4-92304923-C-G

Position:

• chr4-92304923-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRID2	NM_001510.4	c.88+179C>G		intron_variant		ENST00000282020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRID2	ENST00000282020.9	c.88+179C>G		intron_variant		1	NM_001510.4	P1
GRID2	ENST00000510992.5	c.88+179C>G		intron_variant		1
GRID2	ENST00000505687.5	n.260+179C>G		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.0446

Gnomad4 AMR AF: 0.0861

Gnomad4 ASJ AF: 0.0753

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.0754

Gnomad4 FIN AF: 0.0751

Gnomad4 NFE AF: 0.0807

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0262 Hom.: 15

Bravo AF: 0.0674

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.63

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: rs62310990; hg19: chr4-93226074;