rs17019608

Positions:

• chr4-92579518-C-A

Variant summary

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

The NM_001510.4(GRID2):​c.89-10613C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,630 control chromosomes in the GnomAD database, including 12,495 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 (12495 hom., cov: 31)
• Consequence: GRID2 NM_001510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRID2	NM_001510.4	c.89-10613C>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.89-10613C>A		intron_variant		1	NM_001510.4	ENSP00000282020.4
GRID2	ENST00000510992.5	c.89-10613C>A		intron_variant		1		ENSP00000421257.1
GRID2	ENST00000505687.5	n.261-10613C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61169 AN: 151510 Hom.: 12465 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.404 AC: 61250 AN: 151630 Hom.: 12495 Cov.: 31 AF XY: 0.403 AC XY: 29867 AN XY: 74054

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.397

Alfa AF: 0.376 Hom.: 1845

Bravo AF: 0.412

Asia WGS AF: 0.471 AC: 1629 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.5
DANN	Benign	0.37

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: rs17019608; hg19: chr4-93500669;