rs11097383

Variant names:

• chr4-93662689-T-C
• rs11097383
• NM_001510.4:c.2360+36254T>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.2360+36254T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,142 control chromosomes in the GnomAD database, including 1,321 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 0.12 (1321 hom., cov: 32)
• Consequence: GRID2 NM_001510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 6 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRID2	NM_001510.4	c.2360+36254T>C		intron_variant	Intron 14 of 15	ENST00000282020.9	NP_001501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRID2	ENST00000282020.9	c.2360+36254T>C		intron_variant	Intron 14 of 15	1	NM_001510.4	ENSP00000282020.4
GRID2	ENST00000611049.4	c.2117+36254T>C		intron_variant	Intron 12 of 13	1		ENSP00000483084.1
GRID2	ENST00000510992.5	c.2075+36254T>C		intron_variant	Intron 13 of 14	1		ENSP00000421257.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18729 AN: 152024 Hom.: 1321 Cov.: 32

Gnomad AFR AF: 0.0657

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.0907

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.123 AC: 18740 AN: 152142 Hom.: 1321 Cov.: 32 AF XY: 0.120 AC XY: 8934 AN XY: 74396

African (AFR) AF: 0.0660 AC: 2739 AN: 41518

American (AMR) AF: 0.102 AC: 1557 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3468

East Asian (EAS) AF: 0.169 AC: 876 AN: 5174

South Asian (SAS) AF: 0.0910 AC: 438 AN: 4814

European-Finnish (FIN) AF: 0.131 AC: 1386 AN: 10590

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10908 AN: 67974

Other (OTH) AF: 0.122 AC: 257 AN: 2114

Alfa AF: 0.145 Hom.: 1086

Bravo AF: 0.119

Asia WGS AF: 0.116 AC: 403 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.6
DANN	Benign	0.69
PhyloP100		0.048
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: rs11097383; hg19: chr4-94583840;