Genetic Variant NM_001510.4:c.-317C>T (chr4-92304340-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.768

Variant links:

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 links:

ENSG00000248511 (HGNC:):

ENSG00000248511 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRID2	NM_001510.4 link	c.-317C>T		5_prime_UTR_variant	Exon 1 of 16	ENST00000282020.9	NP_001501.2	O43424-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GRID2	ENST00000282020 link	c.-317C>T	5_prime_UTR_variant	Exon 1 of 16	1	NM_001510.4	ENSP00000282020.4	O43424-1
GRID2	ENST00000505687.5 link	n.-145C>T	upstream_gene_variant		1
ENSG00000248511	ENST00000504213.1 link	n.-162G>A	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0310

AC:

4723

AN:

152122

Hom.:

236

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00278

AC XY:

340

AN XY:

122174

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.00669

Gnomad4 ASJ exome

AF:

0.000489

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000189

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000515

Gnomad4 OTH exome

AF:

0.00771

GnomAD4 genome

AF:

0.0311

AC:

4728

AN:

152240

Hom.:

236

Cov.:

AF XY:

0.0290

AC XY:

2156

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0269

Hom.:

Bravo

AF:

0.0354

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over