rs7682842

Variant names:

• chr4-92568136-G-A
• rs7682842
• NM_001510.4:c.89-21995G>A

Variant summary

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

The NM_001510.4(GRID2):​c.89-21995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,778 control chromosomes in the GnomAD database, including 5,499 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 0.26 (5499 hom., cov: 32)
• Consequence: GRID2 NM_001510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRID2	NM_001510.4	c.89-21995G>A		intron_variant	Intron 1 of 15	ENST00000282020.9	NP_001501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRID2	ENST00000282020.9	c.89-21995G>A		intron_variant	Intron 1 of 15	1	NM_001510.4	ENSP00000282020.4
GRID2	ENST00000510992.5	c.89-21995G>A		intron_variant	Intron 1 of 14	1		ENSP00000421257.1
GRID2	ENST00000505687.5	n.261-21995G>A		intron_variant	Intron 1 of 5	1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40135 AN: 151660 Hom.: 5496 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.265 AC: 40160 AN: 151778 Hom.: 5499 Cov.: 32 AF XY: 0.267 AC XY: 19821 AN XY: 74142

African (AFR) AF: 0.165 AC: 6848 AN: 41446

American (AMR) AF: 0.317 AC: 4819 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1202 AN: 3464

East Asian (EAS) AF: 0.257 AC: 1322 AN: 5146

South Asian (SAS) AF: 0.315 AC: 1516 AN: 4808

European-Finnish (FIN) AF: 0.286 AC: 3012 AN: 10528

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20447 AN: 67892

Other (OTH) AF: 0.270 AC: 569 AN: 2106

Alfa AF: 0.298 Hom.: 11624

Bravo AF: 0.262

Asia WGS AF: 0.272 AC: 947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.38
PhyloP100		0.0050
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: rs7682842; hg19: chr4-93489287;