rs1972860

Variant names:

• chr4-93658489-G-A
• rs1972860
• NM_001510.4:c.2360+32054G>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.2360+32054G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,876 control chromosomes in the GnomAD database, including 13,191 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 0.40 (13191 hom., cov: 32)
• Consequence: GRID2 NM_001510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRID2	NM_001510.4	c.2360+32054G>A		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+32054G>A		intron_variant	Intron 14 of 15	1	NM_001510.4	ENSP00000282020.4
GRID2	ENST00000611049.4	c.2117+32054G>A		intron_variant	Intron 12 of 13	1		ENSP00000483084.1
GRID2	ENST00000510992.5	c.2075+32054G>A		intron_variant	Intron 13 of 14	1		ENSP00000421257.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60504 AN: 151758 Hom.: 13170 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.399 AC: 60574 AN: 151876 Hom.: 13191 Cov.: 32 AF XY: 0.400 AC XY: 29714 AN XY: 74220

African (AFR) AF: 0.576 AC: 23858 AN: 41428

American (AMR) AF: 0.363 AC: 5539 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3466

East Asian (EAS) AF: 0.589 AC: 3039 AN: 5162

South Asian (SAS) AF: 0.406 AC: 1950 AN: 4806

European-Finnish (FIN) AF: 0.307 AC: 3236 AN: 10532

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20777 AN: 67908

Other (OTH) AF: 0.382 AC: 805 AN: 2108

Alfa AF: 0.345 Hom.: 6830

Bravo AF: 0.412

Asia WGS AF: 0.488 AC: 1694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.46
PhyloP100		-1.3
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: rs1972860; hg19: chr4-94579640;