4-92822750-TCCAGGGCATG-TCCAGGGCATGCCAGGGCATG

Variant names:

• chr4-92822750-T-TCCAGGGCATG
• rs543784712
• NM_001510.4:c.244+232466_244+232475dupCAGGGCATGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001510.4(GRID2):​c.244+232466_244+232475dupCAGGGCATGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00832 in 160,306 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (0 hom.)
• Consequence: GRID2 NM_001510.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.342
• Publications: 0 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]

RACK1P3 (HGNC:55465): (RACK1 pseudogene 3)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-92822750-T-TCCAGGGCATG is Benign according to our data. Variant chr4-92822750-T-TCCAGGGCATG is described in ClinVar as Benign. ClinVar VariationId is 2571209.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00845 (1286/152218) while in subpopulation NFE AF = 0.0129 (874/68004). AF 95% confidence interval is 0.0121. There are 9 homozygotes in GnomAd4. There are 632 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR,AD gene

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.244+232466_244+232475dupCAGGGCATGC		intron	N/A	NP_001501.2	O43424-1
	GRID2	NM_001440459.1		c.244+232466_244+232475dupCAGGGCATGC		intron	N/A	NP_001427388.1
	GRID2	NM_001286838.1		c.244+232466_244+232475dupCAGGGCATGC		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.244+232466_244+232475dupCAGGGCATGC		intron	N/A	ENSP00000282020.4	O43424-1
	GRID2	ENST00000510992.5	TSL:1	c.244+232466_244+232475dupCAGGGCATGC		intron	N/A	ENSP00000421257.1	O43424-2
	GRID2	ENST00000505687.5	TSL:1	n.416+232466_416+232475dupCAGGGCATGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00845 AC: 1286 AN: 152100 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00581 AC: 47 AN: 8088 Hom.: 0 Cov.: 0 AF XY: 0.00450 AC XY: 19 AN XY: 4218

African (AFR) AF: 0.00 AC: 0 AN: 82

American (AMR) AF: 0.00 AC: 0 AN: 218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 202

East Asian (EAS) AF: 0.00 AC: 0 AN: 80

South Asian (SAS) AF: 0.000904 AC: 1 AN: 1106

European-Finnish (FIN) AF: 0.0135 AC: 5 AN: 370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 38

European-Non Finnish (NFE) AF: 0.00713 AC: 39 AN: 5470

Other (OTH) AF: 0.00383 AC: 2 AN: 522

GnomAD4 genome AF: 0.00845 AC: 1286 AN: 152218 Hom.: 9 Cov.: 32 AF XY: 0.00849 AC XY: 632 AN XY: 74416

African (AFR) AF: 0.00149 AC: 62 AN: 41564

American (AMR) AF: 0.00295 AC: 45 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.00374 AC: 18 AN: 4816

European-Finnish (FIN) AF: 0.0221 AC: 235 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 874 AN: 68004

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.0181 Hom.: 6

ClinVar

ClinVar submissions

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
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs543784712; hg19: chr4-93743901;