4-92822750-T-TCCAGGGCATG

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRID2	NM_001510.4	c.244+232466_244+232475dupCAGGGCATGC		intron_variant	Intron 2 of 15	ENST00000282020.9	NP_001501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRID2	ENST00000282020.9	c.244+232466_244+232475dupCAGGGCATGC		intron_variant	Intron 2 of 15	1	NM_001510.4	ENSP00000282020.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000904

Gnomad4 FIN exome AF: 0.0135

Gnomad4 NFE exome AF: 0.00713

Gnomad4 OTH exome AF: 0.00383

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

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00295

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00374

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.0181 Hom.: 6

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GRID2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs543784712; hg19: chr4-93743901;