rs17319672

Variant names:

• chr4-92546651-C-T
• rs17319672
• NM_001510.4:c.89-43480C>T

Variant summary

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

The ENST00000282020.9(GRID2):​c.89-43480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 152,182 control chromosomes in the GnomAD database, including 393 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 0.067 (393 hom., cov: 33)
• Consequence: GRID2 ENST00000282020.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000282020.9. 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.89-43480C>T		intron	N/A	NP_001501.2
	GRID2	NM_001440459.1		c.89-43480C>T		intron	N/A	NP_001427388.1
	GRID2	NM_001286838.1		c.89-43480C>T		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.89-43480C>T		intron	N/A	ENSP00000282020.4
	GRID2	ENST00000510992.5	TSL:1	c.89-43480C>T		intron	N/A	ENSP00000421257.1
	GRID2	ENST00000505687.5	TSL:1	n.261-43480C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10274 AN: 152064 Hom.: 392 Cov.: 33

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0560

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.0805

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

GnomAD4 genome AF: 0.0675 AC: 10271 AN: 152182 Hom.: 393 Cov.: 33 AF XY: 0.0664 AC XY: 4937 AN XY: 74380

African (AFR) AF: 0.0339 AC: 1408 AN: 41540

American (AMR) AF: 0.0614 AC: 938 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.0556 AC: 268 AN: 4816

European-Finnish (FIN) AF: 0.0904 AC: 956 AN: 10576

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0887 AC: 6030 AN: 68010

Other (OTH) AF: 0.0797 AC: 168 AN: 2108

Alfa AF: 0.0785 Hom.: 401

Bravo AF: 0.0648

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.78
DANN	Benign	0.73
PhyloP100		-0.18
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: rs17319672; hg19: chr4-93467802;