.4
	GRID2	ENST00000510992.5	TSL:1	c.89-36716G>A		intron	N/A	ENSP00000421257.1
	GRID2	ENST00000505687.5	TSL:1	n.261-36716G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33743 AN: 151812 Hom.: 4638 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33804 AN: 151930 Hom.: 4657 Cov.: 32 AF XY: 0.217 AC XY: 16122 AN XY: 74230

African (AFR) AF: 0.395 AC: 16373 AN: 41414

American (AMR) AF: 0.153 AC: 2341 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3468

East Asian (EAS) AF: 0.169 AC: 868 AN: 5142

South Asian (SAS) AF: 0.175 AC: 842 AN: 4816

European-Finnish (FIN) AF: 0.123 AC: 1295 AN: 10560

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.158 AC: 10729 AN: 67964

Other (OTH) AF: 0.217 AC: 458 AN: 2108

Alfa AF: 0.161 Hom.: 1701

Bravo AF: 0.234

Asia WGS AF: 0.238 AC: 827 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.030
DANN	Benign	0.28
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6815704; hg19: chr4-93474566;