rs6532378

Positions:

• chr4-92636788-G-A
• chr4-92636788-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000282020.9(GRID2):​c.244+46502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,768 control chromosomes in the GnomAD database, including 12,923 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 (12923 hom., cov: 32)
• Consequence: GRID2 ENST00000282020.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRID2	NM_001510.4	c.244+46502G>A		intron_variant		ENST00000282020.9	NP_001501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRID2	ENST00000282020.9	c.244+46502G>A		intron_variant		1	NM_001510.4	ENSP00000282020	P1
GRID2	ENST00000510992.5	c.244+46502G>A		intron_variant		1		ENSP00000421257
GRID2	ENST00000505687.5	n.416+46502G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60673 AN: 151650 Hom.: 12883 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.400 AC: 60760 AN: 151768 Hom.: 12923 Cov.: 32 AF XY: 0.401 AC XY: 29733 AN XY: 74118

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.378

Alfa AF: 0.355 Hom.: 5693

Bravo AF: 0.413

Asia WGS AF: 0.459 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.1
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs6532378; hg19: chr4-93557939;