rs1349350

Variant names:

• chr4-92621617-A-G
• rs1349350
• NM_001510.4:c.244+31331A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-92621617-A-G
• chr4-92621617-A-T

Variant summary

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

The NM_001510.4(GRID2):​c.244+31331A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,400 control chromosomes in the GnomAD database, including 12,004 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 0.39 (12004 hom., cov: 31)
• Consequence: GRID2 NM_001510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRID2	NM_001510.4	c.244+31331A>G		intron_variant	Intron 2 of 15	ENST00000282020.9	NP_001501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRID2	ENST00000282020.9	c.244+31331A>G		intron_variant	Intron 2 of 15	1	NM_001510.4	ENSP00000282020.4
GRID2	ENST00000510992.5	c.244+31331A>G		intron_variant	Intron 2 of 14	1		ENSP00000421257.1
GRID2	ENST00000505687.5	n.416+31331A>G		intron_variant	Intron 2 of 5	1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58841 AN: 151282 Hom.: 11967 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.389 AC: 58926 AN: 151400 Hom.: 12004 Cov.: 31 AF XY: 0.390 AC XY: 28836 AN XY: 73940

African (AFR) AF: 0.519 AC: 21422 AN: 41280

American (AMR) AF: 0.383 AC: 5796 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1266 AN: 3458

East Asian (EAS) AF: 0.415 AC: 2116 AN: 5102

South Asian (SAS) AF: 0.435 AC: 2094 AN: 4818

European-Finnish (FIN) AF: 0.273 AC: 2879 AN: 10548

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.326 AC: 22089 AN: 67756

Other (OTH) AF: 0.374 AC: 786 AN: 2102

Alfa AF: 0.339 Hom.: 14037

Bravo AF: 0.401

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.38
PhyloP100		-0.67
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: rs1349350; hg19: chr4-93542768;