chr4-92304923-C-G

Variant names:

• chr4-92304923-C-G
• rs62310990
• NM_001510.4:c.88+179C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001510.4(GRID2):​c.88+179C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 152,122 control chromosomes in the GnomAD database, including 390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.068 (390 hom., cov: 32)
• Consequence: GRID2 NM_001510.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660
• Publications: 1 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-92304923-C-G is Benign according to our data. Variant chr4-92304923-C-G is described in ClinVar as Benign. ClinVar VariationId is 1242806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0822 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001510.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRID2	NM_001510.4	MANE Select	c.88+179C>G		intron	N/A	NP_001501.2	O43424-1
	GRID2	NM_001440459.1		c.88+179C>G		intron	N/A	NP_001427388.1
	GRID2	NM_001286838.1		c.88+179C>G		intron	N/A	NP_001273767.1	O43424-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRID2	ENST00000282020.9	TSL:1 MANE Select	c.88+179C>G		intron	N/A	ENSP00000282020.4	O43424-1
	GRID2	ENST00000510992.5	TSL:1	c.88+179C>G		intron	N/A	ENSP00000421257.1	O43424-2
	GRID2	ENST00000505687.5	TSL:1	n.260+179C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0683 AC: 10377 AN: 152004 Hom.: 388 Cov.: 32

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0862

Gnomad ASJ AF: 0.0753

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.0751

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0683 AC: 10384 AN: 152122 Hom.: 390 Cov.: 32 AF XY: 0.0685 AC XY: 5097 AN XY: 74368

African (AFR) AF: 0.0446 AC: 1849 AN: 41502

American (AMR) AF: 0.0861 AC: 1316 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 261 AN: 3466

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5162

South Asian (SAS) AF: 0.0754 AC: 363 AN: 4812

European-Finnish (FIN) AF: 0.0751 AC: 795 AN: 10588

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0807 AC: 5486 AN: 67982

Other (OTH) AF: 0.0705 AC: 149 AN: 2112

Alfa AF: 0.0262 Hom.: 15

Bravo AF: 0.0674

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.63
PhyloP100		-0.066
PromoterAI		-0.00090	Neutral
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: rs62310990; hg19: chr4-93226074;