4-92304340-C-T

Variant names:

• chr4-92304340-C-T
• rs79693811
• NM_001510.4:c.-317C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001510.4(GRID2):​c.-317C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 375,586 control chromosomes in the GnomAD database, including 265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (236 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (29 hom.)
• Consequence: GRID2 NM_001510.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.768
• 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ENSG00000248511 (HGNC:58854):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 4-92304340-C-T is Benign according to our data. Variant chr4-92304340-C-T is described in ClinVar as Benign. ClinVar VariationId is 1278181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 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.-317C>T		5_prime_UTR	Exon 1 of 16	NP_001501.2	O43424-1
	GRID2	NM_001440459.1		c.-317C>T		5_prime_UTR	Exon 1 of 16	NP_001427388.1
	GRID2	NM_001286838.1		c.-317C>T		upstream_gene	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.-317C>T		5_prime_UTR	Exon 1 of 16	ENSP00000282020.4	O43424-1
	GRID2	ENST00000505687.5	TSL:1	n.-145C>T		upstream_gene	N/A
	ENSG00000248511	ENST00000504213.2	TSL:2	n.-123G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4723 AN: 152122 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0230

GnomAD4 exome AF: 0.00327 AC: 730 AN: 223346 Hom.: 29 Cov.: 0 AF XY: 0.00278 AC XY: 340 AN XY: 122174

African (AFR) AF: 0.102 AC: 505 AN: 4972

American (AMR) AF: 0.00669 AC: 47 AN: 7028

Ashkenazi Jewish (ASJ) AF: 0.000489 AC: 3 AN: 6138

East Asian (EAS) AF: 0.00 AC: 0 AN: 9050

South Asian (SAS) AF: 0.000189 AC: 7 AN: 36958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10484

Middle Eastern (MID) AF: 0.00773 AC: 7 AN: 906

European-Non Finnish (NFE) AF: 0.000515 AC: 70 AN: 136008

Other (OTH) AF: 0.00771 AC: 91 AN: 11802

GnomAD4 genome AF: 0.0311 AC: 4728 AN: 152240 Hom.: 236 Cov.: 32 AF XY: 0.0290 AC XY: 2156 AN XY: 74438

African (AFR) AF: 0.107 AC: 4451 AN: 41530

American (AMR) AF: 0.0114 AC: 174 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68024

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0269 Hom.: 21

Bravo AF: 0.0354

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		0.77
PromoterAI		0.020	Neutral

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: rs79693811; hg19: chr4-93225491;